[Use of positron-emission tomography in oncology].
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Biomedical subjects
Publications and source records attributed to H Lode.
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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.
The incidence of community-acquired pneumonia due to Chlamydia pneumoniae was evaluated in a 1-year prospective study of 236 hospitalized patients with 237 manifestations of pneumonia. The microbiological diagnosis was based on results of cultures of blood and sputum or bronchoalveolar lavage fluid and results of complement fixation tests and indirect immunofluorescence of acute- and convalescent-phase sera for C. pneumoniae, Mycoplasma pneumoniae, Legionella species, Coxiella burnetii, and respiratory viruses. Diagnosis of acute C. pneumoniae infection was made on the basis of the results of microimmunofluorescence of paired serum samples. A microbiological diagnosis was obtained in 160 cases (67.5%). C. pneumoniae was the causative agent in 27 patients (11.4%). The following organisms were the other etiologic agents of pneumonia: Streptococcus pneumoniae, 30 cases (12.7%) (bacteremia occurred in 53.3%); Mycoplasma pneumoniae, 22 (9.3%); respiratory viruses, 22 (9.3%); and Enterobacteriaceae, 18 (7.6%). The prevalence of C. pneumoniae antibody in our study population was 47.5%. As has been increasingly reported in recent years and confirmed by this study, C. pneumoniae appears to be a common etiologic agent of community-acquired pneumonia and upper respiratory tract infection in Germany.
A pooled data analysis of two double-blind studies encompassing 1137 episodes of community-acquired pneumonia in hospitalised adults, of which 560 were treated with sparfloxacin and 577 were randomised to comparator antibacterial agents (amoxycillin/clavulanic acid, erythromycin or amoxycillin administered at reference dosages), was performed. The global efficacy rate at the end of treatment in evaluable patients treated with sparfloxacin was 88.3% compared with 84.1% in those who received comparator antibacterial agents. This analysis verified the efficacy of this new aminofluoroquinolone, given orally once daily, in the treatment of community acquired pneumonia. The overall outcome favoured sparfloxacin for use in the empirical treatment of community-acquired pneumonia.
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.
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.
The aim of this study was to determine the current incidence of side-effects severe enough to cause intolerance of standard antituberculosis therapy with isoniazid, rifampin and pyrazinamide in patients hospitalized as a result of pulmonary tuberculosis. Five hundred and nineteen patients with proven pulmonary tuberculosis, who initially received standard antituberculosis therapy, were retrospectively studied in the department of infectious diseases in a teaching chest hospital. The incidence of severe side-effects related to the therapy, which led to the definitive termination of one of the three standard drugs, was measured and the risk factors for intolerance were analysed. Final termination of either isoniazid, rifampin or pyrazinamide because of severe side-effects was necessary in 121 of the 519 patients (23%). The most severe side-effects leading to final termination of one drug were hepatotoxicity (11%), exanthema (6%), and arthralgia (2%). Pyrazinamide showed more severe side-effects (15%) than isoniazid (7%) and rifampin (1.5%). Significant risk factors for intolerance of the standard therapy following a multivariate analysis were a history of hepatitis (odds ratio (OR) 3.4; 95% confidence interval (95% CI) 1.6-7.6; p = 0.0026) and an age > or = 60 yrs (OR 1.9; 95% CI 1.2-3.2; p = 0.017). Both of these risk factors were also significantly associated with the intolerance of pyrazinamide (history of hepatitis: OR 2.5; 95% CI 1.4-4.3; p = 0.0045; age > or = 60 yrs: OR 2.1, 95% CI 1.3-3.5; p = 0.0029) but not of isoniazid and rifampin. The side-effects of standard antituberculosis therapy are frequent in hospitalized patients aged > or = 60 yrs or with a history of previous hepatitis, and are probably due to pyrazinamide rather than to isoniazid or rifampin.
Resistance of Mycobacterium tuberculosis (M. tb) strains is an increasing problem worldwide. Since no public health data are available for urban populations in Germany, we investigated resistance in our hospitalized patients (n = 1011) during the last seven years. We evaluated clinical data and results of susceptibility tests (break-point technique/proportion method) for isoniazid, streptomycin, rifampin, pyrazinamide, protionamide, and ethambutol. Since 1987 there has been a relatively constant rate of 5.9% (3.9-7.8%) for single-drug resistance (SDR) but an increasing rate of multidrug-resistant (MDR) strains (> or = 2 first-line drugs) from 1.7% in 1987 to 5.8% in 1993. 69% of patients with MDR strains showed resistance to two drugs and 31% to three or more drugs. Risk factors for SDR and MDR tuberculosis revealed previous therapy (odds ratio (OR) [CI95%] SDR: 2.2 [1.7-4.0]; MDR: 4.5 [2.3-8.8]) and foreign-born status (SDR: 2.2 [1.3-3.6]; MDR: 3.5 [1.8-6.8]) to be the most important factors associated with resistance (p < 0.006-0.0001). Both primary and acquired resistance was higher in foreign-born than in German-born patients (p < 0.005). There was a considerable increase in multidrug-resistant tuberculosis in our hospital during 1987 and 1993. Since previously treated patients and patients born in countries with a high level of primary resistance had an increased risk of drug-resistant tuberculosis, we would advise a four-drug regimen as initial therapy in those patients.
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UNLABELLED: During the period from January to September 1995, 19 patients suffering from ventilatory insufficiency were adjusted to nocturnal nasal intermittent positive pressure ventilation (nIPP) therapy with a new ventilatory apparatus conforming to German regulations governing medical equipment (MedGV III). This equipment had not been available previously. 5 patients were suffering from obstructive ventilatory disorder, 5 patients from an underlying neurological disease and 3 patients from thoracic restriction. In 6 patients the reason for their ventilatory disorder was obesity hypoventilation or disorder of central ventilatory regulation. The average age was 54 years (15-73 years). Whereas 14 patients were suffering from global respiratory insufficiency already during the day, the others had marked respiratory disorder only at night. In all cases ventilation was carried out during the whole night. RESULTS: nIPPV achieved normoxia in all patients whereas in 10 patients hypercapnia was not completely eliminated. In all cases, however, the previously elevated pCO2 could be reduced. Hence, sufficient nIPPV can be achieved also with a respirator complying with the new German MedGV III regulations.
Methicillin-resistant Staphylococcus aureus (MRSA) has become a major nosocomial pathogen. We investigated MRSA-infections in patients with pulmonary diseases referring to epidemiological aspects. Between 9/92 and 2/92 we found MRSA-infections in our hospital in 24 patients (11 female, 13 male, average age 54.6 years). Clinical presentation, main and accompanying disorders and previous antibiotic therapy regimens were registered. Strains were typed using DNA-RFLP and lysotyping. MRSA detection were done in specimen from sputum (12/24) and from the bronchial secret (9/24). In 18/24 cases the MRSA-colonisation was associated with infection. In 15/24 cases the first acquisition of MRSA happened in our hospital, 6/24 times the germ was carried off other institutions and in 3/24 cases it was possibly community acquired. Most frequently patients suffered from bronchial cancer (6/24), from chronical bronchitis (5/24), from pneumonia (4/24) or Cystic fibrosis (4/24). Usually the patients showed other severe comorbidity. 13/24 patients had an antibiotic course before detecting MRSA. Typing revealed a strain already known in different hospitals of Berlin, another known strain of northern Germany and two so far unknown strains. Of interest was a different behaviour of resistance and the lost of resistance of strains in the course. MRSA-infection in pulmonary medicine emerged as a problem mostly in patients with multimorbidity and severe underlying diseases. Change of resistance in strains and new strains were observed.
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