Einfluß der parenteralen Gabe von langkettigen Fettsäuren auf den Prostanoidstoffwechsel bei septischen Patienten

In der vorliegenden Studie wurde im Rahmen einer totalen parenteralen Ernährung der Einfluß von Liposyn 20%, einer Fettemulsion die aus ungesättigten langkettigen Fettsäuren, insbesondere Linolsäure besteht, auf den Eikosanoidstoffwechsel von septischen Patienten untersucht. Auf der septischen Intensivstation des Zentralklinikums Augsburg wurden eine Kurzzeit-studie und eine Langzeitstudie an septischen Patienten durchgeführt. An der Kurzzeitstudie, die über 4 Tage ging nahmen 12 Patienten teil, an der Langzeit-studie mit einer Dauer von 10 Tagen nahmen 6 Patienten teil. In jeder der beiden Studien wurde die eine Hälfte der Patienten ausschließlich mit einem Kohlenhydratgemisch ernährt, während in der anderen Gruppe 50% der Nichteiweißkalorien durch Liposyn 20% bereitgestellt wurden. Insgesamt bekamen die Patienten 30 kcal/kg Körpergewicht pro Tag an Nichteiweißkalorien parenteral verabreicht. Zusätzlich wurde in allen Gruppen den Patienten 100g Aminosäuren pro Tag gegeben. Zur Vergleichbarkeit der Patienten in Hinblick auf ihre Erkrankungsschwere untereinander wurde nachträglich bei jedem Patienten der APACHE III-Score für jeden Studientag ermittelt. In dem Eikosanoidlabor der Kinderklinik der Universität Marburg wurden mittels Gaschromatographie/Massenspektrometrie folgende Indexmetabolite der Eikosanoide gemessen: - 11-dehydro-TxB2 im Plasma (Maß für die phasische TxA2-Produktion), - TxB2 im 24h Urin (Maß für die renale TxA2-Produktion), - 2,3-dinor-TxB2 im 24h Urin (Maß für die systemische TxA2-Produktion), - 2,3-dinor-6-keto-PGF1 im 24h Urin (Maß für die systemische PGI2- Produktion), - PGE-M im 24h-Urin (Maß für die systemische PGE2-Produktion). Zusätzlich wurden die Triglyceride und Cholesterinester im Plasma, sowie der Linolsäuregehalt in den Cholesterinestern bestimmt. Unter Berücksichtigung des APACHE-Score bestanden keine wesentlichen Unterschiede in Hinblick auf die Erkrankungsschwere bei den untersuchten Patienten. Die Letalität war in der Kurzzeitstudie in der Kontrollgruppe etwas höher als in der Fettgruppe. In der Langzeitstudie war die Letalität in beiden Gruppen gleich groß. Die Triglycerid- und Cholesterinwerte lagen im Normbereich was für eine gute Elimination und Verstoffwechslung der infundierten Fettemulsion spricht. Bei allen Patienten zeigten sich stark erhöhte Eikosanoidwerte. Weder in der Kurzzeit- noch in der Langzeitstudie ließen sich deutliche Unterschiede in der Eikosanoidproduktion unter Gabe von Liposyn 20% nachweisen. Ursache hierfür scheint zu sein, dass es durch die bei der Sepsis verstärkte Lipolyse zu einer vermehrten Freisetzung von Arachidonsäure aus den Phospholipiden der Zellmembranen kommt. Dieser Anstieg an verfügbarer Arachidonsäure führte zu einer Erhöhung der Eikosanoidproduktion in beiden Gruppen. Die zusätzliche Gabe von Linolsäure führte offensichtlich jedoch nicht zu einer vermehrten Bereitstellung von Arachidonsäure in der Fettgruppe, was durch die geschwindigkeitsbestimmenden Desaturasen erklärt werden kann. Sicherlich besteht bei Zufuhr von Linolsäure über einen längeren Zeitraum auch die Möglichkeit einer vermehrten Bereitstellung von Arachidonsäure. Die in der Studie gewählten Zeiträume waren aber offensichtlich zu kurz, um dies zu bewirken. Die Ergebnisse dieser Studie zeigen somit, dass in Bezug auf die gemessenen Eikosanoide keine Gründe gegen die Verwendung von langkettigen ungesättigten Fettsäuren als Bestandteil der totalen parenteralen Ernährung für die Dauer des untersuchten Beobachtungszeitraumes sprechen

The Tamar Trough revisited: correlations berween sedimentary beds, basalts, their ages and valley evolution, North Tasmania

The Tamar Trough, an Early Palaeogene fault structure, contains sedimentaty beds and interleaved basaltic flows that infill the structure along its 70 km length. These infills represent a complex interplay between sedimentation, channel erosion, eruptive dislocations, and even 'out of trough' diyersions of the ancestral Tamar drainage. Several areas of resistant basalt flows remain in the south, upper, middle and lower Tamar reaches. Although some palynological control was known, radiometric dating of previously untested basalts now allows close integration and age-pegging for observed palynological biozones. The K-Ar and Ar-Ar ages of the basalt bodies indicate eruptive events at 47, 33-37 and 25 Ma, correlating with Proteacidites asperopolus-Malvacipollis diversus, Nothofagites asperus and Proteacidites tuberculatus biozone age sedimentary beds respectively. Basanite, alkali basalt and hawaiite flows dominate basalt lithology with lesser olivine nephelinite, transitional olivine basalt, olivine tholeiite and quartz tholeiite. Basalt geochemistry suggests derivation from different degrees of partial mande melting (from 7 to 35%), with alkaline and tholeiitic basalts being derived from separate source regions. Most alkaline basalts have high-jl (HIMU) related trace element signatures, which are absent in the tholeiitic rocks. A basalt plug on the trough margin at Loira gave a Jurassic age and has Jurassic dolerite-like geochemistry. The Tamar sequence suggests that the initial fluvio-Iacustrine and later channel-fill sedimentation from 65(?) to 24(?) Ma was then punctuated in places by periods of alkaline volcanism between 47 to 33(?) Ma, and alkaline and tholeiitic volcanism between 33 to 24(?) Ma. No Neogene fossils are known, so this later period was probably one of net erosion. These contrasting quiet sedimentary and more volcanic intervals are related here to a tectonic model that involves northerly drift of Victorian and Tasmanian lithosphere over several former Tasman metasomatised mantle plume sources

A Cretaceous phonolite dyke from the Tomahawk River, northeast Tasmania

Field mapping and indicate that a phonolite which intrudes Devonian granite in the upper Tomahawk River area, Tasmania, is 3.2 km long and with a true thickness of 10-15 m. The rock contains of anorthoclase, sparse fayalitic olivine and low-Ti and rare biotite in a alkali feldspar laths, with interstitial clinopyroxene to amphibole or analcime and accessory apatite. It is peralkaline and evolved, even for phonolites, with very and CaO, and high and incompatible elements. However, relatively high Sr and Ba and the absence of a negative Eu anomaly suggest little feldspar fractionation in its petrogenesis. Its Late Cretaceous age 80.4 ± 1.6 Ma, 4oAr/39Ar plateau 75.8 ± 0.3 Ma, 4oAr/39Ar total fusion 76 ± 3.1 Ma) and geochemistry are unique for Tasmania and it represents a recognised, although very minor, igneous episode. It may be related to a change in dynamic regime following continental rifting, the opening of the Tasman Sea and the subsidence of Bass Basin

Continental weathering and recovery from ocean nutrient stress during the Early Triassic Biotic Crisis

Following the latest Permian extinction ∼252 million years ago, normal marine and terrestrial ecosystems did not recover for another 5-9 million years. The driver(s) for the Early Triassic biotic crisis, marked by high atmospheric CO2 concentration, extreme ocean warming, and marine anoxia, remains unclear. Here we constrain the timing of authigenic K-bearing mineral formation extracted from supergene weathering profiles of NW-Pangea by Argon geochronology, to demonstrate that an accelerated hydrological cycle causing intense chemical alteration of the continents occurred between ∼254 and 248 Ma, and continued throughout the Triassic period. We show that enhanced ocean nutrient supply from this intense continental weathering did not trigger increased ocean productivity during the Early Triassic biotic crisis, due to strong thermal ocean stratification off NW Pangea. Nitrogen isotope constraints suggest, instead, that full recovery from ocean nutrient stress, despite some brief amelioration ∼1.5 million years after the latest Permian extinction, did not commence until climate cooling revitalized the global upwelling systems and ocean mixing ∼10 million years after the mass extinction

[2,4-13C]β-hydroxybutyrate Metabolism in Astrocytes and C6 Glioblastoma Cells

This study was undertaken to determine if the ketogenic diet could be useful for glioblastoma patients. The hypothesis tested was whether glioblastoma cells can metabolize ketone bodies. Cerebellar astrocytes and C6 glioblastoma cells were incubated in glutamine and serum free medium containing [2,4-13C]β-hydroxybutyrate (BHB) with and without glucose. Furthermore, C6 cells were incubated with [1-13C]glucose in the presence and absence of BHB. Cell extracts were analyzed by mass spectrometry and media by 1H magnetic resonance spectroscopy and HPLC. Using [2,4-13C]BHB and [1-13C]glucose it could be shown that C6 cells, in analogy to astrocytes, had efficient mitochondrial activity, evidenced by 13C labeling of glutamate, glutamine and aspartate. However, in the presence of glucose, astrocytes were able to produce and release glutamine, whereas this was not accomplished by the C6 cells, suggesting lack of anaplerosis in the latter. We hypothesize that glioblastoma cells kill neurons by not supplying the necessary glutamine, and by releasing glutamate

Association between expression of the Bone morphogenetic proteins 2 and 7 in the repair of circumscribed cartilage lesions with clinical outcome

<p>Abstract</p> <p>Background</p> <p>Although there is much known about the role of BMPs in cartilage metabolism reliable data about the <it>in vivo </it>regulation in natural and surgically induced cartilage repair are still missing.</p> <p>Methods</p> <p>Lavage fluids of knee joints of 47 patients were collected during surgical therapy. 5 patients had no cartilage lesion and served as a control group, the other 42 patients with circumscribed cartilage defects were treated by microfracturing (19) or by an Autologous Chondrocyte Implantation (23). The concentrations of BMP-2 and BMP-7 were determined by ELISA. The clinical status was evaluated using the IKDC Score prior to and 1 year following the operation.</p> <p>Results</p> <p>High level expression in the control group was found for BMP-2, concentrations of BMP-7 remained below detection levels. No statistical differences could be detected in concentrations of BMP-2 or BMP-7 in the lavage fluids of knees with cartilage lesions compared to the control group. Levels of BMP-7 did not change after surgical cartilage repair, whereas concentrations of BMP-2 statistically significant increased after the intervention (p < 0.001). The clinical outcome following cartilage regenerating surgery increased after 1 year by 29% (p < 0.001). The difference of the IKDC score after 1 year and prior to the operation was used to quantify the degree of improvement following surgery. This difference statistically significant correlated with initial BMP-2 (R = 0.554, p < 0.001) but not BMP-7 (R = 0.031, n.s.) levels in the knee joints.</p> <p>Conclusions</p> <p>BMP-2 seems to play an important role in surgically induced cartilage repair; synovial expression correlates with the clinical outcome.</p

Regression toward the mean – a detection method for unknown population mean based on Mee and Chua's algorithm

<p>Abstract</p> <p>Background</p> <p>Regression to the mean (RTM) occurs in situations of repeated measurements when extreme values are followed by measurements in the same subjects that are closer to the mean of the basic population. In uncontrolled studies such changes are likely to be interpreted as a real treatment effect.</p> <p>Methods</p> <p>Several statistical approaches have been developed to analyse such situations, including the algorithm of Mee and Chua which assumes a known population mean <it>μ</it>. We extend this approach to a situation where <it>μ </it>is unknown and suggest to vary it systematically over a range of reasonable values. Using differential calculus we provide formulas to estimate the range of <it>μ </it>where treatment effects are likely to occur when RTM is present.</p> <p>Results</p> <p>We successfully applied our method to three real world examples denoting situations when (a) no treatment effect can be confirmed regardless which <it>μ </it>is true, (b) when a treatment effect must be assumed independent from the true <it>μ </it>and (c) in the appraisal of results of uncontrolled studies.</p> <p>Conclusion</p> <p>Our method can be used to separate the wheat from the chaff in situations, when one has to interpret the results of uncontrolled studies. In meta-analysis, health-technology reports or systematic reviews this approach may be helpful to clarify the evidence given from uncontrolled observational studies.</p

Einfluss des Beckenregisters der DGU auf die Versorgung von Beckenringfrakturen

Fractures of the pelvic ring are comparatively rare with an incidence of 2-8 % of all fractures depending on the study in question. The severity of pelvic ring fractures can be very different ranging from simple and mostly "harmless" type A fractures up to life-threatening complex type C fractures. Although it was previously postulated that high-energy trauma was necessary to induce a pelvic ring fracture, over the past decades it became more and more evident, not least from data in the pelvic trauma registry of the German Society for Trauma Surgery (DGU), that low-energy minor trauma can also cause pelvic ring fractures of osteoporotic bone and in a rapidly increasing population of geriatric patients insufficiency fractures of the pelvic ring are nowadays observed with no preceding trauma.Even in large trauma centers the number of patients with pelvic ring fractures is mostly insufficient to perform valid and sufficiently powerful monocentric studies on epidemiological, diagnostic or therapeutic issues. For this reason, in 1991 the first and still the only registry worldwide for the documentation and evaluation of pelvic ring fractures was introduced by the Working Group Pelvis (AG Becken) of the DGU. Originally, the main objectives of the documentation were epidemiological and diagnostic issues; however, in the course of time it developed into an increasingly expanding dataset with comprehensive parameters on injury patterns, operative and conservative therapy regimens and short-term and long-term outcome of patients. Originally starting with 10 institutions, in the meantime more than 30 hospitals in Germany and other European countries participate in the documentation of data. In the third phase of the registry alone, which was started in 2004, data from approximately 15,000 patients with pelvic ring and acetabular fractures were documented. In addition to the scientific impact of the pelvic trauma registry, which is reflected in the numerous national and international publications, the dramatically changing epidemiology of pelvic ring fractures, further developments in diagnostics and the changes in operative procedures over time could be demonstrated. Last but not least the now well-established diagnostic and therapeutic algorithms for pelvic ring fractures, which could be derived from the information collated in registry studies, reflect the clinical impact of the registry.Zusammenfassung Die Inzidenz von Beckenringfrakturen ist mit einem Anteil von je nach Studienlage 2–8 % aller Frakturen vergleichsweise gering. Das Erscheinungsbild einer Beckenringfraktur ist sehr vielfältig und reicht von einfachen und meist „harmlosen“ Typ-A-Verletzungen bis hin zu lebensbedrohlichen komplexen Typ-C-Verletzungen. Während in der Vergangenheit postuliert wurde, dass ein hohes Energieniveau erforderlich ist, um den Beckenring zu frakturieren, wurde in den letzten Jahren nicht zuletzt durch Daten des Beckenregisters der DGU evident, dass bei osteoporotischem Knochen oft auch ein Bagatelltrauma zu einer Beckenringfraktur führen kann. Es kristallisierte sich heraus, dass bei einem rasant wachsenden geriatrischen Patientenkollektiv sogar ohne vorangegangenes Trauma Insuffizienzfrakturen des Beckenrings zu beobachten sind. Auch an großen Traumazentren ist die Anzahl der Patienten mit Beckenringfrakturen vielfach nicht ausreichend, um durch Monocenterstudien valide Aussagen über epidemiologische, diagnostische und therapeutische Entwicklungen treffen zu können. Aus diesem Grunde wurde bereits 1991 von der AG Becken der DGU das weltweit erste und bis heute einzige Register zur Dokumentation und Evaluation von Beckenverletzungen ins Leben gerufen. Standen anfänglich v. a. epidemiologische und diagnostische Fragestellungen im Vordergrund der Dokumentation, entwickelte sich im Laufe der Zeit ein zunehmend wachsender Datensatz mit umfassenden Parametern zu Verletzungsmustern, operativen und konservativen Therapieregimen sowie dem kurz- und langfristigen Outcome der Patienten. Während das Beckenregister ursprünglich in 10 Einrichtungen gestartet wurde, nehmen mittlerweile über 30 Kliniken auch außerhalb Deutschlands an der Datendokumentation teil. Allein in der dritten Phase der Registerarbeit konnten seit 2004 an die 15.000 Patienten mit Becken- und Azetabulumfrakturen in die Datenbank eingeschlossen werden. Neben dem wissenschaftlichen Einfluss des Beckenregisters, der sich in zahlreichen nationalen und internationalen Publikationen widerspiegelt, konnten durch die Datenerhebungen die sich dramatisch wandelnde Epidemiologie von Beckenringverletzungen, Weiterentwicklungen in der Diagnostik sowie die sich über den Zeitverlauf ändernden operativen Therapieverfahren aufgezeigt werden. Nicht zuletzt die aus der Datenlage abgeleiteten und heute etablierten Diagnostik- und Therapiealgorithmen bei Beckenringfrakturen spiegeln den klinischen Wert des Beckenregisters wider

Changing patterns in diagnostic strategies and the treatment of blunt injury to solid abdominal organs

Background: In recent years there has been increasing interest shown in the nonoperative management (NOM) of blunt traumatic injury. The growing use of NOM for blunt abdominal organ injury has been made possible because of the progress made in the quality and availability of the multidetector computed tomography (MDCT) scan and the development of minimally invasive intervention options such as angioembolization. Aim: The purpose of this review is to describe the changes that have been made over the past decades in the management of blunt trauma to the liver, spleen and kidney. Results: The management of blunt abdominal injury has changed considerably. Focused assessment with sonography for trauma (FAST) examination has replaced diagnostic peritoneal lavage as diagnostic modality in the primary survey. MDCT scanning with intravenous contrast is now the gold standard diagnostic modality in hemodynamically stable patients with intra-abdominal fluid detected with FAST. One of the current discussions in the l erature is whether a whole body MDCT survey should be implemented in the primary survey. Conclusions The progress in imaging techniques has contributed to NOM being currently the treatment of choice for hemodynamically stable patients. Angioembolization can be used as an adjunct to NOM and has increased the succe