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Biomedical subjects

U Ullmann

Publications and source records attributed to U Ullmann.

At least 37 records · Page 2Linked to original sources

Relative bioavailability of imipramine (Tofranil) coated tablets in healthy volunteers.

OBJECTIVES: Imipramine is a tricyclic antidepressant drug with a considerable hepatic first-pass metabolism resulting in highly variable pharmacokinetic characteristics and desipramine as active major metabolite. This study describes the bioavailability of 3 formulations of imipramine. METHODS: In a randomized, three-period crossover study, 18 healthy male Caucasian subjects received single oral doses of Tofranil 25, Tofranil mite (10 mg) and an aqueous solution containing 25 mg imipramine-HCl. Serum concentrations of imipramine-HCl and its main metabolite desipramine were measured. The pharmacokinetic characteristics, Cmax, AUC, t1/2 and tmax were determined and the relative bioavailability of the two coated tablet formulations was calculated with the aqueous solution as reference. Safety and tolerability were assessed using vital signs, ECG, clinical laboratory and adverse event recording. RESULTS: The relative bioavailabilities of Tofranil 25 and Tofranil mite were 97% and 81%, respectively. The study medication was well tolerated. CONCLUSIONS: A sufficiently high extent of absorption was found for the test formulations ensuring therapeutic efficacy.

Administration, Oral↗

Characterization of Klebsiella terrigena strains from humans: haemagglutinins, serum resistance, siderophore synthesis, and serotypes.

Klebsiella terrigena is very rarely isolated from humans; as yet, its clinical significance is uncertain. The aim of the present study was to evaluate whether this species is able to express putative virulence factors. A total of 72 faecal (n = 50) and clinical (n = 22) K. terrigena isolates was investigated and compared with faecal and clinical strains of K. pneumoniae. Mannose-sensitive haemagglutination (MSHA) was observed less often in K. terrigena (64-74%) than in K. pneumoniae strains. In contrast, the incidence of mannose-resistant haemagglutinin indicative of type 3 pili (MR/K-HA) (77-94%), serum resistance properties (10-23%), and production of enterobactin (100%) was similar in both species. None of the K. terrigena isolates were able to synthesize aerobactin; however, the frequency of aerobactin synthesis in K. pneumoniae was also only 5%. Serotyping showed capsular types K5 and K70 to be predominant. The virulence-associated serotype K2 was common in both K. terrigena and K. pneumoniae isolates. Taken together, the present results suggest that K. terrigena and K. pneumoniae are indistinguishable with respect to the expression of virulence factors.

Blood Bactericidal Activity↗

[Results of an evaluation of psychotherapeutic care from the viewpoints of patients and therapists in Saxony-Anhalt].

With the enforcement of the German law for psychotherapeutics at the beginning of 1999, the field of psychotherapy detached from a widespread "delegation procedure" through the possibility of first-access for patients to a psychotherapist. In the form of an experiment, Saxony-Anhalt practiced as the only land in the Feral Republic of Germany a modified form of delegation procedure in the legal health insurance since 1992. The most important modification consisted in the possibility of first-access for the patient to the psychotherapist. Using selected results of the investigation in the view of psychotherapy patients and from medical and psychological psychotherapists, the situation after 5 years since introduction of this model in the out-patient, psychotherapeutic care in Saxony-Anhalt will be shown, as well as experience gained from this model.

Ambulatory Care↗

Capsule impedes adhesion to and invasion of epithelial cells by Klebsiella pneumoniae.

The adhesion of K21a, K26, K36, and K50 capsulated Klebsiella strains to ileocecal (HCT-8) and bladder (T24) epithelial cell lines was significantly lower than that of their corresponding spontaneous noncapsulated variants K21a/3, K26/1, K36/3, and K50/3, respectively. Internalization of the bacteria by both epithelial cell lines was also significantly reduced. Similarly, a capsule-switched derivative, K2(K36), that exhibited a morphologically larger K36 capsule and formed more capsular material invaded the ileocecal epithelial cell line poorly compared to the corresponding K2 parent strain. None of the capsulated strains exhibited significant mannose-sensitive type 1 fimbriae, whereas two of the noncapsulated variants K21a/3 and K50/3 exhibited potent mannose-sensitive hemagglutinating activity. Although hemagglutinating activity that could be attributed to mannose-resistant Klebsiella type 3 fimbriae was weak in all strains, in several cases the encapsulated parent strains exhibited lower titers than their corresponding noncapsulated variants. Although the level of adhesion to the ileocecal cells is not different from adhesion to bladder cells, bacterial internalization by bladder cells was significantly lower than internalization by ileocecal cells, suggesting that bladder cells lack components required for the internalization of Klebsiella.

Bacterial Adhesion↗

Rapid detection by reverse hybridization of mutations in the UL97 gene of human cytomegalovirus conferring resistance to ganciclovir.

UNLABELLED: BACKGROUND OF STUDY: Diseases due to human cytomegalovirus (HCMV) infection constitute a major threat in marrow and solid organ transplant recipients. Ganciclovir (GCV) is widely used in prophylaxis and pre-emptive therapy of active HCMV infection. Resistance to ganciclovir (GCV) may arise at variable frequency under GCV therapy and is conferred by mutations (i) in the UL97 gene (codons 460, 520, and 591-607) encoding a phosphotransferase which is essential for monophosphorylation of GCV and, to a lesser extent, (ii) in the UL54 gene coding for the DNA polymerase of HCMV. OBJECTIVE: The purpose was to develop a rapid assay to screen for emerging GCV resistance mutations in the UL97 gene of HCMV whereby avoiding virus isolation and nucleotide sequencing procedures. STUDY DESIGN: A nested PCR (nPCR) amplifying UL97 codons 450-672 was developed. Nested amplicons were subsequently sequenced directly. Oligonucleotides for use in a reverse hybridization assay were designed to detect relevant non-synonymous mutations at codons UL97 460, 520, 603 and 607. Strain AD169 served as a wild-type control. RESULTS: UL97-specific nPCR amplicons were obtained from 18 EDTA blood samples of ten transplant recipients receiving GCV for more than 30 days. In three consecutive samples from a single patient a GCV resistance mutation at codon 603 (C-->W) was detected. In addition, two out of four cell culture-adapted HCMV isolates known to exhibit GCV resistance in vitro revealed mutations at codons 460 (M-->V) and 607 (C-->Y), respectively. By reverse hybridization a discrimination of single nucleotide changes at codons 460, 520, 603 and 607 was possible whereby matching exactly the results of the nucleotide sequence analysis for all 23 amplicons examined. CONCLUSIONS: Reverse hybridization appeared to be a rapid and convenient alternative to nucleotide sequencing when screening the UL97 gene of HCMV for selected markers of GCV resistance.

Antiviral Agents↗

Comparative in-vitro activity of levofloxacin, other fluoroquinolones, doxycycline and erythromycin against Ureaplasma urealyticum and Mycoplasma hominis.

The susceptibility of 56 Ureaplasma urealyticum and 57 Mycoplasma hominis strains to levofloxacin, ofloxacin, ciprofloxacin, fleroxacin, doxycycline and erythromycin was determined by an agar dilution method. The reference strain used was M. hominis PG 21. Agar plates containing serial dilutions of antibiotics (range 0.03-16 mg/L), and control plates (without antibiotics) were inoculated with bacteria suspended in modified Shepard's broth using a multipoint inoculator. Levofloxacin showed greater activity against all U. urealyticum and M. hominis strains compared with all other antibiotics tested. The MIC90 values for U. urealyticum were as follows: levofloxacin, 1 mg/L; ofloxacin, 2 mg/L; ciprofloxacin, 4 mg/L; fleroxacin, 4 mg/L; doxycycline, 1 mg/L; erythromycin, 8 mg/L. The MIC90s for M. hominis were: levofloxacin, 1 mg/L; ofloxacin, 2 mg/L; ciprofloxacin, 4 mg/L; fleroxacin, 4 mg/L; doxycycline, 4 mg/L; erythromycin, > or = 16 mg/L. In conclusion, the results of this study suggest that levofloxacin may be useful in the treatment of mycoplasma genital infections.

Anti-Bacterial Agents↗

A novel type of AmpC beta-lactamase, ACC-1, produced by a Klebsiella pneumoniae strain causing nosocomial pneumonia.

A Klebsiella pneumoniae strain resistant to oxyimino cephalosporins was cultured from respiratory secretions of a patient suffering from nosocomial pneumonia in Kiel, Germany, in 1997. The isolate harbors a bla resistance gene located on a transmissible plasmid. An Escherichia coli transconjugant produces a beta-lactamase with an isoelectric point of 7.7 and a resistance phenotype characteristic of an AmpC (class 1) beta-lactamase except for low MICs of cephamycins. The bla gene was cloned and sequenced. It encodes a protein of 386 amino acids with the active site serine of the S-X-X-K motif at position 64, as is characteristic for class C beta-lactamases. Multiple alignment of the deduced amino acid sequence with 21 other AmpC beta-lactamases demonstrates only very distant homology, reaching at maximum 52.3% identity for the chromosomal AmpC beta-lactamase of Serratia marcescens SR50. The beta-lactamase of K. pneumoniae KUS represents a new type of AmpC-class enzyme, for which we propose the designation ACC-1 (Ambler class C-1).

Adult↗

Klebsiella spp. as nosocomial pathogens: epidemiology, taxonomy, typing methods, and pathogenicity factors.

Bacteria belonging to the genus Klebsiella frequently cause human nosocomial infections. In particular, the medically most important Klebsiella species, Klebsiella pneumoniae, accounts for a significant proportion of hospital-acquired urinary tract infections, pneumonia, septicemias, and soft tissue infections. The principal pathogenic reservoirs for transmission of Klebsiella are the gastrointestinal tract and the hands of hospital personnel. Because of their ability to spread rapidly in the hospital environment, these bacteria tend to cause nosocomial outbreaks. Hospital outbreaks of multidrug-resistant Klebsiella spp., especially those in neonatal wards, are often caused by new types of strains, the so-called extended-spectrum-beta-lactamase (ESBL) producers. The incidence of ESBL-producing strains among clinical Klebsiella isolates has been steadily increasing over the past years. The resulting limitations on the therapeutic options demand new measures for the management of Klebsiella hospital infections. While the different typing methods are useful epidemiological tools for infection control, recent findings about Klebsiella virulence factors have provided new insights into the pathogenic strategies of these bacteria. Klebsiella pathogenicity factors such as capsules or lipopolysaccharides are presently considered to be promising candidates for vaccination efforts that may serve as immunological infection control measures.

Cross Infection↗

Isolation of Klebsiella planticola from newborns in a neonatal ward.

This is the first report on the isolation of Klebsiella planticola from neonates. Over a period of 1 year, oropharyngeal and rectal swab specimens from 131 newborns on a neonatal ward were monitored for Klebsiella spp. Thirteen strains of K. planticola could be isolated, and these represented 9% of all Klebsiella spp. found. Capsule type K27 predominated, followed by capsule type K68. Our findings suggest a significant rate of colonization by K. planticola among neonates.

Anti-Bacterial Agents↗

Humoral immune response to Klebsiella capsular polysaccharides in HLA-B27-positive patients with acute anterior uveitis and ankylosing spondylitis.

Klebsiella is suggested to trigger ankylosing spondylitis (AS) and acute anterior uveitis (AAU) in HLA-B27-positive individuals. Previous investigations showed an increased antibody response to the Klebsiella capsular types K26, K36, and K50 in sera from HLA-B27-positive AS patients. In the present study the prevalence and titers of antibodies against Klebsiella capsular antigens were measured by means of an ELISA in 32 sera from HLA-B27-positive AAU patients either with (n = 10) or without AS (n = 22) and compared with sera from HLA-B27-negative AS-patients (n = 13). Sera from either HLA-B27-positive (n = 45) or negative (n = 40) healthy individuals served as control. Sera from HLA-B27-positive AAU with or without AS showed significantly higher antibody prevalence and IgG-titers against capsular antigens of the Klebsiella serotypes K26, K36, and K50 when compared with sera from HLA-B27-negative AS patients or with healthy controls. These results might be taken to indicate the predominance of these serotypes in the HLA-B27-associated AS and AAU.

Acute Disease↗

Molecular mechanisms of action of bacterial exotoxins.

Toxins are one of the inventive strategies that bacteria have developed in order to survive. As virulence factors, they play a major role in the pathogenesis of infectious diseases. Recent discoveries have once more highlighted the effectiveness of these precisely adjusted bacterial weapons. Furthermore, toxins have become an invaluable tool in the investigation of fundamental cell processes, including regulation of cellular functions by various G proteins, cytoskeletal dynamics and neural transmission. In this review, the bacterial toxins are presented in a rational classification based on the molecular mechanisms of action.

Animals↗

The immunomodulatory effects of antibiotics: in vitro and ex vivo investigations of 21 substances by means of the lymphocyte transformation test.

Besides their antimicrobial activity antibiotics can modulate immune response. The paper provides original data about in vitro and in vivo influence of antibiotics on lymphocyte transformation test (LTT) and gives a comprehensive overview of literature data. In the study presented here the influence of several antimicrobial substances on unstimulated and PHA-stimulated lymphocyte transformation was investigated. The proliferative response was measured as (3H) thymidine uptake by lymphocytes. For initial screening the lymphocyte transformation test was performed on murine lymphocytes in vitro. As a whole 21 antimicrobial substances were tested including representative substances of the most important main groups. As a second step experiments were done with selected substances on human lymphocytes that had shown a distinct influence on murine cells in vitro. At therapeutic concentrations a pronounced stimulation of murine lymphocyte transformation was caused by carbapenems, aminothiazole cephalosporins and imidazoles. Purine analogs had only suppressive effects. However, the increased (3H) thymidine uptake in murine cells could not be regularly reproduced in human lymphocytes and in ex vivo experiments.

Animals↗

Bacteriocin typing of Klebsiella spp. isolated from different sources.

To evaluate whether clinical Klebsiella isolates differ from nonclinical strains with respect to bacteriocin susceptibility patterns, a total of 452 Klebsiella pneumoniae and K. oxytoca strains isolated from different sources were examined. Bacteriocin typing was done by a modification of the scrape-and-point method, using a set of eight producer strains. 96% of the strains were typable. Forty-one different bacteriocin susceptibility patterns were observed. While two thirds of the K. oxytoca isolates belonged to only three different bacteriocin types, the K. pneumoniae strains showed a more heterogeneous distribution of patterns. No differences in pattern distribution were observed between isolates from clinical, fecal, or environmental sources. Certain bacteriocins showed a very broad spectrum of activity; e.g. 93% of all isolates were susceptible to bacteriocin type 3. The results suggest that nonclinical Klebsiella strains do not show other bacteriocin susceptibility types than clinical isolates do.

Bacteriocins↗

Serum antibodies to Klebsiella capsular polysaccharides in ankylosing spondylitis.

OBJECTIVE: To measure antibodies to Klebsiella capsular polysaccharides in the sera of HLA-B27 positive patients with ankylosing spondylitis (AS), compared with HLA-B27 positive and HLA-B27 negative healthy control subjects. METHODS: Antibodies were detected by means of an enzyme-linked immunosorbent assay specific for each of the 77 known Klebsiella serotypes. RESULTS: Significantly elevated frequencies and titers of antibodies to capsular polysaccharides K26, K36, and K50 were detected in sera from AS patients, compared with controls. CONCLUSION: These results suggest the predominance of Klebsiella serotypes K26, K36, and K50 in patients with AS.

Adult↗