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I Bauer

Publications and source records attributed to I Bauer.

At least 19 recordsLinked to original sources

Mixed agonistic-antagonistic cytokine response in whole blood from patients undergoing abdominal aortic aneurysm repair.

OBJECTIVE: To characterize the impact of abdominal aortic aneurysm repair (AAAR) on spontaneous as well as lipopolysaccharide (LPS)-induced gene expression of pro- and anti-inflammatory cytokines. DESIGN: Prospective, controlled in vivo/ex vivo study. SETTING: University hospital. PATIENTS AND INTERVENTIONS: Whole blood from 14 consecutive patients undergoing AAAR withdrawn prior to surgery (T1), at the end of ischemia (T2), 90 min after declamping (T3) and on the first postoperative day (T4) was cultured in the absence or presence of LPS. Five patients undergoing elective inguinal hernia repair served as controls. MEASUREMENTS AND RESULTS: While tumor necrosis factor (TNF), Interleukin (IL)-1 and IL-10 plasma concentrations did not increase significantly, IL-6 was elevated at each time point, as compared with T1. Despite the spontaneous release of trace amounts of IL-6, the ability of cultured whole blood to mount a cytokine response in vitro to LPS was impaired for all cytokines studied at T2 (TNF-62%, IL-1-51%, IL-6 -20%, IL-10-51%). The stimulated IL-6 response was restored early after declamping (T3: +56 %) and enhanced 1 day after operation (T4: +144%). In contrast, stimulated TNF and IL-1 responses remained depressed at T3 (TNF -48%, IL-1-64%) and T4 (TNF-40%, IL-1-24%). A biphasic pattern was observed for IL-10 with initial depression at T3 (-51%) and restoration at T4 (+40%). Among the different cytokines monitored, only impaired TNF responsiveness at early reperfusion (T3) correlated with the postoperative course, as reflected by APACHE II. Cytokine response to LPS was maintained or even increased during and after surgery in the whole blood from patients undergoing hernia repair. CONCLUSIONS: Despite consistent development of clinical signs of systemic inflammatory response syndrome (SIRS) and spontaneous release of IL-6 abdominal aortic aneurysm repair produces a state of impaired pro-inflammatory cytokine response upon a subsequent in vitro Gram-negative stimulus. This early impairment of TNF responsiveness seems to correlate with an unfavorable postoperative course.

Aged

Expression pattern of heme oxygenase isoenzymes 1 and 2 in normal and stress-exposed rat liver.

Heme oxygenase (HO) catalyzes the oxidative cleavage of the alpha-mesocarbon of Fe-protoporphyrin-IX yielding equimolar amounts of biliverdin-IXa, iron, and carbon monoxide. The HO-system consists of two isoenzymes, namely HO-2 and the inducible isoform HO-1, also referred to as heat shock protein (hsp) 32. Although both parenchymal and non-parenchymal liver cells participate in heme metabolism, the expression pattern of the isoenzymes in normal and stress exposed liver is unknown. To study this, rats underwent either endotoxin (lipopolysaccharide [LPS]) challenge, hemorrhagic hypotension, glutathione (GSH) depletion, or cobalt chloride injection, all known to provoke oxidative stress. HO-2 messenger RNA (mRNA) and protein were constitutively expressed in hepatocytes, Kupffer/endothelial-, and stellate (Ito-) cell enriched fractions. Although both non-parenchymal cell fractions expressed HO-1 transcripts, HO-1 immunoreactive protein was restricted to Kupffer cells in the normal liver. In contrast to HO-2, a significant increase in HO-1 on the whole organ level was noted by hemorrhagic hypotension, GSH depletion, and cobalt chloride injection. However, the distinct stress models led to a strikingly different cell-type specific and sublobular expression pattern of HO-1 gene expression. HO-1 was inducible in sinusoidal lining cells (hemorrhagic hypotension, LPS challenge), in periportal (cobalt chloride), or pericentral (GSH depletion, hemorrhagic hypotension) hepatocytes. The blockade of protein translation before hemorrhage by cycloheximide reduced upregulation of HO-1/hsp32 mRNA significantly (65.4% reduction, P < .05), whereas the inducibility of hsp70 transcript was maintained. In addition to transcriptional regulation, HO-1 seems to be subject to posttranscriptional control in particular in non-parenchymal cells.

Animals

[Organ specific expression pattern of a carbon monoxide generating stress protein (hemoxygenase-1/heatshock protein 32) following hemorrhagic shock].

OBJECTIVE: Recent evidence suggests a possible role for Haeme oxygenase (HO)-derived carbon monoxide (CO) in the regulation of vascular tone through elevation of cyclic 3'-5' guanosine monophosphate (cGMP). Previous work from our laboratory has shown that blockade of the HO pathway by tin-protoporphyrin-IX (SnPP) after resuscitation from hemorrhage leads to a specific and profound increase in portal resistance while neither systemic nor hepatic arterial resistance are affected. We therefore investigated the organ-specific expression pattern of the stress-inducible protein haeme oxygenase-1/heat shock protein 32 after haemorrhage and resuscitation. MATERIALS AND METHODS: After approval of the protocol by the local review board, male Sprague-Dawley rats (n = 6/group) were anaesthetised with pentobarbitone, instrumented for assessment of central haemodynamics and subjected to haemorrhagic hypotension (40 mm Hg for 1 h) followed by resuscitation with 60% shed blood and Ringer's solution or a time-matched sham protocol. Samples of liver, spleen, kidney intestine, aorta, and lungs were harvested 5 h after the onset of resuscitation and subjected to Western-blot analysis using a specific anti-rat HO-1/hsp 32 antibody (StressGen, Sidney, Canada). RESULTS: Resuscitation with shed blood/Ringer's solution restored central haemodynamics and acid-base status while significant haemodilution was observed. Haemorrhage and resuscitation led to strong induction of HO-1 in the liver and slight induction in aortic tissue, while no increase in steady-state protein levels was observed in the other organs studied. CONCLUSION: These results suggest a specific contribution of the HO/CO pathway to maintenance of low hepatic portal resistance in vivo in a clinically relevant model of haemorrhagic shock and adequate resuscitation.

Animals

Remodeling of hepatic microvascular responsiveness after ischemia/reperfusion.

Although there is substantial evidence suggesting that the integrity of the microcirculation is an important determinant of tissue viability during reperfusion after ischemia in the liver, as well as other tissues, the mechanisms responsible for microvascular failure are not fully understood. It is now recognized that the microvascular response to reperfusion, similar to the whole organism response to shock, can consist of either a rapid exacerbation of injury after a severe ischemic episode or, alternatively, a more slowly developing alteration in responsiveness that occurs after a less severe insult. In the more slowly developing response, the alterations in vascular status are the result of up-regulation of stress-induced vascular mediators such as endothelin, nitric oxide synthase (NOS), and heme oxygenase, as well as changes in the reactivity of the effector cells to the mediators. The mechanisms for change in reactivity of vascular cells range from changes in receptor expression to overt phenotypic transformation, as can occur in the hepatic stellate cells in response to repeated injury. When maintained in balance, these counteracting constrictor and dilator influences can be protective; however, local imbalance can result in focal ischemia, thus propagating the injury. Thus, the remodeling of the hepatic microvascular responsiveness during reperfusion after ischemia may serve as a useful paradigm for consideration of the overall response of the organism to shock.

Animals

2,4-dioxygenases catalyzing N-heterocyclic-ring cleavage and formation of carbon monoxide. Purification and some properties of 1H-3-hydroxy-4-oxoquinaldine 2,4-dioxygenase from Arthrobacter sp. Rü61a and comparison with 1H-3-hydroxy-4-oxoquinoline 2,4-dioxygenase from Pseudomonas putida 33/1.

1H-3-Hydroxy-4-oxoquinaldine 2,4-dioxygenase (MeQDO) was purified from quinaldine-grown Arthrobacter sp. Rü61a. It was enriched 59-fold in a yield of 22%, and its properties were compared with 1H-3-hydroxy-4-oxoquinoline 2,4-dioxygenase (QDO) purified from Pseudomonas putida 33/1. The enzyme-catalyzed conversions were performed in an (18O)O2/(16O)O2 atmosphere. Two oxygen atoms of either (18O)O2 or (16O)O2 were incorporated at C2 and C4 of the respective substrates, indicating that these unusual enzymes, which catalyze the cleavage of two carbon-carbon bonds concomitant with CO formation, indeed are 2,4-dioxygenases. Both enzymes are small monomeric proteins of 32 kDa (MeQDO) and 30 kDa (QDO). The apparent K(m) values of MeQDO for 1H-3-hydroxy-4-oxoquinaldine and QDO for 1H-3-hydroxy-4-oxoquinoline were 30 microM and 24 microM, respectively. In both 2,4-dioxygenases, there was no spectral evidence for the presence of a chromophoric cofactor. EPR analyses of MeQDO did not reveal any signal that could be assigned to an organic radical species or to a metal, and X-ray fluorescence spectrometry of both enzymes did not show any metal present in stoichiometric amounts. Ethylxanthate, metal-chelating agents (tiron, alpha, alpha'-bipyridyl, 8-hydroxyquinoline, o-phenanthroline, EDTA, diphenylthiocarbazone, diethyldithiocarbamate), reagents that modify sulfhydryl groups (iodoacetamide, N-ethylmaleimide, p-hydroxymercuribenzoate), and reducing agents (sodium dithionite, dithiothreitol, mercaptoethanol) either did not affect 2,4-dioxygenolytic activities at all or inhibited at high concentrations only. With respect to the supposed lack of any cofactor and with respect to the inhibitors of dioxygenolytic activities, MeQDO and QDO resemble aci-reductone oxidase (CO-forming) from Klebsiella pneumoniae, which catalyzes 1,3-dioxygenolytic cleavage of 1,2-dihydroxy-3-keto-S-methylthiopentene anion (Wray, J. W. & Abeles, R. H. (1993) J. Biol. Chem. 268, 21466-21469; Wray, J. W. & Abeles, R. H. (1995) J. Biol. Chem. 270, 3147-3153). 1H-3-Hydroxy-4-oxoquinaldine and 1H-3-hydroxy-4-oxoquinoline were reactive towards molecular oxygen in the presence of the base catalyst potassium-tert.-butoxide in the aprotic solvent N,N-dimethylformamide. Base-catalyzed oxidation, yielding the same products as the enzyme-catalyzed conversions, provides a non-enzymic model reaction for 2,4-dioxygenolytic release of CO from 1H-3-hydroxy-4-oxoquinaldine and 1H-3-hydroxy-4-oxoquinoline.

Arthrobacter

Geographic distribution and origin of CFTR mutations in Germany.

The geographic distribution and origin of CFTR mutations in Germany was evaluated in 658 three-generation families with cystic fibrosis (CF). Fifty different mutations were detected on 1305 parental CF chromosomes from 22 European countries and overseas. The major mutation. delta F508 was identified on 71.5% of all CF chromosomes, followed by R553X (1.8%), N1303K (1.3%), G542X (1.1%), G551D (0.8%) and R347P (0.8%). According to the grandparents' birthplace, 74% of CF chromosomes had their origin in Germany; the delta F508 percentage was 77%, 75%, 70% and 62% in northern, southern, western and eastern Germany, respectively. Ten or more mutant alleles in the investigated CF gene pool originated from Austria, the Czech Republic, Poland, Russia, Turkey and the Ukraine. This widespread geographic origin of CFTR mutations in today's Germany reflects the many demographic changes and migrations in Central Europe during the 20th century.

Cystic Fibrosis

Evidence for a functional link between stress response and vascular control in hepatic portal circulation.

Heme oxygenase (HO)-derived carbon monoxide (CO) may contribute to vascular control through elevation of guanosine 3',5'-cyclic monophosphate. In the present study, we investigated the functional significance of expression of the isoenzyme HO-1 (heat-shock protein 32) in liver after hemorrhage/resuscitation (H/R) in rats anesthetized with pentobarbital sodium. An increase of mRNA levels for HO-1 was observed at 3 h after resuscitation, followed by induction of the protein at 6 h in pericentral hepatocytes and sinusoidal lining cells. Concomitantly, lower portal resistance was observed in H/R (0.33 +/- 0.060 mmHg.ml-1.min) compared with control rats (0.47 +/- 0.035 mmHg.ml-1.min). Blockade of the HO-CO pathway by tin protoporphyrin-IX (SnPP-IX) led to a transient increase in portal pressure with no effect on portal low in controls, whereas an increase in pressure and a decrease in flow contributed to the sustained increase in portal resistance after H/R. These results indicate that HO contributes to maintenance of hepatic perfusion in vivo under stressful conditions, suggesting a functional link between stress response and vascular control in portal circulation.

Animals

Chronic ethanol consumption exacerbates liver injury following hemorrhagic shock: role of sinusoidal perfusion failure.

Although the deleterious effect of chronic ethanol consumption on subsequent stressful events has long been recognized, the pathophysiological mechanisms are incompletely understood. This study tested whether chronic ethanol consumption in doses that increase sinusoidal contractility increases susceptibility to hepatic microvascular failure and liver injury after hemorrhagic shock. Liver microcirculation was assessed by in vivo microscopy during hemorrhage and up to 24 h after onset of resuscitation and was compared with liver histology and serum enzyme levels. Mean sinusoidal blood flow was neither impaired by chronic ethanol feeding at baseline nor during hemorrhage and early resuscitation. However, failure of individual sinusoids to conduct flow was observed more frequently after fluid resuscitation in ethanol-fed animals (e.g. at 1 h after onset of volume therapy: 26% of sinusoids) than in controls (11%), reflecting substantial flow heterogeneity. Failing sinusoids had substantially smaller diameters than sinusoids conducting flow with a more profound and sustained response in ethanol-fed rats. At 24 h marked pericentral necrosis and increase in serum alanine aminotransferase levels were observed in six of nine surviving ethanol-fed animals but only in 1 of 10 pair fed controls and correlated with microvascular failure. These data suggest that early as well as late microvascular failure in this model of hemorrhagic shock and resuscitation is primarily mediated at the level of individual sinusoids. Chronic ethanol feeding exacerbates microvascular and hepatocellular injury after shock/resuscitation, probably involving increased sinusoidal contractile responsiveness.

Alanine Transaminase

Rank-ordering: a suitable method for nursing research.

Rank-ordering is an easy to use and easy to analyse method of organising comparative data for judgement. It is a method that can be used in nursing research whenever the opinions of people are sought. As it is very difficult to find a simple, practical guide for this procedure, data from a study on patients' perception of their privacy in hospital are used to illustrate the analysis and presentation of rank-ordered data.

Data Interpretation, Statistical

Chronic ethanol consumption increases hepatic sinusoidal contractile response to endothelin-1 in the rat.

Recent evidence suggests that hepatic stellate cells function as liver-specific pericytes that are highly contractile in response to endothelin-1 (ET-1). Liver injury has been shown to lead to "activation" of stellate cells producing a phenotypic change to a more myofibroblastic cell type including loss of vitamin A and increased contractility. The present study was undertaken to test the effects of short-term chronic ethanol consumption (36% of total calories for 5 weeks according to the Lieber-DeCarli protocol) on hepatic vitamin A storage, expression of smooth muscle alpha-actin, and sinusoidal contractility in Sprague-Dawley rats. Using in vivo epifluorescence video microscopy, we quantified the number of sites of vitamin A fluorescence (purportedly stellate cells) and assessed sinusoidal microhemodynamics at baseline and during a 20-minute infusion period of ET-1 (1 pmol * 100 g body weight [bw]*1*min-1). Retinol and retinyl palmitate were measured after the experiment by means of high-pressure liquid chromatography (HPLC). A highly significant decrease in liver retinyl palmitate level (control: 622.5 +/- 50.9; ethanol: 273.0 +/- 38.0 microgram/g liver; P< .001) was found that correlated with a decrease in sites of vitamin A fluorescence (control: 531.4 +/- 76.1; ethanol: 141.1 +/- 30.2* mm-2; r = .82, P <.001). Concomitantly scattered expression of smooth muscle alpha-actin in sinusoids was observed. Although sinusoidal hemodynamics were not affected at baseline, a significant increase in sinusoidal contractility on endothelin-1 infusion (e.g., sinusoidal resistance [% of baseline value]: control: 10 minutes: 288.7 +/- 71.7, 20 minutes: 200.5 +/- 46.9; ethanol: 10 minutes: 1,916.0 +/- 701.7, 20 minutes: 656.8 +/- 103.3; P < .05 and .01, respectively) was observed. These data indicate that chronic ethanol consumption in this moderate model initiates stellate cell activation. Increased sinusoidal responsiveness to the vasoconstrictor ET-1 in vivo may contribute to the increased susceptibility of ethanol-fed rats to secondary stresses that increase ET-1 expression, such as endotoxemia.

Actins

Nursing at dawn. Nursing tasks in the first hour of the morning shift in a German hospital.

Nurses' working hours are known to be one reason for high wastage rates. The early start of work seems to be particularly difficult. The aim of the present study was to examine which nursing tasks were performed during the time from 6:00 to 7:00 a.m. The study was conducted in a general hospital in Germany where such an early start of work is still common practice. An activity analysis was carried out using non-participant observation. One surgical and one medical ward were used for comparison. The work on the wards was differently organized. The observed tasks were classified into direct care, indirect care, administrative, and other tasks. The distribution of these task categories over one hour and the percentage of time spent on these categories were compared. Both wards showed different working patterns and a different form of initiation of direct care (entering patients' rooms). Some possible reasons for these findings are offered and suggestions for further research are made.

Germany

ET-1 induced alterations of hepatic microcirculation: sinusoidal and extrasinusoidal sites of action.

Using epifluorescence microscopy, we investigated the dynamic changes in hepatic sinusoidal hemodynamics in vivo during continuous infusion of endothelin-1 (ET-1) in pentobarbital-anesthetized rats. ET-1 was infused for 20 min at rates of 2 or 10 pmol/min either systemically or into the portal vein, followed by a 90-min recovery period. In contrast to systemic application of ET-1 that did not cause a consistent hepatic microvascular effect, we observed two different patterns of microcirculatory alterations during portal application. Infusion of 2 pmol/min elicited a rapid, reversible decrease in sinusoidal diameter that was paralleled by a slight increase in red cell velocity, resulting in conservation of volumetric flow and sinusoid density. Infusion of 10 pmol/min resulted in a biphasic narrowing followed by transient increase in sinusoidal diameter and a profound and lasting decrease in red cell velocity, leading to an almost complete cessation of hepatic microvascular blood flow. These results indicate that ET-1 is a potent constrictor in the liver microcirculation in vivo and acts at both extrasinusoidal and sinusoidal sites, although the sinusoidal sites appear to be more sensitive to lower concentrations.

Animals

Endothelin-1 as a regulator of hepatic microcirculation: sublobular distribution of effects and impact on hepatocellular secretory function.

Endothelin-1 is a potent vasoconstrictor in the portal circulation causing sinusoidal constriction as well as presinusoidal resistance changes. Using in vivo videomicroscopy we studied the sublobular differences in dose response characteristics of sinusoid constriction at 10-13 min into continuous infusion of 5, 1.0, 3.0, and 5.0 pmol of endothelin-1 (ET-1)/100 g body weight/min in pentobarbital anesthetized rats. In addition, bile flow was monitored to estimate parenchymal secretory function. ET-1 evoked a profound constrictor effect in both sublobular regions studied. However, the maximal decrease of sinusoidal width in periportal inflow region (zone 1; 1 pmol/100 g/min: 4.8 +/- .1 microns) was reached at slightly lower concentrations of the peptide than in pericentral outflow region (zone 3; 3 pmol/100 g/min: 6.2 +/- .3 microns) compared to respective baseline values (zone 1: 7.1 +/- .1 microns; zone 3: 10.2 +/- .1 microns), suggesting upstream binding and clearance of the peptide. The constrictor response in zone 1 was biphasic and at higher concentrations of the peptide (5 pmol/100 g/min: 5.5 +/- .2 microns) sinusoidal widths increased again compared to the maximal response with the 1 pmol. Secretory function as reflected by the bile flow was maintained or even slightly increased with the lower doses (.5 and 1 pmol) of ET-1 and during the first 10 min into infusion of the higher doses (3 and 5 pmol). Subsequently, an approximately 20-25% decrease in bile flow accompanied the infusion of higher doses of ET-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

[Classification, a suitable method for nursing research--practical advice for data collection and data analysis].

Arranging subjective data in rank order is a simple method for making comparisons of judgements and evaluating them. Since it is difficult to find practical instructions for this which can be easily understood, this paper uses data obtained in a study of patients' opinions about their privacy. Results are analysed, presented and explained. The method is appropriate for a wide range of research in which individuals are asked for opinions.

Data Collection

A clinical application of the multiple sorting technique.

The interview technique is a common method of collecting data in human research. This paper provides an example of the use of the multiple sorting technique for structuring and analysing qualitative interviews. The technique is described around a recently completed study which explored practising nurses' perception of their work in a German hospital. A multiple sorting technique was employed to structure interviews with 11 nurses. Nursing tasks were sorted into categories and labelled by respondents. The frequencies with which each task was paired with all of the other tasks were calculated and this allowed us to produce a similarity matrix which was entered as input into a multidimensional scaling procedure (Smallest Space Analysis SSA-1). The SSA-1 procedure was used to analyse and interpret the data. The results of the analysis indicated that the nurses conceptualized their work into four separate domains including basic care skills, indirect care, technical skills and administration. The example of the multiple sorting technique described here shows how it is possible to develop an insight into the nurses' world in a structured yet flexible way.

Data Collection