Papers by Olafur Baldursson
Humana Press eBooks, Oct 7, 2010
The lung epithelium is structurally and functionally a complex tissue composed of different cell ... more The lung epithelium is structurally and functionally a complex tissue composed of different cell types. It is exposed to toxic agents and pathogens that can with time result in various lung diseases, including lung cancer. The major cell types in the proximal tracheobronchial part are basal cells, goblet cells, ciliated cells, and cells of the submucosal glands. Further down the bronchial tree, Clara cells replace basal cells. Neuroendocrine cells can be found spread throughout the bronchial tree and in cell clusters referred to as neuroendocrine bodies. The most distal part of the lung contains the type I and type II respiratory alveolar cells. The branching form of the lung epithelium necessitates that stem cells located within special niches down the respiratory tree maintain the structural and functional integrity of the lung during normal cellular turnover and during repair. The stem cell niche in the lung is poorly defined, but as in many other organs, stromal cells and extracellular matrix likely play a fundamental role in regulating stem cell activity. Basal cells and cells in the neck of the submucosal glands have been shown to contain stem cell characteristics in trachea and large bronchi. In the bronchioles a subpopulation of Clara cells, the so-called variant Clara cells, and bronchioalveolar stem cells can generate both epithelial cells of the bronchioles and alveolar type II cells that in turn can generate type I cells. Increased knowledge of the cellular context of the lung epithelium, including spatial location of endogenous stem cells and characterization of the stem cell niche, may in the near future have a major impact on the understanding and treatment of many lung diseases.
Laeknabladid, Dec 1, 2008
The purpose of this paper is to give a brief overview of cystic fibrosis; its pathogenesis, diagn... more The purpose of this paper is to give a brief overview of cystic fibrosis; its pathogenesis, diagnosis, treatment and prognosis. Cystic fibrosis is an autosomal recessive disorder, which is caused by a mutation in the CFTR protein, a chloride channel in epithelial cell membranes. More than 1500 mutations are known. The incidence is 1/2.000-3.000 in nations of European origin. The CFTR mutation influences the secretion and absorption by epithelium in various organs. The consequences are different depending on the organ, but there is a global tendency for obstruction of secretory glands. The primary organs affected are the respiratory tract, pancreas, gastrointestinal tract and sweat glands. The disease is most often diagnosed during the first months of life, with a common presentation of salty tasting sweat, failure to thrive and diverse faecal problems. Possible diagnostic tools are sweat test and DNA testing. Respiratory symptoms cause most morbidity, with chronic infections and an exaggerated inflammatory response. Abnormal water and electrolyte composition leads to thicker respiratory secretions compared to that of healthy individuals. The interaction of pathogens with the epithelium causes S. aureus, and later P. aeuruginosa, to transform into a mucoid form which is much more difficult to eradicate with antibiotics, making them a significant part of the disease burden of cystic fibrosis. The main respiratory medications are antibiotics, bronchodilators, mucolytic agents and anti-inflammatory agents. 90% of cystic fibrosis patients have pancreas insufficiency which is treated with pancreas enzymes. A good nutritional status is a necessary basis for any further treatment. The prognosis of cystic fibrosis patients has improved greatly over the last few decades in parallel with increased knowledge, and the average survival is currently 37 years in the United States.
Journal of Biological Chemistry, 2001
Laeknabladid, Apr 1, 2014
Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/OpenA... more Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/OpenA 63 year old woman seeks medical attention for symptoms of fever, headache and increasing dyspnoea. She has a history of psoriatic-arthritis and uses 10 mg/week of methotrexate as arthritic treatment. There is also a history of severe alcohol abuse. She is in respiratory failure, with basal pulmonary crackles and increased serum inflammatory markers, a normal white-cell count but with a lowered lymphocyte count. A CT-scan reveals ground-glass lung changes. Bronchial biopsy reveals the fungus P. jiroveci which infects immunodeficient hosts. After extensive testing it was concluded that the patient's immunodeficiency was attributed to the combination of methotrexate, ethanol and psoriatic-arthritis. In this article, a case of pneumocystis pneumonia is reviewed as well as the infective mechanism of P. jiroveci and host-defence against the fungus. Additionally, symptoms and signs of the ...
Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/OpenT... more Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/OpenThe purpose of this paper is to give a brief overview of cystic fibrosis; its pathogenesis, diagnosis, treatment and prognosis. Cystic fibrosis is an autosomal recessive disorder, which is caused by a mutation in the CFTR protein, a chloride channel in epithelial cell membranes. More than 1500 mutations are known. The incidence is 1/2.000-3.000 in nations of European origin. The CFTR mutation influences the secretion and absorption by epithelium in various organs. The consequences are different depending on the organ, but there is a global tendency for obstruction of secretory glands. The primary organs affected are the respiratory tract, pancreas, gastrointestinal tract and sweat glands. The disease is most often diagnosed during the first months of life, with a common presentation of salty tasting sweat, failure to thrive and diverse faecal problems. Possible diagnostic tools are sweat ...
Pharmacological Reviews, 2021
Based on its immunomodulatory properties and ability to enhance the protective role of the lung e... more Based on its immunomodulatory properties and ability to enhance the protective role of the lung epithelium against pathogens, azithromycin has proven superior to other macrolides in treating chronic respiratory inflammation. A nonantibiotic azithromycin derivative is likely to offer prophylactic benefits against inflammation and epithelial damage of differing causes while preserving the use of macrolides as antibiotics.
Figure S2. Azm induced MVB and LB formation. A) BCi-NS1.1 cells differentiated in ALI cultures tr... more Figure S2. Azm induced MVB and LB formation. A) BCi-NS1.1 cells differentiated in ALI cultures treated with Azm showed a marked increase in MVB and LB formations. Shown are two different cross sectional TEM images of transwell filters. Scale bars are from left 10.0, 2.0, 1.0 and 1.0 μm. B) Treating differentiated VA10 cells with a clinical formulation of Azm (Zithromax) also resulted in increased MVB and LB formations. Top scale bars are 5.0 μm and bottom scale bars are 1.0 μm. C) Differentiated BCi-NS1.1 cells showed similar MVB and LB formations after treatment with Azm (Zithromax). Top scale bars are 5.0 μm and bottom scale bars are 1.0 μm. (TIF 33306 kb)
Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/Open ... more Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/Open The quality of doctor-patient communication is critical for the practice of medicine. Studies show that effective communication results in patient satisfaction and improved compliance. To better understand one aspect of this complex phenomenon we estimated the ability of people to comprehend 11 commonly used medical terms. We used multiple choice questions in a telephone survey of 1167 Icelanders aged 16-75 years. Results (% of participants with correct answers): Gastroesophageal reflux (72), emphysema (25), steroids (40), one tablet twice a day (79), side effects (67), bronchitis (68), white blood cells (56), erythrocyte sedimentation rate (33), diabetes mellitus (72), antibiotics (87), chronic obstructive pulmonary disease (42). Variables associated with better comprehension were: Female gender (better in 7/10 questions), university degree (10/10) and high income (9/10). Decision tree ...
Laeknabladid, 2005
Results: 100 subjects completed the questionnaire (response rate 45%), 61 interns and residents a... more Results: 100 subjects completed the questionnaire (response rate 45%), 61 interns and residents and 39 medical students. Of those completing the questionnaire, most interns and residents (97%) and medical students (87%) agreed or agreed strongly with the concept of postgraduate training in Iceland. The majority of responders wanted to undergo part of their postgraduate training in Iceland if this option would be available. Those who preferred postgraduate training in Iceland did so for the following reasons: The importance of “hands-on” training, availability of consultants, favorable social setting and organized teaching. Those who wanted to do all their postgraduate training abroad rated case variability, “hands-on” training, organized teaching and research opportunities as the main factors influencing their decision.
Laeknabladid
The purpose of this paper is to give a brief overview of cystic fibrosis; its pathogenesis, diagn... more The purpose of this paper is to give a brief overview of cystic fibrosis; its pathogenesis, diagnosis, treatment and prognosis. Cystic fibrosis is an autosomal recessive disorder, which is caused by a mutation in the CFTR protein, a chloride channel in epithelial cell membranes. More than 1500 mutations are known. The incidence is 1/2.000-3.000 in nations of European origin. The CFTR mutation influences the secretion and absorption by epithelium in various organs. The consequences are different depending on the organ, but there is a global tendency for obstruction of secretory glands. The primary organs affected are the respiratory tract, pancreas, gastrointestinal tract and sweat glands. The disease is most often diagnosed during the first months of life, with a common presentation of salty tasting sweat, failure to thrive and diverse faecal problems. Possible diagnostic tools are sweat test and DNA testing. Respiratory symptoms cause most morbidity, with chronic infections and an ...
Open Forum Infectious Diseases
Background. The microbial etiology of community-acquired pneumonia (CAP) is often unclear in clin... more Background. The microbial etiology of community-acquired pneumonia (CAP) is often unclear in clinical practice, and previous studies have produced variable results. Population-based studies examining etiology and incidence are lacking. This study examined the incidence and etiology of CAP requiring hospitalization in a population-based cohort as well as risk factors and outcomes for specific etiologies. Methods. Consecutive admissions due to CAP in Reykjavik, Iceland were studied. Etiologic testing was performed with cultures, urine-antigen detection, and polymerase chain reaction analysis of airway samples. Outcomes were length of stay, intensive care unit admission, assisted ventilation, and mortality. Results. The inclusion rate was 95%. The incidence of CAP requiring hospitalization was 20.6 cases per 10 000 adults/year. A potential pathogen was detected in 52% (164 of 310) of admissions and in 74% (43 of 58) with complete sample sets. Streptococcus pneumoniae was the most common pathogen (61 of 310, 20%; incidence: 4.1/10 000). Viruses were identified in 15% (47 of 310; incidence: 3.1/10 000), Mycoplasma pneumoniae were identified in 12% (36 of 310; incidence: 2.4/10 000), and multiple pathogens were identified in 10% (30 of 310; incidence: 2.0/10 000). Recent antimicrobial therapy was associated with increased detection of M pneumoniae (P < .001), whereas a lack of recent antimicrobial therapy was associated with increased detection of S pneumoniae (P = .02). Symptoms and outcomes were similar irrespective of microbial etiology. Conclusions. Pneumococci, M pneumoniae, and viruses are the most common pathogens associated with CAP requiring hospital admission, and they all have a similar incidence that increases with age. Symptoms do not correlate with specific agents, and outcomes are similar irrespective of pathogens identified.
Respiratory Research
Background: Azithromycin (Azm) is a macrolide recognized for its disease-modifying effects and re... more Background: Azithromycin (Azm) is a macrolide recognized for its disease-modifying effects and reduction in exacerbation of chronic airway diseases. It is not clear whether the beneficial effects of Azm are due to its anti-microbial activity or other pharmacological actions. We have shown that Azm affects the integrity of the bronchial epithelial barrier measured by increased transepithelial electrical resistance. To better understand these effects of Azm on bronchial epithelia we have investigated global changes in gene expression. Methods: VA10 bronchial epithelial cells were treated with Azm and cultivated in air-liquid interface conditions for up to 22 days. RNA was isolated at days 4, 10 and 22 and analyzed using high-throughput RNA sequencing. qPCR and immunostaining were used to confirm key findings from bioinformatic analyses. Detailed assessment of cellular changes was done using microscopy, followed by characterization of the lipidomic profiles of the multivesicular bodies present. Results: Bioinformatic analysis revealed that after 10 days of treatment genes encoding effectors of sterol and cholesterol metabolism were prominent. Interestingly, expression of genes associated with epidermal barrier differentiation, KRT1, CRNN, SPINK5 and DSG1, increased significantly at day 22. Together with immunostaining, these results suggest an epidermal differentiation pattern. We also found that Azm induced the formation of multivesicular and lamellar bodies in two different airway epithelial cell lines. Lipidomic analysis revealed that Azm was entrapped in multivesicular bodies linked to different types of lipids, most notably palmitate and stearate. Furthermore, targeted analysis of lipid species showed accumulation of phosphatidylcholines, as well as ceramide derivatives. Conclusions: Taken together, we demonstrate how Azm might confer its barrier enhancing effects, via activation of epidermal characteristics and changes to intracellular lipid dynamics. These effects of Azm could explain the unexpected clinical benefit observed during Azm-treatment of patients with various lung diseases affecting barrier function.
Open Forum Infectious Diseases, 2015
Laeknabladid, Apr 1, 2014
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Papers by Olafur Baldursson