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Biomedical subjects

L P Nielsen

Publications and source records attributed to L P Nielsen.

At least 19 recordsLinked to original sources

Intranasal and inhaled fluticasone propionate for pollen-induced rhinitis and asthma.

BACKGROUND: Studies suggest that nasal treatment might influence lower airway symptoms and function in patients with comorbid rhinitis and asthma. We investigated the effect of intranasal, inhaled corticosteroid or the combination of both in patients with both pollen-induced rhinitis and asthma. METHODS: A total of 262 patients were randomized to 6 weeks' treatment with intranasal fluticasone propionate (INFP) 200 microg o.d., inhaled fluticasone propionate (IHFP) 250 microg b.i.d., their combination, or intranasal or inhaled placebo, in a multicentre, double-blind, parallel-group study. Treatment was started 2 weeks prior to the pollen season and patients recorded their nasal and bronchial symptoms twice daily. Before and after 4 and 6 weeks' treatment, the patients were assessed for lung function, methacholine responsiveness, and induced sputum cell counts. RESULTS: Intranasal fluticasone propionate significantly increased the percentages of patients reporting no nasal blockage, sneezing, or rhinorrhoea during the pollen season, compared with IHFP or intranasal or inhaled placebo. In contrast, only IHFP significantly improved morning peak-flow, forced expiratory volume in 1 second (FEV1) and methacholine PD20, and the seasonal increase in the sputum eosinophils and methacholine responsiveness. CONCLUSIONS: In patients with pollen-induced rhinitis and asthma, the combination of intranasal and IHFP is needed to control the seasonal increase in nasal and asthmatic symptoms.

Administration, Inhalation↗

Anaerobic ammonium oxidation by marine and freshwater planctomycete-like bacteria.

Recently, two fresh water species, " Candidatus Brocadia anammoxidans" and " Candidatus Kuenenia stuttgartiensis", and one marine species, " Candidatus Scalindua sorokinii", of planctomycete anammox bacteria have been identified. " Candidatus Scalindua sorokinii" was discovered in the Black Sea, and contributed substantially to the loss of fixed nitrogen. All three species contain a unique organelle--the anammoxosome--in their cytoplasm. The anammoxosome contains the hydrazine/hydroxylamine oxidoreductase enzyme, and is thus the site of anammox catabolism. The anammoxosome is surrounded by a very dense membrane composed almost exclusively of linearly concatenated cyclobutane-containing lipids. These so-called 'ladderanes' are connected to the glycerol moiety via both ester and ether bonds. In natural and man-made ecosystems, anammox bacteria can cooperate with aerobic ammonium-oxidising bacteria, which protect them from harmful oxygen, and provide the necessary nitrite. The cooperation of these two groups of ammonium-oxidising bacteria is the microbial basis for a sustainable one reactor system, CANON (completely autotrophic nitrogen-removal over nitrite) to remove ammonia from high strength wastewater.

Anaerobiosis↗

Effect of ciclesonide on allergen challenge in subjects with bronchial asthma.

BACKGROUND: The aim of this clinical trial was to investigate whether repeated inhalation of the new inhaled steroid ciclesonide reduces the early-phase (EAR) and late-phase (LAR) reactions after allergen challenge in patients with mild allergic asthma. Also, this study provides further data on safety and tolerance of ciclesonide. METHODS: The study was designed as a double-blind placebo-controlled randomized crossover trial. Following a baseline period, patients were randomized to either of two treatment sequences (ciclesonide/placebo, placebo/ciclesonide) each of which lasted for one week and were separated by 3-5 weeks from the alternate treatment sequence. Patients received 800 micro g ciclesonide twice daily by means of a Cyclohaler. At the end of each treatment patients were subjected to an allergen challenge. RESULTS: Thirteen asthmatic patients (mean FEV1 of 91% predicted) who experienced an EAR and LAR after allergen challenge participated in the study. The time-average FEV1 decreases 0-2 h (2-12 h) after allergen challenge as measure of the EAR (LAR) were significantly reduced (P < 0.05, one-sided) from 0.426 L to 0.233 L (EAR) and from 0.443 L to 0.213 L (LAR), respectively. Thus, the study results suggest that ciclesonide significantly lowered the extent of EAR and LAR compared to placebo. Ciclesonide was well tolerated and no drug-related adverse events were reported. Cortisol excretion in 24-h urine showed no significant difference between ciclesonide and placebo. CONCLUSIONS: The study supports the efficacy and safety of ciclesonide.

Administration, Inhalation↗

Detection and subtyping (H5 and H7) of avian type A influenza virus by reverse transcription-PCR and PCR-ELISA.

Avian influenza virus infections are a major cause of morbidity and rapid identification of the virus has important clinical, economical and epidemiological implications. We have developed a one-tube Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) for the rapid diagnosis of avian influenza A. A panel of reference influenza strains from various hosts including avian species, human, swine and horse were evaluated in a one tube RT-PCR using primers designed for the amplification of a 218 bp fragment of the NP gene. The PCR products were detected by PCR-ELISA by use of an internal catching probe confirming the NP influenza A origin. The PCR-ELISA was about 100 times more sensitive than detection of PCR products by agarose gel electrophoresis. RT-PCR and detection by PCR-ELISA is comparable in sensitivity to virus propagation in eggs. We also designed primers for the detection of the influenza. A subtypes H5 and H7 shown to have pathogenic potential in poultry. The H5 primers cover the cleavage site of the HA gene and specifically amplify influenza A subtype H5. The H7 primers also cover the HA cleavage site and detected all H7 reference strains investigated. In addition, the H7 primers also amplified very weak and/or additional bands on an agarose gel from other subtypes. However, the H7 origin and the pathogenic potential defined by the presence or absence of basic amino acids at the cleavage site can be determined by sequencing of the PCR product. As far as we know this is the first demonstration of RT-PCR detection on a panel of H7 strains using only one primer set.

Animals↗

Methane microprofiles in a sewage biofilm determined with a microscale biosensor.

Microprofiles of the methane concentration in a 3.5-mm-thick sewage outlet biofilm were measured at high spatial and temporal resolution using a microscale biosensor for methane. In the freshly collected biofilm, methane was building up to a concentration of 175 mumol l-1 at 3 mm depth with a total methanogenesis of 0.14 mumol m-2 s-1, as compared to an aerobic respiration (including methane oxidation) of 0.80 mumol m-2 s-1. A model biofilm was established by homogenisation of an in situ biofilm and 12 days of incubation with surplus sodium acetate. The homogenised biofilm was able to maintain 50% of the methanogenic activity in the absence of external electron donor. Oxygen had only a minor effect on the methane production, but aerobic respiration consumed a substantial part of the produced methane and was thus an important control on methane export from the biofilm. A concentration of 2 mmol l-1 nitrate was shown to inhibit methanogenesis only in the upper layer of the biofilm, whereas a further addition of 2 mmol l-1 sulphate inhibited methanogenesis in the entire biofilm. The study demonstrated the power of the methane microsensor in the study of microhabitats with concurrent production and consumption of methane.

Bacteria↗

Mode of action of intranasal corticosteroids.

The mode of action of intranasal corticosteroids (INCS) is complex. It is not known whether INCS penetrate the nasal mucosa or act on target cells; however, their low systemic activity supports the concept of local action on nasal mucosa. This local effect can nonetheless influence a variety of inflammatory cells and their mediators such as epithelial cells, lymphocytes, basophils, mast cells, and Langerhans cells. Corticosteroid-induced inhibition of immunoglobulin E-dependent release of histamine is a possible but unproven mode of action. Epithelial cells are an important target for corticosteroids, and INCS concentration is high at the epithelial surface. INCS may combine with the corticosteroid receptors in epithelial cells, which are then expelled into the airway lumen together with the dead epithelial cells or migrating inflammatory cells. A reduced influx of mediator cells may explain some of the effects of INCS on rhinitis symptoms, but it cannot explain all of the effects because INCS also reduce the early-phase sneezing and rhinorrhea after an allergen challenge outside the pollen season. In this situation, the number of surface mast cells/basophils is very low, as it is in the absence of allergic rhinitis. The mechanism by which INCS treatment of allergic rhinitis reduces itching, sneezing, and rhinorrhea, the characteristic symptoms of an early-phase response involving mast cell release of histamine, remains to be determined. Studies should be conducted to characterize the broad range of mechanisms by which INCS produce their therapeutic effects in allergic rhinitis.

Administration, Intranasal↗

Respiratory tract infections in cytomegalovirus-excreting and nonexcreting infants.

BACKGROUND: There is evidence of an immunosuppressive effect of cytomegalovirus (CMV), and CMV has been claimed to be a copathogen in respiratory tract infections (RTI). We therefore studied the significance of CMV viral load in infants with RTI, compared the frequency of infection with respiratory viruses and followed the course of RTI in CMV-excreting vs. nonexcreting infants. METHODS: We examined 201 infants consecutively admitted to the Department of Pediatrics for RTI. At admission nasopharyngeal aspirates, throat swabs and urine were examined for CMV, and nasopharyngeal aspirates were examined for respiratory viruses. RESULTS: In these patients 23.3% had CMV in the urine, 15.3% had CMV in the throat and 10.9% had CMV in the nasopharynx; 26.2% excreted CMV in at least one site. No relationship was found between CMV viral load and clinical symptoms. Infection with respiratory viruses was as common in infants excreting CMV as in nonexcreting infants. Symptoms and the course of infection were not different in the two groups except that CMV-excreting infants had a significantly higher frequency of rhonchi at admission (P = 0.007) and a tendency for longer duration of cough (P = 0.06). CONCLUSION: CMV viral load was not related to clinical symptoms. The frequency of infection with common respiratory viruses in infants was independent of CMV excretion. The course of infection was not more complicated in infants excreting CMV; however, a higher frequency of rhonchi was demonstrated in patients with CMV.

Child, Preschool↗

Ecology of Thioploca spp.: nitrate and sulfur storage in relation to chemical microgradients and influence of Thioploca spp. on the sedimentary nitrogen cycle.

Microsensors, including a recently developed NO3(-) biosensor, were applied to measure O(2) and NO3(-) profiles in marine sediments from the upwelling area off central Chile and to investigate the influence of Thioploca spp. on the sedimentary nitrogen metabolism. The studies were performed in undisturbed sediment cores incubated in a small laboratory flume to simulate the environmental conditions of low O(2), high NO3(-), and bottom water current. On addition of NO3(-) and NO2(-), Thioploca spp. exhibited positive chemotaxis and stretched out of the sediment into the flume water. In a core densely populated with Thioploca, the penetration depth of NO3(-) was only 0.5 mm and a sharp maximum of NO3(-) uptake was observed 0.5 mm above the sediment surface. In sediments with only few Thioploca spp., NO3(-) was detectable down to a depth of 2 mm and the maximum consumption rates were observed within the sediment. No chemotaxis toward nitrous oxide (N2O) was observed, which is consistent with the observation that Thioploca does not denitrify but reduces intracellular NO3(-) to NH(4)(+). Measurements of the intracellular NO3(-) and S(0) pools in Thioploca filaments from various depths in the sediment gave insights into possible differences in the migration behavior between the different species. Living filaments containing significant amounts of intracellular NO3(-) were found to a depth of at least 13 cm, providing final proof for the vertical shuttling of Thioploca spp. and nitrate transport into the sediment.

Biosensing Techniques↗

Intranasal corticosteroids for allergic rhinitis: superior relief?

Whether first-line pharmacological treatment of allergic rhinitis should be antihistamines or intranasal corticosteroids has been discussed for several years. First-generation antihistamines are rarely used in the treatment of allergic rhinitis, mainly because of sedative and anticholinergic adverse effects. On the basis of clinical evidence of efficacy, no second-generation antihistamine seems preferable to another. Similarly, comparisons of topical and oral antihistamines have been unable to demonstrate superior efficacy for one method of administration over the other. Current data documents no striking differences in efficacy and safety parameters between intranasal corticosteroids. When the efficacy of antihistamines and intranasal corticosteroids are compared in patients with allergic rhinitis, present data favours intranasal corticosteroids. Interestingly, data do not show antihistamines as superior for the treatment of conjunctivitis. Safety data from comparative studies in patients with allergic rhinitis do not indicate differences between antihistamines and intranasal corticosteroids. Combining antihistamines and intranasal corticosteroids in the treatment of allergic rhinitis does not provide any additional effect to intranasal corticosteroids alone. On the basis of current data, intranasal corticosteroids seem to offer superior relief in allergic rhinitis than antihistamines.

Administration, Inhalation↗

Herpesvirus type 1-8 in sinus aspirates from HIV-infected patients and immunocompetent individuals.

Sinusitis is frequently occurring in HIV-infected patients, but in a substantial number of cases the etiology is unknown. The purpose of this study was by PCR 1) to determine the prevalence of the eight human herpesviruses in sinus aspirates from 24 HIV-positive/AIDS patients with sinusitis 2) to relate the presence of herpesvirus DNA to clinical and immunological parameters and 3) to compare the prevalence of herpesvirus DNA in sinus aspirates from HIV-infected patients with the prevalence observed in 50 immunocompetent patients with sinusitis. DNA from HSV-1, EBV, CMV and HHV-8 was detected in 8 (33%) of the sinus aspirates from HIV-infected patients. In the immunocompetent patients, one of the herpesviruses, HHV-6, was found in one sinus aspirate. These data indicate that herpesviruses are frequently found in sinus aspirates from HIV-infected patients with sinusitis, whereas they do not seem to be related to clinical signs of sinusitis in immunocompetent individuals. The cause of these discrepancies may be due to uncontrolled reactivation of herpesviruses, which is known to occur in immunocompromised individuals. It remains to be established whether the herpesviruses play a pathogenic role in the development of sinusitis in HIV-infected patients.

Adult↗

Regulated exocytosis in immune function: are SNARE-proteins involved?

Inflammation is an important feature in the pathogenesis of most chronic lung diseases. It is characterized by tissue infiltration with various inflammatory cells, including eosinophils, mast cells, basophils, macrophages, neutrophils, T- and B-lymphocytes and dendritic cells (1). In the tissue granulocytes release their toxic granule proteins after being stimulated by soluble mediators released by other inflammatory cells (2). Therefore, it is important to characterize the intracellular mechanisms regulating the transport of the granule contents in inflammatory cells. Intracellular vesicle-traffic in mammalian cells is mediated by transport vesicles that emerge from donor compartments and are specifically targeted to acceptor compartments where they deliver their contents after membrane fusion (3). This traffic leads to three types of fusion: vesicle-intracellular membranes, vesicle-vesicle or vesicle-plasma membrane. The process leading to fusion of vesicle-plasma membrane is called exocytosis, and it delivers proteins to the cell surface (receptors e.g. CD11b, CD18) and exports soluble molecules (mediators e.g. ECP) from the cell. A number of key proteins involved in regulated exocytosis have been identified from inflammatory cells. This review is a brief summary of these proteins and it includes recent results from studies on regulated exocytosis in inflammatory cells.

B-Lymphocytes↗

Therapeutic ratio of inhaled corticosteroids in adult asthma. A dose-range comparison between fluticasone propionate and budesonide, measuring their effect on bronchial hyperresponsiveness and adrenal cortex function.

Inhaled corticosteroids have become the mainstay treatment of bronchial asthma. However, simultaneous evaluations of efficacy and side effects are few. This study aimed to compare the relative effect of fluticasone propionate (FP) and budesonide (BUD) on bronchial responsiveness and endogenous cortisol secretion in adults with asthma. The study was double-blind and included 66 adults with asthma, who were randomized to FP (n = 33) or BUD (n = 33). Prestudy, all participants were clinically stable, using inhaled corticosteroids and hyperresponsive to methacholine. Eligible patients were randomized to three consecutive 2-wk periods with either FP 250 microg twice daily, FP 500 microg twice daily, and FP 1,000 microg twice daily, or BUD 400 microg twice daily, BUD 800 microg twice daily, and BUD 1,600 microg twice daily, delivered by Diskhaler and Turbuhaler, respectively. Before randomization and at the end of each treatment, bronchial methacholine PD(20), 24-h urinary cortisol excretion (24-h UC), plasma cortisol, serum osteocalcin, and blood eosinophils were determined. The relative PD(20) potency between FP and BUD was 2.51 (95% CI, 1.05-5.99; p < 0. 05), while the relative 24-h UC potency was 0.60 (95% CI, 0.44-0.83; p < 0.01). The differential therapeutic ratio (FP/BUD) based on PD(20) potency and 24-h UC was 4.18 (95% CI, 1.16-15.03; p < 0.05). The difference in systemic potency was also seen for plasma cortisol, serum osteocalcin, and blood eosinophils. Therapeutic ratio over a wide dose range, determined by impact on bronchial responsiveness and endogenous corticosteroid production, seems to favor FP.

Administration, Inhalation↗

[Treatment of HIV infections and AIDS with protease inhibitor and two nucleoside analogs].

Until December 31st 1997, 163 HIV/AIDS patients were treated with HAART at the Department of Infectious Diseases, Aarhus University Hospital. The patients mainly received a combination of zidovudine, lamivudine and saquinavir. They were observed for an average period of 375 days. HAART was found to increase the amount of CD4 lymphocytes in peripheral blood and decrease the number of HIV-RNA copies. Both effects were seen to be more pronounced in patients naive to antiretroviral treatment. However, 64 patients had their protease inhibitor changed during the observation period, 53% due to failure of suppression of the viral load, 25% due to adverse events and 22% due to other reasons.

Acquired Immunodeficiency Syndrome↗