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Biomedical subjects

B Hartmann

Publications and source records attributed to B Hartmann.

At least 37 records · Page 2Linked to original sources

DNA fine structure and dynamics in crystals and in solution: the impact of BI/BII backbone conformations.

Sugar-phosphate backbone conformations are an important structural element for a complete understanding of specific recognition in nucleic acid-protein interactions. They can be involved both in early stages of target discrimination and in structural adaptation upon binding. In the first part of this study, we have analyzed high-resolution structures of double-stranded B-DNA either isolated or bound to proteins, and explored the impact of both the standard BI and the unusual BII phosphate backbone conformations on neighboring sugar puckers and on selected helical parameters. Correlations are found to be similar for free and bound DNA, and in both categories, the possible facing backbone conformations (BI.BI, BI.BII, and BII.BII) define well-characterized substates in the B-DNA conformational space. Notably, BII.BII steps are characterized by specific, and sequence-independent, structural effects involving reduced standard deviations for almost all conformational parameters. In the second part of this work, we analyze four 10 ns molecular dynamics simulations in explicit solvent on the DNA targets of NF-kappaB and bovine papillomavirus E2 proteins, highlighting the multiplicity of backbone dynamical behavior. These results show sequence effects on the percentages of BI and BII conformers, the preferential state of facing backbones, the occurrence of coupled transitions. The backbone states can consequently be seen as a mechanism for transmitting information from the bases to the phosphate groups and thus for modulating the overall structural properties of the target DNA.

Base Sequence↗

[Burn shock fluid resuscitation and hemodynamic monitoring].

Successful surgical and intensive care treatment of severely burned patients requires adequate prehospital management and fluid resuscitation adjusted to individual needs of the patient. Burn shock fluid resuscitation is now predominantly performed utilizing crystalloid solutions. Whenever possible, colloid solutions should not be given in the first 24 h after burn injury. The rate of administration of resuscitation fluids should maintain urine outputs between 0.5 ml/kg per h and 1 ml/kg per h and mean arterial pressures of >70 mmHg. Extended hemodynamic monitoring can provide valuable additional information, if burn resuscitation is not proceeding as planned or volume therapy guided by these typical vital signs is not attaining the desired effect. We recommend this in patients with TBSA burns of >30%. Inhalation injuries, pre-existing cardiopulmonary diseases, or TBSA burns of >50% definitely require extended hemodynamic monitoring during burn shock resuscitation. The Swan-Ganz catheter or less invasive transcardiopulmonary indicator dilution methods can be utilized to assess hemodynamic data.

Burn Units↗

Glucagon-like peptide 2 (GLP-2) accelerates the growth of colonic neoplasms in mice.

BACKGROUND: Glucagon-like peptide 2 (GLP-2) is an intestinotrophic mediator with therapeutic potential in conditions with compromised intestinal capacity. However, growth stimulation of the intestinal system may accelerate the growth of existing neoplasms in the intestine. AIMS: In the present study, the effects of GLP-2 treatment on the growth of chemically induced colonic neoplasms were investigated. METHODS: In 210 female C57bl mice, colonic tumours were initially induced with the methylating carcinogen 1,2-dimethylhydrazine (DMH) and mice were then treated with GLP-2. Two months after discontinuation of the carcinogen treatment, 135 of the mice were allocated to one of six groups which were treated twice daily with 25 microg GLP-2, 25 microg Gly2-GLP-2 (stable analogue), or phosphate buffered saline for a short (10 days) or long (one month) period. The remaining 75 mice had a treatment free period of three months and were then allocated to groups subjected to long term treatment, as above. RESULTS: Colonic polyps developed in 100% of the mice, regardless of treatment. Survival data revealed no statistical significant differences among the different groups but histopathological analysis demonstrated a clear and significant increase in tumour load of mice treated with Gly2-GLP-2. The tumour promoting effect of native GLP-2 was less pronounced but the number of small sized polyps increased following long term treatment. CONCLUSIONS: The present results clearly indicate that GLP-2 promotes the growth of mucosal neoplasms. Our findings highlight the need for future investigations on the effects of GLP-2 in conditions needing long time treatment or with increased gastrointestinal cancer susceptibility.

Adenoma↗

Peripheral administration of GLP-2 to humans has no effect on gastric emptying or satiety.

Glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) are secreted in parallel to the circulation after a meal. Intravenous (IV) GLP-1 has an inhibitory effect on gastric emptying, hunger and food intake in man. In rodents, central administration of GLP-2 increases satiety similar to GLP-1. The aim of the present study was to assess the effect of IV administered GLP-2 on gastric emptying and feelings of hunger in human volunteers. In eight (five men) healthy subjects (age 31.1+/-2.9 years and BMI 24.1+/-1.0 kg m(-2)), scintigraphic solid gastric emptying, hunger ratings (VAS) and plasma concentrations of GLP-2 were studied during infusion of saline or GLP-2 (0.75 and 2.25 pmol kg(-1) min(-1)) for a total of 180 min. Concentrations of GLP-2 were elevated to a maximum of 50 and 110 pmol l(-1) for 0.75 and 2.25 pmol kg(-1) min(-1) infusion of GLP-2, respectively. There was no effect of GLP-2 on either the lag phase (29.5+/-4.4, 26.0+/-5.2 and 21.2+/-3.6 min for saline, GLP-2 0.75 or 2.25 pmol kg(-1) min(-1), respectively) or the half emptying time (84.5+/-6.1, 89.5+/-17.8 and 85.0+/-7.0 min for saline, GLP-2 0.75 or 2.25 pmol kg(-1) min(-1), respectively). The change in hunger rating after the meal to 180 min was also unaffected by infusion of GLP-2. GLP-2 does not seem to mediate the ileal brake mechanism.

Adult↗

Injected TFF1 and TFF3 bind to TFF2-immunoreactive cells in the gastrointestinal tract in rats.

Peptides of the trefoil factor family (TFF1, TFF2 and TFF3) are co-secreted with mucus in most organ systems and are believed to interact with mucins to produce high-viscosity, stable gel complexes. We have previously demonstrated that cells in the GI tract possess binding sites to TFF2 and that injected TFF2 ends up in the mucus layer. In the present study, tissue binding and metabolism of parenterally administered human TFF1 and TFF3 in rats were described and compared to the immunohistochemical localization of the TFF peptides. 125I-TFF1 monomer and 125I-TFF3 mono- and dimer were given intravenously to female Wistar rats. The tissue distribution was assessed by gamma counting of organ samples and by autoradiography of histological sections. The degradation of 125I-TFF3 was studied by means of trichloracetic acid (TCA) precipitation and the saturability of the binding by administration of excess unlabelled peptide. The TFF peptides were localized in histologic sections from the GI tract by immunohistochemistry. Injected TFF3 dimer (12%) was taken up by the GI tract. At autoradiography, grains were localized to the same cells that were immunoreactive to TFF2. The binding could be displaced by excess TFF3. Similar binding was observed for the TFF1 and TFF3 monomers apart from binding in the stomach, where the uptake was only 15% in comparison to the dimer. There was no specific binding outside the GI tract and no binding to TFF1 or TFF3 immunoreactive cells. In conclusion, the TFF2-binding cells in the gastrointestinal tract seem to have basolateral, receptor-like activity to all three TFF peptides. The mucous neck cells of the stomach predominantly take up TFFs with two trefoil domains, indicating a different receptor-like activity in the stomach compared to the rest of the GI tract.

Animals↗

Pax6 in the sepiolid squid Euprymna scolopes: evidence for a role in eye, sensory organ and brain development.

The cloning of a Pax6 orthologue from the sepiolid squid Euprymna scolopes and its developmental expression pattern are described. The data are consistent with the presence of a single gene encoding a protein with highly conserved DNA-binding paired and homeodomains. A detailed expression analysis by in situ hybridization and immunodetection revealed Pax6 mRNA and protein with predominantly nuclear localization in the developing eye, olfactory organ, brain lobes (optic lobe, olfactory lobe, peduncle lobe, superior frontal lobe and dorsal basal lobe), arms and mantle, suggestive of a role in eye, brain, and sensory organ development.

Amino Acid Sequence↗

User acceptance of an anaesthesia information management system.

BACKGROUND AND OBJECTIVE: This paper describes the user acceptance of an anaesthesia information management system at the University Hospital in Giessen, Germany, after 5 yr of routine use. METHODS: A questionnaire with 75 items was distributed to all anaesthesiologists and anaesthetic nurses of the Department of Anaesthesiology. The questions were answered anonymously on a five-point Likert scale. RESULTS: The return rate was 60% (44 physicians and 24 nurses). The results indicated that the system generally met user expectations. The respondents thought that electronic record keeping improved the quality of their work, and they did not want to switch back to paper records. Problems arose with hardware placement and software features, e.g. coding tools for diagnoses and type of surgery. The perceived quality of training strongly influenced user acceptance. CONCLUSIONS: Despite the deficits revealed by the survey, the respondents did not want to switch back to manual record keeping. A structured user survey is a useful tool for the development, adaptation and implementation of an anaesthesia information management system. A training strategy that takes the needs of the users into account is recommended.

Adult↗

No effect of physiological concentrations of glucagon-like peptide-2 on appetite and energy intake in normal weight subjects.

OBJECTIVE: To examine the effect of a GLP-2 infusion on appetite sensations and ad libitum energy intake in healthy, normal weight humans. DESIGN: The experiment was performed in a randomised, blinded, and placebo-controlled crossover design. Placebo or GLP-2 was infused (infusion rate of 25 pmol/kg body wth) for 4.5 h. SUBJECTS: A total of 18 healthy, normal weight young subjects participated; eight women and 10 men. MEASUREMENTS: During the infusion, subjects recorded their appetite sensations every 30 min using visual analogue scales, and blood was sampled frequently. After 2 h of infusion, an ad libitum meal, consisting of sandwiches, was served. RESULTS: The concentration of GLP-2 was significantly higher during the GLP-2 infusion compared with placebo (P<0.0001) and increased further in both conditions in response to the meal. Neither appetite sensations, nor palatability of the test meals, or energy intake were different on the two occasions. Glucose, GLP-1, insulin, and GIP responses were also unaffected by the infusion, whereas glucagon levels were higher during the GLP-2 treatment (P<0.05). CONCLUSION: Circulating GLP-2 in physiological concentrations does not seem to play a significant role in human appetite regulation.

Adult↗

[Correlation of a computerized SOFA score and derived measures with length of stay at an operative ICU].

OBJECTIVE: The purpose of this study was to assess whether or not the information on progression of illness and therapeutic interventions included in a computerized SOFA (Sequential Organ Failure Assessment) score and derived measures (maximum SOFA, total maximum SOFA and delta SOFA) influences the correlation with length of stay (LOS) at an operative intensive care unit (ICU). METHODS: During a period of one year 524 patients aging over 18 years who stayed more than 24 hours at an operative ICU were included into this study. Based on SQL scripts (Structured Query Language), a computerized SOFA score and the derived measures "maximum-SOFA", "total-maximum-SOFA" and "delta-SOFA" of all patients were retrospectively calculated for each day at ICU using routine data recorded with the patient data management system ICUData (IMESO GmbH, Hüttenberg, Germany). "Maximum-SOFA" and "total-maximum-SOFA" are measures for the severity of illness or cumulative organ dysfunction. "Delta-SOFA" measures the magnitude of organ dysfunction developing during ICU stay and is therefore potentially influenced by therapeutic measures. Analysis was based on exact LOS in hours. RESULTS: Mean LOS of the whole collective was 5.2 +/- 6.8 days (median 2.8, range 1 - 51). Correlation of LOS depending on score results increased from "admission-SOFA" (r = 0.280), to "maximum-SOFA" (r = 0.444), "total-maximum-SOFA" (r = 0.503), and "delta-SOFA" (r = 0.576). CONCLUSION: Therefore, the sum of information on progression of illness and therapeutic interventions included in derived measures improves the correlation with LOS at an ICU compared to the "admission-SOFA".

Adult↗

[Minimal invasive cannulated screw osteosynthesis of Bennett's fractures].

PURPOSE OF THE STUDY: The current study presents a new technique and results of minimal invasive screw osteosynthesis in the treatment of Bennett's fractures and discusses its advantages and disadvantages. OPERATIVE TECHNIQUE: The Bennett's fragment has to be of sufficient size (at least one quarter of the articular surface) and closed reduction must be possible to achieve. Temporary fixation by K-wire is followed by minimal invasive osteosynthesis using a cannulated 3.0 mm screw in the lag screw technique. RESULTS: 18 patients underwent minimal screw osteosynthesis, of whom two were lost for follow-up. Average time of follow-up of the remaining 16 patients was 17.2 weeks. Fracture healing was achieved in all of the 16 patients. There were good to excellent results in 13 patients, fair results in one patient and poor results in two patients. CONCLUSION: Good results can be achieved by minimal invasive screw osteosynthesis in the treatment of Bennett's fractures. Correct indications and minute operation technique are indispensable preconditions for this new kind of treatment.

Adult↗

Conformational characteristics and correlations in crystal structures of nucleic acid oligonucleotides: evidence for sub-states.

Sugar phosphate backbone conformations are a structural element inextricably involved in a complete understanding of specific recognition nucleic acid ligand interactions, from early stage discrimination of the correct target to complexation per se, including any structural adaptation on binding. The collective results of high resolution DNA, RNA and protein/DNA crystal structures provide an opportunity for an improved and enhanced statistical analysis of standard and unusual sugar-phosphate backbone conformations together with corresponding dinucleotide sequence effects as a basis for further exploration of conformational effects on binding. In this study, we have analyzed the conformations of all relevant crystal structures in the nucleic acids data base, determined the frequency distribution of all possible epsilon, zeta, alpha, beta and gamma backbone angle arrangements within four nucleic acid categories (A-RNA and A-DNA, free and bound B-DNA) and explored the relationships between backbone angles, sugar puckers and selected helical parameters. The trends in the correlations are found to be similar regardless of the nucleic acid category. It is interesting that specific structural effects exhibited by the different unusual backbone sub-states are in some cases contravariant. Certain alpha/gamma changes are accompanied by C3' endo (north) sugars, small twist angles and positive values of base pair roll, and favor a displacement of nucleotide bases towards the minor groove compared to that of canonical B form structures. Unusual epsilon/zeta combinations occur with C2' (south) sugars, high twist angles, negative values of base pair roll, and base displacements towards the major groove. Furthermore, any unusual backbone correlates with a reduced dispersion of equilibrium structural parameters of the whole double helix, as evidenced by the reduced standard deviations of almost all conformational parameters. Finally, a strong sequence effect is displayed in the free oligomers, but reduced somewhat in the ligand bound forms. The most variable steps are GpA and CpA, and, to a lesser extent, their partners TpC and TpG. The results provide a basis for considering if the variable and non-variable steps within a biological active sequence precisely determine morphological structural features as the curvature direction, the groove depth, and the accessibility of base pair for non covalent associations.

Carbohydrate Conformation↗

Potential benefits of Anaesthesia Information Management Systems for multicentre data evaluation: risk calculation of inotropic support in patients undergoing cardiac surgery.

OBJECTIVE: The aim of this study was to test the hypothesis whether it is easily possible to transfer and apply the methods of data extraction and analysis of a performed study to a data pool of a different medical centre using the same type of Anaesthesia Information Management System (AIMS). For this purpose the objective of a study in cardiac anaesthesia, investigated at the University Hospital Giessen, was applied to the data pool of the Heart Centre Siegburg. RESEARCH DESIGN AND METHODS: The Giessen study evaluated factors related to the use of positive inotropic drugs (PIDs) in adults undergoing elective cardiac surgery with cardiopulmonary bypass (CPB). The same objective and methods were applied to data of 1672 patients of the Heart Centre Siegburg. In both centres anaesthetic procedures were recorded with the AIMS NarkoData. Existing database queries were adapted according to the Siegburg database configuration for detection of patients having received PIDs during or after weaning from CPB. RESULTS: It was revealed that data from the Siegburg database using the same data model and configuration, were identical to the Giessen database except for a few items only. Thus database queries of the Giessen study could be applied to the new data pool requiring no considerable additional input. CONCLUSIONS: We could demonstrate that multicentre data analysis in anaesthesia using AIM systems can be carried out successfully. Once the methods of data extraction and analysis are established they can be transferred to data pools of different centres without requiring additional time, personnel and material resources.

Aged↗

Homocysteine promotes the LDL oxidase activity of ceruloplasmin.

Ceruloplasmin (CP) oxidises low density lipoprotein (LDL). The oxidising potential depends on the formation of Cu(+)-CP which is redox-cycled during oxidation. Homocysteine (HCY) reduces free Cu(2+), potentiating its cell-damaging property. We show that HCY enhanced LDL oxidation by CP, but did not activate the LDL oxidising potential of Cu(2+)-diamine oxidase. Selective removal of the redox-active Cu(2+) abolished the LDL oxidase activity of CP. However, HCY partially restored the LDL oxidase activity of redox-copper depleted CP, indicating that the remaining six copper atoms in CP may also be involved in the process. Spectroscopic and oxidation inhibition studies using the Cu(+)-reagent bathocuproine revealed that HCY induced Cu(+)-CP formation, thus promoting its LDL oxidase activity.

Ceruloplasmin↗

Shorter discharge time after regional or intravenous anaesthesia in combination with laryngeal mask airway compared with balanced anaesthesia with endotracheal intubation.

BACKGROUND AND OBJECTIVE: The efficiency of operating room times can be significantly improved using rapid changes between operative procedures. We performed a retrospective analysis using electronic anaesthesia charts that compared anaesthesia-related times between the three most frequently performed types of anaesthesia (for orthopaedic surgery) to evaluate the potential for a quicker turn-around between cases. METHODS: A total of 5614 anaesthetic procedures in trauma-related orthopaedic surgery were performed from 1997 to 1999. All were documented with an automatic record-keeping system. Data were compared for intravenous anaesthesia with the laryngeal mask airway, balanced anaesthesia with tracheal intubation and regional anaesthesia. The primary outcome measure was the time needed for emergence from anaesthesia after the end of surgery. Statistical evaluation was performed with matched triples for all three types of anaesthesia (155 triples for ambulatory surgery, 249 triples for in-patient care). RESULTS: For ambulatory surgery, the induction time was significantly shorter for general anaesthesia (23.7 min for intravenous anaesthesia, 22.7 min for balanced anaesthesia techniques) compared with regional anaesthesia (27.2 min). The time from the end of the surgical procedure to transfer of the patient out of the operating room was shortest for regional anaesthesia (6.3 min) compared with intravenous anaesthesia (9.0 min) and balanced anaesthesia (12.5 min) techniques. Results were comparable for in-patients: regional anaesthesia required significantly longer for its induction, but less time for patient discharge from the operating room. CONCLUSIONS: The use of a regional anaesthesia technique or one involving intravenous anaesthesia in combination with the laryngeal mask airway may lead to a reduction in discharge time compared with a balanced anaesthesia technique with endotracheal intubation. Thus, improved use of resources may be achieved.

Adult↗

[Registration of material consumption in anesthesia using a data management system].

BACKGROUND: The aim of this study was to investigate whether an Anesthesia Information Management System (AIMS) can provide reliable data on the consumption of single-use anesthetic material without necessitating an expensive and time-consuming inventory. To this end, the number of selected anesthesia-related materials and the total costs in orthopedic theatres for which the department of anesthesia had been charged in the year 2000 were compared to the data calculated by the AIMS. METHODS: Anesthesia-related material is provided by a computer-based system of storage facilities (KLIMA II) in the Department of Anesthesiology and Intensive Care Medicine at the University Hospital Giessen. All costs arising in orthopedic theatres are exclusively charged to one single account. At the same time, the online-documentation software, NarkoData (IMESO GmbH, Hüttenberg, Germany), collects all data on consumption of anesthetic single-use material. The total amount of peripheral (PVC) and central-venous catheters (CVC), urinary catheters (UC) and endotracheal tubes (ET) used in the year 2000 was ascertained by the AIMS and compared to the respective data accounted by the administration. RESULTS: In the year 2000, the number of patients treated in orthopedic theatres totaled 1,865. By means of the AIMS, a consumption of 783 CVCs, 644 UCs and 949 ETs could be documented. In contrast, hospital administration had billed 880 CVCs, 700 UCs, and 1,050 ETs: discrepancies of 11.0 % for CVCs, 8.0 % for UCs and 9.6 % for ETs. Concerning the two most frequently used CVCs, the AIMS failed to document costs of 3,238 DM. For PVCs (16 gauge and 14 gauge), the official cost was 10.8 % and 46.7 % higher compared to the number documented by the AIMS. Since the number of PVCs totaled 3,400, the AIMS failed to document costs of 1,900 DM. CONCLUSION: Comparison of both methods revealed substantial deficits in documenting cost-relevant materials. There were no detailed data available on the whereabouts of the materials used, i.e. whether tubes and catheters were undocumented, used or discarded. However, the AIMS may provide additional valuable information about possible sources of material wastefulness. This is especially true for infrequently used anesthesia-related materials.

Anesthesiology↗

[Risk predictors, scoring systems and prognostic models in anesthesia and intensive care. Part II. Intensive Care].

The aim of the second part of this review article was to describe common scoring systems in intensive care, and to point out their possible benefits and limitations. Intensive care medicine multipurpose scoring-systems are currently used to estimate severity of illness, mortality and the amount of treatment required. Costs (only commercial available scores e.g. Acute Physiology and Chronic Health Evaluation [APACHE] III) and time needed for calculation have to be taken into consideration. Prognostic models of the third generation (APACHE III, Simplified Acute Physiology Score [SAPS] II, Mortality Prediction Model [MPM] II) should be preferred having better prognostic performance compared to scoring systems of prior generations. Although no prospective study exists comparing these three common scoring systems, it appears that all three systems are able to provide useful information to the clinician and researcher. These scoring systems were designed to classify severity of illness or the course of diagnostic and therapeutic interventions and to perform a risk stratification for scientific studies in a standardized way. In quality management and cost control, scoring systems and predictors are used for risk adjustment and evaluation of care performance.

APACHE↗