[The antibiotic therapy of community-acquired pneumonias].
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Biomedical subjects
Publications and source records attributed to T Schaberg.
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In this report we demonstrate evidence which strongly suggests that human alveolar macrophages possess receptor for the platelet activating factor (PAF). We investigated the effects of PAF by measuring (a) the intracellular free calcium concentration [Ca2+]i, using the fura-2 method in single isolated cells and (b) the production of superoxide anion. PAF increased [Ca2+]i in a dose-dependent manner (EC50 = 1 x 10(-8) M), whereas lyso-PAF had no effect. The initial increase of [Ca2+]i was followed by a slow decrease to a sustained elevation of [Ca2+]i significantly above basal values. While the initial rise in [Ca2+]i was only slightly reduced in Ca(2+)-free medium (1 mM EGTA), the sustained phase was totally abolished. The sustained calcium increase was also blocked after preincubation of AM with the calcium-channel blocker nitrendipine. PAF increased the production of superoxide anion (O2-) by human alveolar macrophages in a dose- dependent manner. The effects of PAF on [Ca2+]i and (O2-) could be blocked by the PAF-specific antagonist WEB 2086 dose dependently, indicating a receptor-mediated event.
The goal of the present study was to investigate whether endothelin (ET) increases O2-.production in alveolar macrophages and to establish which second messengers are activated by ET. We measured the effects of ET on cytosolic free calcium concentration [Ca2+]i, protein phosphorylation, and O2-.production in human alveolarmacrophages (HAM). Human macrophages were obtained by bronchoalveolar lavage. [Ca2+]i was measured by the fura-2 method both in cell suspensions and in isolated single macrophages. Protein phosphorylation was assessed by gel electrophoresis and autoradiography after labeling the cells with 32P. ET increased [Ca2+]i in a dose-dependent manner (50% effective concentration = 1 x 10(-7)M). At a concentration of 10(-6)M ET, [Ca2+]i rose from basal values of 121 +/- 23 to 456 +/- 41 nM. This increase was comparable with the increase of [Ca2+]i induced by N-formyl-L-methionyl-L-leucyl-L-phenylalanine and platelet-activating factor (PAF; 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine). The initial rise in [Ca2+]i and the sustained phase were significantly reduced in calcium-free medium (1 mM ethyleneglycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid) and after preincubation of HAM with the calcium channel blocker nitrendipine (10(-7)M). Exposure of 32P-labeled HAM to ET for 1 min induced the phosphorylation of a group of 48-kDa proteins and of a 35-kDa protein. The ET-induced 32P incorporation into the 48-kDa proteins was less pronounced than the 12-O-tetra-decanoylphorbol-13-acetate or PAF-induced response (168 +/- 24 vs. 356 +/- 68 and 278 +/- 61% of control).(ABSTRACT TRUNCATED AT 250 WORDS)
Pulmonary involvement of schistosomiasis is usually characterized by a miliary mottling or diffuse nodular infiltrates. In most cases, pulmonary involvement is associated with an apparent clinical involvement of other organs. This report describes a 35 yr old patient who developed a cavity, a parenchymatous infiltrate and hilar adenopathy in association with pulmonary schistosomiasis. Schistosoma eggs were demonstrated in transbronchial biopsies from the lung. Pulmonary involvement of schistosomiasis is reviewed and atypical features are discussed, which may lead to diagnostic difficulties, particularly compared to tuberculosis.
Considering the incidence of infectious endocarditis this disease is still an important clinical entity in internal medicine departments. Leading symptoms are fever, cardiac murmurs, embolic phenomena, skin alterations and also sometimes CNS-disturbances. Two different clinical endocarditis entities can be separated: an acute aggressive course of endocarditis and the subacute course (endocarditis lenta). Diagnostic procedures are mainly based on positive blood cultures and echocardiographic detection of cardiac vegetations. In case of a progressive development of cardiac insufficiency, non treatable infection, large vegetations on valve and embolic phenomena a prosthetic valve implantation is indicated.
The here described investigations show correspondingly that the administration of isoniazid, rifampicin and pyrazinamide in a fixed combination of the administration of the individual substances is bioequivalent under pharmacokinetic aspects. Further investigations on large populations of patients must, however, still confirm whether or not the advantages of the fix combination striven for or theoretically to be expected can be proved in practice.
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The effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) on the expression of c-fos and c-myc protooncogenes was studied in rat alveolar macrophages (AM). AM were exposed in vitro to GM-CSF (100 U/ml) or M-CSF (1,000 U/ml) for 30-120 min, and c-fos and c-myc mRNA expression was determined by in situ hybridization and Northern blot analysis. GM-CSF caused a rapid induction of c-fos mRNA after 30 min and c-myc mRNA after 60 min. Exposure to M-CSF stimulated maximal expression of c-fos mRNA after 60 min and c-myc mRNA after 120 min. Under the same experimental conditions lipopolysaccharide (100 ng/ml) induced a comparable amount of c-fos and c-myc mRNA expression, whereas culture of AM with medium alone did not induce c-fos or c-myc expression. Thus GM-CSF and M-CSF induce AM in vitro to express the nuclear protooncogenes c-fos and c-myc. This effect of colony-stimulating factors on protooncogene expression may be of importance in the local regulation of AM activation and/or proliferation in an inflammatory lung response.
Thoracoscopy was performed under local anesthesia in 419 patients suffering from a diffuse lung disease. In 85% of the cases diagnosis was clarified by thoracoscopy. All other cases were confirmed by means of an open lung biopsy. The best results were obtained in sarcoidosis of the stages II and III, the sensitivity being 0.98. Tumour-conditioned diffuse lung diseases were clarified in 88% of the cases; proof of an interstitial pulmonary fibrosis or interstitial pneumonia was established in 85% of the patients. Results regarding histiocytosis X were poor: thoracoscopic-bioptic proof was successful in only 42% of the patients. In 419 examinations we only detected a severe complication (air embolism). Drainage times were on the average between 4 and 5 days. On the whole, the method was characterised in the field of diagnosis of diffuse lung diseases by a high degree of sensitivity and satisfactory specificity. Both in respect of the invasiveness of the examination and its sensitivity it occupies an intermediate position between peripheral bronchoscopically obtained biopsy and surgical open lung biopsy, representing a valuable extension of the diagnostic instrumentarium if the indication is carefully considered.
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Prosthetic valve replacement was performed in 113 patients above the age of 60 with advanced valvular heart disease, whose prognosis without surgical correction was extremely poor. Although there was high risk of early mortality in isolated aortic valve disease (20%), in isolated mitral valve disease (28%) and in multiple valve disease (50%), improvement for the survivors was evident. Late mortality was rather low. Individual risk can be estimated by considering the patient's age, type and stage of valvular disease as well as the clinical condition and hemodynamic parameters.