[Spectrum of microbial colonisation and resistance of a surgical ICU in a systematic comparison of the 10-year time period 1996-2005 using routine microbiological testing]. / Erreger- und Resistenzspektrum einer chirurgischen ITS im systematischen 10-Jahres-Vergleich 1996-2005 im Rahmen des mikrobiologischen Routinemonitorings.

INTRODUCTION: Knowledge on potentially pathogenic microbes including characteristics of their antibiotic resistance in septic patients as well as on the ward- and department-specific microbial spectrum can be considered essential for an efficient initiation of an adequate antimicrobial treatment, which turns out to become pivotal for patient outcome. Permanent changes in microbial patterns and antibiotic resistance can only be identified by a continuous investigation of various microbiological specimens. AIM: Based on the retrospective evaluation of prospectively collected data on microbiological investigations of the surgical ICU in 1996, 2002, 2004 and 2005, the short- and long-term changes by trend of microbial spectrum and antibiotic resistance following reorganisation and restructuring of the University Hospital from the more traditional pavillon-based system to a multidisciplinary complex building in 2003 were investigated. MATERIAL AND METHODS: Twice a week, routine microbiological testing of blood and urinary cultures as well as swabs from wound areas and endotracheal swabs were initiated in septic patients (suspect, manifestation) or in case of their clinical impairment. The microbial spectrum was sub-divided according to Gram-staining (Gram-positive/ -negative), various species and fungi with descriptive absolute and relative data values. -Various groups and time periods were statistically compared using χ² test as appropriate. P values < 0.05 were considered statistically significant. RESULTS: In total (n (Total) = 4 899), microbiological testing resulted in the detection of microbes in 699 and 833 blood and urinary cultures (14.3 % and 17 %, respectively) as well as 1 232 wound swabs (25.1 %) together with 2 135 samples from the endotracheal sites (43.6 %). During the short- (2002 vs. 2004) and long-term analyses (1996 vs. 2005), the proportion of Gram-positive microbes increased. Al-though Gram-positive bacteria can be considered the most frequent microbes for bacteriemia, there was a shift onto urinary and wound infections as well as pneumonias through the observation period. Despite the decreasing incidence of Enterococcus and the consistent proportion of MRSA, the increase of resistant Enterococcus strains (0 % vs. 43.2 %; P < 0.05) is critical. However, in the Gram-negative microbial spectrum there was an increase of the bacteraemia rate but a fall of the detection rate in wound and endotracheal swabs. In parallel, an increase of the detection rate of E. coli in blood (6.5 % vs. 45.5 %; P < 0.05) and endotracheal swabs (9.2 % vs. 16.2 %; P < 0.05) is associated with an increase of multiresistant Enterobacteriaceae strains (0 % vs. 30.7 %; P < 0.05). The portion of multiresistant strains of Pseudomonas with 31 % stayed the same through the 10-year time period. While Candida-based colonisation showed a decreased incidence (25 % vs. 15 %; P < 0.05) during the whole investigation period, there was a relative rise in the frequency of candidemia. CONCLUSION: ICU relocation from the pavillon-based system to a new complex clinic building was not associated with any significant alteration of the microbial spectrum on the surgical ICU. Increasing incidences of resistant Enterococcus and Gram-negative problematic microbes may indicate a general spread of multi-resistant microbes under the steady selecting pressure of a not always adequately initiated antibiotic / antimicrobial therapeutic regimen and underline the required but specific and selected microbiological screening.

Essential oil composition of Piper guineense and its antimicrobial activity. Another chemotype from Nigeria.

The analysis of the essential oil of Piper guineense from Nigeria presents a new chemotype of constituents different from earlier reports with the absence of the usual myristicin. Ishwarane, a common constituent of Aristolochia indica and Bixa orellana, was also isolated from the essential oil of the fruit. The essential oil inhibited the growth of Pseudomonas aeruginosa UCH 655 strain at 5 mg/mL on which standard antibiotic drugs were ineffective.

Sesquiterpenoid constituents of the liverworts Lepidozia fauriana and Lepidozia vitrea.

The sesquiterpene constituents of the essential oils of the Taiwanese liverworts Lepidozia fauriana and L. vitrea were investigated. 11,12-Dihydrochiloscyphone and 7,10-anhydro-11,12-dihydrochiloscypholone were isolated from L. fauriana and spectroscopically characterised together with their hydrogenation products. From the same species three amorphane derivatives amorpha-4,9-dien-14-al, amorpha-4,9-dien-2-ol and 7,14-anhydroamorpha-4,9-diene, and from L. vitrea two oxygenated elemanes, namely 7-acetoxy-elema-1,3-dien-8-ol and elema-1,3-dien-7-ol, were isolated and identified. Structure elucidation was carried out by NMR spectroscopy and chemical correlations in conjunction with enantioselective gas chromatography were utilized to establish absolute configurations.

Sesquiterpene hydrocarbons with trifarane backbone in the liverwort Trocholejeunea sandvicensis.

The hydrocarbon fraction of the liverwort Trocholejeunea sandvicensis was investigated. Four new sesquiterpene hydrocarbons including the trifaranes (-)-trifara-9,14-diene (6) and (-)-3,7-di-epi-3,7-trifara-9,14-diene (7), as well as (+)-sandvicene (8), a sesquiterpene with uncommon skeleton, and the rearranged trifarane sesquiterpene (+)-neotrifaradiene (9) were isolated and their structure elucidated. A biogenetic pathway for the four compounds is proposed, with nerolidol as their common precursor.

[Is appendectomy really performed too frequently? Results of the prospective multicenter study of the Swiss Society of General Surgery]. / Wird tatsächlich zu häufig appendektomiert? Resultate der prospektiven Multicenterstudie der Schweizerischen Gesellschaft für Allgemeinchirurgie (SGAC).

Scientific publications and provoking criticism from the lay press have recently pointed out, that appendices may be surgically removed too frequent and without indisputable necessity. In an attempt to verify these questionable statements, the Swiss Society for General Surgery (SGAC) initiated a prospective controlled multi center trial. From September 1997 to December 1998, hundred and twenty-five institutions documented 4603 appendectomies performed due to a suspected appendicitis. Histological investigation of all specimens revealed a 7% rate of normal appendices, 7.2% for patients with national health service (NHS) and 5.9% for patients with private insurances respectively. Compared to the results of the literature, where a frequency of normal appendices around 15% is judged as standard, these results are excellent. In 17.2% of the patients (15.9% NHS and 23.6% privately insured patients) an "appendicitis perforata" was observed. This percentage remains in the range reported by other authors. The analysis of time of admission (i.e. day or night) and the delay from admission to surgery shows a distribution independent to the insurance of the patients. Therefore, the planned appendectomy for patients with private insurances does not exist. A different choice of the surgical technique could be observed depending on the insurance status. In 30.4% of the private insured patients a laparoscopic appendectomy was performed as compared to 22.6% of patients with NHS. Surprisingly, an identical median hospitalization time can be observed for both groups (laparoscopic 5.5 days, open surgery 5.5 days).

Amorpha-4,11-diene synthase catalyses the first probable step in artemisinin biosynthesis.

The endoperoxide sesquiterpene lactone artemisinin and its derivatives are a promising new group of drugs against malaria. Artemisinin is a constituent of the annual herb Artemisia annua L. So far only the later steps in artemisinin biosynthesis--from artemisinic acid--have been elucidated and the expected olefinic sesquiterpene intermediate has never been demonstrated. In pentane extracts of A. annua leaves we detected a sesquiterpene with the mass spectrum of amorpha-4,11-diene. Synthesis of amorpha-4,11-diene from artemisinic acid confirmed the identity. In addition we identified several sesquiterpene synthases of which one of the major activities catalysed the formation of amorpha-4,11-diene from farnesyl diphosphate. This enzyme was partially purified and shows the typical characteristics of sesquiterpene synthases, such as a broad pH optimum around 6.5-7.0, a molecular mass of 56 kDa, and a K(m) of 0.6 microM. The structure and configuration of amorpha-4,11-diene, its low content in A. annua and the high activity of amorpha-4,11-diene synthase all support that amorpha-4,11-diene is the likely olefinic sesquiterpene intermediate in the biosynthesis of artemisinin.

Total parenteral nutrition with glutamine dipeptide after major abdominal surgery: a randomized, double-blind, controlled study.

OBJECTIVE: To assess the efficacy of glutamine (Gln) dipeptide-enriched total parenteral nutrition (TPN) on selected metabolic, immunologic, and clinical variables in surgical patients. SUMMARY BACKGROUND DATA: Depletion of Gln stores might lead to severe clinical complications. Recent studies indicate that the parenteral provision of Gln or Gln-containing dipeptides improves nitrogen balance, maintains the intracellular Gln pool, preserves intestinal permeability and absorption, and shortens hospital stay. METHODS: Twenty-eight patients (age range, 42-86 years, mean 68 years) undergoing elective abdominal surgery were allocated, after randomization, to two groups to receive isonitrogenous (0.24 g nitrogen kg(-1) day(-1)) and isoenergetic (29 kcal/122 kJ kg(-1) day(-1)) TPN over 5 days. Controls received 1.5 g of amino acids kg(-1) day(-1), and the test group received 1.2 g of amino acids and 0.3 g of L-alanyl-L-glutamine (Ala-Gln) kg(-1) day(-1). Venous heparinized blood samples were obtained before surgery and on days 1, 3, and 6 after surgery for routine clinical chemistry and for the measurement of plasma free amino acids. Lymphocytes were counted and the generation of cysteinyl-leukotrienes from polymorphonuclear neutrophil granulocytes was analyzed before surgery and on days 1 and 6 after surgery. Nitrogen balances were calculated postoperatively on days 2, 3, 4, and 5. RESULTS: No side effects or complaints were noted. Patients receiving Gln dipeptide revealed improved nitrogen balances (cumulative balance over 5 days: -7.9 +/- 3.6 vs. -23.0 +/- 2.6 g nitrogen), improved lymphocyte recovery on day 6 (2.41 +/- 0.27 vs. 1.52 +/- 0.17 lymphocytes/nL) and improved generation of cysteinyl-leukotrienes from polymorphonuclear neutrophil granulocytes (25.7 +/- 4.89 vs. 5.03 +/- 3.11 ng/mL). Postoperative hospital stay was 6.2 days shorter in the dipeptide-supplemented group. CONCLUSION: We confirm the beneficial effects of Gln dipeptide-supplemented TPN on nitrogen economy, maintenance of plasma Gln concentration, lymphocyte recovery, cysteinyl-leukotriene generation, and shortened hospital stay in surgical patients.

Arachidonic acid induces DNA-fragmentation in human polymorphonuclear neutrophil granulocytes.

We analyzed DNA-fragmentation in human polymorphonuclear neutrophil granulocytes (PMNs) from healthy donors after addition of exogenous arachidonic acid (AA) and eicosapentaenoic acid (EPA) by flow cytometry (propidium iodide staining of DNA and DNA strand break detection). The PMNs were incubated from 30 min up to 48 hours in RPMI 1640 which was supplemented with different concentrations of AA or EPA (5-40 microM). In contrast to EPA the addition of AA led to a significant increase in apoptosis up to 67.8% compared to the RPMI-control whereas the addition of EPA led to an inhibition of DNA-fragmentation. When the cells were incubated with MK 886 (1 microM, inhibitor of leukotriene biosynthesis) an increase in DNA-fragmentation (up to 63.3%) was observed. Conversely, in the presence of indomethacin (1 microM, inhibitor of prostanoid synthesis) an inhibition in DNA-fragmentation (up to 60.9%) occurred. Furthermore, preincubation of PMNs with pentoxifylline (1mM, phosphodiesterase inhibitor) reduced AA-stimulated DNA-fragmentation up to 43.4%. These data provide evidence for the involvement of AA and distinct AA metabolites in the regulation of apoptosis in human PMNs.

Influence of a total parenteral nutrition enriched with omega-3 fatty acids on leukotriene synthesis of peripheral leukocytes and systemic cytokine levels in patients with major surgery.

OBJECTIVE: Nutritive immunomodulation of patients after major surgery. DESIGN: Prospective, randomized controlled double-blind study. PATIENTS: Forty patients undergoing major intestinal surgery. Patients were divided into two groups: one received a total parenteral nutrition enriched with omega-3 fatty acids for 5 days postoperatively, the other an isocaloric, control nutrition. MATERIALS AND METHODS: We analyzed the leukocyte ability to release leukotrienes from whole blood leukocytes stimulated with the calcium ionophore A23187 (5 micromol/L) by reverse phase high-performance liquid chromatography and circulating cytokines by enzyme-linked immunosorbent assay. RESULTS: Leukocytes from patients of the omega-3 fatty acids group generated significantly higher amounts of less biologically active leukotriene B5 as compared to the control group (p < or = 0.001). This was accompanied by a significant decrease in the generation of proinflammatory leukotriene B4 (p < or = 0.006) in the study group. In contrast to interleukin-1beta, interleukin-6, and interleukin-10 systemic levels of tumor necrosis factor-alpha (p < or = 0.05) were postoperatively decreased in the study group. CONCLUSION: Our data provide evidence that a total parenteral nutrition enriched with omega-3 fatty acids modulates the lipid mediator pattern and systemic tumor necrosis factor-alpha levels.

Enantioselective and nonenantioselective degradation of organic pollutants in the marine ecosystem.

Enantiomeric ratios of 11 chiral environmental pollutants determined in different compartments of the marine ecosystem by chiral capillary gas chromatography and chiral high-performance liquid chromatography allow discrimination between the following processes: enantioselective decomposition of both enantiomers with different velocities by marine microorganisms (alpha-HCH, beta-PCCH, gamma-PCCH); enantioselective decomposition of one enantiomer only by marine microorganisms (DCPP); enantioselective decomposition by enzymatic processes in marine biota (alpha-HCH, beta-PCCH, trans-chlordane, cis-chlordane, octachlordane MC4, octachlordane MC5, octachlordane MC7, oxychlordane, heptachlor epoxide); enantioselective active transport through the "blood-brain barrier" (alpha-HCH); nonenantioselective photochemical degradation (alpha-HCH, beta-PCCH).

Effect of an immunostimulatory substance of Klebsiella pneumoniae on inflammatory responses of human granulocytes, basophils and platelets.

RU 41740 (Biostim), a biological response modifier of bacterial origin obtained from the 01.K2 strain of K. pneumoniae, was studied with regard to its effect to modulate the chemiluminescence response, phagocytosis and leukotriene formation from polymorphonuclear leukocytes (PMNs), the histamine release from basophils and the aggregation of human platelets. For histamine release human basophils were analyzed with either the calcium ionophore A23187 or hemolysin producing bacteria. RU 41740 reduced the E. coli K12 pANN5211 induced histamine release whereas the calcium ionophore A23187 induced histamine release was not affected. The studies with regard to adherence and phagocytosis showed a significant increase in phagocytosis for S. aureus in the presence of RU 41740. With regard to the chemiluminescence response of human granulocytes, donor cells were divided into cells with a high and a low response. The chemiluminescence response of high responder cells towards a potent stimulus, e.g. the calcium ionophore A23187, was decreased by RU 41740 whereas weak stimuli (e.g. E. coli K12) were not affected. In contrast to these results the chemiluminescence response of low responder cells to a weak stimulus e.g. E. coli K12 was increased by RU 41740 and the potent stimuli were not affected. RU 41740 also modulates the eicosanoid synthesis of human polymorphonuclear granulocytes. For the calcium ionophore A23187 induced leukotriene production an increase of LTB4 and a decrease of LTC4 by RU 41740 was observed. Furthermore, preincubation of platelets with various concentrations of RU 41740 for 5 min shows an inhibition of platelet aggregation, when an additional stimulation with the calcium ionophore A23187 was carried out.

Modulation of leukotriene generation by pertussis toxin.

The purpose of our study was to characterize the properties of the interaction of pertussis toxin with human polymorphonuclear leukocytes for the modulation of leukotriene generation and metabolism. The cells were stimulated with either the Ca ionophore A23187, opsonized zymosan, or the bacterial peptide formyl-methionyl-leucyl phenylalanine. Incubation of the cells with pertussis toxin led to a rapid inhibition of LTB4 generation when formyl-methionyl-leucyl phenylalanine was used as the stimulus, whereas there was no effect with the Ca ionophore and just a low effect with opsonized zymosan. The inhibition of leukotriene generation was dependent on the incubation time, temperature, and pertussis toxin concentration. The effect was not dependent on the presence of calcium. Incubation of the cells with guanosine 5'-O-(3-thiotriphosphate) the stable analog of GTP, led to a time-dependent increase in leukotriene generation induced by formyl-methionyl-leucyl phenylalanine which was abolished by the simultaneous addition of pertussis toxin. Our data suggest that the formyl-methionyl-leucyl phenylalanine-induced generation of leukotrienes is dependent on a GTP-binding protein. The participation of the various G proteins has yet to be elucidated.

Metabolic products of microorganisms. 243. Pyridazomycin, a new antifungal antibiotic produced by Streptomyces violaceoniger.

Pyridazomycin, a new antifungal antibiotic produced by Streptomyces violaceoniger sp. griseofuscus (strain Tü 2557), was detected in a selective screening against Mucor hiemalis (Tü 179/180). The amino acid side chain of 1 can be seen as L-ornithine, whose gamma-nitrogen atom is part of a pyridazine ring building a quaternary ammonium system. The structure of 1 was established by spectroscopic analysis of the parent compound and degradation products. The occurrence of a pyridazine ring in microbial secondary metabolites is unique.

Ciprofloxacin and norfloxacin for selective decontamination in patients with severe granulocytopenia.

In a randomized multicenter study, ciprofloxacin and norfloxacin, each in two different dose regimens and in combination with non-absorbable antimycotics, were administered to 51 patients with acute leukaemia undergoing aggressive remission induction chemotherapy for infection prevention. Both drugs showed an effective elimination of gram-negative potential pathogens and Staphylococcus aureus not affecting the anaerobic flora of the gastrointestinal tract. A low incidence of side effects and a satisfactory patient compliance could be observed. A daily dosage of 1,000 mg ciprofloxacin or 800 mg norfloxacin is recommended for infection prevention in severely granulocytopenic patients.

Allergic and irritant contact dermatitis from falcarinol and didehydrofalcarinol in common ivy (Hedera helix L.).

Experimental and chemical investigations revealed that common ivy (Hedera helix susp. helix) contains 3 compounds which are powerful irritants and moderate sensitizers. Only 2 of these constituents, falcarinol and didehydrofalcarinol, are present in the plant during the whole year. Besides Panax ginseng and Schefflera arboricola, this is the third species of the Araliaceae in which these polyacetylenic sensitizers have been found. Falcarinol and didehydrofalcarinol also occur in Hedera helix subsp. canariensis. 4 patients have been patch tested. Even in low concentrations (0.03%), the main allergen falcarinol elicited strong reactions in all of them. One of the authors became sensitized during the investigations.

Detection of proteins in wheat flour extracts that bind human IgG, IgE, and mouse monoclonal antibodies.

Wheat flour was extracted with phosphate-buffered saline. The biologic significance of the extracted cereal proteins was demonstrated. Basophil leukocytes were obtained from patients suffering from "baker's asthma disease." Histamine release in vitro was induced by addition of the aqueous flour extract. By means of ELISA, as well as immunoblotting technique, IgG and IgE binding to wheat flour proteins was demonstrated. Wheat-specific antibodies could be detected in sera obtained from healthy and atopic individuals. Further analysis of the cereal components by monoclonal antibodies revealed that several wheat molecules exhibit identical epitopes.

[Phospholipase A2 inhibitors in hemorrhagic-necrotizing pancreatitis. Animal experiment evaluation of a new treatment concept]. / Phospholipase A2-Inhibitoren bei hämorrhagisch-nekrotisierender Pankreatitis. Tierexperimentelle Uberprüfung eines neuen Behandlungskonzeptes.

In mongrel dogs with induced pancreatitis we studied the effects of the nonspecific phospholipase A2-inhibitors chlorpromazine, gabexate mesilate and CaNa2EDTA on the course of pancreatogenic shock and the intrapancreatic lysolecithin production. The local level of lysolecithine the metabolite of phospholipase A2 was lower in the treated than in the untreated control groups. Gabexate mesilate was the most active inhibitor. However, none of the drugs had a beneficial influence on hemodynamics, chlorpromazine made it even worse. Morphologically no difference was seen between the treated and untreated groups.

[Integration of psychotherapy into clinical medicine in Germany--contribution of J. H. Schultz]. / Die Integration der Psychotherapie in die klinische Medizin in Deutschland--der Beitrag von J. H. Schultz.

Based on a short description of the situation of the psychotherapy in Germany during the 20ties Schultz's achievements in this period are defined and compared. In the first instance Schultz played a leading role in the integration-process of psychotherapy in several clinical branches. Furthermore Schultz tried to develop a medico-psychological concept for practical medicine in general which possesses a high importance in the present discussion about medico-psychological problems.

Susceptibility of naturally occurring carbapenem antibiotics to renal dehydropeptidase-I. An easy assay using a plate technique based on a novel chromogenic beta-lactamase substrate.

A general screening procedure is described which allows the rapid determination of the susceptibility of naturally occurring carbapenem antibiotics to renal dehydropeptidase-I at the broth level. The procedure is based on the incubation of carbapenem-containing solutions with dehydropeptidase-I and the subsequent assay of residual beta-lactamase-inhibiting/inactivating activity of carbapenems by means of a plate technique using the chromogenic beta-lactamase substrate PADAC.