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Biomedical subjects

M Trautmann

Publications and source records attributed to M Trautmann.

At least 55 records · Page 3Linked to original sources

Comparison of fosfomycin and teicoplanin in serum bactericidal activity against staphylococci.

A serum bactericidal test was established employing human sera of volunteers after intravenous administration of fosfomycin (CAS 23155-02-4) and teicoplanin (CAS 61036-62-2) against 40 staphylococcal strains (20 Staphylococcus aureus and 20 coagulase-negative staphylococci, 10 of each group being susceptible and 10 being resistant to oxacillin). Median serum inhibitory titres were highest for fosfomycin against oxacillin-susceptible Staphylococcus aureus. In the three other groups of strains, the activity of fosfomycin was comparable to that of teicoplanin. The killing curves showed over 99% killing within 24 h for both antibiotics. Here, fosfomycin exerted a rapid killing activity within 4-6 h and was more effective in bacterial growth reduction. It can be concluded that fosfomycin and teicoplanin exerted comparable serum bactericidal antibacterial activity against staphylococci.

Adult↗

An investigation on the role of vacuolar-type proton pumps and luminal acidity in calcium sequestration by nonmitochondrial and inositol-1,4,5-trisphosphate-sensitive intracellular calcium stores in clonal insulin-secreting cells.

To test whether in RINm5F rat insulinoma cells luminal acidity and the activity of a vacuolar-type proton pump are involved in calcium sequestration by intracellular calcium stores sensitive to inositol 1,4,5-trisphosphate (InsP3) we examined the effects of various proton-conducting ionophores and ammonium chloride, and of bafilomycin, a specific inhibitor of vacuolar proton pumps, on this parameter. Bafilomycin in concentrations up to 1 microM did not affect calcium sequestration by nonmitochondrial, InsP3-sensitive stores at all; 50 microM carbonylcyanide m-chlorophenylhydrazone, 50 microM monensin and 30 mM NH4Cl, which are diverse ways to dissipate transmembrane pH gradients, did not inhibit calcium sequestration. This argues against signficant involvement of internal acidity and vacuolar proton pumps in calcium sequestration by InsP3-sensitive stores in RINm5F cells. The proton-potassium-exchanging ionophore nigericin (20-100 microM), however, inhibited calcium sequestration by nonmitochondrial and InsP3-sensitive stores. This effect was dependent on the presence of potassium and could be reversed by inclusion of carbonylcyanide m-chlorophenylhydrazone or acetate in the incubation medium. Thus, the inhibitory effect of nigericin appears to be based on proton extrusion coupled to potassium influx across the membrane of calcium stores in RINm5F cells, creating an internal alkalinization of these stores. The effect of nigericin implies the continuous maintenance of an outside-to-inside potassium concentration gradient by nonmitochondrial calcium stores in RINm5F cells. This feature will be of potential interest in the identification of InsP3-sensitive calcium-storing organelles.

Ammonium Chloride↗

Use of a receiver operating characteristic in the evaluation of two commercial enzyme immunoassays for detection of Helicobacter pylori infection.

Two novel commercial IgG enzyme immunoassay (EIA) systems based on acid-glycine-extracted (Pyloriset IgG EIA, Orion Diagnostica) or fast protein liquid chromatography-purified (Cobas Core Anti-H. pylori EIA, Roche Diagnostic Systems) Helicobacter antigens were evaluated in a prospective study involving 127 patients. All patients underwent upper endoscopy with biopsy, and biopsies were examined for the presence of Helicobacter pylori by a rapid urease test, microscopy and culture. Of the 71 patients found to be infected with Helicobacter pylori, 69 (97.2%) and 65 (91.5%) tested positive with the Cobas Core and Pyloriset test, respectively. A detailed receiver operating characteristic analysis of the two tests showed that the Cobas Core assay was more sensitive and specific at every possible cut-off level; gave a better resolution of individual results, indicating a greater fine-sensitivity; and had no grey zone compared to a large grey zone encompassing 13.4% of the serum samples tested with the Pyloriset EIA. The Cobas Core assay appears to be a valuable tool for epidemiological purposes as well as for pre-endoscopic screening of dyspeptic patients.

Antigens, Bacterial↗

Complicated tuberculosis and residual disease.

Complicated and extrapulmonary manifestations of tuberculosis (TB) may cause prolonged suffering for the individual patient and represent a high economic burden for the society concerned. Complications of pulmonary TB may be the consequence of reduced individual resistance, immunosuppression or specific immune defects. In HIV patients, pulmonary TB is often associated with extrapulmonary lesions, while the radiologic appearance of lung infiltrates may be less prominent compared to HIV negative persons. The present review summarizes data obtained during a 12-year study of extrapulmonary TB in Berlin, Germany, and outlines the role of residual TB lesions for disease reactivation in later life. Indications and limitations of INH preventive chemotherapy will be discussed.

HIV Seropositivity↗

The pharmacokinetics of fluconazole after a single intravenous dose in AIDS patients.

The pharmacokinetics of fluconazole after a single 100 mg i.v. dose were studied in 10 healthy subjects (5 M; 5 F) and 10 HIV-positive patients (8 M; 2 F). The mean value of plasma clearance was 25% lower in the patient groups (17 +/- 6 (s.d.) vs 23 +/- 4 ml min-1; 95% CI of difference -11 to -0.7; P < 0.05). This difference may have been related to slightly reduced kidney function in the patient group (mean creatinine clearance -18%) but is unlikely to be clinically significant. Therefore, no adjustment of the dose of intravenously administered fluconazole appears to be necessary in AIDS patients without clinical signs of enteropathy.

Acquired Immunodeficiency Syndrome↗

A murine monoclonal antibody defines a unique epitope shared by Klebsiella lipopolysaccharides.

A hybridoma secreting a monoclonal antibody (MAb) directed against Klebsiella lipopolysaccharide (LPS) was derived from spleen cells of mice immunized a smooth, nonencapsulated Klebsiella strain (Friedländer 201; serogroup O1). The MAb, called V/9-5 (immunoglobulin G2a), cross-reacted with LPS preparations produced from reference strains for the Klebsiella O serogroups O1, O2ab, O2ac, O3, O4, O5, and O12. Furthermore, the MAb reacted with LPSs from serogroup reference strains O6/O8, O9, and O11, which are regarded as being identical to O1, O2, and O4, respectively. When testing the supernatant of clinically isolated Klebsiella strains by means of an inhibition enzyme-linked immunosorbent assay, we found that 86 (92.4%) of 93 Klebsiella pneumoniae subsp. pneumoniae isolates and 24 (96.0%) of 25 K. oxytoca isolates harbored the cross-reactive epitope. By contrast, two laboratory strains of K. pneumoniae subsp. rhinoscleromatis did not react with MAb V/9-5. The MAb proved to be specific for the genus Klebsiella, since it did not react with any of a total of 73 strains belonging to other gram-negative bacterial genera. In conjunction with other LPS-specific MAbs, MAb V/9-5 might become a useful reagent for rapid identification of klebsiellae in clinical specimens. Furthermore, the epitope recognized by MAb V/9-5 might serve as a target epitope for the production of human MAbs for immunotherapeutic purposes.

Animals↗

Emergence of fluconazole-resistant strains of Candida albicans in patients with recurrent oropharyngeal candidosis and human immunodeficiency virus infection.

After repeated use of fluconazole for therapy of oropharyngeal candidosis, the emergence of in vitro fluconazole-resistant Candida albicans isolates (MIC, > or = 25 micrograms/ml) together with oral candidosis unresponsive to oral dosages of up to 400 mg of fluconazole were observed in patients with human immunodeficiency virus (HIV) infection. Antifungal susceptibility testing was done by broth microdilution and agar dilution techniques on C. albicans isolates recovered from a cohort of patients with symptomatic HIV infection who were treated repeatedly with fluconazole for oropharyngeal candidosis. In vitro findings did show a gradual increase in the MICs for C. albicans isolates recovered from selected patients with repeated episodes of oropharyngeal candidosis. Primary resistance of C. albicans to fluconazole was not seen. Cross-resistance in vitro occurred between fluconazole and other azoles (ketoconazole, itraconazole), but to a lesser extent. The results of the study suggest that the development of clinical resistance to fluconazole could be clearly correlated to in vitro resistance to fluconazole. Itraconazole may still serve as an effective antifungal agent in patients with HIV infection and oropharyngeal candidosis nonresponsive to fluconazole.

AIDS-Related Opportunistic Infections↗

Malaria prophylaxis: identifying risk groups for non-compliance.

To investigate behaviour in the use of drug prophylaxis against malaria and the risk factors for non-compliance, 507 European or North American travelers returning from endemic areas were studied retrospectively at Berlin in a 11-year period from 1980 to 1990. Compliance was significantly correlated with shorter travel duration: the group with good compliance stayed 37.2 +/- 38.5 days (mean +/- SD) in contrast to 69.8 +/- 93.5 days in the group of patients with no compliance (p = 0.00001). Older patients were significantly more compliant than patients aged < 55 years (20/27 compliant at > 54 years vs. 175/476 at < 55 years; p = 0.0001). Compliance was significantly affected by travel destination (Southern and East African regions; p = 0.0054), age (< or = 15 and > or = 55 years, respectively; p = 0.0001), and reason of travel (package tours; p = 0.0001). CART analysis confirmed logistic regression analysis with respect to age and travel type, and revealed that patients using only one information source were significantly more compliant than those using two or more information sources. Travel agencies were nearly as well informed as Institutes of Tropical Medicine, but family doctors had a significant incidence of giving wrong advice. This study should enable medical personnel dealing with prophylactic advice against malaria to identify patients at high risk for non-compliance, and to educate them more carefully than other travellers regarding antimalarial drug prophylaxis.

Adolescent↗

Effects of standard breakfast on pharmacokinetics of oral zidovudine in patients with AIDS.

The influence of a standard breakfast on the single-dose pharmacokinetics of zidovudine (AZT) after oral administration of 100 and 250 mg of AZT was studied in 27 subjects with advanced human immunodeficiency virus infection (Centers for Disease Control stage IV). Concentrations of AZT and the 5'-glucuronide metabolite (GAZT) in serum and urine were measured by a high-pressure liquid chromatographic method. Pharmacokinetic analysis was done by an open one-compartment model as well as noncompartmentally. The results were summarized as medians with 50% confidence ranges because of the high degree of interindividual variability. Peak levels in plasma were moderately reduced after administration of 100 mg AZT in the nonfasting group (1.79 mumol/liter in the fasting group [F], 1.12 mumol/liter in the group that received breakfast [B]) and were markedly reduced after administration of 250 mg AZT (6.51 mumol/liter [F], 1.79 mumol/liter [B]). The terminal half-life in plasma was prolonged almost twofold after breakfast with 100 and 250 mg of AZT (100 mg, 36.4 min [F] and 51.6 min [B]; 250 mg, 35.3 min [F] and 63.6 min [B]). Recoveries (AZT and GAZT) in urine varied with both dosages, reflecting more a problem of accounting for the metabolite GAZT in urine than a relevant difference (100 mg, 115% [F] and 76.5% [B]; 250 mg, 71% [F] and 99.4% [B]). Our data suggest that absorption of AZT in human immunodeficiency virus-infected subjects is extremely variable, with a high degree of interindividual differences. Furthermore, breakfast had a marked influence on the absorption of AZT, suggesting that the drug should be taken in a fasting state.

Acquired Immunodeficiency Syndrome↗

Role of eicosanoids, nitric oxide, and afferent neurons in antacid induced protection in the rat stomach.

The mechanism underlying the mucosal protective effect of antacids is still unclear. This study shows that in rats the aluminum containing antacid, hydrotalcit, induces dose dependent protection against gastric mucosal damage caused by ethanol or indomethacin which is considerably enhanced by acidification. Hydrotalcit did not increase gastric mucosal formation or the intraluminal release of prostaglandins, and did not prevent the increase in mucosal leukotriene C4 formation in response to ethanol. Pretreatment with indomethacin did not attenuate the protective effect of unmodified or acidified hydrotalcit. Furthermore, hydrotalcit significantly reduced the gastric damage caused by indomethacin even when it was administered up to 2 hours after the ulcerogen. In indomethacin treated rats, simultaneous administration of hydrotalcit did not affect the concentrations of indomethacin in serum or inflammatory exudates nor did it attenuate the inhibition of prostaglandin release into the exudates. In hydrotalcit treated rats there was no attenuation of the increase in sulphidopeptide leukotriene release or decrease in leukocyte influx into inflammatory exudates elicited by indomethacin administration. Functional ablation of afferent neurons and inhibition of endogenous nitric oxide partially antagonised the protective effect of unmodified, but not of acidified, hydrotalcit. It is concluded that (i) the protective effect of unmodified and acidified hydrotalcit is independent of the eicosanoid system; (ii) protection against indomethacin induced gastric lesions does not require treatment before dosing of the ulcerogen and does not interfere with absorption and anti-inflammatory actions of indomethacin; (iii) endogenous nitric oxide and afferent neurons contribute partly to the effect of unmodified, but not of acidified, hydrotalcit suggesting that different mechanisms mediate their mucosal protective activity.

Aluminum Hydroxide↗

Leukotriene B4 and C4 production in isolated rat gastric mucosal cells.

Dispersed rat gastric mucosal cells (F0) were separated into five fractions (F1-F5) by counterflow elutriation, with F1 representing the smallest and F5 the largest cell diameters. In F0-F5, leukotriene B4 (LTB4) release in response to 10(-5) M calcium ionophore A-23187 was 7.68 +/- 1.26, 51.6 +/- 10.8, 72.4 +/- 10.4, 7.1 +/- 0.7, 5.7 +/- 0.6, and 11.6 +/- 3.4 pg.10(6) cells-1 x 30 min-1. In the identical fractions, sulfidopeptide release in response to A-23187 was 200.6 +/- 20.5, 1,116.0 +/- 166.6, 1,309.4 +/- 163.2, 189.8 +/- 25.8, 108.0 +/- 18.0, and 158.4 +/- 54.0 pg.10(6) cells-1 x 30 min-1. High-pressure liquid chromatography verified the radioimmunologically determined LTB4 and identified LTC4 as the only sulfidopeptide LT released. LT release from F2 cells in response to A-23187 was time and dose dependent, reaching maximal stimulation at 10(-5) M A-23187. This response was blocked by the dual inhibitor of cyclooxygenase and lipoxygenases, BW755C (2 x 10(-5)-2 x 10(-4) M), by the selective 5-lipoxygenase inhibitor L-651,392 (10(-7)-10(-5) M), and by MK-886 (10(-9)-10(-7) M), which blocks translocation of 5-lipoxygenase. The postreceptor stimuli dibutyryl adenosine 3',5'-cyclic monophosphate, forskolin, 12-O-tetradecanoyl-phorbol-13-acetate, and oleyl-acetyl-glycerol failed to induce LT release. However, 10(-4) M arachidonic acid increased basal LT release up to eightfold and increased A-23187-stimulated LT release by an additional 30%.(ABSTRACT TRUNCATED AT 250 WORDS)

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

[Epidemiologic and clinical aspects of HIV infection in homosexual patients and intravenous drug addicts in a comparative study].

The clinical course of HIV-infection was analysed in a group of homosexual patients (n = 76, 72%) compared to intravenous drug abusers (IVDA, n = 30, 28%) in a retrospective cross-sectional study. The mean age of homosexual patients was 37.5 years compared to 28 years for IVDA. The following diseases are found significantly more frequently in homosexual patients compared to IVDA: Pneumocystis-carinii pneumonia (PCP) 17.1% vs. 0% (p < 0.05); Kaposi' sarcoma 16% vs. 0% (p < 0.05); diarrhoea 47.4% vs. 23.3% (p < 0.05); oral candidiasis 51.3% vs. 23.3% (p < 0.01); non-specific pneumonia of bacterial aetiology or due to unknown organisms 30% vs. 0% (p < 0.001) und seborrhoeic dermatitis 13.2% vs. 0% (p < 0.05). In contrast, viral hepatitis, non-specific abscesses and gonorrhoea were seen significantly more often in IVDA. The data show clearly that the spectra of HIV-associated diseases and HIV-unconnected diseases are significantly different in the two main groups. A risk-oriented preventive prophylaxis of HIV-related diseases and other infections is therefore required for each of these groups.

AIDS-Related Opportunistic Infections↗

Malaria therapy in 452 patients, with special reference to the use of quinine.

We investigated the efficacy and toxic potential of antimalarial therapy regimens in 452 malaria patients treated between 1980 and 1990. Drug regimens in 330 non-immune travellers were compared with those of 122 semi-immunes with acute malaria; 71% patients acquired their infection in tropical Africa, and the 288 Plasmodium falciparum infections were the most prevalent species. Because of increasing drug resistance or toxicity of chloroquine, pyrimethamine-sulfadoxine and even mefloquine, quinine proved to be the most effective antimalarial against P. falciparum and the only one which did not lead to recrudescences. These occurred in 10% patients after chloroquine and 6% after mefloquine. Cinchonism occurred in 25% of those treated with quinine, but it was fully reversible and never necessitated withdrawal of the drug. We conclude that quinine is highly effective in the treatment of P. falciparum infection and is mandatory if the clinical condition requires a fast-acting blood schizonticide, in cases of hyper-parasitaemia and if multi-drug resistance occurs; its use should not be restricted by reversible side-effects such as cinchonism.

Adolescent↗

Monoclonal antibody against Klebsiella capsular polysaccharide reduces severity and hematogenic spread of experimental Klebsiella pneumoniae pneumonia.

Klebsiella pneumoniae is an important nosocomial pathogen causing severe pulmonary infections. The majority of clinical Klebsiella isolates produce a high-molecular-weight capsular polysaccharide (CPS) which is one of the dominant virulence factors. In the present study, we examined the potency of a murine immunoglobulin M monoclonal antibody (MAb) with specificity to Klebsiella type 2 CPS to protect rats against experimental Klebsiella pneumonia. The MAb did not prevent the invasion of virulent bacteria into the interalveolar space. However, the resolution of infection was accelerated in MAb-treated animals. This was demonstrated by (i) less severe weight loss and (ii) markedly reduced inflammatory reactions in the lung. The elimination of bacteria was significantly increased not only in the lungs but also in the livers of antibody-treated rats. This was reflected by reduced levels of circulating, soluble CPS and MAb-bound CPS. A mixture of human MAbs with specificity to CPS of clinically important Klebsiella serotypes may prove to be a useful tool for the prevention or supportive treatment of Klebsiella pneumonia.

Animals↗

[Fluconazole in therapy of candidiasis of the oropharyngeal space in patients with HIV infection. Results of an open multicenter study of assessing the effectiveness and tolerance of fluconazole].

50 HIV-positive patients (CDC stage III to VI) with oral candidiasis proven by culture and typical clinical findings were treated with fluconazole (50 to 100 mg/day) over a period of eight to 22 days. After completion of treatment, clinical signs of oral candidiasis had disappeared in 45/50 patients. In 10/50 patients, however, increased concentrations of candida both in pharyngeal washes (greater than 10(2) PFU/ml) and throat swabs (greater than 20 colonies/culture) persisted. Four weeks later, clinical candidiasis had reappeared in 22/42 patients and another 14/42 patients without clinical symptoms had pathological concentrations of candida in culture. In no case did treatment with fluconazole itself have to be aborted because of adverse reactions. Most of the patients had multiple concomitant bacterial and/or viral infections requiring comprehensive medication. The side effects observed (nausea, headache, changes in the blood picture, etc.) were due to the concomitant infections and their specific therapy.

Administration, Oral↗

Aspirin-like drugs, ethanol-induced rat gastric injury and mucosal eicosanoid release.

The effect of oral administration of various non-steroidal antiinflammatory drugs on ethanol-induced rat gastric injury and mucosal release of leukotriene C4, 6-keto-prostaglandin F1 alpha and 15-hydroxy-5,8,11,13-eicosatetraenoic acid was investigated. It was found that besides sodium salicylate and high doses of aspirin, other salicylate-type drugs, such as diflunisal, 4-aminosalicylic acid, 2,4-dihydroxybenzoic acid and methyl salicylate, and several non-acidic compounds, such as proquazone, benzydamine and paracetamol, were gastroprotective. All these drugs inhibited ex vivo leukotriene C4 formation by ethanol-stimulated gastric mucosa. However, naproxen, lonazolac, ibuprofen, gentisic acid and 5-aminosalicylic acid also inhibited leukotriene C4 formation, but were not protective. Gastroprotection was independent of 6-keto-prostaglandin F1 alpha formation. Both protective and non-protective drugs inhibited the ethanol-stimulated, but not the basal, release of 15-hydroxy-5,8,11,13-eicosatetraenoic acid. The results indicate that the differential effects of various non-steroidal antiinflammatory drugs on gastroprotection against ethanol are not correlated with specific effects on mucosal cyclooxygenase, 5-lipoxygenase or 15-lipoxygenase activity.

6-Ketoprostaglandin F1 alpha↗