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Biomedical subjects

G Döring

Publications and source records attributed to G Döring.

At least 73 records · Page 4Linked to original sources
PubMed1992

Antianginal and anti-ischemic efficacy of nicorandil in comparison with isosorbide-5-mononitrate and isosorbide dinitrate: results from two multicenter, double-blind, randomized studies with stable coronary heart disease patients.

The purpose of the two double-blind studies summarized in this article was to compare the antianginal and anti-ischemic effects of nicorandil with those of two different nitrate preparations. A total of 129 patients with stable New York Heart Association functional class II or III coronary heart disease were enrolled in the studies. Ninety-five patients received nicorandil, 34 received isosorbide dinitrate (ISDN), and 63 received isosorbide-5-mononitrate (MN). In study 1, nicorandil was compared with MN in a crossover design with 54 protocols eligible for efficacy assessment of MN and 52 eligible for nicorandil, respectively. Twenty milligrams of nicorandil and 20 mg MN administered b.i.d. for 4 weeks were equally effective in the treatment of stress-induced angina. Both drugs prolonged bicycle exercise tolerance and reduced weekly anginal attack rates. In study 2, nicorandil and ISDN were administered to two parallel groups of patients at a dose of 10 mg t.i.d. for 2 weeks and then 20 mg t.i.d. for 4 weeks. Under the assumption that the repetitive administration of nitrates with short dosing intervals might induce the development of tolerance to the nitrate mechanism of action, the t.i.d.-dosing regimen had been chosen in this study. Thirty-two protocols from those receiving nicorandil and 34 protocols from those receiving ISDN were eligible for efficacy assessment. Both drugs increased exercise capacity and reduced ST-segment depression at identical work loads with no significant difference between groups (p > 0.05). For both drugs, the higher doses were more effective than the lower doses. tolerance to the nitrate mechanism of action did not develop with either drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Pseudomonas aeruginosa LasB mutant constructed by insertional mutagenesis reveals elastolytic activity due to alkaline proteinase and the LasA fragment.

The extracellularly secreted endopeptidase elastase (LasB) is regarded as an important virulence factor of Pseudomonas aeruginosa. It has also been implicated in the processing of LasA which enhances elastolytic activity of LasB. In order to investigate the role of LasB in virulence and LasA processing, a LasB-negative mutant, PAO1E, was constructed by insertional mutagenesis of the LasB structural gene, lasB, in P. aeruginosa PAO. An internal 636 bp lasB fragment of the plasmid pRB1803 was ligated into a derivative of the mobilization vector pSUP201-1. The resulting plasmid, pBRMOB-LasB, was transformed into Escherichia coli and transferred by filter matings to the LasB-positive P. aeruginosa strain, PAO1. Plasmid integration in the lasB site of the chromosome was confirmed by Southern blot analysis. Radioimmunoassay and immunoblotting of PAO1E supernatant fluids yielded no detectable LasB (less than 1 ng ml-1 LasB). The absence of LasB in PAO1E was further proven by the inability of its culture supernatant fluid to cleave transferrin or rabbit immunoglobulin G (IgG) after a 72 h incubation. The residual proteolytic activity of PAO1E culture supernatant fluid was attributed to alkaline proteinase (Apr), since it was totally inhibited by specific antibodies against Apr. Residual elastolytic activity in culture supernatant fluid of PAO1E was due to the LasA fragment and to the combined action of the LasA fragment with Apr on elastin. The sizes of purified LasA from PAO1 and PAO1E were identical (22 kDa). These results show that, besides LasB and the LasA fragment, Apr may also act on elastin in the presence of the LasA fragment and that the proteolytic processing of LasA in P. aeruginosa is independent of LasB.

Bacterial Proteins↗
PubMed1991

Generation of Pseudomonas aeruginosa aerosols during handwashing from contaminated sink drains, transmission to hands of hospital personnel, and its prevention by use of a new heating device.

Pseudomonas aeruginosa was isolated from sinks of washing basins, showers, toilets and bathtubs, from the personnel and patients of a mixed infectious disease ward in a German children's hospital during a prospective 4-week epidemiological study. 81% of all sinks were contaminated with P. aeruginosa strains. Upon entering the hospital, all personnel hand cultures were P. aeruginosa-negative. However, during duty, 42.5% of the personnel members carried different P. aeruginosa strains on their hands. Detection of P. aeruginosa strains in sinks preceding the isolation of identical genotypes from personnel hands suggested a transmission route from sinks to hands. Opening of water taps generated aerosols containing P. aeruginosa sink organisms which contaminated hands during hand washing. Survival times of various P. aeruginosa strains in aerosols was dependent on strain characteristics, light and humidity, and t 1/2 differed between 3-76 min. Heating of washing basin sinks to 70 degrees C with a new, safe and inexpensive device inhibited bacterial growth in sinks, generation of P. aeruginosa aerosols, and resulted in hand cultures negative for P. aeruginosa after washing.

Aerosols↗
PubMed1990

Molecular epidemiological study of Pseudomonas aeruginosa isolates from patients with acute leukemia.

In an attempt to determine the genetic relationship between strains of Pseudomonas aeruginosa isolated from patients with acute leukemia, a recently described restriction fragment from the region upstream of the exotoxin A structural gene was used as a probe in Southern hybridization. The overall rate of cultures positive for Pseudomonas aeruginosa during 169 admissions (119 patients) was 17%. Twelve genotypically distinct strains were found among 18 colonized and/or infected individuals. Three of these strains were recovered from more than one patient, suggesting a certain risk of nosocomial transmission of Pseudomonas aeruginosa and cross-infection. Genotypic comparison showed identical restriction patterns in multiple isolates from single patients, and also in colonizing and subsequently infecting strains. Genotyping distinguished isolates with similar O serotypes and established the identity between isolates with differing susceptibility to agents used for antibacterial prophylaxis.

Acute Disease↗
PubMed1990

[Results of a physician survey on the status of knowledge and attitude to natural family planning in West Germany 1988].

Based on a questionnaire, reporters of the EMNID Poll Institute interviewed 229 general practitioners and 237 practising gynaecologists by telephone. When questioned which method for family planning was, in the physicians' opinion, most frequently used and which was most frequently recommended by physicians, contraceptive pills were far ahead of any other method. Somewhat surprising was the fact that up to 36% of the interviewed physicians considered that the intrauterine device is either the most frequently used or the most recommended method. Even the quantity of reports on condoms being the most frequently used method was relatively high (8-10%). 6% of the questioned physicians stated NFP methods as being mainly used, and 10% of the physicians recommended these methods. NFP methods also held the fourth place preceded by contraceptive pills, IUD and condom in the 1985 EMNID survey. Among the NFP methods, body basal temperature was reported to be the most popular and most frequently recommended method. The sympto-thermal method which is world-wide proposed as first choice by the experts, is still fairly unknown. The results arising from this survey indicate the necessity for physicians to gain a more thorough knowledge of modern NFP methods. Unjustified prejudices should be removed, the high reliability, which may be achieved at present, should be propagated and the undeniable advantages of NFP methods should be pointed out. The possible difficulties due to the necessary abstinence during the fertile period should, however, be kept in mind.

Adult↗
PubMed1990

Typing of polyagglutinable Pseudomonas aeruginosa isolates from cystic fibrosis patients.

The study assesses the reproducibility, typability and discriminatory power of several typing methods for Pseudomonas aeruginosa isolated from cystic fibrosis patients. 178 polyagglutinable Pseudomonas aeruginosa isolates from cystic fibrosis patients were serotyped using polyclonal sera and monoclonal antibodies, phage typed, pyocin typed and reverse phage typed. 31 of these polyagglutinable isolates, six monoagglutinable isolates and three nontypable isolates were also typed by means of hybridization using a DNA probe. In a comparison of the methods used, on polyagglutinable isolates only, typability was 0% with polyclonal sera, 90% with monoclonal sera, 94% with phage typing, 85% with pyocin typing, 36% with reverse phage typing and 100% with DNA-prope typing. Using monoclonal antibodies, the reproducibility was 75%, while that of phage typing was 88%, pyocin typing 53% and reverse phage typing 62%. Typing with the DNA probe was not repeated. using polyclonal sera, repeated typing showed that 94% of the isolates were polyagglutinable. Using phage typing, 40% of the isolates belonged to phage type 31, while 60% were distributed amongst 32 phage types. Using monoclonal antibodies, 71% of the isolates belonged to 0-group 3, and these isolates showed 16 different phage types. Subdivision of the phage types was further achieved by both pyocin typing and reverse phage typing. The DNA probe typing made it possible in some cases to discriminate between isolates which were otherwise found identical with the conventional typing methods, while in other cases typing with the DNA probe recorded as identical isolates which conventional methods had typed as being different. These differences may be due to a high mutation rate caused by the selection pressure of antibiotics, and by the host immune response. According to our results, investigations of reproducibility and typability of old and new typing methods are essential when they are used in clinical situations. The low reproducibility of some of the typing methods in the present study affects the reliability of epidemiological investigations in cystic fibrosis patients. Usage of only one method may not be sufficient in cases of polyagglutinable strains from cystic fibrosis patients.

Agglutination Tests↗
PubMed1990

Immunology of Pseudomonas aeruginosa infection in cystic fibrosis.

Adherence of P. aeruginosa to the lining of the respiratory tract is probably mediated by interaction of pili or alginate with lactosyl and sialosyl residues on the respiratory cells. The toxins produced by P. aeruginosa (for example, elastase and alkaline protease) may play a key role during the initial persistent colonization as they interfere with important defense mechanisms. Neutralizing antibodies are eventually produced, and a poor prognosis is correlated to a pronounced antibody response. The bacteria are protected against the host's defense mechanisms by production of alginate which encapsulates microcolonies of P. aeruginosa in the lungs. During the chronic infection, toxins of P. aeruginosa probably play little if any direct pathogenic role, however, immune complexes seem to be a major trigger of chronic inflammation in the lungs. Proteolytic enzymes and oxygen radicals released from the abundance of neutrophils in the lungs are probably responsible for most of the tissue damage. The individual course of the chronic infection may be explained by regulatory mechanisms, such as cleavage of immune complexes by neutrophil elastase, and by the balance between the different IgG subclass-specific antibody responses.

Bacterial Adhesion↗
PubMed1989

Long-term tobramycin aerosol therapy in cystic fibrosis.

The long-term efficacy and safety of aminoglycoside aerosol therapy for Pseudomonas aeruginosa colonization/infection in cystic fibrosis has not been fully investigated. In the present study, 14 patients with cystic fibrosis, ages 8-19 years (mean: 13.3 years), received tobramycin aerosol therapy for a mean duration of 20 months. Eighty milligrams of a tobramycin solution were inhaled twice daily after physiotherapy via a jet nebulizer. After 1 year, weight for height increased significantly by 2.9% of the predicted normal, and the Kraemer clinical score increased by 2.1 points (P less than 0.05). The frequency of hospital admissions decreased from 2.0 to 1.3 per patient, respectively, during the years before and after the study onset. The antibody response to P. aeruginosa elastase, exotoxin A, and alkaline phosphatase showed a reduction in serum titers against one or more enzymes in eight patients. The best long-term results after 12-38 months of treatment were obtained in moderately ill children. No evidence of ototoxicity or renal damage was observed. Although intermittent bacterial resistance occurred in five patients after 10-21 months of tobramycin inhalation, this was not associated with clinical deterioration. The study demonstrates the safety and clinical efficacy of long-term tobramycin aerosol therapy. Double-blind studies with larger patient cohorts are required to determine the value of aminoglycoside inhalation as an adjunct to the established therapeutic regimens.

Administration, Inhalation↗
PubMed1989

A rapid method for purification of homogeneous Legionella pneumophila cytotoxic protease using fast protein liquid chromatography.

A purification method was developed to isolate Legionella pneumophila cytotoxic protease in a form suitable for biological assays. Culture supernatant of a clinical isolate of L. pneumophila, Knoxville 1 strain, was used as the starting material. The protease was purified by FPLC on a Mono Q column followed by ultrafiltration. The isolated proteolytic enzyme has a specific activity of 90 azocasein units/mg protein and is a 42 kDa monomeric protein as determined by SDS-PAGE and gel filtration chromatography. It is heat-labile and toxic to a variety of cells e.g. McCoy, SIRC, HeLa, and rhabdomyosarcoma cells, baby hamster and green monkey kidney cells, and human embryonic lung fibroblasts.

Cell Line↗
PubMed1989

Different sensitivity of Pseudomonas aeruginosa exotoxin A and diphtheria toxin to enzymes from polymorphonuclear leukocytes.

We demonstrate that exotoxin A (ExoA) of Pseudomonas aeruginosa is one to two orders of magnitude more sensitive than diphtheria toxin (DT) of Corynebacterium diphtheriae to lysosomal enzymes from polymorphonuclear leukocytes (PMN). It is especially sensitive to PMN elastase which inactivates its cell free enzymatic activity and its cytotoxicity as measured with the Chinese hamster ovary cell assay and the rabbit skin test. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) showed a rapid fragmentation of ExoA into small peptides at low PMN elastase concentrations, whereas DT remained largely uncleaved at PMN elastase concentrations 10 times higher. PMN elastase also removed the cell surface receptors for ExoA and DT on Chinese hamster ovary cells, suggesting that both toxins may be ineffective at local sites of severe inflammation. A comparison of fibroblasts from cystic fibrosis patients and normal healthy individuals revealed no differences in susceptibility to either DT or ExoA; this tends to exclude a genetic defect as an explanation for the absence of ExoA effects in cystic fibrosis patients.

ADP Ribose Transferases↗
PubMed1989

Pseudomonas aeruginosa cross-colonization and persistence in patients with cystic fibrosis. Use of a DNA probe.

To investigate cross-colonization with and persistence of Pseudomonas aeruginosa in cystic fibrosis (CF), 181 isolates from 76 CF patients were typed using a P. aeruginosa-specific DNA probe. Whereas sibling pairs predominantly harboured genotypically identical P. aeruginosa strains, all of the other patients harboured different strains. Seventy-nine per cent (22/31) of the infected CF patients harboured the same strains at the beginning and the end of a summer camp. A change of strains was seen in 10% (3/31) of the patients at the end of the camp. Forty-six per cent (6/13) of the patients who were apparently initially uninfected, acquired P. aeruginosa by the end of the period. Genotyping proved that strain change or acquisition was due to cross-colonization in four of nine cases. Very little P. aeruginosa was isolated from the inanimate environment. Persistence of P. aeruginosa after a temporary loss due to antibiotic therapy was seen in 12/16 paired patient strains before and after antibiotic therapy. Thus, suppression followed a flare-up seemed to occur in these patients rather than eradication and a new infection. When 35 patients were followed over a period of 6 months, 7 (20%) changed the strain in their sputum. Only one of 43 patients harboured two different P. aeruginosa strains simultaneously over a long period.

Adolescent↗
PubMed1989

Genotyping of Pseudomonas aeruginosa sputum and stool isolates from cystic fibrosis patients: evidence for intestinal colonization and spreading into toilets.

Three hundred and fifty-eight stool and 131 sputum specimens from 40 cystic fibrosis (CF) patients and 100 toilet sinks were investigated for occurrence of Pseudomonas aeruginosa; 67% (21/31) of the patients with chronic P. aeruginosa lung infections carried the organism repeatedly in the stool but the organism was found only once in the stools of nine uninfected patients. P. aeruginosa stool carriage was correlated to high P. aeruginosa numbers in patients' sputa. Typing of P. aeruginosa with a DNA probe showed identity of sputum and stool strains. Seven patients repeatedly carried additional stool strains, not found in the sputum, suggesting intestinal colonization. No differences were seen in the clinical state of patients with P. aeruginosa-negative stool samples and patients with positive stool samples. Toilets in households of P. aeruginosa-infected CF patients were significantly more often contaminated with P. aeruginosa (42%) than toilets in households of non-infected CF patients (20%; P less than 0.03). The study shows that P. aeruginosa-infected CF patients may harbour the organisms also in the intestinal tract, and may spread the bacteria into toilets.

Adolescent↗
PubMed1989

Host response to Pseudomonas aeruginosa.

Patients with cystic fibrosis (CF) do not reveal a primary immune defect and respond with high numbers of functional polymorphonuclear leukocytes (PMN) and specific antibodies to lung infection with Pseudomonas aeruginosa. The mucoid character of P. aeruginosa, an altered epithelial cell surface, and high concentrations of PMN-derived lysosomal enzymes contribute to impaired bacterial lung clearance and result in chronic infection. Released PMN-elastase inactivates exotoxin A, the major toxin of P. aeruginosa, thus reducing its virulence. The imbalance between PMN-proteinases and their inhibitors leads to lung tissue damage, impaired opsonophagocytosis, and T-cell and B-cell imbalance. New therapeutical concepts in CF therefore combine anti-inflammatory drugs with effective antibiotics.

Bronchial Diseases↗
PubMed1989

Increased levels of IgG subclasses specific for Pseudomonas aeruginosa exoenzyme and polysaccharide antigens in chronically infected patients with cystic fibrosis.

IgG subclass levels to Pseudomonas aeruginosa alginate, alkaline proteinase, elastase and exotoxin A in sera of healthy adults, non-infected and infected cystic fibrosis patients were investigated by enzyme linked immunosorbent assay. Whereas healthy adults and non-infected cystic fibrosis patients revealed mostly negative IgG subclass levels to the four antigens, infected cystic fibrosis patients had significantly elevated IgG1, IgG2, IgG3 and IgG4 levels to both the protein antigens as well as the polysaccharide antigen. The study does not support previous findings of an impaired natural IgG2 response to polysaccharide antigen. The study does not support previous findings of an impaired natural IgG2 response to polysaccharide in chronically infected cystic fibrosis patients.

ADP Ribose Transferases↗