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Biomedical subjects

G Kronborg

Publications and source records attributed to G Kronborg.

At least 19 recordsLinked to original sources
PubMed2005

Predictive value of soluble haemoglobin scavenger receptor CD163 serum levels for survival in verified tuberculosis patients.

Pre-treatment serum levels of sCD163 were measured in a cohort of 236 suspected tuberculosis (TB) cases from Guinea-Bissau, with a median follow-up period of 3.3 years (range 0-6.4 years). In 113 cases, the diagnosis of TB was verified by positive sputum microscopy and/or culture. Among the verified TB cases, a decreased survival rate was found in 27 patients with sCD163 levels above the upper reference limit (3.95 microg/mL). The difference in survival was significant during TB treatment (log rank, p<0.02) and after long-term follow-up (log rank, p<0.001). The decrease in survival rate during TB treatment remained significant in a multivariate Cox model controlling for human immunodeficiency virus (HIV) status, age and gender, with a mortality increase of 1.19 (95% CI, 1.04-1.36) per microg of sCD163, and a hazard ratio (HR) for sCD163 levels above the upper reference limit of 4.18 (95% CI, 1.06-16.4). The difference was not significant after excluding patients with concomitant HIV-1 and HIV-2 infection in Kaplan-Meier analyses (log rank, p 0.11). In contrast, the difference in survival remained significant in Kaplan-Meier analyses after long-term follow-up, even after excluding patients with concomitant HIV-1 and HIV-2 infection (log rank, p 0.002). In the Cox model, the mortality increase per microg of sCD163 was 1.27 (95% CI, 1.14-1.40), with an HR for elevated sCD163 levels of 2.85 (95% CI, 1.44-5.63). The HRs for concomitant HIV-1 and HIV-2 infection were 6.92 (95% CI, 3.28-14.58) and 2.48 (95% CI, 1.09-5.67), respectively. Thus, sCD163 levels appeared to be an independent predictor of survival in verified TB patients.

Adult↗
PubMed2004

The plasma level of soluble urokinase receptor is elevated in patients with Streptococcus pneumoniae bacteraemia and predicts mortality.

This multicentre prospective study was conducted to investigate whether the level of the soluble form of urokinase-type plasminogen activator receptor (suPAR) is elevated during pneumococcal bacteraemia and is of predictive value in the early stage of the disease. Plasma levels of suPAR were increased significantly (median 5.5; range 2.4-21.0 ng/mL) in 141 patients with pneumococcal bacteraemia, compared to 31 healthy controls (median 2.6, range 1.5-4.0 ng/mL, p 0.001). Furthermore, suPAR levels were elevated significantly in patients who died from the infection (n = 24) compared to survivors (n = 117; p < 0.001). No correlation was found between suPAR levels and C-reactive protein. In univariate logistic regression analysis, hypotension, renal failure, cerebral symptoms and high serum concentrations of protein YKL-40 and suPAR were associated significantly with mortality (p < 0.05). In multivariate analysis, only suPAR remained a significant predictor of death (mortality rate of 13 for suPAR levels of > 10 ng/mL; 95% CI: 1.1-158). The increase in suPAR levels may reflect increased expression by vascular or inflammatory cells in the setting of pneumococcal sepsis. This plasma protein may be used to identify patients who are severely ill with pneumococcal bacteraemia.

Adult↗
PubMed2001

[Is polysaccharide pneumococcal vaccine effective in adults?].

Pneumococcal (PC) infections are common and dangerous. Polysaccharide PC vaccine is recommended in some countries for use in adults who have an increased risk of PC infection. Randomised studies of the clinical effect of polysaccharide PC vaccine in healthy adults reported a protective effect, which, in general, was not reproduced in subsequent studies of risk groups. Case-control studies showed a protective effect, but were potentially biased. Two meta-analyses found that the vaccine had an effect on the incidence of PC bacteraemia and pneumonia in healthy adults, but had no effect in risk groups; one meta-analysis found no evidence of less effect in risk groups. There is insufficient evidence to support mass vaccination of risk groups, including elderly people, with polysaccharide PC vaccine.

Adult↗
PubMed2001

[Sample size and number needed to treat--a statistical case study].

The sample size necessary in each group to detect a significant effect of a vaccine on a given disease in a randomised clinical trial (RCT) can be calculated from the observed disease incidence without vaccine, the expected incidence with vaccine, and the desired level of significance and statistical power of the study. In this example, sample size is calculated for an RCT of the effect of pneumococcal vaccine on the incidence of pneumococcal sepsis. The number of persons needed to be vaccinated to prevent one episode of pneumococcal sepsis can be similarly calculated from the observed incidences with and without vaccine.

Humans↗
PubMed2001

Hypotension during endotoxemia in aged humans.

BACKGROUND: and objective The aim of this study was to determine possible age-associated differences in human blood pressure regulation during an immunological challenge in healthy subjects. METHODS: Eight healthy young volunteers (median age 24 yr) and nine healthy elderly volunteers (median age 66 yr) received an intravenous bolus injection of Escherichia coli endotoxin (2 ng kg(-1)). Blood pressure, heart rate and core temperature were monitored during the first 7 h. Plasma catecholamine concentrations were measured at hourly intervals. RESULTS: The elderly showed a significantly more pronounced decrease in mean arterial pressure 4-7 h after endotoxin administration compared with the young controls (ANOVA; age x time; P < 0.0005). This mainly reflected a decrease in the systolic blood pressure in the elderly. The heart rate of both groups increased without difference between groups. Increased plasma epinephrine concentrations were found 2-3 h after endotoxin administration in both groups. Five hours after the endotoxin challenge, the epinephrine concentration had returned to control values in the elderly group only, in spite of decreased blood pressure. CONCLUSION: In conclusion, healthy elderly subjects fail to maintain a constant mean arterial pressure in response to the immunological challenge of endotoxemia.

Adult↗
PubMed2001

Ageing is associated with a prolonged fever response in human endotoxemia.

The purpose of this study was to investigate whether an age-associated impaired acute-phase response exists. Nine healthy elderly volunteers (median, 66 years; range, 61 to 69 years) and eight young controls (median, 24 years; range, 20 to 27 years) were given an intravenous bolus of endotoxin (2 ng/kg). The rectal temperature was monitored continuously, and blood samples for cytokine measurements were obtained before endotoxin administration as well as 0.5, 1, 1.5, 2, 3, 4, 8, 12, and 24 h after the injection. The elderly subjects showed a more prolonged fever response compared to the young controls. Levels of tumor necrosis factor alpha (TNF-alpha), soluble TNF receptors (sTNFR-I), interleukin-6 (IL-6), IL-8, IL-10, and IL-1 receptor antagonist (IL-1ra) in plasma increased markedly following endotoxin administration in both groups. The elderly group showed larger initial increases in TNF-alpha and sTNFR-I levels and prolonged increased levels of sTNFR-I. Monocyte concentrations decreased in both groups, with the elderly group showing a more rapid decrease and a slower subsequent increase than did the young group. Furthermore, the elderly group had a more rapid increase in C-reactive protein levels than did the young group. In conclusion, ageing is associated with an altered acute-phase response including initial hyperreactivity, prolonged inflammatory activity, and prolonged fever response.

Acute-Phase Reaction↗
PubMed2000

[Non-antibiotic treatment of sepsis].

Treatment of patients with sepsis with monoclonal antibodies against lipopolysaccharide, tumour necrosis factor or treatment with soluble TNF-receptors or interleukin-1 receptor antagonist have not had any effect on mortality. Treatment with intravenous polyclonal nonspecific immunoglobulin has been shown to have beneficial efficacy on mortality. However, the number of patients included in the latter treatment studies are limited, the patients studied are heterogeneous and do not allow to conclude that sepsis patients should be routinely treated with immunoglobulins.

Animals↗
PubMed1999

Mannose-binding lectin polymorphisms and susceptibility to infection in systemic lupus erythematosus.

OBJECTIVE: To determine whether variant alleles in the coding portion of the mannose-binding lectin (MBL) gene are associated with increased susceptibility to systemic lupus erythematosus (SLE) and concomitant infections. METHODS: MBL alleles and serum concentrations were determined by polymerase chain reaction and enzyme-linked immunosorbent assay, respectively, in 91 Danish patients with SLE and in 250 controls. RESULTS: Homozygosity for MBL variant alleles was observed in 7.7% of the SLE patients compared with 2.8% of the controls (P = 0.06), while no difference was seen for heterozygosity (33.0% versus 34.4%). Homozygotes had an increased risk of acquiring serious infections compared with patients who were heterozygous or homozygous for the normal allele (odds ratio 8.6, 95% confidence interval 1.5-47.6, P = 0.01). The time interval from the diagnosis of SLE to the first infectious event was shorter (P = 0.017), and the annual number of infectious events was 4 times higher, among homozygotes (P = 0.00002). They were especially prone to acquire pneumonia (P = 0.00004). CONCLUSION; Homozygosity for MBL variant alleles may explain much of the increased risk of complicating infections seen in SLE patients. Additionally, it is a minor risk factor for acquiring SLE.

Adolescent↗
PubMed1998

Immunomodulating effect of blood transfusion: is storage time important?

OBJECTIVES: TNF-alpha and IL-2 are important cytokines in macrophage and T-lymphocyte activity against infection and dissemination of malignant cells. We studied the influence of supernatants from stored whole blood and buffy-coat-depleted SAGM (saline, adenine, glucose and mannitol) blood in stimulating TNF-alpha and IL-2 release in an ex vivo assay. METHODS: Supernatants of 10 units of whole blood and 10 units of SAGM blood were collected after 1, 21 and 35 days of standard blood bank storage. Heparinized blood from 20 healthy volunteers (as 'recipients'), corresponding in ABO and Rh type to the stored blood, were used in a culture system with LPS and PHA as stimulators of TNF-alpha and IL-2 release. The effect of added supernatants, from either stored whole blood or SAGM blood, on cytokine release was evaluated compared to saline as control. TNF-alpha concentration was analyzed by ELISA after culture for 24 h and IL-2 after 72 h, respectively. RESULTS: Supernatants from both stored whole blood and SAGM blood showed a significant decrease in both LPS- and PHA-stimulated TNF-alpha release that was dependent on storage time. IL-2 was not detected in response to LPS stimulation. PHA-stimulated IL-2 release was significantly reduced and related to storage time of both whole blood and SAGM blood. CONCLUSIONS: Recipient cytokine release induced by blood transfusion seems to be dependent on storage time. This may have implications in transfusion-induced immune modulation.

Adenine↗
PubMed1997

Serotonin modulates immune function in T cells from HIV-seropositive subjects.

We have shown earlier increased intracellular levels of cAMP in peripheral lymphocytes from HIV-seropositive subjects and that a chemically induced decrease in this level increases cell proliferation and cytotoxicity. Others have shown that serotonin indirectly decreases intracellular cAMP levels in normal peripheral lymphocytes. In this study, we show that addition of serotonin decreases intracellular levels of cAMP in lymphocytes from HIV-seropositive subjects and significantly increases the proliferative capacity in vitro. However, the effect of serotonin varies with the initial proliferative response; e.g., these with the highest initial responses have the highest increases. An increase in IL-2 production may be a part of this mechanism since addition of serotonin to in vitro cultures of PHA-stimulated cells increases the expression of mRNA for IL-2 and IFN-gamma. The effect on lymphocyte proliferation was most likely mediated through the serotonin 5HT1a receptor because similar results could be obtained by using DPAT, a specific activator of this receptor. Changes in the expression of 5HT1a receptors as judged by the expression of mRNA could not explain why serotonin in vitro had a stronger enhancing effect on cell proliferation in some HIV-seropositive individuals than in others.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1997

The major surface glycoprotein of Pneumocystis carinii induces release and gene expression of interleukin-8 and tumor necrosis factor alpha in monocytes.

Recent studies suggest that interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF-alpha) may play a central role in host defense and pathogenesis during Pneumocystis carinii pneumonia. In order to investigate whether the major surface antigen (MSG) of human P. carinii is capable of eliciting the release of IL-8 and TNF-alpha, human monocytes were cultured in the presence of purified MSG. MSG-stimulated cells released significant amounts of IL-8 within 4 h, and at 20 h, cells stimulated with MSG released 45.5 +/- 9.3 ng of IL-8/ml versus 3.7 +/- 1.1 ng/ml for control cultures (P = 0.01). In a similar fashion, MSG elicited release of TNF-alpha. Initial increases were also seen at 4 h, and at 20 h, TNF-alpha levels reached 6.4 +/- 1.1 ng/ml, compared to 0.08 +/- 0.01 ng/ml for control cultures (P < 0.01). A concentration-dependent increase in IL-8 and TNF-alpha secretion was observed at 20 h with 0.2 to 5 microg of MSG/ml (P < 0.01). Secretion of IL-8 and TNF-alpha from MSG-stimulated monocytes at 20 h was inhibited by 60 and 86%, respectively, after coincubation with soluble yeast mannan (P = 0.01). With an RNase protection assay, increases in steady-state mRNA levels for IL-8 and TNF-alpha were detectable at 4 h. These data show that recognition of MSG by monocytes involves a mannose-mediated mechanism and results in the release of the proinflammatory cytokines IL-8 and TNF-alpha.

Cells, Cultured↗
PubMed1997

Controlled trial of inhaled budesonide in patients with cystic fibrosis and chronic bronchopulmonary Psuedomonas aeruginosa infection.

The efficacy and safety of anti-inflammatory treatment with inhaled glucocorticosteroids in patients with cystic fibrosis (CF) and complicating chronic Pseudomonas aeruginosa (P.a.) lung infection was studied in a placebo-controlled, parallel, double-blind single center trial. Active treatment consisted of budesonide dry powder, 800 microg twice daily, delivered from a Turbuhaler. The study period covered two successive 3-mo intervals between elective courses of intravenous anti-Pseudomonas antibiotics. Fifty-five patients entered the study, with a mean age of 20 yr and a mean FEV1 of 63% of predicted. Analysis of all patients entered, irrespective of trial adherence ("intention to treat"), showed a decrease in FEV1 in the first period of -0.032 L in patients on budesonide versus -0.187 L in patients on placebo (p = 0.08). The corresponding figures for the patients adhering to the protocol during the first period were -0.017 L versus -0.198 L (p < 0.05, confidence interval of the difference: -0.035 to +0.327 L). For all patients entered, as well as for patients adhering to the trial, there was always a trend in favor of budesonide, as judged by changes in FEV1 and FVC in both 3-mo periods. None of the patients had asthma, but the patients on budesonide had a mean improvement in histamine reactivity of +1.15 dose steps over the entire 6-mo period, as opposed to +0.017 dose steps in patients on placebo (p < 0.05). There was also a significant (p = 0.01) correlation between pre-trial histamine reactivity and the change in FEV1 in the first period in patients on budesonide. We conclude that inhaled glucocorticosteroids can be of short-term benefit in patients with CF and chronic P.a. infection and that those patients most likely to benefit from this treatment are patients with hyperreactive airways. Prolonged studies in larger number of patients are necessary to determine the long-term efficacy of this treatment.

Administration, Inhalation↗
PubMed1996

Interleukin-8 in cerebrospinal fluid from patients with septic and aseptic meningitis.

Using a monoclonal antibody enzyme immunoassay, the concentration of interleukin-8 (IL-8) in cerebrospinal fluid (CSF) from 52 patients suspected of having meningitis was studied. The CSF IL-8 concentration was significantly higher in septic meningitis of known and unknown etiology than in aseptic meningitis and significantly higher in aseptic meningitis than in patients without meningitis. The CSF levels of IL-8 correlated with the levels of tumor necrosis factor-alpha, leukocyte count, neutrophil count, protein level, CSF/blood glucose ratio, and the number of days patients were hospitalized. The IL-8 values used to distinguish septic from aseptic meningitis, at a cut-off point of 3.00 micrograms/l, showed a sensitivity of 81%, a specificity of 92%, and a positive predictive value of 96%. The results suggest that determining IL-8 levels may be useful in the differential diagnosis of meningitis.

Adolescent↗
PubMed1996

Buspirone, a serotonin receptor agonist, increases CD4 T-cell counts and modulates the immune system in HIV-seropositive subjects.

OBJECTIVE: We have previously shown that drugs that decrease intracellular cAMP levels increase/restore the proliferative and cytotoxic capacity of T cells from HIV-seropositive subjects in vitro. Buspirone, a serotonin receptor agonist, indirectly decreases intracellular cAMP levels in T cells and has the same increasing/restoring effect on T-cell proliferation in lymphocytes from HIV-seropositive subjects in vitro. DESIGN: Buspirone was given as a single high dose to six HIV-seropositive subjects, or as continuous medication with increasing dosage over 6 weeks to nine HIV-seropositive subjects, with CD4 T-cell counts of 150-300 x 10(6)/l. RESULTS: Significant increases in CD4 T cells, CD4 percentage and CD4/CD8 ratio were found 1 week after a single high dose of buspirone was administered. With continuous administration, a significant increase in CD4 T cells was observed after 1 and 4 weeks. Serum HIV RNA showed a significant decrease 1 h after a single dose of buspirone was administered. With continuous administration of buspirone, plasma HIV RNA first increased within the first 2 weeks of treatment and then decreased towards and below baseline concurrently with a significant decrease in CD8T cells. The proliferative T-cell response to poke weed mitogen and membrane expression of IL-2R increased significantly during continuous treatment with a significant decrease in expression of HLA-DR on CD8+ T cells. Development of "flu-like' symptoms, so severe that two patients withdrew from the study and two patients ceased medication before time, was a clinical indication of modulation of the immune system by buspirone. CONCLUSION: The study shows that buspirone modulates the immune system and leads to changes in the CD4 and CD8 T-cell numbers, functional capacity, cell maturation and viral load.

Adult↗
PubMed1995

Lipopolysaccharide (LPS), LPS-immune complexes and cytokines as inducers of pulmonary inflammation in patients with cystic fibrosis and chronic Pseudomonas aeruginosa lung infection.

The aim of the present thesis was to summarize some important immunological mechanisms in the pathogenesis of chronic Pseudomonas aeruginosa lung infection in patients with cystic fibrosis (CF). The continuous presence of bacteria in the lungs induce a strong immunological response in the patients both locally in the lungs and systemically with high amounts of circulating specific anti-P. aeruginosa antibodies. Our work has been concentrating on anti-lipopolysaccharide (LPS) antibodies. We have shown an increasing antibody response in CF patients, to all three parts of the LPS molecule; lipid A, core, and O-sugars, during the course of chronic P. aeruginosa infection. The antibodies belonged to both IgA, IgM, and all four subclasses of IgG, and were detected in serum and sputum. We detected immune complexes (IC)s in sputum from chronically infected CF patients. The ICs were composed of P. aeruginosa LPS and immunoglobulins of both IgG1-4, IgA and IgM. The concentration of circulating ICs were significantly higher in chronically infected patients compared to non-infected CF patients. The presence of ICs containing LPS in sputum were positively correlated to the amount of tumor necrosis factor alpha (TNF alpha) in the same sputum sample. TNF alpha is a very potent inflammatory mediator, stimulating cells for release of several cytokines attracting polymorphonuclear neutrophil granulocytes (PMNs), which release proteolytic enzymes and toxic oxygen radicals. We detected high concentrations of both TNF alpha, interleukin (IL)-1 alpha, IL-1 beta, IL-6, and the IL-1 receptor antagonist (IRAP) in sputum from chronically infected CF patients. The corresponding concentrations of the cytokines in serum were low or undetectable. Relatively high concentrations of serum-IRAP before the diagnosis of chronic P. aeruginosa infection were correlated to development of poor pulmonary function. We made ICs in vitro of purified P. aeruginosa LPS and hyperimmune serum from chronically infected CF patients. The biological activity of these ICs was investigated in two different assays. LPS by itself induced TNF alpha liberation in vitro, but the ICs made in vitro were also able to stimulate TNF alpha release from mononuclear cells, and they were a more potent stimuli compared to the corresponding amount of LPS alone. The IC preparation did also induce an oxidative burst response in PMNs. We conclude P. aeruginosa LPS is biological active and formation of ICs involving P. aeruginosa LPS and anti-LPS antibodies takes place in the lungs of chronically infected CF patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Antigen-Antibody Complex↗
PubMed1994

[Biofilm, foreign bodies and chronic infections].

Most bacteria occur in the environment as sessile cells adhering to a surface, whereas a minority exists as free floating (planktonic) cells. Biofilms consist of microcolonies embedded in a polysaccharide matrix produced by the bacteria. This polysaccharide slime protects the bacteria against hostile environmental factors. Planktonic daughter cells are liberated from the surface of biofilms and may colonize new surfaces and subsequently produce new biofilms. Biofilms are often consortia of several different bacterial species. The normal microflora on the skin or on the mucous membranes in the human body occurs as a biofilm, which is removed by the shedding of old cells and by the excretion of mucus. Subsequently new cells and new mucus are colonized by biofilm forming bacteria without giving rise to any symptoms. When body surfaces with a normally occurring microflora (A) are connected by means of an implanted foreign body with body surfaces or tissue compartments without a microflora (B) e.g. bronchi, gall bladder, peritoneum, veins, then a translocation of the normal microflora from (A) to (B) may easily occur leading to acute infection, formation of new biofilms on the implanted foreign body and induction of inflammation in the environment of this biofilm. Chronic bacterial infections are frequently caused by biofilm producing bacteria and the pathogenesis of the tissue damage is dominated by a persistent immune complex mediated inflammation. Bacteria growing in biofilms cannot be eradicated by antibiotics and biofilms resist the immunological and non-specific defence mechanisms of the body.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗
PubMed1993

Cytokines in sputum and serum from patients with cystic fibrosis and chronic Pseudomonas aeruginosa infection as markers of destructive inflammation in the lungs.

The presence of interleukin (IL)-1 receptor antagonist (IRAP) in plasma and sputum from patients with cystic fibrosis (CF) and chronic Pseudomonas aeruginosa lung infection was investigated together with IL-1 alpha, IL-1 beta, IL-6, and tumor necrosis factor-alpha (TNF) in a cross-sectional study. All cytokines were assayed by ELISAs. High concentrations of IRAP, IL-1 alpha, IL-1 beta, IL-6, and TNF in sputum samples and low or nondetectable levels of circulating cytokines were frequently found. Increased concentrations of plasma IRAP are positively correlated with decreasing pulmonary function. In a longitudinal study of serum IRAP, a higher level of IRAP was detected in a group of patients with poor pulmonary function compared to a group with good pulmonary function.

Adolescent↗