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Biomedical subjects

H Lode

Publications and source records attributed to H Lode.

At least 55 records · Page 3Linked to original sources
PubMed1991

Fibrin degradation product D-dimer in the diagnosis of pulmonary embolism.

The study objective was to determine the specificity and sensitivity of plasma concentrations of D-dimer, a fibrin degradation product, as a marker for ongoing thrombotic and thrombolytic events in pulmonary embolism. A prospective study was performed in 74 patients with suspected pulmonary embolism who appeared in the emergency room with dyspnea and/or chest pain. The presence of pulmonary embolism was established by positive findings either in pulmonary angiography or lung scan. D-dimer concentrations were determined in all patients. In 11 patients with positive pulmonary angiography, D-dimer concentrations were monitored for 6-12 days. D-dimer concentrations were determined by a quantitative enzyme-linked immunoassay. Plasma probes of 26 patients (16 with/10 without positive pulmonary angiography) were re-assayed with a semiquantitative latex agglutination assay. D-dimer levels were significantly higher in patients with pulmonary embolism (greater than 1000 ng/mL in 41 out of 43) than in those without (less than 1000 ng/mL in all 21 patients) (p less than 0.01). The sensitivity and specificity for the ELISA were found to be 95% and 100%, respectively, for establishing the diagnosis of pulmonary embolism. In the latex assay the values were 81% and 60%, respectively. It is concluded that in patients with dyspnea and/or chest pain, determination of D-dimer in plasma by ELISA adds a valuable tool to the noninvasive diagnostic procedure for pulmonary embolism. From the time-course of D-dimer values we conclude that this assay might be valuable up to at least 6 days after symptom onset. The assay, however, is unreliable in malignancies or after surgery.

Adult↗
PubMed1991

Evidence for a platelet-activating factor receptor on human alveolar macrophages.

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.

Adult↗
PubMed1991

[Use and risk of antibacterial chemotherapy from the medical point of view].

The evaluation of the efficacy and possible intolerance of an antibacterial chemotherapy is based on the exact analysis of patient specific signs and symptoms, pathogenetic factors of the specific bacteria and parameters of the specific substance. One has to differentiate between usefulness of the antibiotics (effect) and the possible risks for the patient as well as for the physician involved. Today the legal regulations have become so strict for treatment with new substances in phase II to III studies that in most of the new chemotherapeutic substances the relationship between efficacy and possible intolerance reactions may be judged as optimal for both the patient and the physician. Our own experiences have shown that patients involved in studies with well designed protocols are better controlled and in most instances also better treated than patients treated outside such protocols.

Anti-Bacterial Agents↗
PubMed1991

The pharmacokinetics of azithromycin and their clinical significance.

The usefulness of erythromycin is limited by its poor pharmacokinetic profile which is characterised by low blood levels and poor gastric acid stability. Erythromycin's short half-life means that a four-times daily dosage schedule is required for effective treatment. In comparison, the azalide structure of azithromycin confers a much improved pharmacokinetic profile. The bioavailability of azithromycin is approximately 37% in humans (25% for erythromycin). Serum concentrations decline in a polyphasic manner and the relatively short serum half-life (11-14 hours recorded 8-24 hours after last dose) is an indication of the initial rapid distribution of drug into the tissues. The low serum levels recorded 24 hours or more after the end of administration are thought to reflect the slow release of azithromycin from tissues. Tissue concentrations exceed serum concentrations by as much as 100-fold following a single 500 mg oral dose. Macrophages and polymorphonuclear leucocytes concentrate azithromycin at levels greater than those found in tissues themselves. During multiple dosing, tissue half-life increases with duration of administration and the tissue to serum ratio further increases. High concentrations of drug are found in tissues such as tonsil, lung, prostate, liver and lymph nodes with relatively low concentrations in fat and muscle. Significantly, the sustained high levels of drug in the tissues appears to correlate with good in vivo activity. Two 1.5 g regimens have been investigated in clinical trials: 500 mg on day 1, followed by 250 mg daily on days 2 to 5; or 500 mg daily for three days.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1991

The use of oral temafloxacin compared with a parenteral cephalosporin in hospitalized patients with pneumonia.

In a European open, multicentre, prospective clinical trial, 100 hospitalized adult patients (61 males; 18-91 years old (mean age 62] with bacterial pneumonia, diagnosed clinically and radiographically, were randomized to receive either oral temafloxacin 600 mg twice daily (n = 49) or intravenous cefotaxime 2 g thrice daily (n = 51). Signs, symptoms and chest radiographs were assessed during, at the end of therapy and at follow-up eight to ten days after the last dose. Patients were treated for a maximum of ten days. Sputum was obtained for culture before, during and after therapy. The clinical cure rate for the temafloxacin treatment group was 90%, the bacteriological cure rate was 91% and the radiological response rate was 95%. The respective rates for the cefotaxime-treated group were 92%, 96% and 100%. There were no significant differences between the treatment groups for clinical or microbiological outcome, premature study discontinuation, or adverse events. Oral temafloxacin was clinically and bacteriologically equivalent to intravenous cefotaxime in the treatment of hospitalized adults with bacterial pneumonia.

Administration, Oral↗
PubMed1991

Endothelin increases [Ca2+]i, protein phosphorylation, and O2-. production in human alveolar macrophages.

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)

Adult↗
PubMed1991

Pulmonary schistosomiasis resembling acute pulmonary tuberculosis.

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.

Adult↗
PubMed1991

[Clinical aspects of endocarditis].

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.

Endocarditis, Bacterial↗
PubMed1991

[Pharmacokinetic aspects of tuberculosis therapy with a fixed combination of rifampicin, isoniazide and pyrazinamide].

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.

Biological Availability↗
PubMed1990

Evaluation of safety and tolerance in clinical trials with antimicrobial agents.

In this review the general and specific difficulties encountered in the evaluation of safety and tolerance of antimicrobial agents in clinical trials are discussed. In addition to the usual pharmacological and toxicological effects (adverse drug reactions) occurring in individual patients, microbiologically induced side-effects also have to be considered. The different methods for registration of side-effects and their limitations are discussed. A system is proposed for evaluation of the cause/effect relationships of adverse drug reactions. A system is also discussed for the evaluation of the severity of adverse drug reactions, and different classifications are presented.

Anti-Bacterial Agents↗
PubMed1990

Quinolone pharmacokinetics and metabolism.

The pharmacokinetic properties of the new fluoroquinolones are characterized by a high volume of distribution, long biological half-life, low serum protein binding, elimination by renal and extrarenal mechanisms with high total and renal clearances, limited biotransformation and moderate to excellent bioavailability after oral administration. However, each quinolone derivative (ciprofloxacin, enoxacin, fleroxacin, norfloxacin, ofloxacin and pefloxacin) possesses individual pharmacokinetic parameters, which should be considered in the treatment of patients, especially when liver or renal dysfunction exists.

Administration, Oral↗
PubMed1990

Pharmacokinetics and serum bactericidal activities of quinolones in combination with clindamycin, metronidazole, and ornidazole.

To enhance the antimicrobial spectrum of the quinolones against anaerobic organisms and gram-positive bacteria, we investigated in two studies the parenteral combinations of ciprofloxacin (200 mg) and ofloxacin (200 mg) with metronidazole (500 mg) or clindamycin (600 mg) and the oral combinations of enoxacin (400 mg) and fleroxacin (400 mg) with metronidazole (400 mg), clindamycin (300 mg), or ornidazole (500 mg) (only with fleroxacin). The pharmacokinetics and serum bactericidal activities (SBAs) against 5 aerobic and 2 anaerobic species (total, 58 strains) were determined in two groups of 10 healthy volunteers by using a randomized crossover study design. The additions of metronidazole, clindamycin, and ornidazole did not affect the pharmacokinetics of the quinolones. The combination of clindamycin with ciprofloxacin, ofloxacin, and, to a lesser extent, fleroxacin resulted in an increase of the SBA against gram-positive strains (mean peak titers): Staphylococcus aureus, ciprofloxacin alone, 1:5.5; ciprofloxacin-clindamycin, 1:19.9; ofloxacin alone, 1:3.6; ofloxacin-clindamycin, 1:17.5; fleroxacin alone, 1:4.3; fleroxacin-clindamycin, 1:8.1; Streptococcus pneumoniae (fleroxacin and enoxacin were not tested), ciprofloxacin alone, 1:2.0; ciprofloxacin-clindamycin, 1:53; ofloxacin alone, 1:2.6; and ofloxacin-clindamycin, 1:49.2. The high SBA of quinolones against gram-negative bacteria was not affected by the combinations; however, relatively low activities against Pseudomonas aeruginosa were detected. In general, against anaerobic bacteria, low bactericidal activities were determined in both studies (mean peak titers ranged from 1:2.1 to 1:3.1; mean trough titers range from 1:2.0 to 1:2.9). In clinical settings with severe mixed infections, a parenteral therapy consisting of modern quinolones together with clindamycin or imidazole derivatives seems to be active and offers no obvious interactions.

4-Quinolones↗