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Biomedical subjects

T Schaberg

Publications and source records attributed to T Schaberg.

At least 55 records · Page 3Linked to original sources

[Changes in the spectrum of the causative agents of community-acquired pneumonias (1982-1992)].

BACKGROUND AND OBJECTIVE: The picture of pneumonia acquired out of hospital is continually changing. Microbial aetiology as well as predisposing factors, course and prognosis of this disease were prospectively analysed over a period of 10 years. PATIENTS AND METHODS: In three prospective studies, undertaken between 1982 and 1992, data from 448 patients with out-of-hospital acquired pneumonia were analysed. Microbiological evidence was obtained through blood cultures, from purulent sputum or bronchial secretions, as well as by determining serum antibodies or antigens in urine. RESULTS: Proof of causative organism was achieved in 282 patients (64.1%), with identification of 337 different ones. The spectrum of causative microbes shifted during the study period from predominantly gram-positive bacteria to largely atypical organisms (from 12.5% during 1982/1983, to 36.7% in 1991/1992). Although pneumococci continued to dominate, Chlamydia pneumoniae appeared as an important cause of pneumonia, at 11.4% the most important atypical organism in 1991/1992. -Most patients (74.3%) had a chronic underlying disease. The death rate remained relatively constant at 12.9% during the 10-year period. CONCLUSION: The observed changes in microbial spectrum should be taken into account when specific antibiotic treatment is given. History as well as clinical, radiological and laboratory findings are of only limited value as pointers to the possible microbial cause.

AIDS-Related Opportunistic Infections↗

Lymphocyte subsets in peripheral blood and smoking habits.

The investigation of peripheral blood lymphocyte (PBL) subpopulations is of interest in a wide variety of inflammatory diseases. Since the number of circulating lymphocytes has been shown to be affected by smoking habits, it seems useful to know how PBL subpopulations are influenced. We therefore determined percentages and absolute numbers of a wide range of PBL subpopulations in smokers (n = 14) and nonsmokers (n = 14). PBLs were obtained from healthy volunteers and analyzed by flow cytometry using antibodies for the detection of CD3, CD4, CD8, CD19, CD56, CD57, CD45RO, CD45RA, alpha/beta and gamma/delta T cell receptor epitopes. With the exception of CD3+ cells, no differences between smokers and nonsmokers were found regarding percentages of PBL subpopulations. Smokers were found to have higher absolute numbers of PBLs in the following subpopulations compared with nonsmokers: CD3+, CD4+, CD3+ alpha/beta +, CD45RO+/CD4+, and CD45RA+/CD4+. Cytotoxic lymphocytes, natural killer cells, and B cells did not differ in number between smokers and nonsmokers. There was likewise no difference in the number of the CD8+ alpha/beta + and all cells bearing the gamma/delta T cell receptor. Smoking increased the number of T cells and mainly CD4+ PBLs. The smoking habits of healthy control groups should therefore be taken into account when comparing lymphocyte subpopulations in different diseases.

Adult↗

Penetration of sparfloxacin and ciprofloxacin into alveolar macrophages, epithelial lining fluid, and polymorphonuclear leucocytes.

Sparfloxacin (SPX), a novel fluoroquinolone with a broad spectrum of antibacterial activity, has been shown, in vitro, to be more effective against common pulmonary pathogens, particularly Streptococcus pneumoniae, Mycoplasma pneumoniae and some intracellular organisms, than ciprofloxacin (CPX). The objective of this open, comparative, randomized study in two parallel groups was to assess the serum concentrations and penetration of SPX and CPX into alveolar macrophages (AMs), epithelial lining fluid (ELF), and peripheral polymorphonuclear leucocytes (PMNs). Patients received either a single oral dose of SPX, 400 mg (16 patients), or CPX, 500 mg (15 patients), at various times before a routine diagnostic bronchoscopy was performed. Antibiotic concentrations were determined by using a microbiological assay. The median serum elimination half-lives were 17.3 h for SPX and 5.3 h for CPX. Peak levels (median+/-68% confidence range) of CPX were attained in AMs (7.6+/-1.7 mg x L(-1)) at 5 h after admission, and in both ELF (2.13+/-0.91 mg x L(-1)) and PMNs (9.1+/-6.2 mg x L(-1)) at 2.5 h after administration. SPX achieved comparable peak levels in PMNs (median+/-68% range, 9.4+/-1.1 mg x L(-1) at 5 h), but peak concentrations attained in AMs and ELF (35.1+/-15.4 and 32.2+/-28.2 mg x L(-1), respectively, at 24 h) were several times higher than those of CPX. SPX demonstrated substantially greater accumulation in all three sites than did CPX (peak site to serum ratios of 11.0+/-4.3, 65.5+/-28.4 and 63.0+/-66 versus 4.94+/-0.64, 10.6+/-3.7 and 10.6+/-3.7 for PMNs, AMs and ELF, respectively). The results indicate, that sparfloxacin has a long elimination half-life and that it achieves higher concentrations in alveolar macrophages and epithelial lining fluid than ciprofloxacin. Site concentrations of sparfloxacin greatly exceeded the minimal inhibitory concentrations of common respiratory pathogens.

Anti-Infective Agents↗

Molecular diagnosis of tuberculosis: current clinical validity and future perspectives.

The rapid development and availability of a variety of new molecular genetic technologies present the clinician with an array of options for the accurate diagnosis of infectious diseases. This is particularly the case for tuberculosis, since molecular methods have been rapidly introduced into all working areas of the mycobacteriology laboratory. Nucleic acid amplification methods to detect Mycobacterium tuberculosis in clinical specimens are increasingly used as a tool to diagnose tuberculosis. The bulk of recently available data from clinical evaluations performed under routine laboratory conditions indicate that these molecular methods are rapid and sensitive, but yet inferior, to culture with regard to sensitivity and specificity. Therefore, until gene amplification tests have proved to be reliable and quality control procedures exist, their clinical validity remains controversial. Consequently, definition of selected clinical applications of gene amplification to routine diagnosis of tuberculosis is important and need to be discussed. This review will focus on the clinical role of molecular methods in the direct detection and diagnosis of M. tuberculosis in clinical samples. In addition, molecular genetic approaches designed to determine drug susceptibility and to discriminate strains below the species level will be outlined and discussed in terms of their current and future clinical applicability.

DNA Fingerprinting↗

Lung function tests in patients with idiopathic pulmonary fibrosis. Are they helpful for predicting outcome?

STUDY OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) varies widely in its course. To evaluate predictive parameters at presentation to the hospital, we investigated 99 patients with IPF (47 women), focusing on extensive lung function tests. METHODS: Standard tests of lung volumes, arterial oxygen tension, and gas exchange at rest and during bicycle exercise were performed. Survival rates in relation to functional parameters were calculated using the actuarial method. Differences in survival proportions were summarized as hazard ratios, and significance levels were determined by log-rank test. RESULTS: At presentation, most patients showed a reduced total lung capacity (TLC) of 79.2 +/- 21.1%, an arterial oxygen tension (PaO2) considered pathologic in 63%, when related to age, a significant decrease of PaO2 with 11.8 +/- 12.1 mm Hg and an increase of the alveolar-arterial oxygen pressure difference with 46.4 +/- 16.4 (12.2 to 76.8) mm Hg during bicycle exercise. Diminished survival was associated with an age older than 50 years, a reduced value to more than 2 SDs below the predicted values of both, TLC alone, or in combination with a reduced vital capacity. Factors not influencing survival were gender, parameters of gas exchange at rest, and PaO2 at rest and during bicycle exercise. CONCLUSIONS: We conclude that standard lung function tests make it possible to assess the prognosis of patients with IPF, while extensive tests like gas exchange measurements at rest and during bicycle exercise do not contribute additional information to make the prognostic estimations more precise.

Exercise Test↗

[Pulmonary melioidosis in a German Southeast Asia tourist].

HISTORY AND CLINICAL FINDINGS: A patient who returned from a 3-year stay in Thailand and India one year ago, was admitted with fever of 38.5 degrees C and productive cough for the last four weeks. He remembered wounding his foot three years ago in India with contamination by soil. Subsequently, recurrent pustulae appeared on his feet. One such pustule was found on admittance. The clinical examination showed low body weight, without further abnormalities. INVESTIGATIONS: The blood examinations revealed high inflammation parameters and ruled out any immunodeficiency. Smouldering infiltrates in the upper lobes were found on the chest radiography. Sputum was free of acid fast bacilli and no mycobacterial DNA was detected by polymerase chain reaction. Bronchoscopy showed a normal endobronchal situation, Burkholderia pseudomallei were found to grow from specimens of bronchial mucus. TREATMENT AND COURSE: Under the empirical treatment with ampicillin/sulbactam, we could not find any response. After switching to Ceftazidime and trimethoprim/sulfamethoxazol (TMP/SMZ) we observed quick clinical improvement and normalisation of the inflammation parameters and notable radiological response over three weeks. We continued a five months TMP/SMZ therapy after discharge in order to prevent relapses. CONCLUSION: For travellers and immigrants from Southeast Asia presenting smouldering infiltrations of the upper lobes, one should include Melioidosis in the differential diagnosis.

Adult↗

Expression of adhesion molecules in peripheral pulmonary vessels from smokers and nonsmokers.

INTRODUCTION AND RATIONALE: An accumulation of intraalveolar cells, especially of macrophages and granulocytes, can be observed in smokers. Since adhesion molecules are involved in the process of cell accumulation, in this study we investigated the hypothesis that the expression of endothelial adhesion molecules on pulmonary vascular endothelial cells is different in smokers and nonsmokers. METHODS: We investigated lung biopsies from 26 patients who underwent thoracic surgery for localized malignancies (smokers: 15; nonsmokers: 11). Cryostat sections were stained by using immunohistochemistry (APAAP method) with antibodies against E- and P-selectin, the vascular adhesion molecule-1 (VCAM-1), and the intercellular adhesion molecule-1 (ICAM-1). The number of adhesion molecule-positive stained vessels was compared to the total number of vessels identified by the expression of von Willebrand's factor (vWF) and anti-CD31. RESULTS: The two groups investigated showed no differences in the expression of E-, and P-selectin and of VCAM-1. In contrast, the expression of ICAM-1 was significantly increased in smokers (median 25 vessels/section, CI95%: 19-31) compared to nonsmokers (median 16 vessels/section, CI95%: 9-21) (p = 0.030). In smoking subjects, we were also able to demonstrate a positive correlation between the duration of smoking expressed as pack years and the expression of ICAM-1 on pulmonary vessels (Spearman rank coefficient of correlation 0.857; p = 0.0002). CONCLUSION: The observed increased expression of ICAM-1 on pulmonary vascular endothelial cells in smokers compared to nonsmokers may be involved in the increased recruitment of inflammatory cells to the alveolar space of smokers.

Adult↗

Azithromycin--review of key chemical, pharmacokinetic and microbiological features.

One of the chemical features that distinguishes the 15-membered ring azalide azithromycin from the 14-membered ring macrolide compound erythromycin is the former's increased stability at acid pH. Azithromycin also differs pharmacokinetically from erythromycin, an important feature being azithromycin's ability to achieve high tissue concentrations, with the agent being delivered to the sites of infection by direct uptake and by targeted delivery via phagocytes. High tissue concentrations are maintained for prolonged periods because of azithromycin's long half-life, leading to once-daily dosing for 3 or 5 days. Notable microbiological features of azithromycin are in-vitro activity against many pyogenic bacteria (e.g. Neisseria gonorrhoeae and Moraxella catarrhalis), as well as organisms against which beta-lactam antibiotics are usually ineffective (e.g. Legionella and Chlamydia spp.), organisms that are resistant to benzylpenicillin and erythromycin (e.g. Haemophilus influenzae) and organisms for which satisfactory therapy is limited (e.g. Toxoplasma gondii and the Mycobacterium avium-intracellulare complex). These properties of azithromycin suggest that it might be a useful agent for the treatment of a wide range of bacterial infections.

Animals↗

Serum bactericidal activities and comparative pharmacokinetics of meropenem and imipenem-cilastatin.

The pharmacokinetics and serum bactericidal activities (SBAs) of imipenem and meropenem were investigated in a randomized crossover study. Twelve healthy male volunteers received a constant 30-min infusion of either 1 g of imipenem plus 1 g of cilastatin or 1 g of meropenem. The concentrations of the drugs in serum and urine were determined by bioassay and high-pressure liquid chromatography. Pharmacokinetic parameters were based on an open two-compartment model and a noncompartmental technique. At the end of infusion, the mean concentrations of imipenem and meropenem measured in serum were 61.2 +/- 9.8 and 51.6 +/- 6.5 mg/liter, respectively; urinary recoveries were 48.6% +/- 8.2% and 60.0% +/- 6.5% of the dose in 12 h, respectively; and the areas under the concentration-time curve from time zero to infinity were 96.1 +/- 14.4 and 70.5 +/- 10.3 mg.h/liter, respectively (P < or = 0.02). Imipenem had a mean half-life of 66.7 +/- 10.4 min; that of meropenem was 64.4 +/- 6.9 min. The volumes of distribution at steady state of imipenem and meropenem were 15.3 +/- 3.3 and 18.6 +/- 3.0 liters/70 kg, respectively, and the mean renal clearances per 1.73 m2 were 85.6 +/- 17.6 and 144.6 +/- 26.0 ml/min, respectively. Both antibiotics were well tolerated in this single-dose administration study. The SBAs were measured by the microdilution method of Reller and Stratton (L. B. Reller and C. W. Stratton, J. Infect. Dis. 136:196-204, 1977) against 40 clinically isolated strains. Mean reciprocal bactericidal titers were measured 1 and 6 h after administration. After 1 and 6 h the median SBAs for imipenem and meropenem, were 409 and 34.9 and 97.9 and 5.8, respectively, against Staphylococcus aureus, 19.9 and 4.4 and 19.4 and 4.8, respectively, against Pseudomonas aeruginosa, 34.3 and 2.2 and 232 and 15.5, respectively, against Enterobacter cloacae, and 13.4 and 2.25 and 90.7 and 7.9, respectively, against Proteus mirabilis. Both drugs had rather short biological elimination half-lives and a predominantly renal route of elimination. Both carbapenems revealed high SBAs against clinically important pathogens at 1 h; meropenem had a higher SBA against E. cloacae and P. mirabilis, and the SBA of imipenem against S. aureus was greater than the SBA of meropenem.

Adult↗

An analysis of decisions by European general practitioners to admit to hospital patients with lower respiratory tract infections. The European Study Group of Community Acquired Pneumonia (ESOCAP) of the European Respiratory Society.

BACKGROUND: The purpose of this study was to identify factors on which European general practitioners (GPs) base their decisions to admit to hospital patients with lower respiratory tract infections (LRTI). METHODS: A survey was carried out from December 1993 to January 1994 to identify factors that affect GPs' decisions to admit to hospital patients with LRTI by collecting data on 2056 patients from 605 GPs in France, Germany, Italy, Spain, and the UK. RESULTS: Only 93 (4.5%) of the patients included in the study were admitted to hospital. Univariate analysis showed that age > 60 years, institutionalisation of the patient, concomitant diseases, cardiac insufficiency, asthma, a diagnosis of pneumonia, and clinical signs such as chest pain, cyanosis, tachypnoea and hypotension significantly (odds ratio (OR) > 2.0, p < 0.002) influenced the decision to admit to hospital. No influence could be shown for sex, smoking habits, history of bronchiectasis or chronic bronchitis, the presence of fever, chills, myalgia, cough or purulent sputum, and the diagnoses of acute bronchitis, influenza or exacerbation of chronic bronchitis. In the multivariate analysis only the presence of chest pain (OR 2.3, 95% confidence interval (CI) 1.5 to 3.5), cyanosis (OR 4.1, 95% CI 2.4 to 7.1), dyspnoea (OR 4.9, 95% CI 3.1 to 7.9), and hypotension (OR 2.9, 95% CI 1.6 to 5.2), as well as a diagnosis of pneumonia (OR 6.6, 95% CI 4.3 to 10) (all p < 0.00001) remained as factors that significantly affected the decision to admit to hospital. CONCLUSIONS: Clinical signs of severe infection and a diagnosis of pneumonia are the main factors that induce GPs to admit patients with LRTI to hospital in Europe.

Europe↗