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Biomedical subjects

O Schröder

Publications and source records attributed to O Schröder.

At least 19 recordsLinked to original sources
PubMed2006

[Antibiotic-associated diarrhea].

The incidence of antibiotic-associated diarrhea (AAD) differs with the antibiotic and varies from 15 - 25 %. Most cases of AAD are directly or indirectly caused by alterations of gut microflora by the antibiotics resulting in clinically mild AAD cases due to functional disturbances of intestinal carbohydrate or bile acid metabolism. Alternatively, changes in the gut flora allow pathogens to proliferate. Clostridium difficile is responsible for 10 - 15 % of all cases of AAD and almost of all cases of antibiotic-associated pseudomembraneous colitis. There is also a growing body of evidence which supports the responsibility of Klebsiella oxytoca for the development of antibiotic-associated hemorrhagic colitis. Diagnosing Clostridium difficile-associated diarrhea should be based both on fecal-cytotoxin detection and culture. With respect to specific therapy, metronidazol has become the first choice whereas treatment with oral vancomycin should be reserved for patients who have contraindications or intolerance to or who have failed to respond to metronidazole. Probiotics such as Sacharomyces boulardii can reduce the risk of development. Restrictive antibiotic policies (e. g. restricting clindamycin and cephalosporins) and the implementation of a comprehensive hospital infection control have also been shown to be effective in reducing the incidence of AAD.

Anti-Bacterial Agents↗
PubMed2005

Microsomal glutathione S-transferases: selective up-regulation of leukotriene C4 synthase during lipopolysaccharide-induced pyresis.

Cysteinyl-leukotrienes (cys-LTs) are potent smooth muscle contracting agents, which play key roles in inflammatory and allergic diseases. The committed step in cys-LT biosynthesis is catalyzed by leukotriene C(4) synthase (LTC4S) as well as microsomal glutathione S-transferase type 2 (MGST2) and type 3 (MGST3). Here we report that intraperitoneal injections of lipopolysaccharide in rats lead to a strong increase of LTC4S messenger RNA (mRNA) levels after approximately 1 h, particularly in the heart, brain, adrenal glands and liver, without any significant effect on MGST2 and MGST3 mRNA levels. After 6 h, LTC4S mRNA returns to basal levels, concomitant with a 4.9-, 4.0-, 2.9- and 2.3-fold induction of LTC4S protein in brain, heart, liver and adrenal gland, respectively. Hence, challenge with lipopolysaccharide in vivo causes an organ-selective, local priming for leukotriene C(4) synthesis. Moreover, these data suggest that LTC4S and cys-LTs may be involved in acute systemic inflammatory responses such as fever and tachycardia.

Animals↗
PubMed2004

Combining infliximab and methotrexate in fistulizing Crohn's disease resistant or intolerant to azathioprine.

BACKGROUND: Crohn's disease is complicated by fistulas in 20-40% of patients at some time during the course of their illness. Azathioprine has been reported to heal fistulas in 30-40% of cases. Long-lasting effects by the anti-tumour necrosis factor-alpha antibody infliximab most often require repeated infusions. Methotrexate has been shown to be an effective drug in maintaining remission in Crohn's disease. AIM: To evaluate the combination of infliximab and methotrexate as therapy for fistulas in patients with Crohn's disease. METHODS: Twelve consecutive patients (mean age, 29.5 years) with fistulizing Crohn's disease resistant or intolerant to azathioprine were followed prospectively. Patients received three infusions of infliximab (5 mg/kg) and long-term methotrexate (20 mg/week). Therapy success was defined as sustained closure of fistulas > or = 6 months after fistula closure. RESULTS: In four of the 12 patients, complete closure of fistulas that persisted for > or = 6 months (median follow-up, 13.25 months) was observed. In three further patients, a partial response was noted. In five patients, persistent therapy success could not be achieved or therapy had to be stopped due to side-effects. CONCLUSIONS: A combination of infliximab with long-term methotrexate may be a promising concept in fistulizing Crohn's disease. Our data indicate the need for larger controlled trials.

Adult↗
PubMed2004

A study for the evaluation of safety and tolerability of intravenous high-dose iron sucrose in patients with iron deficiency anemia due to gastrointestinal bleeding.

INTRODUCTION: The provision of adequate iron to support erythropoiesis in iron deficient patients is a time-consuming process which may present compliance problems for patients in the outpatient setting. The aim of the present study was to evaluate the safety and tolerability of intravenous high-dose iron sucrose therapy specifically in patients with iron deficiency anemia (IDA) due to gastrointestinal blood loss. METHODS: A single dose of iron sucrose of 7 mg iron/kg body weight (not exceeding 500 mg) was infused over 3.5 hours in 31 consecutive patients with IDA due to gastrointestinal blood loss. Safety and tolerability of the therapy was assessed by the occurrence of adverse events under therapy and up to one week after completion of the study. Further examinations comprised vital parameters, ECG, and clinical chemistry including iron indices. RESULTS: A total of 14 adverse events were observed in 10 patients, of which two adverse events in two patients were considered as being definitely related to drug administration. None of the patients had to be withdrawn from therapy. Significant changes in vital parameters and ECG during therapy and follow-up were not observed and clinical chemistry remained unchanged. DISCUSSION: A single intravenous high-dose iron sucrose therapy in patients with IDA due to gastrointestinal blood loss appears to be safe and therefore is a therapeutic option which may save time and improve patient compliance.

Adult↗
PubMed2004

Enteral nutrition by endoscopic means; I. Techniques, indications, types of enteral feed.

Enteral nutritional support plays a major role in the management of patients who are critically ill in intensive care units (ICU), those with poor volitional intake, persons with chronic neurological or mechanical dysphagia, and individuals with gut dysfunction. Part I of this review will briefly discuss the principles governing nasoenteral feeding and will describe in detail the endoscopic-assisted methods for placing enteral feeding tubes. These include percutaneous endoscopic gastrostomy, jejunal extension through a percutaneous endoscopic gastrostomy or direct endoscopic jejunostomy, and the "one-step button". In addition, the types of enteral food with focus on disease-specific enteral diets will be discussed. Finally, the latest innovations in enteral feeding including immune-enhancing nutrients such as arginine, omega-3 fatty acids, glutamine, and nucleotides advocated for critically ill patients will be discussed. Questions regarding possible complications and long-term results of the various methods of enteral feeding will be discussed separately in part II.

Critical Care↗
PubMed2004

Enteral Nutrition by Endoscopic Means; II. Complications and Management.

Despite the benefits and the widespread use of enteral and tube feeding (ETF) some patients experience complications, which can be divided in three categories: mechanical, e. g., tube blockage or removal; gastrointestinal, e. g., vomiting, diarrhea; and metabolic, e. g., re-feeding syndrome, hyperglycemia. The type and frequency of complications related to tube feeding varies considerably in accordance with the access to the intestinal tract (e. g., nasoenteric vs. percutaneous gastric vs. small bowel), the composition of the formula diet used, and the severity of the underlying disease. For example, tube-related complications have been reported to occur in 0-20 % and gastrointestinal complications in 8-65 % of patients during early postoperative feeding via a needle catheter jejunostomy (NCJ) using comparable techniques. The complication rate can be reduced by careful observance of guidelines on tube feeding including those related to food composition, administration rate, portion size, food temperature, and supervision of the patient. Gastrointestinal side effects (including diarrhea) are without doubt the most frequent.

Endoscopy, Gastrointestinal↗
PubMed2002

[Vomiting in pregnancy. When is it more than only a bothersome nuisance?].

In industrial countries more than half of women complain of nausea and vomiting during the first trimenon. Morning sickness, the common term of gestational nausea and vomiting, is usually temporary and harmless, it persists in less than 20% of all pregnancies. Maternal and fetal prognosis of uncomplicated emesis gravidarum is good. The responsible hormone as the pathogenetical trigger has not been defined yet, genetical and psychosocial factors may influence the intensity and duration of disease. The uncomplicated emesis has to be distinguished from hyperemesis gravidarum, a disorder which occurs in 0.3-2% of all pregnancies and is potentially of life-threatening character. While the uncomplicated form generally does not need any special therapy, hyperemesis gravidarum requires immediate compensation of fluid- and electrolyte loss, adequate supplementation of calories and vitamins as well as antiemetic therapy. Prospective studies have demonstrated that antihistamines are safe and effective for treatment of nausea and vomiting of pregnancy, in addition, also metoclopramide posses a high efficacy and safety profile.

Antiemetics↗
PubMed2002

Expression of microsomal glutathione S-transferase type 3 mRNA in the rat nervous system.

Microsomal glutathione S-transferase type 3 (MGST3) is a recently identified member of a large superfamily of enzymes involved in biotransformation of xenobiotics and biosynthesis of eicosanoids, including prostaglandins and leukotrienes. Using in situ hybridization histochemistry and reverse transcription polymerase chain reaction, we characterized the expression of MGST3 mRNA in the rat nervous system based on the cloned rat MGST3 gene, under normal conditions and after systemic administration of lipopolysaccharide (LPS). The MGST3 mRNA seemed to be confined to neurons. The broad distribution in the brain was characterized by a strong signal in the hippocampal formation and in the nuclei of the cranial nerves. A moderate signal was found in the cortex, thalamus, amygdala and substantia nigra and a weak signal in the hypothalamus. Motoneurons in the spinal cord and sensory neurons in dorsal root ganglia displayed strong MGST3 mRNA signal. No significant changes in the level of expression of MGST3 mRNA in the brain were found 1, 3 or 6 h after LPS administration. The pattern of distribution of MGST3 mRNA in the rat nervous system and the lack of response to LPS do not support a role for MGST3 in the biosynthesis of proinflammatory eicosanoids but rather suggest other functions, perhaps in metabolic detoxication and neuroprotection.

Animals↗
PubMed2002

A new immunological test strip device for the rapid, qualitative detection of faecal occult blood.

OBJECTIVE: Guaiac tests for faecal occult blood are still the most commonly performed screening procedure for colorectal cancer. Because both sensitivity and specificity of faecal occult blood testing are critical to cost-effective colorectal cancer screening programs, we investigated a rapid immunological test strip device for bedside detection of faecal occult blood. METHODS: Stool specimen from 100 patients were chosen for this study based on the presence (n = 50) or absence (n = 50) of faecal occult blood as measured with a human haemoglobin ELISA (cut-off level </= 10 micro g Hb/g stool). All specimens were analysed for faecal occult blood by a guaiac test (Hemocare) and an immunological test strip device (Prevent ID CC). RESULTS: Sensitivity and specificity of the immunological faecal occult blood test strip device were 76 % and 92 %, compared to 30 % and 90 % for the guaiac test. Increasing the cut-off level of the haemoglobin ELISA to </= 20 micro g Hb/g stool, the corresponding sensitivity and specificity were 86 % and 83 % for the immunological test strip device and 42 % and 92 % for the guaiac faecal occult blood test, respectively. The highest positive predictive value was achieved with the immunological test strip device. CONCLUSIONS: The new immunological test strip device is more sensitive than a guaiac test for the detection of faecal occult blood, whereas the specificity of both tests was comparable. However, the clinical validity of this new immunological faecal occult blood test strip device for colorectal cancer screening has to be established, yet.

Colorectal Neoplasms↗
PubMed2002

The value of routinely performed ultrasonography in patients with Crohn disease.

BACKGROUND: In active Crohn disease (CD), abdominal ultrasound can demonstrate morphological changes in the bowel wall. By contrast, the role of ultrasonography in periods with no disease activity has never been evaluated. In this prospective study we investigated the outcome of routinely performed abdominal ultrasonography in CD patients irrespective of symptoms and disease activity. METHODS: 255 consecutive patients with chronic CD (117 M, 138 F, mean age (+/-s) 38 +/- 14) were evaluated by high-resolution ultrasonography of the bowel wall and abdomen. The findings were graded with respect to further diagnostic and/or therapeutic implications. In addition, the CD activity index (CDAI) was determined. In patients with pathological sonographic findings, complementary procedures (e.g. endoscopy, computed tomography, biopsy or operation) were performed to validate the suspected diagnosis. RESULTS: In 46/255 (18%) patients with CD, the diagnosis of a transmural inflammatory reaction (TMR) with or without fistula was made by ultrasonography. In respect of CDAI, 29/46 (63%) of these patients were graded as active disease (CDAI > 150) and 17/46 (37%) as inactive disease (CDAI < or = 150). Of the 17 patients with a TMR and CDAI < or = 150, 4 patients revealed interenteric fistula, 7 patients mesenteric or perirectal fistula, whereas 6 patients presented with a transmural mesenteric inflammatory reaction without fistula. All fistulae were confirmed by radiography. Ultrasonography of the remaining abdominal organs revealed pathological findings with further diagnostic implications in 25/255 (10%) patients and with therapeutic implications in 9/255 (4%) patients. CONCLUSION: Routinely performed ultrasonography of the abdomen reveals pathological findings with therapeutic implications not only in symptomatic but also in asymptomatic patients with CD. It can therefore be recommended as a screening tool for this group of patients.

Abdomen↗
PubMed2001

Toward the three-dimensional structure of the Escherichia coli DNA-binding protein H-NS: A CD and fluorescence study.

The DNA-binding protein H-NS compacts DNA and acts as a specific transcription factor regulating the expression of various bacterial genes. The small abundant protein binds to curved DNA without apparent sequence specificity and the exact nature of its DNA interaction is still unknown. H-NS lacks any common DNA-binding or oligomerization motif and except for a C-terminal fragment of the protein no high resolution structural information is available today. Since the complete structure of H-NS is of considerable interest for understanding its versatile regulatory features, and in lack of high-resolution data for the complete molecule, we have combined circular dichroism (CD) and fluorescence measurements to collect secondary- and higher-order structural information on H-NS. Comparison of CD analyses of wild type H-NS and functional defective mutants allowed assigning secondary structure elements to the N-terminal oligomerization domain of the protein. Moreover, according to fluorescence energy-transfer data we calculate a 45 A distance between the DNA-binding and the oligomerization domain of H-NS.

Bacterial Proteins↗
PubMed2001

The determination of ketone bodies: preanalytical, analytical and physiological considerations.

The arterial ketone body ratio is calculated as the ratio of arterial levels of acetoacetate/beta-hydroxybutyrate. It correlates with survival in experimental hemorrhagic shock and outcome after liver surgery and myocardial infarction. Procedures for determination of ketone bodies are often laborious and unreliable. As yet the relationship between results from arterial and venous samples is unclear. We therefore describe the determination of the ketone bodies acetoacetate and 3-hydroxybutyrate by an easy, reliable, rapid, inexpensive enzymatic assay using 3-hydroxybutyrate dehydrogenase (E.C. 1.1.1.30) in a semi-automated setting that does not require deproteinization. Preanalytical parameters, including separation from corpuscular elements within 1 h and storage on ice for less than 1 h, must be strictly observed to avoid rapid decay of acetoacetate by spontaneous decarboxylation. The assay has high sensitivity, specificity (+/-5%), and precision (CV <2.5%) with a measurable range of 5-500 micromol/l for either ketone body, and requires only 23.5 microl of plasma. At temperatures below -17 degrees C plasma may be stored for prolonged periods. Results from prospectively scheduled simultaneous sampling of arterial blood and venous blood from the right atrium in 100 consecutive patients with severe multiple trauma (mean Injury Severity Score 38+/-13) support the view that the lung has no role in ketone body metabolism. We conclude that central venous blood can safely be substituted for arterial blood for determination of the ketone body ratio.

3-Hydroxybutyric Acid↗
PubMed2000

The bacterial DNA-binding protein H-NS represses ribosomal RNA transcription by trapping RNA polymerase in the initiation complex.

The interaction of the bacterial regulatory protein H-NS with RNA polymerase and the ribosomal RNA P1 promoter was analyzed to better understand the mechanism of H-NS-dependent transcriptional repression. We could show that initial binding of RNA polymerase to the promoter was not inhibited by the simultaneous interaction of H-NS, although H-NS binding sites extend into the core promoter region. Binding of sigma(70)-saturated RNA polymerase and H-NS to the promoter DNA occurs cooperatively and results in a stable complex of slower gel electrophoretic mobility as compared to complexes formed with the single proteins. The presence of the upstream curved H-NS binding site contributes strongly to the cooperative RNA polymerase-promoter interaction. By KMnO(4) modification of single-stranded template nucleotides we could show that open complex formation at the rrnB P1 promoter was not inhibited by H-NS binding. An increased KMnO(4) reactivity of several positions within the open complex rather supports the view that open complex formation is stimulated in presence of H-NS. Moreover, subtle changes in the modification pattern indicate that the open complex formed in the presence of H-NS are structurally distinct from the H-NS-free complex. In vitro transcriptional analysis of the abortive and productive yields revealed that the formation of transcription products longer than three nucleotides is dramatically reduced in the presence of H-NS, while the amount of shorter abortive products remained unaffected. Together the results demonstrate that H-NS inhibits transcription at the rrnB P1 promoter not by interfering with initial RNA polymerase binding but by blocking chain elongation steps subsequent to the first (two) phosphodiester bond formations. The mechanism of H-NS dependent repression at rRNA promoters can thus be explained as a trap which inhibits substrate NTP incorporation beyond template position +3 into the initial transcribing complex.

Allosteric Site↗
PubMed2000

Cytotoxic and mutagenic effects, particle size and concentration analysis of diesel engine emissions using biodiesel and petrol diesel as fuel.

Diesel engine exhaust particles (DEP) contribute substantially to ambient air pollution. They cause acute and chronic adverse health effects in humans. Biodiesel (rapeseed oil methyl ester. RME) is used as a "green fuel" in several countries. For a preliminary assessment of environmental and health effects of RME, the particulate-associated emissions from the DEP of RME and common fossil diesel fuel (DF) and their in vitro cytotoxic and mutagenic effects were compared. A test tractor was fuelled with RME and DF and driven in a European standard test cycle (ECE R49) on an engine dynamometer. Particle numbers and size distributions of the exhausts were determined at the load modes "idling" and "rated power". Filter-sampled particles were extracted and their cytotoxic properties tested using the neutral red assay. Mutagenicity was tested using the Salmonella typhimurium/microsome assay. Despite higher total particle emissions, solid particulate matter (soot) in the emissions from RME was lower than in the emissions from DF. While the size distributions and the numbers of emitted particles at "rated power" were nearly identical for the two fuels, at "idling" DF emitted substantially higher numbers of smaller particles than RME. The RME extracts caused fourfold stronger toxic effects on mouse fibroblasts at "idling" but not at "rated power" than DF extracts. The extracts at both load modes were significantly mutagenic in TA98 and TA100. However, extracts of DF showed a fourfold higher mutagenic effect in TA98 (and twofold in TA100) than extracts of RME. These results indicate benefits as well as disadvantages for humans and the environment from the use of RME as a fuel for tractors. The lower mutagenic potency of DEP from RME compared to DEP from DF is probably due to lower emissions of polycyclic aromatic compounds. The higher toxicity is probably caused by carbonyl compounds and unburned fuel, and reduces the benefits of the lower emissions of solid particulate matter and mutagens from RME.

Animals↗
PubMed2000

Short-chain fatty acid (SCFA) uptake into Caco-2 cells by a pH-dependent and carrier mediated transport mechanism.

The short-chain fatty acids, acetate, propionate, and butyrate, are the most abundant organic anions in the human colon. SCFA play a pivotal role in maintaining homeostasis in the colon. Particularly butyrate induces cell differentiation and regulates growth and proliferation of colonic mucosal epithelial cells, whereas it reduces the growth rate of colorectal cancer cell. Previous studies by several groups, including our own, using isolated membrane vesicles have demonstrated that the uptake of butyrate is at least in part mediated by a non-electrogenic SCFA-/HCO3- antiporter. The purpose of the present study was to determine (1) whether Caco-2 cells could serve as an experimental model to assess the mechanisms of SCFA transport, and (2) whether monocarboxlate transporters could play a role in SCFA transport in these cells. Caco-2 cells were found to transport 14C-butyrate in a concentration and time dependent manner. The uptake was sodium independent, but was stimulated by lowering extracellular pH. The uptake of 500 microM butyrate was reduced by 49.6% +/- 3.3% in the presence of propionate and by 57.2% +/- 4.8% in the presence of 10 mM L-lactate. The addition of 1 mM alpha-cyano-4-hydroxycinnamate and phloretin, both known to be potent inhibitors of MCT1, decreased the uptake of 500 microM 14C-butyrate by 59.4% +/- 4.1% and 48.9% +/- 3.3%, respectively, whereas similar concentrations of DIDS did not have any effect. These data suggest that the uptake of butyrate in Caco-2 cells occurs via a carrier mediated transport system specific for monocarboxylic acids, which is in accordance with characteristics of the MCT 1.

Biological Transport, Active↗
PubMed2000

Substrate and inhibitor specificity of butyrate uptake in apical membrane vesicles of the rat distal colon.

BACKGROUND/AIMS: There is substantial evidence that transcellular flux of short-chain fatty acid (SCFA) absorption, at least in part, is mediated by an anion exchange process with bicarbonate. METHODS: This anion exchange system was further characterized in apical membrane vesicles of the rat distal colon by studying substrate and inhibitor specificities of a variety of substituted monocarboxylic acids as well as of known inhibitors of the recently described monocarboxylate transporter MCT1 and MCT2. RESULTS: SCFA transport was significantly reduced in the presence of branched and unbranched SCFAs and several bromo, chloro and mercapto analogues as well as nicotinic acid and L-lactate. In contrast, known inhibitors of monocarboxylate transporter proteins like stilbene derivatives, phloretin and 2-cyano-4-hydroxycinnamate did not inhibit bicarbonate-gradient stimulated butyrate transport. Kinetic analysis of increasing substrate concentrations of 3-mercaptopropionate, L-lactate and nicotinic acid showed saturation kinetics with apparent K(i) of 6.1, 18.3 and 14.7 mmol/l, respectively. CONCLUSIONS: The data not only confirm earlier results that absorption of SCFAs in apical membranes of the rat distal colon is mediated by a relatively low affinity/high capacity SCFA(-)/HCO(-)(3) exchange mechanism, but also indicate that although this anion transporter shares some functional similarities, is not identical with the recently cloned MCT isoforms.

Animals↗