Search PubMed⌕ Search

Biomedical subjects

H Lode

Publications and source records attributed to H Lode.

At least 55 records · Page 3Linked to original sources
PubMed1992

Septicemia in 980 patients at a university hospital in Berlin: prospective studies during 4 selected years between 1979 and 1989.

A total of 980 episodes of clinically and bacteriologically proven septicemia were included in four prospective 1-year studies at a 1,300-bed university hospital in Berlin between 1979 and 1989. The incidence was 8.1 per 1,000 admissions. The percentage of patients with severe underlying diseases increased significantly from 67% to 95% over the decade. Septicemia due to gram-positive bacteria decreased from 47.3% in 1979 to 43.7% in 1986 and increased again to 51.2% in 1989. Septicemia due to gram-negative organisms decreased constantly from 45.0% in 1979 to 39.8% in 1989. The most frequently isolated species were Escherichia coli (26.4%), Staphylococcus aureus (18.9%), coagulase-negative staphylococci (10.2%), enterococci (7.7%), viridans streptococci (6.4%), Klebsiella species (5.5%), and pneumococci (5.0%). The overall mortality rate decreased significantly from 33.6% in 1979 to 20.8% in 1989. Mortality for episodes of septicemia due to gram-positive bacteria (25.5%) was higher than that for septicemia due to gram-negative bacteria (18.3%). Mortality rates associated with polymicrobic and fungal septicemia were higher than the overall mortality rate.

Bacteremia↗
PubMed1992

Multiple dose pharmacokinetics, safety, and effects on faecal microflora, of cefepime in healthy volunteers.

In a randomized, double-blind, placebo-controlled study in 12 healthy volunteers pharmacokinetics, safety and impact on the faecal microflora of cefepime were determined. For eight days eight volunteers received cefepime 1000 mg bd by constant infusion over 30 min, four volunteers received placebo. Concentrations of cefepime in serum and urine were measured by bioassay and HPLC. The correlation between the two methods was good and the bioassay results were used for pharmacokinetic calculations. The faecal flora was analysed twice before the study, twice during the study and four times after cefepime administration. There were no significant differences in the pharmacokinetic parameters between days 1 and 8. The following values (mean +/- S.D.) represent day 1. The maximum concentration of 72.69 +/- 12.2 mg/L immediately after infusion decreased to 0.56 +/- 0.17 mg/L after 12 h. The mean 12 h recovery in urine was 93.69 +/- 2.14%. Pharmacokinetic parameters based on an open two-compartment model were as follows (mean +/- S.D.): area under the curve, 142.65 +/- 18.35 mg.h/L; elimination half-life 110.3 +/- 8.3 min; steady state volume of distribution 16.0 +/- 1.9 L/70 kg; total clearance, 107.0 +/- 16.0 mL/min; renal clearance 103.0 +/- 15.2 mL/min. No accumulation was observed during the eight day study period with cefepime at this dosage; trough levels on days 2-7 ranged from 0.52 +/- 0.26 mg/L to 0.90 +/- 0.33 mg/L. In the cefepime treated group the following side-effects were noted: headache (5), fatigue (4), nausea/stomach ache (2), soft stool (2), transient scotoma (1). Side-effects in the placebo group were: headache (2) fatigue (3), nausea/stomach-ache (1), soft stool (2) and photophobia (1). During cefepime administration a decrease in the number of Escherichia coli and bifidobacteria in faeces was observed, whereas Bacteroides spp. and clostridia showed a slight increase. The numbers of faecal bacteria returned to normal 20 to 48 days after the study was completed.

Bacteroides↗
PubMed1992

Multiple-dose pharmacokinetics of cefprozil and its impact on intestinal flora of volunteers.

The pharmacokinetics of cefprozil were determined with 12 volunteers (8 received cefprozil and 4 received a placebo) after oral administration of 500 mg every 12 h over an 8-day period in a randomized, double-blind, placebo-controlled design. Concentrations in serum and urine were measured by high-pressure liquid chromatography and bioassay. The pharmacokinetic parameters were calculated on the basis of an open one-compartment model. The mean maximum concentration in serum on day 1 was 11.5 +/- 2.6 mg/liter, and the time to reach maximum concentration was 122.3 +/- 30 min after administration. Bioavailability parameters (area under the concentration-time curve from zero to infinity, maximum concentration of the drug in serum, and urinary recovery) indicated an excellent absorption. No accumulation over the 8-day period was registered. Cefprozil had a short biological elimination half-life of 58 +/- 10 min and a renal clearance of 210 +/- 51 ml/min, indicating high rates of renal excretion and tubular secretion. Analysis of the fecal flora showed an ecological impact of cefprozil on the intestinal microflora, such as a moderate decrease in enterobacteria and a slight increase in enterococci, staphylococci, and bacteroides during the study. The number of all bacterial species was already normalized 4 days after the administration period. The tolerance of cefprozil proved to be excellent; only a slight and reversible increase of liver enzymes (in two volunteers), mild cephalalgia, tiredness, and soft stool were registered during the 8-day period. Cefprozil had excellent absorption, no accumulation over an 8-day period, and only a limited impact on the intestinal microflora.

Administration, Oral↗
PubMed1992

Pharmacokinetics of cefpodoxime proxetil and interactions with an antacid and an H2 receptor antagonist.

Cefpodoxime proxetil is a new oral esterified cephem antibiotic with a broad antibacterial spectrum. The dissolution of cefpodoxime proxetil is pH dependent. The objectives of this study were to characterize the pharmacokinetics of cefpodoxime proxetil in two different oral doses and to examine possible interactions with an antacid, aluminum magnesium hydroxide (Maalox 70), and an H2 receptor antagonist, famotidine. Two studies involving the same 10 healthy volunteers were performed. In the first study, cefpodoxime proxetil was administered in two doses, 0.1 and 0.2 g. In the second study, two interventions were performed in a randomized crossover design. For one intervention, the volunteers were pretreated with 40 mg of famotidine 1 h before 0.2 g of cefpodoxime proxetil was administered. In the second trial, participants were given 10 ml of Maalox 70 2 h and 10 ml of Maalox 70 15 min before they received 0.2 g of cefpodoxime proxetil. Serum and urine concentrations were determined by high-performance liquid chromatography. For the statistical evaluation, these data were tested by using the pharmacokinetics of 0.2 g of cefpodoxime proxetil from the first study. The maximum concentrations were 1.19 +/- 0.32 mg/liter after 0.1 g of cefpodoxime proxetil and 2.54 +/- 0.64 mg/liter after 0.2 g of cefpodoxime proxetil. The elimination half-lives were 149 min for 0.1 g and 172 min for 0.2 g of cefpodoxime proxetil. The total increase in the area under the concentration-time curve (AUC) was dose dependent. Combination with Maalox 70 caused a reduction in the AUC from 14.0 +/- 3.9 to 8.44 +/- 1.85 mg.h/liter. After famotidine, the AUC decreased to 8.36 +/- 2.0 mg . h/liter. Corresponding changes were registered for the maximum concentration of drug in serum, 24-h urine recovery, and the time to maximum concentration of drug serum. Cefpodoxime proxetil was well tolerated without any seriously adverse drug reactions.

Administration, Oral↗
PubMed1992

Increased number of alveolar macrophages expressing adhesion molecules of the leukocyte adhesion molecule family in smoking subjects. Association with cell-binding ability and superoxide anion production.

This study was designed to investigate whether the expression and functional properties of leukocyte adhesion molecules (LeuCAM; CD11/CD18) are altered in human alveolar macrophages (AM) from smokers. Cells were obtained from 38 smokers (S) and 27 nonsmokers (NS) by bronchoalveolar lavage (BAL). Expression of LeuCAM on freshly isolated cells was studied using a sensitive peroxidase-antiperoxidase method with monoclonal antibodies (mAB) against CD11a, CD11b, CD11c, and CD18. The functional properties of the adhesion molecules were studied by measuring in vitro the binding of AM to the intracellular adhesion molecule-1 (ICAM-1) on human umbilical-vein endothelial cells (HUVEC). The influence of LeuCAM on the increased superoxide anion production (O2-) of smoker AM was quantified after blocking the CD18 molecule by a mAB. Compared with nonsmoker AM, significantly more AM from smokers expressed CD11b (p < 0.001), CD11c (p < 0.001), CD18 (p < 0.001), and CD11a (p < 0.004), whereas there was no difference in the expression of other common epitopes of human macrophages such as CD68, CD71, CD45, HLA-DQ, and HLA-DR. The number of AM expressing CD11a, CD11c, and CD18 showed a correlation to the total number of AM obtained by BAL (p < 0.001). Adherence of AM to HUVEC was higher for smoker than for nonsmoker AM (p < 0.05). The increased binding of smoker AM to endothelial cells could be inhibited by treating the HUVEC with a mAB against ICAM-1. The mAB anti-CD18 reduced O2- release from smoker AM by 42 +/- 5% after 120 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Superoxide anion release induced by platelet-activating factor is increased in human alveolar macrophages from smokers.

This study was designed to investigate the effects of the platelet-activating factor (PAF) on the superoxide anion production (O2.) of human alveolar macrophages (AM) from nonsmoking (n = 18) and smoking (n = 30) subjects. Freshly isolated cells were stimulated with (PAF) or with a phorbol ester (phorbol 12-myristate 13 acetate (PMA)). Stimulation with PAF led to a dose-dependent increase of O2. production by AM in both groups. The median effective dose (EC50) for PAF action on O2. production of smoker AM was 0.5 x 10(-8) M, compared to nonsmoker AM with an EC50 of 1.0 x 10(-7) M. This effect of PAF was blockable by the PAF-antagonist WEB 2086 in a dose-dependent manner. Comparison of the relative increase of O2. production after PAF-stimulation showed that smoker cells were significantly more sensitive to PAF than nonsmoker cells (p less than 0.01). In contrast to the findings with PAF, the relative increase of O2. production after PMA-stimulation showed no differences between smoker and nonsmoker AM. Our data suggest that AM from smoking subjects are more sensitive to PAF than AM from nonsmokers.

Bronchoalveolar Lavage Fluid↗
PubMed1992

Azithromycin in lower respiratory tract infections.

Azithromycin is a new azalide antimicrobial agent which has a broad spectrum of activity against common lower respiratory tract pathogens including pneumococci, staphylococci, Legionella species, Mycoplasma and Chlamydia species. In particular, it is more active against Haemophilus influenzae than other macrolides. In comparison to other new macrolides, azithromycin achieves higher tissue and intracellular concentrations and these concentrations are sustained for several days after dosing due to a long elimination half-life. The efficacy of azithromycin against lower respiratory tract infections has been proven in several clinical studies. Once-daily dosing with azithromycin, over a 3- or 5- day period was as effective as a 10-day course of other commonly used antibiotics such as amoxycillin/clavulanic acid, erythromycin or cefaclor in lower respiratory tract infections. Azithromycin short-course therapy may offer an advantage in terms of patient compliance and the duration of treatment.

Animals↗
PubMed1992

[Ambulant atypical pneumonia: clinical diagnosis and therapy].

Atypical pneumonias are caused by mycoplasma, chlamydia and legionella species. From a clinical point of view the disease is comparable to influenza-like infections. Macrolide antibiotics covered the species which are most important. Especially new macrolides displayed better pharmacokinetic properties, allowing dose reduction and reduced frequency of intake. For legionella infections also therapy with modern quinolones is possible.

Chlamydia Infections↗
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↗