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Pathophysiology of fluid imbalance
Uwe Kreimeier
Critical Care , 2000, DOI: 10.1186/cc968
Abstract: A discussion of the pathophysiology of fluid imbalance typically focuses on hypovolemia. A relevant clinical scenario is described in the following case report.A laboratory worker was taken to the emergency department with malaise, headache, nausea and vomiting [1]. There was evidence of circulatory failure and infection. The patient's pulse was 114 beats/min, blood pressure 42/20 mmHg and oral temperature 40°C. The pre-load filling pressure was very low, while cardiac index was elevated. Clinical symptoms were consistent with a generalized capillary leak syndrome. The patient received 14.9 l fluid in excess of measured output during the period of hypotension. Inotropic support with dopamine and nor-epinephrine was also provided. The presumptive diagnosis was septic shock.It was discovered 11 h after admission that the patient had self-administered 1 mg Salmonella minnesota endotoxin 2.5 h prior to arrival at the emergency department in an attempt to treat a recently diagnosed tumor. This single, large intravenous dose of endotoxin had provoked the manifestations of septic shock syndrome, including hypotension with high cardiac output, disseminated intravascular coagulation, abnormalities of hepatic and renal function, and pulmonary edema. A dose of 100 mg human monoclonal antibody against the lipid A moiety of bacterial lipopolysaccharide (HA-1A) antibody was administered 23 h after the injection of endotoxin. Norepinephrine infusion was discontinued 50 h after the endotoxin injection. The patient was discharged on the eighth hospital day.Although the precipitating cause of this patient's condition was unusual, hypovolemia necessitating fluid administration is a common occurrence. Nevertheless, a proper consideration of fluid imbalance extends beyond hypovolemia alone. Fluid imbalance indeed encompasses a triad of conditions consisting of hypovolemia, normovolemia with maldistribution of fluid, and hypervolemia. Each of these is now discussed.One frequent cause of
Hypertonic volume therapy: feasibility in the prevention and treatment of multiple organ failure and sepsis
Pacheco Jr., Adhemar Monteiro;Coimbra, Raul Sérgio Martins;Kreimeier, Uwe;Frey, Lorenz;Messmer, Konrad;
Sao Paulo Medical Journal , 1995, DOI: 10.1590/S1516-31801995000600008
Abstract: small-volume resuscitation by means of bolus infusion of hypertonic saline solutions was first applied for the primary treatment of severe hemorrhagic and traumatic shock and promptly restored central hemodynamics and regional organ blood flow. mechanisms of action are diverse - i. maintenance of high cardiac output (direct myocardial stimulation; increase in intravascular volume); ii. maintenance of peripheral arterial vasodilation (effect of hyperosmolality; plasma volume effect) and iii. reduction of tissue edema (shifting of tissue water along the osmotic gradient). these mechanisms promote the restoration of the severely impaired microcirculation frequently seen also in sepsis. hypertonic volume therapy has been the object of several experimental studies of acute hyperdynamic endotoxemia, however, a greater number of clinical studies have to be developed for the better understanding of the positive, and perhaps hazardous, effects of small-volume resuscitation in sepsis and multiple organ failure. the aim of this paper is to review the concepts involving such solutions, and their potential use in treatment of profound hypovolemia and microcirculatory deterioration associated with sepsis and endotoxic shock.
Analysis of N-terminal pro-B-type natriuretic peptide and cardiac index in multiple injured patients: a prospective cohort study
Chlodwig Kirchhoff, Bernd A Leidel, Sonja Kirchhoff, Volker Braunstein, Viktoria Bogner, Uwe Kreimeier, Wolf Mutschler, Peter Biberthaler
Critical Care , 2008, DOI: 10.1186/cc7013
Abstract: Twenty-six multiple injured patients presenting a New Injury Severity Score of greater than 16 points were included. The MODS score was calculated on admission as well as 24, 48, and 72 hours after injury. Patients were subdivided into groups: group A showed minor signs of organ dysfunction (MODS score less than or equal to 4 points) and group B suffered from major organ dysfunction (MODS score of greater than 4 points). Venous blood (5 mL) was collected after admission and 6, 12, 24, 48, and 72 hours after injury. NT-proBNP was determined using the Elecsys proBNP? assay. The hemodynamic monitoring of cardiac index (CI) was performed using transpulmonary thermodilution.Serum NT-proBNP levels were elevated in all 26 patients. At admission, the serum NT-proBNP values were 116 ± 21 pg/mL in group A versus 209 ± 93 pg/mL in group B. NT-proBNP was significantly lower at all subsequent time points in group A in comparison with group B (P < 0.001). In contrast, the CI in group A was significantly higher than in group B at all time points (P < 0.001). Concerning MODS score and CI at 24, 48, and 72 hours after injury, an inverse correlation was found (r = -0.664, P < 0.001). Furthermore, a correlation was found comparing MODS score and serum NT-proBNP levels (r = 0.75, P < 0.0001).Serum NT-proBNP levels significantly correlate with clinical signs of MODS 24 hours after multiple injury. Furthermore, a distinct correlation of serum NT-proBNP and decreased CI was found. The data of this pilot study may indicate a potential value of NT-proBNP in the diagnosis of post-traumatic cardiac impairment. However, further studies are needed to elucidate this issue.Currently, severe trauma is still the leading cause of death in young patients. Whereas early post-traumatic mortality is determined by the primary traumatic impact, late mortality is caused by the development of sepsis and systemic inflammatory response syndrome (SIRS). SIRS possibly leads to multiple organ failure (MOF) and f
Trauma management incorporating focused assessment with computed tomography in trauma (FACTT) - potential effect on survival
Karl-Georg Kanz, April O Paul, Rolf Lefering, Mike V Kay, Uwe Kreimeier, Ulrich Linsenmaier, Wolf Mutschler, Stefan Huber-Wagner, the Trauma Registry of the German Trauma Society
Journal of Trauma Management & Outcomes , 2010, DOI: 10.1186/1752-2897-4-4
Abstract: In a retrospective, multicentre study, we compared our time management and probability of survival (Ps) in major trauma patients who received FACTT during trauma resuscitation with the trauma registry of the German Trauma Society (DGU). FACTT is defined as whole-body computed tomography (WBCT) during primary trauma survey. We determined the probability of survival according to the Trauma and Injury Severity Score (TRISS), the Revised Injury Severity Classification score (RISC) and the standardized mortality ratio (SMR).We analysed 4.817 patients from the DGU database from 2002 until 2004, 160 (3.3%) were from our trauma centre at the Ludwig-Maximilians-University (LMU) and 4.657 (96.7%) from the DGU group. 73.2% were male with a mean age of 42.5 years, a mean ISS of 29.8. 96.2% had suffered from blunt trauma. Time from admission to FAST (focused assessment with sonography for trauma)(4.3 vs. 8.7 min), chest x-ray (8.1 vs. 16.0 min) and whole-body CT (20.7 vs. 36.6 min) was shorter at the LMU compared to the other trauma centres (p < 0.001). SMR calculated by TRISS was 0.74 (CI95% 0.40-1.08) for the LMU (p = 0.24) and 0.92 (CI95% 0.84-1.01) for the DGU group (p = 0.10). RISC methodology revealed a SMR of 0.69 (95%CI 0.47-0.92) for the LMU (p = 0.043) and 1.00 (95%CI 0.94-1.06) for the DGU group (p = 0.88).Trauma management incorporating FACTT enhances a rapid response to life-threatening problems and enables a comprehensive assessment of the severity of each relevant injury. Due to its speed and accuracy, FACTT during primary trauma survey supports rapid decision-making and may increase survival.In central European trauma centres there is an increasing trend towards focused assessment with computed tomography in trauma (FACTT) [1,2]. According to the annual report 2008 of the German trauma registry, more than 44.9% reporting trauma centres utilize whole-body computed tomography (WBCT) in major trauma due to its speed and accuracy [3].In 1997 L?w was the first to cons
Towards Quantitative Characterisation of the Small Force Transducer Used in Nanoindentation Instruments  [PDF]
Zhi Li, Uwe Brand
Modern Instrumentation (MI) , 2013, DOI: 10.4236/mi.2013.24009

Quantitative characterization of the mechanical properties of materials in micro-/nano-scale using depth-sensing indentation technique demands high performance of nanoindentation instruments in use. In this paper, the efforts to calibrate the capacitive force transducer of a commercial nanoindentation instrument are presented, where the quasi-static characteristic of the force transducer has been calibrated by a precise compensation balance with a resolution of ~1 nN. To investigate the dynamic response of the transducer, an electrostatic MEMS (Micro-Electro-Mechanical System) based on nano-force transfer standard with nano-Newton (10-9 Newton) resolution and a bandwidth up to 6 kHz have been employed. Preliminary experimental results indicate that 1) the force transducer under calibration has a probing force uncertainty less than 300 nN (1σ) in the calibration range of 1 mN; 2) the transient duration at contact points amounts to 10 seconds; 3) the overshoot of engagement is pre-load dependent.

Affiliation of Dihydrolipoyl Dehydrogenase Allozymes in Mycorrhizae of European Forest Trees and Characterization of the Enzyme of the Matt Bolete (Xerocomus pruinatus) and the Bay Bolete (X. badius)  [PDF]
Uwe Schirkonyer, Gunter M. Rothe
Open Journal of Ecology (OJE) , 2018, DOI: 10.4236/oje.2018.86022
Abstract: Mycorrhizal roots of the deciduous trees European beech (Fagus sylvatica (L.)) and Sessile oak (Quercus petraea (MattuschkaLiebl.)) and the conifers Norway spruce (Picea abies (L.) H. Karst.) and European larch (Larix decidua (Mill.)) associated with the ectomycorrhizal fungi matt bolete (Xerocomus pruinatus (Fries 1835)) or bay bolete (X. badius (Fries 1818)) were analysed with respect to the occurrence of dihydrolipoyl dehydrogenase (EC allozymes. In root tissues of the two deciduous trees, two gene loci could be visualized after cellulose acetate electrophoresis while three loci were expressed in root tissues of the two coniferous species. The two fungal species and further ectomycorrhizal fungi expressed exclusively one dihydrolipoyl dehydrogenase gene. In Xerocomus pruinatus and X. badius, the dihydrolipoyl dehydrogenase gene consists of 1460 bp and 1370 bp, respectively, including five introns each consisting of 52 bp. Their DNA sequences correspond to 70 to 90% to other fungal dihydrolipoyl dehydrogenase genes. One monomer of the dimeric dihydrolipoyl dehydrogenase enzyme consists of 486 (X. pruinatus) or 454 (X.
Drosophila muscleblind Codes for Proteins with One and Two Tandem Zinc Finger Motifs
Uwe Irion
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0034248
Abstract: Muscleblind-like proteins, Muscleblind (Mbl) in Drosophila and MBNL1-3 in vertebrates, are regulators of alternative splicing. Human MBNL1 is a key factor in the etiology of myotonic dystrophy (DM), a muscle wasting disease caused by the occurrence of toxic RNA molecules containing CUG/CCUG repeats. MBNL1 binds to these RNAs and is sequestered in nuclear foci preventing it from exerting its normal function, which ultimately leads to mis-spliced mRNAs, a major cause of the disease. Muscleblind-proteins bind to RNAs via N-terminal zinc fingers of the Cys3-His type. These zinc fingers are arranged in one (invertebrates) or two (vertebrates) tandem zinc finger (TZF) motifs with both fingers targeting GC steps in the RNA molecule. Here I show that mbl genes in Drosophila and in other insects also encode proteins with two TZF motifs, highly similar to vertebrate MBNL proteins. In Drosophila the different protein isoforms have overlapping but possibly divergent functions in vivo, evident by their unequal capacities to rescue the splicing defects observed in mbl mutant embryos. In addition, using whole transcriptome analysis, I identified several new splicing targets for Mbl in Drosophila embryos. Two of these novel targets, kkv (krotzkopf-verkehrt, coding for Chitin Synthase 1) and cora (coracle, coding for the Drosophila homolog of Protein 4.1), are not muscle-specific but expressed mainly in epidermal cells, indicating a function for mbl not only in muscles and the nervous system.
Modeling the Risk of Secondary Malignancies after Radiotherapy
Uwe Schneider
Genes , 2011, DOI: 10.3390/genes2041033
Abstract: In developed countries, more than half of all cancer patients receive radiotherapy at some stage in the management of their disease. However, a radiation-induced secondary malignancy can be the price of success if the primary cancer is cured or at least controlled. Therefore, there is increasing concern regarding radiation-related second cancer risks in long-term radiotherapy survivors and a corresponding need to be able to predict cancer risks at high radiation doses. Of particular interest are second cancer risk estimates for new radiation treatment modalities such as intensity modulated radiotherapy, intensity modulated arc-therapy, proton and heavy ion radiotherapy. The long term risks from such modern radiotherapy treatment techniques have not yet been determined and are unlikely to become apparent for many years, due to the long latency time for solid tumor induction. Most information on the dose-response of radiation-induced cancer is derived from data on the A-bomb survivors who were exposed to γ-rays and neutrons. Since, for radiation protection purposes, the dose span of main interest is between zero and one Gy, the analysis of the A-bomb survivors is usually focused on this range. With increasing cure rates, estimates of cancer risk for doses larger than one Gy are becoming more important for radiotherapy patients. Therefore in this review, emphasis was placed on doses relevant for radiotherapy with respect to radiation induced solid cancer. Simple radiation protection models should be used only with extreme care for risk estimates in radiotherapy, since they are developed exclusively for low dose. When applied to scatter radiation, such models can predict only a fraction of observed second malignancies. Better semi-empirical models include the effect of dose fractionation and represent the dose-response relationships more accurately. The involved uncertainties are still huge for most of the organs and tissues. A major reason for this is that the underlying processes of the induction of carcinoma and sarcoma are not well known. Most uncertainties are related to the time patterns of cancer induction, the population specific dependencies and to the organ specific cancer induction rates. For radiotherapy treatment plan optimization these factors are irrelevant, as a treatment plan comparison is performed for a patient of specific age, sex, etc. If a treatment plan is compared relative to another one only the shape of the dose-response curve (the so called risk-equivalent dose) is of importance and errors can be minimized.
Pyoderma gangrenosum – a review
Uwe Wollina
Orphanet Journal of Rare Diseases , 2007, DOI: 10.1186/1750-1172-2-19
Abstract: The treatment of PG is a challenge. Randomized, double-blinded prospective multicenter trials for PG are not available. The best documented treatments are systemic corticosteroids and ciclosporin A. Combinations of steroids with cytotoxic drugs are used in resistant cases. The combination of steroids with sulfa drugs or immunosuppressants has been used as steroid-sparing modalities. Anti-tumor necrosis alpha therapy in Crohn's disease showed a rapid response of PG. Skin transplants and the application of bioengineered skin is useful in selected cases as a complement to the immunosuppressive treatment. Topical therapy with modern wound dressings is useful to minimize pain and the risk of secondary infections. Despite recent advances in therapy, the prognosis of PG remains unpredictable.Pyoderma gangrenosumPyoderma gangrenosum (PG) is a primarily sterile inflammatory neutrophilic dermatosis. It is characterized by recurrent cutaneous ulcerations with mucopurulent or hemorrhagic exudate. These very painful ulcers present with undermined bluish borders with surrounding erythema. In many cases, PG is associated with inflammatory bowel disease, rheumatic disorder or neoplasia [1-3].Powell et al. [4] suggested a classification of PG into four major clinical types [see Table 1].Accurate epidemiological data on PG are missing. The peak of incidence occurs between the ages of 20 to 50 years with women being more often affected than men [2,6]. Cases in infants and adolescents account for only 4% of PG. PG in elderly people has occasionally been reported [7]. The general incidence has been estimated to be between 3 and 10 per million per year [8].PG occurs most commonly on the lower legs with preference for the pretibial area [Fig. 1 &2]. PG has been reported on other sites of the body as well, including breast, hand, trunk, head and neck, and peristomal skin [Fig. 3 &4]. Extracutaneous manifestations include involvement of upper airway mucosa, eye [9-12], genital mucosa [13],
Combining methods - lack of methodology
Flick, Uwe
Papers on Social Representations , 1992,
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