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- Ahlström-Emanuelsson, Cecilia, et al.
(författare)
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Establishing a model of seasonal allergic rhinitis and demonstrating dose-response to a topical glucocorticosteroid
- 2002
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Ingår i: Annals of Allergy, Asthma & Immunology. - 1081-1206. ; 89:2, s. 159-165
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Tidskriftsartikel (refereegranskat)abstract
- Background: Symptoms of seasonal allergic rhinitis may vary greatly. Hence, for research purposes, there is a need for disease-like models of allergic rhinitis. In a preliminary study, involving 7 days' challenge with allergen, promising symptom consistency was obtained and dose-response to a glucocorticosteroid could, in part, be demonstrated. Objective: To establish this model of seasonal allergic rhinitis and test the hypothesis that mometasone furoate is more potent than budesonide as an antirhinitis drug. Methods: Thirty-eight patients with seasonal allergic rhinitis received treatment with spray-formulations of placebo, budesonide 64 kg, budesonide 256 mug, and mometasone furoate 200 mug in a double-blind, crossover design. After 3 days' treatment, individualized nasal allergen-challenges were administered daily for 7 days while the treatment continued. Nasal symptoms and peak inspiratory flow (PIF) were recorded. Results: During the last 3 days of allergen challenge without active treatment, consistent around-the-clock symptoms were recorded and recordings during these days were used in the analysis. With few exceptions the active treatments reduced nasal symptoms and improved nasal PIF (P values <0.001 to 0.05). Budesonide caused dose-dependent improvements in evening symptoms, morning nasal PIF, and nasal PIF recorded 10 minutes after allergen-challenge (P values <0.05). Budesonide 256 mug produced greater improvement than mometasone furoate 200 mug for nasal PIF 10 minutes after allergen-challenge (P < 0.05). Conclusion: The present allergen challenge method, producing consistent symptoms and nasal PIF data, emerges as a model of seasonal allergic rhinitis well suited for exploring potency and efficacy of drug intervention. The present data do not support the view that mometasone furoate is a more potent antirhinitis drug than budesonide.
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- Akerlund, Cecilia A., I, et al.
(författare)
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Clinical descriptors of disease trajectories in patients with traumatic brain injury in the intensive care unit (CENTER-TBI) : a multicentre observational cohort study
- 2024
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Ingår i: Lancet Neurology. - : Elsevier BV. - 1474-4422 .- 1474-4465. ; 23:1, s. 71-80
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Tidskriftsartikel (refereegranskat)abstract
- Background Patients with traumatic brain injury are a heterogeneous population, and the most severely injured individuals are often treated in an intensive care unit (ICU). The primary injury at impact, and the harmful secondary events that can occur during the first week of the ICU stay, will affect outcome in this vulnerable group of patients. We aimed to identify clinical variables that might distinguish disease trajectories among patients with traumatic brain injury admitted to the ICU. Methods We used data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) prospective observational cohort study. We included patients aged 18 years or older with traumatic brain injury who were admitted to the ICU at one of the 65 CENTER-TBI participating centres, which range from large academic hospitals to small rural hospitals. For every patient, we obtained pre-injury data and injury features, clinical characteristics on admission, demographics, physiological parameters, laboratory features, brain biomarkers (ubiquitin carboxy-terminal hydrolase L1 [UCH-L1], S100 calcium-binding protein B [S100B], tau, neurofilament light [NFL], glial fibrillary acidic protein [GFAP], and neuron-specific enolase [NSE]), and information about intracranial pressure lowering treatments during the first 7 days of ICU stay. To identify clinical variables that might distinguish disease trajectories, we applied a novel clustering method to these data, which was based on a mixture of probabilistic graph models with a Markov chain extension. The relation of clusters to the extended Glasgow Outcome Scale (GOS-E) was investigated. Findings Between Dec 19, 2014, and Dec 17, 2017, 4509 patients with traumatic brain injury were recruited into the CENTER-TBI core dataset, of whom 1728 were eligible for this analysis. Glucose variation (defined as the difference between daily maximum and minimum glucose concentrations) and brain biomarkers (S100B, NSE, NFL, tau, UCH-L1, and GFAP) were consistently found to be the main clinical descriptors of disease trajectories (ie, the leading variables contributing to the distinguishing clusters) in patients with traumatic brain injury in the ICU. The disease trajectory cluster to which a patient was assigned in a model was analysed as a predictor together with variables from the IMPACT model, and prediction of both mortality and unfavourable outcome (dichotomised GOS-E <= 4) was improved. Interpretation First-day ICU admission data are not the only clinical descriptors of disease trajectories in patients with traumatic brain injury. By analysing temporal variables in our study, variation of glucose was identified as the most important clinical descriptor that might distinguish disease trajectories in the ICU, which should direct further research. Biomarkers of brain injury (S100B, NSE, NFL, tau, UCH-L1, and GFAP) were also top clinical descriptors over time, suggesting they might be important in future clinical practice.
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- Bengtsson, T, et al.
(författare)
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Loss of alpha 10 beta 1 integrin expression leads to moderate dysfunction of growth plate chondrocytes
- 2005
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Ingår i: Journal of Cell Science. - : The Company of Biologists. - 0021-9533 .- 1477-9137. ; 118:5, s. 929-936
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Tidskriftsartikel (refereegranskat)abstract
- Integrin alpha 10 beta 1 is a collagen-binding integrin expressed on chondrocytes. In order to unravel the role of the alpha 10 integrin during development, we generated mice carrying a constitutive deletion of the alpha 10 integrin gene. The mutant mice had a normal lifespan and were fertile but developed a growth retardation of the long bones. Analysis of the skeleton revealed defects in the growth plate after birth characterized by a disturbed columnar arrangement of chondrocytes, abnormal chondrocyte shape and reduced chondrocyte proliferation. Electron microscopy of growth plates from newborn mice revealed an increased number of apoptotic chondrocytes and reduced density of the collagen fibrillar network compared to these structures in control mice. These results demonstrate that integrin alpha 10 beta 1 plays a specific role in growth plate morphogenesis and function.
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- Cervin, Anders, et al.
(författare)
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The effect of intranasal budesonide spray on mucosal blood flow measured with laser Doppler flowmetry
- 2001
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Ingår i: Rhinology. - 0300-0729. ; 39:1, s. 13-16
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recent reports have shown that, although rare, findings of mucosal ulcers and perforations of the nasal septum in some cases may be associated with the use of topical nasal glucocorticosteroids (GCS). It can been speculated that, a reduction in septal mucosal blood flow causing ischemia may eventually induce septal perforations. AIM: To evaluate whether a single dose of a potent nasal GCS given in a clinically recommended dose may acutely reduce the mucosal blood flow on the nasal septum. METHODS: Six healthy subjects received in a randomised double blind placebo controlled crossover procedure one dose of 64 micrograms budesonide aqueous nasal spray (Rhinocort aqua, AstraZeneca R&D, Lund, Sweden) and placebo. One dose was delivered into each nasal cavity by means of a pump spray. As a positive control 140 micrograms of xylometazoline (Nezeril, AstraZeneca R&D, Lund, Sweden) was sprayed in the same way, but in an open fashion. A wash-out period of at least 3 days followed each session. Blood flow was measured on the nasal septum with Laser Doppler flowmetry up to 20 min after administration. RESULTS: Budesonide did not affect the nasal septal mucosal blood flow as compared to placebo, but xylometazoline reduced the septal mucosal blood flow by 60.9 +/- 7.1% measured from baseline values. CONCLUSION: A single dose of intranasal budesonide aqueous nasal spray has no acute effects on nasal septal mucosal blood flow.
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- Downie, SR, et al.
(författare)
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Association between nasal and bronchial symptoms in subjects with persistent allergic rhinitis
- 2004
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Ingår i: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 59:3, s. 320-326
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Tidskriftsartikel (refereegranskat)abstract
- Background: The association between nasal and bronchial symptoms, and the course of bronchial responsiveness and airway inflammation in house dust mite sensitive persistent rhinitis over a prolonged time period has not been thoroughly explored. Objective: To determine if nasal symptoms were associated with bronchial symptoms in persistent rhinitic subjects, and to assess their bronchial responsiveness and airway inflammation in comparison to nonrhinitic, nonatopic controls. The additional impact of pollen sensitivity on the lower airways in rhinitic subjects was also addressed. Methods: Rhinitics and controls answered telephone symptom questionnaires once every 2 weeks for 1 year. Every 3 months, exhaled nitric oxide (eNO) and bronchial responsiveness to histamine were measured. Results: Thirty-seven rhinitics and 19 controls completed the study. High nasal symptom scores in rhinitic subjects were associated with bronchial symptoms (OR = 1.7, 95% CI 1.2-2.5). Bronchial hyper-responsiveness was present in 32.4% of rhinitic subjects on at least one clinical visit during the year. Pollen allergy caused seasonal variation in eNO (P = 0.03). Conclusion: In persistent rhinitic subjects, high nasal symptom scores were associated with bronchial symptoms, and many subjects experienced bronchial hyper-responsiveness during the year. Persistent rhinitic subjects were more at risk than healthy adults of bronchial symptoms and airway inflammation, which are likely risk factors for asthma.
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- Duffy, Stephen W., et al.
(författare)
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Mammography screening reduces rates of advanced and fatal breast cancers : Results in 549,091 women
- 2020
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Ingår i: Cancer. - : John Wiley & Sons. - 0008-543X .- 1097-0142. ; 126:13, s. 2971-2979
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is of paramount importance to evaluate the impact of participation in organized mammography service screening independently from changes in breast cancer treatment. This can be done by measuring the incidence of fatal breast cancer, which is based on the date of diagnosis and not on the date of death.Methods: Among 549,091 women, covering approximately 30% of the Swedish screening‐eligible population, the authors calculated the incidence rates of 2473 breast cancers that were fatal within 10 years after diagnosis and the incidence rates of 9737 advanced breast cancers. Data regarding each breast cancer diagnosis and the cause and date of death of each breast cancer case were gathered from national Swedish registries. Tumor characteristics were collected from regional cancer centers. Aggregated data concerning invitation and participation were provided by Sectra Medical Systems AB. Incidence rates were analyzed using Poisson regression.Results: Women who participated in mammography screening had a statistically significant 41% reduction in their risk of dying of breast cancer within 10 years (relative risk, 0.59; 95% CI, 0.51‐0.68 [P < .001]) and a 25% reduction in the rate of advanced breast cancers (relative risk, 0.75; 95% CI, 0.66‐0.84 [P < .001]).Conclusions: Substantial reductions in the incidence rate of breast cancers that were fatal within 10 years after diagnosis and in the advanced breast cancer rate were found in this contemporaneous comparison of women participating versus those not participating in screening. These benefits appeared to be independent of recent changes in treatment regimens.
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- Gravesteijn, Benjamin Y., et al.
(författare)
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Toward a New Multi-Dimensional Classification of Traumatic Brain Injury : A Collaborative European NeuroTrauma Effectiveness Research for Traumatic Brain Injury Study
- 2020
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 37:7, s. 1002-1010
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Tidskriftsartikel (refereegranskat)abstract
- Traumatic brain injury (TBI) is currently classified as mild, moderate, or severe TBI by trichotomizing the Glasgow Coma Scale (GCS). We aimed to explore directions for a more refined multidimensional classification system. For that purpose, we performed a hypothesis-free cluster analysis in the Collaborative European NeuroTrauma Effectiveness Research for TBI (CENTER-TBI) database: a European all-severity TBI cohort (n = 4509). The first building block consisted of key imaging characteristics, summarized using principal component analysis from 12 imaging characteristics. The other building blocks were demographics, clinical severity, secondary insults, and cause of injury. With these building blocks, the patients were clustered into four groups. We applied bootstrap resampling with replacement to study the stability of cluster allocation. The characteristics that predominantly defined the clusters were injury cause, major extracranial injury, and GCS. The clusters consisted of 1451, 1534, 1006, and 518 patients, respectively. The clustering method was quite stable: the proportion of patients staying in one cluster after resampling and reclustering was 97.4% (95% confidence interval [CI]: 85.6-99.9%). These clusters characterized groups of patients with different functional outcomes: from mild to severe, 12%, 19%, 36%, and 58% of patients had unfavorable 6 month outcome. Compared with the mild and the upper intermediate cluster, the lower intermediate and the severe cluster received more key interventions. To conclude, four types of TBI patients may be defined by injury mechanism, presence of major extracranial injury and GCS. Describing patients according to these three characteristics could potentially capture differences in etiology and care pathways better than with GCS only.
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- Olofsson, A M, et al.
(författare)
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Heparin-binding protein targeted to mitochondrial compartments protects endothelial cells from apoptosis
- 1999
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Ingår i: Journal of Clinical Investigation. - 0021-9738. ; 104:7, s. 885-894
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Tidskriftsartikel (refereegranskat)abstract
- Neutrophil-borne heparin-binding protein (HBP) is a multifunctional protein involved in the progression of inflammation. HBP is stored in neutrophil granules and released upon stimulation of the cells in proximity to endothelial cells. HBP affects endothelial cells in multiple ways; however, the molecular and cellular mechanisms underlying the interaction of HBP with these cells are unknown. Affinity isolation and enzymatic degradation demonstrated that HBP released from human neutrophils binds to endothelial cell-surface proteoglycans, such as syndecans and glypican. Flow cytometry indicated that a significant fraction of proteoglycan-bound HBP is taken up by the endothelial cells, and we used radiolabeled HBP to determine the internalization rate of surface-bound HBP. Confocal and electron microscopy revealed that internalized HBP is targeted to perinuclear compartments of endothelial cells, where it colocalizes with mitochondria. Western blotting of isolated mitochondria from HBP-treated endothelial cells showed that HBP is present in 2 forms - 28 and 22 kDa. Internalized HBP markedly reduced growth factor deprivation-induced caspase-3 activation and protected endothelial cells from apoptosis, suggesting that uptake and intracellular routing of exogenous HBP to mitochondria contributes to the sustained viability of endothelial cells in the context of locally activated neutrophils.
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- Tjerneld, F., et al.
(författare)
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Linear Dichroism of Chloroplasts and Subchloroplast Fractions Oriented by Flow
- 1977
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Ingår i: Spectroscopy Letters. - : Informa UK Limited. - 1532-2289 .- 0038-7010. ; 10:6, s. 489-493
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Tidskriftsartikel (refereegranskat)abstract
- Chloroplasts as well as subchloroplast vesicles show linear dichroism (LD) when subjected to a hydrodynamic gradient. LD is positive for the ππ in-plane polarized bands indicating that the chlorophyll porphyrin ring is in average oriented parallel1 to the elongated membrane surfaces. The vesicle fraction enriched inphotosystem I1 shows lower LD/A at 660 nm indicating lower average orientation of chlorophyll and the fraction enriched in photosystem I shows higher LD/A at 700 nm indicating that P700 is more oriented than the bulk chlorophyll.
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- Wullt, Marlene, et al.
(författare)
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IgG Antibody Response to Toxins A and B in Patients with Clostridium difficile Infection.
- 2012
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Ingår i: Clinical and Vaccine Immunology. - 1556-6811. ; 19:9, s. 1552-1554
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Tidskriftsartikel (refereegranskat)abstract
- IgG antibodies against Clostridium difficile toxins A and B were followed in controls and patients with an initial C. difficile infection (CDI). Of the 50 CDI patients, 38 were cured and 12 developed recurrence. Compared to controls, patients had significantly lower anti-toxin A and B IgGs at inclusion, but the subsequent levels rose slightly regardless of clinical outcome. The results imply that the general serum reactivity against toxins A and B in the population reduces the risk of CDI, which suggests implications for vaccine strategies.
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