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T Schaberg

Publications and source records attributed to T Schaberg.

At least 19 recordsLinked to original sources
PubMed1995

Interaction study of lomefloxacin and ciprofloxacin with omeprazole and comparative pharmacokinetics.

To assess whether or not concomitant omeprazole treatment influences the pharmacokinetics of lomefloxacin and ciprofloxacin, a randomized, double-blind four-way-crossover study was performed. Another objective was to compare the pharmacokinetics of lomefloxacin and ciprofloxacin. Twelve healthy volunteers participated. On days 1 to 4 of each study period, each of them took 20 mg of omeprazole or a placebo orally, and on day 4, each took 400 mg of lomefloxacin or 500 mg of ciprofloxacin orally. Blood and urine samples were collected and assayed for the quinolones by high-pressure liquid chromatography. The mean peak concentrations in plasma (Cmax) and the areas under the curves (AUC), respectively, of lomefloxacin and ciprofloxacin, respectively, after prior treatment with placebo were 2.88 +/- 0.73 (mean +/- standard deviation) as against 2.60 +/- 0.76 micrograms/ml and 24.9 +/- 3.13 as against 11.9 +/- 1.89 micrograms.h/ml, and 72.4% +/- 5.10% as against 36.1% +/- 7.50% of the doses of lomefloxacin and ciprofloxacin, respectively, were recovered from the urine. None of the pharmacokinetic parameters differed significantly after prior treatment with omeprazole compared with placebo. The Cmax of lomefloxacin was not significantly higher than that of ciprofloxacin, but lomefloxacin's AUC reached twice that of ciprofloxacin because of its significantly longer half-life in plasma (6.68 +/- 1.94 as against 4.15 +/- 0.92 h, respectively, P < or = 0.01). Concomitant therapy with omeprazole did not alter the pharmacokinetics of lomefloxacin or ciprofloxacin in these single-dose studies.

Adult↗
PubMed1995

Clinical evaluation of a Mycobacterium tuberculosis PCR assay.

On the basis of previously published PCR primer sequences, we have designed a sensitive system for detecting DNA of the Mycobacterium tuberculosis complex (MTB) in patient sputum samples which employs a fast and simplified sample preparation method appropriate for routine diagnostic testing. In order to evaluate the accuracy of the PCR assay, we performed a prospective study with 103 patients, comparing PCR results with culture results of samples obtained from a parallel culture assay as well as with subsequent culture results. Using two MTB-specific PCR primer systems, we found 48 of 49 tuberculosis (Tb) patients to be PCR positive (PCR sensitivity, 0.98). Sixteen of 54 presumably non-Tb patients showed amplifiable MTB DNA (specificity, 0.7). The study demonstrates that for diagnostic applications of MTB PCR two MTB-specific primer pairs should be used. MTB infection is extremely unlikely in cases of MTB PCR-negative samples: with our method for the exclusion of active Tb, the validity of one PCR assay seems to be equivalent to those of at least three culturing procedures. Positive PCR results do not necessarily reflect active MTB infection. It remains to be shown whether positive PCR results in Tb-negative patients mean false-positivity, an early laboratory finding which predicts a subsequent reactivation of a prior Tb infection, or whether asymptomatic patients may carry PCR-amplifiable MTB DNA without any clinical relevance. It is important to point out that the validity of PCR results in clinical studies depends on the use of contamination controls parallel to all PCR steps and the simplicity of the DNA extraction method as well as on the specificity of the PCR results.

Base Sequence↗
PubMed1995

Monocyte infiltration and c-fms expression in hearts of spontaneously hypertensive rats.

To elucidate mechanisms of myocardial hypertrophy in spontaneously hypertensive rats (SHR), we examined by Northern blotting the expression of the proto-oncogenes c-myc, c-fos, c-sis, and c-fms in the hearts of 4- and 14-week-old SHR and normotensive Wistar-Kyoto (WKY) rats. No difference in c-myc or c-fos expression could be found between SHR and WKY rats. In SHR, c-sis gave a weak and c-fms a very strong signal at 14 weeks, whereas no signal for these oncogenes was found in either WKY rats or Sprague-Dawley controls. Since c-fms codes for the receptor of monocyte colony-stimulating factor, we next used in situ hybridization to localize the presence of c-fms in hearts of SHR at 14 weeks. We found strong signals for c-fms around small blood vessels and between cardiac myocytes in 14-week-old SHR but none in WKY rats. Immunohistochemical staining corroborated the presence of clusters of monocyte infiltration at these same perivascular sites in significantly greater numbers in SHR than in WKY rats. We conclude that c-fms expression and macrophage infiltration are increased in the perivascular space of hypertrophied hearts from SHR. We suggest that mononuclear cell recruitment and induction of c-fms may play a role in the development of hypertension-associated myocardial hypertrophy.

Animals↗
PubMed1995

Subpopulations of alveolar macrophages in smokers and nonsmokers: relation to the expression of CD11/CD18 molecules and superoxide anion production.

We were previously able to show that the number of alveolar macrophages (AM) expressing CD11/CD18 molecules is increased in smokers compared with nonsmokers and related to the superoxide anion (O2-) production of these cells. Since it has been demonstrated that AM are a heterogeneous cell population that can be separated by density, we performed this study to investigate the expression of CD11/CD18 molecules and O2- production in relation to cell density of AM from smokers and nonsmokers. AM were obtained by bronchoalveolar lavage (BAL) from smokers (n = 32) and nonsmokers (n = 20). Subpopulations were isolated using discontinuous Percoll density-gradient centrifugation with four densities (fraction 1: 1.030; fraction 2: 1.040; fraction 3: 1.050; and fraction 4: 1.070 g/ml). Expression of CD11/CD18 on freshly isolated cells and on AM before and after density centrifugation was studied using peroxidase-antiperoxidase staining. The contribution of AM subpopulations to O2- production in smokers was determined by monitoring the reduction of ferricytochrome C to ferrocytochrome C. We obtained 0.92 +/- 0.1 x 10(5) AM/ml BAL in nonsmokers and 2.4 +/- 0.3 x 10(5) AM/ml in smokers. Recovery after density centrifugation was > or = 72%. The absolute number of AM in smokers was significantly increased in fractions 3 and 4 (median 4.37 x 10(6) and 2.05 x 10(6), respectively) compared with nonsmokers (median 1.26 x 10(6) and 0.7 x 10(6), respectively) (p < 0.05). In both smokers and nonsmokers, fractions 3 and 4 showed a comparable increase in the percentage of CD11/CD18-positive AM compared with fractions 1 and 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Drug-resistant pulmonary tuberculosis in Berlin, Germany, 1987-1993.

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 = 1,011) over the last 7 yrs. We therefore evaluated clinical data and results of susceptibility tests (breakpoint 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. Sixty nine percent 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) (95% confidence interval (95% CI)); 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. Both primary and acquired resistance were higher in foreign-born than in German-born patients. We conclude that there was a considerable increase in multidrug-resistant tuberculosis in our hospital from 1987 to 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.

Adult↗
PubMed1995

Changing role of carbapenems in the treatment of lower respiratory tract infections.

The acquisition of antibiotic-resistance genes by virtually all major bacterial pathogens is currently a world-wide phenomenon. This problem is especially evident in nosocomial lower respiratory tract infections (LRTI). Carbapenems like imipenem and meropenem offer interesting antibacterial activities and beta-lactamase-stability, as well as adequate pharmacokinetic characteristics, to cover most of the pathogens involved in moderate to severe community-acquired and nosocomial LRTI. In contrast to imipenem, meropenem is not nephrotoxic and offers the advantage of greater stability against renal dehydropeptidase-I, so no concomitant application of an enzyme inhibitor is necessary. Meropenem can also be given by intravenous infusion or injection without the nausea and vomiting often associated with the administration of imipenem/cilastatin. Preliminary results with meropenem in LRTI show excellent cure rates and good tolerance for this new carbapenem.

Adolescent↗
PubMed1994

[Incompatibility of tuberculosis therapy in a patient with AIDS].

A man with advanced HIV infection (CD4 lymphocytes 90/microliter, CD4/CD8 ratio 0.2) was admitted to hospital with fever, cough and weight loss. The radiological and bronchoscopic findings, together with the presence of acid-fast bacilli in the sputum, pointed to open pulmonary tuberculosis caused by Mycobacterium tuberculosis, a diagnosis confirmed by histological examination and culture. Quadruple antibiotic therapy with isoniazid (INH), rifampicin (RMP), ethambutol (EMB) and amikacin was immediately begun and was at first clinically successful. Ten days later, however, a rash appeared; it was ascribed to RMP (anaphylactoid reaction after re-exposure). All the other first-line drugs tried during the ensuing eight months evoked severe adverse reactions (INH: rash and itching; amikacin: hearing impairment and tinnitus; EMB, pyrazinamide, prothionamide, p-aminosalicylic acid: rash and itching). Treatment was nevertheless clinically and microbiologically successful, and the patient insisted upon a 2 1/2 months' rest without therapy. This period was followed by extrapulmonary spread (severe arthritis of the elbow) and recurrence of pulmonary tuberculosis. The tubercle bacilli were sensitive to all the drugs so far employed. Renewed and lasting control of the infection was achieved only by continuous administration of steroids (prednisolone 10 mg twice daily) in conjunction with an unconventional antibiotic regimen consisting of amikacin, protionamide, terizidone, clarithromycin and sparfloxacin for some five months. Because of an episode of cerebral convulsions during treatment of cytomegalovirus retinitis with ganciclovir, the terizidone was discontinued (it was suspected of interacting with ganciclovir). The patient has had no more fits and sputum culture has remained negative for six months.

AIDS-Related Opportunistic Infections↗
PubMed1994

Adhesion molecules in lung diseases.

The human body possesses highly specialized cellular defense mechanisms that, when activated pathologically, can induce a number of immunologic disorders. For a normal cellular immune response, the following conditions must be fulfilled: (1) accumulation of white blood cells, (2) their diapedesis through the vessel walls of the inflammatory area affected by an injurious agent, and (3) normal cellular effector functions in the tissue. This cascade of inflammatory processes has recently been shown to be regulated by a group of molecules that are termed adhesion molecules and consist of three subfamilies: selectins, the immunoglobulin supergene family, and integrins. The cellular functions influenced by adhesion molecules include, among others, cytotoxic T-cell responses, CD4-dependent activation of B lymphocytes by T lymphocytes, activation of granulocytes and macrophages, phagocytosis of opsonized particles by monocytes, macrophages, and granulocytes, antigen-presenting function of macrophages, their antibody-dependent cytotoxicity, initiation of a respiratory burst by white blood cells, and activation of fibroblasts. Studies performed in recent years have shown that pathogenetically relevant changes in the expression and function of adhesion molecules are involved in a variety of pulmonary diseases. These changes include the accumulation and activation of alveolar macrophages in smokers, experimentally induced bronchial hyperreactivity in bronchial asthma, accumulation of eosinophils in allergic rhinitis, bleomycin-induced pulmonary fibrosis, binding of viruses and bacteria to respiratory mucosa, and various mechanisms of acute damage to pulmonary parenchyma. Though their role in tumor development is still unclear, adhesion molecules are obviously involved in determining the route and organotropism of metastases. Further studies of the function of adhesion molecules in pulmonary diseases will contribute to our understanding of the pathomechanisms of these diseases and, through the development of specific antibodies, may provide attractive new therapeutic approaches to problems for which treatment is not yet available.

Animals↗
PubMed1994

Surfactant protein A modulates release of reactive oxygen species from alveolar macrophages.

The production and release of reactive oxygen species (the respiratory burst) is a common metabolic pathway linked to several macrophage-related reactions. The most abundant surfactant protein A (SP-A) binds to alveolar macrophages (AM) through a specific surface receptor with high affinity. Because such binding might initiate or modulate the respiratory burst, we wanted to know whether and how SP-A affects the oxygen radical release from AM. To answer these questions, we measured the release of reactive oxygen species from rat AM under various in vitro conditions using enhanced chemiluminescence systems. We prepared SP-A from pulmonary surfactant isolated either from silica-treated rats or adult dogs. Resident AM were harvested from pathogen-free Wistar rats by lung lavage. Adhered and nonadhered AM were assessed on protein-free or protein-coated surfaces of 96-well microtiter plates. On protein-free surfaces, the sole addition of SP-A failed to induce measurable oxygen radical release from 2 x 10(5) adhered or nonadhered AM, while zymosan opsonized with SP-A induced a marked increase over control. On protein-coated surfaces, AM respond differently depending on the coated protein: on SP-A-coated surfaces, a dose-dependent enhancement of oxygen radical release with a mean effective concentration of approximately 1.15 micrograms/ml was found. No such enhancement was seen on plates coated with similar amounts of either human fibronectin or collagen, and the enhancement with serum albumin was not dose related. Our data demonstrate that SP-A only enhances oxygen radical release from AM if SP-A is fixed to zymosan or the surface of the reaction vial in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Simultaneous measurement of collagen type-VI-related antigen and procollagen type-III-N-propeptide levels in bronchoalveolar lavage.

Abnormal collagen metabolism is a hallmark of diffuse lung disease. Biochemical parameters which are correlated with collagen synthesis and degradation may be helpful to monitor fibrosis. In this study, we compared the sensitivity and specificity of procollagen type-III-N-propeptide (PIIINP) and collagen type-VI (C-VI) related antigen levels, as well as a ratio of both parameters (PIIINP/C-VI), in bronchoalveolar lavage fluid (BALF) from patients with diffuse and localized lung disease. We investigated 45 patients with diffuse lung disease (idiopathic pulmonary fibrosis (IPF), n = 21; sarcoidosis, n = 13; and lymphangitic carcinomatosis (LC), n = 11); 58 control subjects; and 92 patients with localized lung disease (bronchial carcinoma, n = 37; pulmonary tuberculosis, n = 31; and pneumonia, n = 24). C-VI and PIIINP were measured by immunoassay in concentrated BALF. Although the PIIINP and C-VI levels were increased in diffuse lung disease, the sensitivity of the individual parameters PIIINP and C-VI was low (IPF: PIIINP = 0.62, C-VI = 0.29; LC: PIIINP = 0.64, C-VI = 0.45; sarcoidosis: PIIINP = 0.69, C-VI = 0.15). When calculating the ratio of PIIINP/C-VI for each individual patient, we found a significant increase in this ratio in IPF (1.28 +/- 0.7), LC (2.34 +/- 1.2), and sarcoidosis (0.26 +/- 0.08) compared to both the controls (0.02 +/- 0.01) and other localized lung diseases (bronchial carcinoma 0.05 +/- 0.01; pulmonary tuberculosis 0.02 +/- 0.01), with the exception of pneumonia (0.18 +/- 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Comparative pharmacokinetics of the new oral cephalosporins.

The comparative pharmacokinetics of the new oral cephalosporins (ester and nonester types), together with that of the first generation carbacephem, loracarbef, are considered in healthy volunteers. Also in this review, pharmacokinetic and microbiological data are combined in order to predict the possible clinical efficacy of this group of agents. Despite apparent similarities in the structure of these agents, single dose studies have revealed marked differences in the pharmacokinetics of the oral cephalosporins. Multiple dose studies showed no evidence of accumulation with these agents. In the elderly, only minor changes in the pharmacokinetics of the oral agents were observed, and were insufficient to warrant dosage adjustment. Unlike that of the nonester compounds, the bioavailability of the ester cephalosporins is increased when they are administered after food. Variable effects are observed when the ester agents are coadministered with antacids or H2-antagonists; while the absorption of cefetamet pivoxil was unaffected by coadministered antacids or H2-antagonists, the absorption of cefpodoxime proxetil was reduced.

Administration, Oral↗