[Empirical antibiotic treatment of sepsis].
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Anti-Bacterial Agents↗
Biomedical subjects
S S Pedersen
Publications and source records attributed to S S Pedersen.
[Experiences with antiretroviral combination therapy].
The purpose of the study was to evaluate the efficacy of treating of HIV infected patients with two nucleoside analogues and one protease inhibitor in clinical practice. Sixty-one patients were included and followed with respect to plasma HIV-RNA, CD4 cell count and side effects up to one year. Median plasma HIV-RNA was reduced from 20,000 to < 200 copies/ml, and the percentage of patients with plasma HIV-RNA < 200 copies per ml increased from 7.5% to 65.2%. The CD4 cell count increased from 180 to 300 x 10(6)/l. Among 49 patients who remained on therapy, the percentage of patients with plasma HIV-RNA < 200 copies/ml increased from 9.8% to 73.7%. It is concluded that triple drug antiretroviral treatment shows significant effects on plasma HIV-RNA and CD4 cell count, and that the results obtained in clinical practice are comparable to results reported from controlled clinical trials.
Adult↗
[Picture of the month. Staphylococcal infection with embolizations)].
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Adult↗
Traumatisation, psychological defence style, coping, symptomatology, and social support in HIV-positive: a pilot study.
This paper examines degree of traumatisation, defence styles, coping strategies, symptomatology, and social support in a small sample of HIV-positive men and women in an effort to ascertain the psychological implications of living with Human Immunodeficiency Virus (HIV). Traumatisation and the potentially mediating effects of defence styles have only been the subject of a few studies of HIV positives. The study is based on a socio-demographic questionnaire, the Impact of Event Scale, the Defence Style Questionnaire, the Coping Styles Questionnaire, the Trauma Symptom Checklist, and the Crisis Support Scale. A degree of traumatisation that warrants treatment was found together with an association between particular coping strategies and symptomatology, and particular defence styles and symptomatology, respectively. Social support had increased over time, which is contrary to other research findings on social support.
Adaptation, Psychological↗
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↗
[Diagnostic procedures in artificially ventilated patients with pneumonia].
Pneumonia is a common complication in patients requiring mechanical ventilation and the mortality is high. The diagnosis is difficult to establish in spite of many available diagnostic techniques: Aspiration from endotracheal tube or tracheostomy, fiberbronchoscopy with bronchial aspiration, protected specimen-brush (PSB), bronchoalveolar lavage (BAL), transbronchial biopsy or percutaneous lung needle aspiration or open lung biopsy. A review of the literature is given. It is concluded that PSB and BAL combined with quantitative cultures are valid tools, but there is no conclusion as to the superiority of one over the other. With the use of prior antibiotics the rate of false negatives increases and the specificity and sensitivity are lowered. However, we do need a prospective, randomized trial in order to demonstrate that invasive methods in fact decrease morbidity and mortality in the patients compared with clinical judgement alone.
Bacteriological Techniques↗
Quantitative analysis of the IgG and IgG subclass immune responses to chromosomal Pseudomonas aeruginosa beta-lactamase in serum from patients with cystic fibrosis by western blotting and laser scanning densitometry.
BACKGROUND: Antibodies against chromosomal beta-lactamase of Pseudomonas aeruginosa (a beta ab) are markers of the development of resistance of P aeruginosa to beta-lactam antibiotics in patients with cystic fibrosis and chronic lung infection. The role of these antibodies in patients with chronic lung infection with P aeruginosa was further investigated by correlating the a beta ab IgG subclasses with pulmonary function in patients with cystic fibrosis. METHODS: Immunoglobulin G (IgG) and IgG subclass a beta ab were investigated by western blotting and quantified by laser scanning densitometry. A longitudinal study on 43 consecutive patients with cystic fibrosis who developed chronic lung infection with P aeruginosa was performed. RESULTS: IgG subclass a beta ab appeared in all patients with chronic infection with P aeruginosa. Eleven years after the onset of infection all the patients had IgG1, 79% had IgG4, 56% IgG2, and only 16% of the patients had IgG3 a beta ab. The IgG1 and IgG4 a beta ab appeared first, and more than 50% of the patients were IgG1 and IgG4 a beta ab positive within 2-3 years of the onset of infection, but IgG2 positivity only appeared after seven years and IgG3 remained absent from most of the patients. The median a beta ab levels increased during chronic infection: 100-fold for IgG1, 22-fold for IgG2, and 45-fold for IgG4. A 16-fold increase in the IgG3 a beta ab levels was detected in the six patients who developed IgG3 a beta ab. In the first four years of the chronic infection the a beta ab titres were higher in patients with good lung function than in those with poor lung function. CONCLUSIONS: The association of a weak IgG3 and a strong IgG4 a beta ab response suggests that the contribution of a beta ab antibodies to lung diseases mediated by immune complexes might be less important than other antipseudomonal antibodies. A beneficial neutralising effect of the a beta ab antibodies on the antibiotic destroying enzymes may be an additional factor.
Adolescent↗
Interleukin-8 induces its own production in CD4+ T lymphocytes: a process regulated by interleukin 10.
The neutrophil and T cell chemotactic factor interleukin 8 (IL-8) is believed to play a pathophysiological role in the development of various inflammatory disorders. So far no other effects of IL-8 on T cells have been observed. We observed that purified CD4+ T cells in particular, but also CD8+ T cells, spontaneously synthesize IL-8 mRNA and secrete IL-8 protein. The culture supernatants of CD4+ T cells contained T cell chemotactic activity as well as IL-8 protein. In addition, we confirmed the ability of CD4+ T cells to produce IL-8 by double immunofluorescence staining and by the demonstration of IL-8 mRNA expression. Further, IL-8 induced its own production in CD4+ T cells, while its synthesis by CD8+ T cells was low and not always auto-stimulatory. Both the spontaneous, as well as the IL-8 induced IL-8 production, could be inhibited in the presence of human interleukin 10 (100 ng/ml). This observation suggests that IL-10 plays a homeostatic role in regulating the IL-8 circuit in CD4+ T cells.
Autoradiography↗
High levels of complement-activation capacity in sera from patients with cystic fibrosis correlate with high levels of IgG3 antibodies to Pseudomonas aeruginosa antigens and poor lung function.
Heat-stable opsonins from sera of cystic fibrosis (CF) patients were investigated for their ability to activate complement. Complement activation by Pseudomonas aeruginosa after opsonization with patient serum was examined in a complement-consumption assay. Absorption of patients' sera with formalin-treated and boiled bacteria removed specific antibodies and the complement activation decreased. We found a positive correlation between serum complement-activation ability and IgG3 antibody levels to lipopolysaccharide (LPS), alginate, and a crude mixture of P. aeruginosa antigens (sonicate) in a group of patients with high levels of anti-Pseudomonas precipitins. In the same group of patients a significant negative correlation was found between complement activation and lung function. Eighteen patients have been followed longitudinally with serum samples covering the pre-infection, the early, and the late stages of chronic infection. Patients with poor lung function showed significantly higher levels of complement-activation capacity. We conclude that patients with high levels of specific IgG3 antibodies are able to induce a high level of complement activation and then develop more aggressive pulmonary tissue damage, probably secondary to local immune complex formation.
Adolescent↗
Antibodies against Pseudomonas aeruginosa chromosomal beta-lactamase inpatients with cystic fibrosis are markers of the development of resistance of P. aeruginosa to beta-lactams.
Chromosomal beta-lactamase production is considered to be the most important resistance mechanism of Pseudomonas aeruginosa against beta-lactams. Recently we have detected serum and sputum antibodies against P. aeruginosa chromosomal beta-lactamase (a beta ab), using immunoblotting techniques. In this study we have developed an enzyme-linked-immunosorbent assay to measure serum a beta ab response in 124 cystic fibrosis patients in a cross-sectional study and in 54 cystic fibrosis patients in a longitudinal study. The a beta ab response occurred after a median of 3 years following onset of chronic infection and was significantly higher (P < 0.0002) in patients chronically infected with resistant strains than in those from whom resistant strains were occasionally isolated. The a beta ab levels correlated (r = 0.51, P = 0.0001) with the number of beta-lactam courses. A 14 fold increase in a beta ab levels occurred during the 14 year period covered by the longitudinal study. The results of this study show that a beta ab to P. aeruginosa is a specific marker for resistance development of P. aeruginosa to beta-lactams.
Adolescent↗
[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↗
Correlation between specific IgG subclass antibodies to Pseudomonas aeruginosa and opsonic activity in serum from patients with cystic fibrosis.
Heat-stable opsonins from sera of patients with cystic fibrosis (CF) non-CF patients with chronic Pseudomonas aeruginosa infection, healthy children, and adults were investigated for their ability to promote phagocytosis of 35S-labeled P. aeruginosa by human polymorphonuclear neutrophils. Healthy children had significantly lower levels of opsonic activity than adults. Sera from patients with CF without chronic P. aeruginosa lung infection showed significantly higher levels of opsonic activity compared to healthy children. Sera from patients with CF in the early stage of chronic infection had similar opsonic activity as non-CF patients with chronic infection. Sera from patients with CF in the late stage of chronic infection had higher opsonic activity than other infected patients, but not different from adult controls. An inverse correlation was found between levels of specific antibodies to P. aeruginosa and opsonic activity in the group of patients in a late stage of infection. An inverse correlation was also found between levels of IgG1 and IgG3 to P. aeruginosa St-Ag and opsonic activity during the late stage of infection. Infection with P. aeruginosa in CF did not induce significantly increased opsonic activity. It seems that antibodies to P. aeruginosa may have inhibitory opsonic activity.
Adult↗
Mechanism of action of antibiotics in chronic pulmonary pseudomonas infection.
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Animals↗
Methodologic problems in establishing normal values for IgG subclass concentrations in a pediatric population; comparison of radial immunodiffusion and ELISA methods.
The aim of this study was to establish an enzyme-linked immunosorbent assay (ELISA) to measure IgG subclasses by means of monoclonal antibodies. The distribution of IgG subclass protein concentrations in sera from 227 healthy Danish children and 90 adults was measured. Furthermore, this newly established ELISA was compared with different assay systems for determination of IgG subclasses: two radial immunodiffusion methods (RID), one using polyclonal and one using monoclonal antibodies, as well as a commercially available ELISA kit. There was good agreement of results obtained by the different methods of measuring IgG3 and IgG4 concentrations. There was good correlation between results obtained by both RID methods. Despite good correlation between the assays, the ELISA kit showed higher levels of IgG1 in all investigated sera, and the ELISA kit showed no correlation with the other methods, when IgG2 was measured. Analysis of the normal ranges measured by ELISA developed in our laboratory and by RID with polyclonal antibodies showed that the levels obtained by RID were higher than those obtained by our ELISA in sera with low levels of both IgG1 and IgG2, and lower in sera with high concentrations of these two immunoglobulins. Our results emphasize the importance of establishing age-related normal limits for any novel assay measuring IgG subclass concentrations.
Adolescent↗
Development of antibiotic resistance in Pseudomonas aeruginosa during two decades of antipseudomonal treatment at the Danish CF Center.
At the Danish CF Center patients with chronic Pseudomonas aeruginosa lung infection were treated 3-4 times a year (from 1976) with a 2-week intravenous antipseudomonal course which included preferentially an aminoglycoside and a beta-lactam antibiotic. We investigated the development of antibiotic resistance in P. aeruginosa strains isolated from Danish CF patients over a period of 18 years by testing the in vitro efficacy of carbenicillin, piperacillin, ceftazidime, tobramycin and ciprofloxacin against P. aeruginosa strains collected in 1973 (51 strains), 1980 (80 strains), 1985 (58 strains), and 1991 (100 strains). All the strains were screened and assayed semiquantitatively for beta-lactamase activity by use of nitrocefin. We found a significant (p < 0.005) increase in the MIC values of the P. aeruginosa strains against piperacillin and ceftazidime. However, no significant correlation was found between the MIC and the number of antipseudomonal courses of antibiotics. The proportion of resistant in vivo selected P. aeruginosa strains, presumed to be stably derepressed producers of chromosomal beta-lactamase, also increased significantly during the period studied. Our results confirm that the beta-lactamase production is an important mechanism of antibiotic resistance in P. aeruginosa.
Anti-Bacterial Agents↗
[Plasmapheresis as life-saving treatment in acute hepatic failure].
Emergency liver transplantation is the treatment of choice in acute liver failure without signs of spontaneous regeneration. However, many patients rapidly contract irreversible neurological complications before transplantation can be performed. We used high-volume plasmapheresis to increase the time span to obtain a donor liver. Four patients with acute liver failure of unknown cause and a galactose elimination capacity indicative of a virtually extinct liver function were assigned maximum priority for liver transplantation. Plasmapheresis were performed daily until transplantation. Each time 8-10 liters of patient plasma were replaced with an equal volume of fresh donor plasma. There were no major complications. None of the patients developed irreversible neurological complications for 48-144 h at which time liver transplantation was performed. High volume plasmapheresis increases the time to obtain a donor liver for emergency liver transplantation and optimizes the condition for the surgical procedure.
Acute Disease↗
Effect of Pseudomonas aeruginosa alginate on Escherichia coli- and Staphylococcus aureus-induced inflammatory mediator release from human cells.
We analyzed the role of soluble purified Pseudomonas aeruginosa alginate on Escherichia coli K-12 (pANN5211) as well as on Staphylococcus aureus 121c-induced inflammatory mediator release from human platelets, granulocytes, and basophils. In the presence of alginate (1-4 mg/ml), the mucoid exopolysaccharide of P. aeruginosa, the bacteria-induced inflammatory mediator release was modulated as follows: (1) the E. coli- as well as S. aureus-induced chemiluminescence response from human neutrophils increased 2- to 3-fold and 5- to 6-fold, respectively; (2) the E. coli-induced leukotriene B4 formation from human neutrophils was enhanced (from 29.17 +/- 1.8 up to 36.9 +/- 4 ng/10(7) cells) as was also observed for the E. coli- and S. aureus-induced histamine release (3- to 4-fold) and the 12-hydroxyeicosatetraenoic acid generation from human platelets (2-fold), and (3) prolonged duration of the E. coli-induced increase in CD11b expression was observed. Alginate by itself was inactive. Our results provide evidence that alginate interacts with hemolysin-producing E. coli and S. aureus bacteria and thus leads to a modulation of the cellular response pattern, which leads to the local destruction of the lung in cystic fibrosis.
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
Fluoroquinolones in the treatment of cystic fibrosis.
Cystic fibrosis patients suffer from recurrent and chronic lung infections mainly caused by Staphylococcus aureus, Haemophilus influenzae and Pseudomonas aeruginosa. The fluoroquinolones, notably ciprofloxacin and ofloxacin, represent an important addition to the therapy of P. aeruginosa infections. They offer the possibility of effective oral treatment for early colonisation as well as chronic infections, even in children. They are associated with only few and mild adverse effects. Development of resistance represents an increasing problem.
Ciprofloxacin↗