bluuebunny/crossref_metadata_2025 huggingface dataset:
Glutaminsupplementierte Ernährung in der klinischen Praxis – Anwendung von glutaminhaltigen Dipeptiden
Authors: Fürst P. , Stehle P.
Published: May 2009

Ziel: In dieser Übersichtsarbeit werden die physiologischen Funktionen der Ami-nosäure Glutamin erläutert und die Auswirkungen einer bei Katabolie, metabolischem Streβ und Mangelernährung auftretenden Glutaminverarmung auf vitale Körperfunktionen diskutiert. Nachfolgend wird die Anwendung von Glutamin- bzw. Glutamindipeptid-Supplementen in der Ernährungstherapie kritisch beleuchtet. Abschlieβend wird die Bedeutung der Glutaminzufuhr besonders im Hinblick auf Praktikabilität und zukünftige Einsatzgebiete diskutiert. Design: Für diese Zusammenstellung wurden sowohl grundlegende Arbeiten aus den Bereichen Physiologie und Ernährungswissenschaft als auch alle aktuellen experimentellen und klinischen Forschungsarbeiten, die sich mit der Verwendung von Glutamin bzw. Glutamindipeptid-Supplementen in der klinischen Ernährung befassen, berücksichtigt. Ergebnisse: Bei einer Vielzahl von Erkrankungen (z. B. schwere Katabolie/metabo-lischer Streβ, intestinale Unter-/Fehlfunktionen, immundefizitäre Syndrome) muβ Glutamin als bedingt essentieller Nährstoff eingestuft und im Rahmen einer Ernährungstherapie in adäquaten Mengen (etwa 10-15 g/Tag) zugeführt werden. Nur dadurch kann einer Verarmung an Glutamin entgegengetreten werden, wodurch die klinische Situation günstig beeinfluβt wird. Durch den Einsatz von gut löslichen und stabilen glutaminhaltigen Dipeptiden ist erstmals eine sichere parenterale Versorgung der Patienten mit Glutamin gewährleistet. Schluβfolgerungen: Die Anwendung einer Glutamintherapie könnte bei verschiedenen Patientengruppen dazu beitragen, den Stickstoffhaushalt zu verbessern, die Häufigkeit von klinischen Infektionen zu vermindern, die Gefahr einer mikrobiellen Besiedlung zu verringern und möglicherweise Liegezeiten zu verkürzen.
Feasibility and Rate of Leucocyte Depletion with a Single Leucocyte Depletion Filter during Massive Transfusion
Authors: Rieger A. , Saefkow M. , Haß I. , Spies C. , Eyrich K.
Published: May 2009

Background: The study examines the feasibility and rate of leucocyte depletion with a single leucocyte depletion filter in combination with the Level 1 heat exchanging infusion/transfusion device H-500/H-25I during massive transfusions. Materials and Methods: LeukoGuard-6 filters (LG-6) were manufactured to fit the infusion sets of the Level 1 H-500/H-25L This modified device was used intraoperatively in six patients with severe haemorrhage. Following determination of the white cell counts (WCC) in each buffy coat poor red cell concentrate prior to administration, WCC were then obtained from blood sampled directly distal to the filter after the first and after the last red cell concentrate was given. Leucocytes were determined in the Nageotte chamber and then calculated to determine leucocytes/250 ml (therapeutic unit). Parameters of feasibility (time for preparation of the system, the amount of transfused red cell concentrates, time interval of transfusions) were recorded. Results: The mean volume of red cell concentrates which were transfused and filtered by a single filter was 2,708 ml (S.D. ± 797 ml) within a mean time interval of 42.5 min (S.D. ± 26 min). With a mean WCC of 1.17 ± 0.68 ×109 leucocytes/250 ml in the red cell concentrate prior to filtration the LG-6 achieved a log-3 reduction of leucocyte counts. During the transfusion the WCC distal to the filter increased on average by a factor of 3 (from 0.9 × 106 leucocytes/250 ml following the first blood unit to 2.7 × 106 leucocytes/250 ml following the last), but remained below 5 × 106. Conclusion: Modification of the Level 1 H-500/H-25i system by incorporating the LG-6 leucocyte depletion filter provides a significant reduction of the WCC in the transfused red cell concentrates during massive transfusion. The rate of leucocyte depletion by a single leucocyte depletion filter achieves low leucocyte counts which are documented to be of therapeutical value. As the significance of leucocyte-reduced blood products for patients with haemorrhagic shock following trauma or major surgery has still to be elucidated, the presented device may be useful in the performance of future studies related to this subject.
Significance of Platelet Serine/ Threonine Phosphatases 1/2A for Storage of Platelet Concentrates
Authors: Aulmann M. , Ruf K.
Published: May 2009

Inhibition of phosphatases 1/2A (ppl/2A) by okadaic acid (OA) prevents thrombin-or collagen-stimulated platelet aggregation, serotonin and ATP release, as well as intracellular Ca2+ increase. OA is added to 12 platelet concentrates (PCs) prepared from 500 ml whole blood. Microcystin LR (MC), a further ppl/2A inhibitor that does not penetrate the cell membrane, is added to 9 PCs. 9 PCs remain untreated. Storage of PCs is carried out on a horizontal agitator for 7 days. Samples are taken daily to estimate WBC, RBC, PLT, cAMP, cGMP and serotonin. 12 h after OA addition, a dose-dependent drop in platelet counts is seen, accompanied by a corresponding increase of particles with sizes of WBC and RBC. Increased WBC and RBC counts are artefacts brought about by platelet aggregation. From day 4 of storage, serotonin is released massively, cAMP consumption is reduced or stopped, and cGMP concentration increases slightly. In untreated and MC-treated PCs no similar reactions are observed. It seems that the inhibition of extracellular ppl/2A (ectophosphatases) prevents platelet activation. The inhibition of intracellular ppl/2A (endophosphata-ses) presumably enhances platelet activation. The different results between OA- and MC-treated PCs lead to these conclusions because, depending on dose and time, OA penetrates platelet membranes, MC does not. Therefore the results of the study give rise to the suspicion that ppl/2A control two sites of signal transduction in platelets of stored PCs: extracellular ppl/2A are included in platelet activation, while intracellular ppl/2A mediate inhibition of activated platelets. Inhibition of ectophosphatases and activation of endophosphatases probably facilitate PC storage.
Clinical Results with a New Continuous Autotransfusion System (C.A.T.S ®, Fresenius AG)
Authors: Schleinzer W. , Biesel W. , Schmeht W.
Published: May 2009

Die Qualität des im «Quality Wash»-Programm des kontinuierlich arbeitenden Autotransfusionsgerätes C.A.T.S® (Fresenius AG) produzierten autologen ge-waschenen Erythrozytenkonzentrates (AGEK) wurde in dieser Studie an 15 Fallen groβer orthopädischer Operationen untersucht. Es ergaben sich gleichmäβig hohe (68+3%) Hämatokritwerte, die vom Volumen des AGEK und von Volumen und Zusammensetzung des intra- und postoperativen Sammelblutes unabhängig waren. Die biochemischen Parameter, die im AGEK gemessen wurden, unterstreichen dessen gute Qualität ebenso wie das während der Aufbereitung im Disposable zurückgehaltene Fett.
Human Disk Cells from Degenerated Disks and Mesenchymal Stem Cells in Co-Culture Result in Increased Matrix Production
Authors: Svanvik T. , Barreto Henriksson H. , Karlsson C. , Hagman M. , Lindahl A. , Brisby H.
Published: May 2009

Transplantation of mesenchymal stem cells (MSCs) has been suggested for disk degeneration, which is characterized by dysfunctional cells and low proteoglycan production. The aim of this study was to examine the effects of a 3D co-culture system using human disk cells (DCs) and MSCs on collagen and proteoglycan production. DCs and MSCs were expanded in monolayer and grown in pellet cultures for 7, 14 and 28 days and analyzed for hydroxyproline (HP), reflecting total collagen production, and glycosaminoglycan (GAG) accumulation. DCs and MSCs co-cultured at different ratios (25/75, 50/50 and 75%/25%) were examined for GAG accumulation. Collagen type II expression was analyzed immunohistochemically. In a second series, conditioned media were added to pellet cultures of degenerated DCs or MSCs. DCs from degenerated disks and MSCs demonstrated lower total collagen production than non-degenerated DC pellets. GAG production was comparable in DCs and MSCs, except in the youngest donor, with MSC producing about 10 times higher GAG/DNA. Co-cultures resulted in approximately 1.5 times higher GAG/DNA production than DCs. Increased collagen type II expression was seen in co-cultures compared to DC or MSC culture alone, except in the case with highly active MSCs. No positive effect of conditioned media was seen. In conclusion, co-culture of MSCs with degenerated DCs increased proteoglycan and collagen-type ceII production, indicating that in future clinical therapy MSCs can be transplanted without pre-differentiation in vitro. The lack of effect of conditioned media suggests that the positive effect of co-culture on matrix production is not due to soluble factors.
Einfluß der Verabreichung von Blutprodukten auf den Verlauf der Tetanus-Antikörperkonzentration bei immuninkompetenten Patienten
Authors: Pietsch M. , Töre S. , Schütt† K.-H.
Published: May 2009

Ziel: Erarbeitung von Daten für die Gabe von Blutprodukten zur Immunprophylaxe des Tetanus bei immuninkompetenten Patienten. Design: Prospektive Einzelfallanalyse. Rahmen: Klinische Behandlung in hämatologischer Abteilung mit konti-nuierlicher Bestimmung der Tetanus-Antikörperkonzentra-tionen in Patientenseren und verabreichten Blutprodukten mittels Enzym-Immunoassay. Patienten: 3 Patienten mit akuter myeloischer Leukämie (FAB-Klassifikationen Ml, M3, M4). Interventionen: Regelmäßige Verabreichung von Blutprodukten im Rahmen der klinischen Therapie. Ergebnisse: Durch die Gabe von etwa 4000 IE Tetanus-Antitoxin i.v. ist die Serumkonzentration um 1 IE/ml anzuheben. Die Serum-halbwertszeit beträgt 7 Tage. Ein Schutz ist damit bis zu 6 Wochen vorhanden. Schlußfolgerungen: Immuninkompe-tente Patienten können durch Auswahl geeigneter Blutprodukte einen mittelfristig wirksamen Schutz gegen Tetanus erhalten. Dieses Verfahren ist auch interessant zur Prophylaxe des postoperativen Tetanus bei immunkompetenten Patienten.
Can Blood Group 0 Red Cells of Donor Origin Acquire Weak Group A Reactivity through Serum A Transferase of the Recipient after Bone Marrow Transplantation?
Authors: Wichmann M.G. , Haferlach T. , Suttorp M. , Zhang Y. , Neppert J.
Published: May 2009

Background: Blood group A substance was detected on red cells of a patient who received a bone marrow transplant from a blood group 0 donor 3.5 years ago. Material and Methods: Peripheral blood was investigated by conventional serological techniques, fluorescence in situ hybridisation, and polymerase chain reaction. Results: All peripheral blood cells are of donor origin. Anti-A and not anti-AB of blood group 0 individuals can be absorbed to the group 0 red cells of the patient. Conclusion: We suppose that the patient’s residual serum A transferase attaches the appropriate sugar to substance H on the red cell membrane to form substance A.
Aufklärungsgrad von zur präoperativen Eigenblutabnahme vorgesehenen Patienten an einer Universitätsklinik
Authors: Nussbaumer W. , Mayer W. , Schönitzer D.
Published: May 2009

Ziel: Aufdeckung der derzeitigen Insuffizienz des Aufklärungssystems bei Eigenblutversorgung zwecks Implementie-rung von Korrekturmaßnahmen. Design: Befragung von zuge-wiesenen Eigenblutspendern mittels Fragebogen. Rahmen: Blutbank einer Universitätsklinik. Teilnehmer: 174 Patienten, welche zwischen dem 1.6.95 und dem 1.8.95 von ihrem behandelnden Arzt erstmals zur präoperativen Eigenblutspende zugewiesen wurden. Ergebnisse: Von 174 Patienten waren 64 (36,8%) von ihrem behandelnden Arzt nach erfolgter Aufklärung, 100 (57,5%) unaufgeklärt dem Transfusionsmediziner zugewiesen; 10 Patienten (5,7%) kamen aus eigener Initiative. Von den 110 nicht vom behandelnden Arzt aufgeklärten Patienten gaben 16 an, durch Berichte aus den Medien über Risi-ko und Alternativen der Fremdbluttransfusion ausreichend informiert zu sein. Bei aufgeklärten Patienten war der Prozentsatz jener, die vor Fremdbluttransfusionen keine Angst hatten, mit 23,4% deutlich geringer als bei unaufgeklärten (35,5%). Irrationale Ängste fanden sich bei aufgeklärten weniger als bei unaufgeklärten (12,2% vs. 16,9%, aufgeklärt vs. unaufgeklärt). Schlußfolgerungen: Eine ständig wachsende Anzahl von Patienten wird in fremdblutsparende Programme eingebunden, die Aufklärung erscheint aber noch nicht ausreichend. Da die Aufklärung vor Zuweisung an die transfusions-medizinische Einrichtung erfolgen muß, erscheint eine verstärkte Aufklärung und Ausbildung aller involvierter Fach-gruppen über die Problematik rechtlicher und medizinischer Probleme der Fremdbluttransfusion dringend erforderlich. Letzterem wurde durch Schaffung einer interdisziplinären Arbeitsgruppe für Transfusionsmedizin Rechnung getragen.
Current Trends in Platelet Transfusion – Transfusion Practices in Europe
Authors: Kretschmer V.
Published: May 2009

Platelet transfusion practices in Europe are summarized based on survey questionnaire returns from 36 centers in 17 countries. In marrow hypoplasia the platelet transfusion trigger varied from 10,000 to 20,000/µl with a minority at 5,000/µl. These levels increased up to 50,000/µl in case of signs of major bleeding. In surgery levels of 50,000 to 100,000/µl were desirable with attempts to maintain postoperative levels of 30,000 to 50,000/µl for up to one week. A large majority of centers used random-pooled platelet concentrates (RPC) for surgical patients, while apheresis platelets were used by a small majority for chronic thrombocytopenic patients. HLA-matched platelets were used in most cases for immunized or refractory patients. An increasing majority prepares RPC by the buffy-coat technique. There is a tendency to store apheresis platelets for shorter times. Leukocyte-depleted platelets were used primarily for refractory chronic thrombocytopenic patients, although levels considered effective rang edfrom < 106 to < 108 About half the centers used leukocyte-depleted platelets in lieu of cytomegalovirus (CMV)-seronegative platelets. A large majority irradiated products for patients at risk of GvHD, although irradiation doses varied widely. The dose of platelets per transfusion also varied widely.
Why Choose Apheresis Platelet Concentrates?
Authors: Andreu G. , Angué M. , Calot J.P. , Coffe C. , Cotte C. , David C. , Ferrer-Lecœur F. , Fontaine O. , Gaschard P. , Girard A. , Hardy E. , Hau F. , Masse M. , Michel M. , Royer D. , Schooneman F. , Vicariot M. , Villard F. , Waller C.
Published: May 2009

Apheresis systems for the production of single-donor platelets may be divided into 3 categories: those which collect high-yield products with low leukocyte contamination, those with high yields but higher WBC residuals, and those giving lower yields with high leukocyte contamination. Systems in the first category have clear advantages. Of the 2 methods for producing platelet concentrates (PC) from whole blood – the platelet-rich-plasma (PRP) and the buffy-coat (BC) methods – platelets produced by the BC method are better in terms of yield, WBC residuals, and in vitro function assays. In studies comparing the in vitro function of apheresis platelets and BC platelets, the apheresis platelets show better results in some assays, however, the differences are small. In a recent study carried out in Bristol, UK, corrected count increments (CCIs) for apheresis platelets were significantly higher than those for PRP platelets and not significantly higher than those for BC platelets. Use of apheresis platelets reduces the number of donors to which a recipient is exposed. A further reduction can be achieved if a larger dose of platelets is used per transfusion. A multicenter study carried out in France confirmed earlier findings that the platelet survival time in thrombocytopenic patients is improved if sufficient platelets are given to bring the post-transfusion platelet count above levels achieved with standard-dose transfusions.
Zur pathophysiologischen Rolle von Zytokinen beim kardiopulmonalen Bypass
Authors: Neuhof H. , Soeparwata R. , Neuhof C. , Scheld H.H.
Published: May 2009

Mit der vorliegenden Kurzübersicht soil der aktuelle Wissens-stand über die Zytokinbildung und -wirkung und ihre patho-physiologische Bedeutung bei herzchirurgischen Eingriffen mit kardiopulmonalem Bypass (CPB) und bei Abstoβungsre-aktionen nach Herztransplantation dargestellt werden. Neben aktuellen wissenschaftlichen Originalarbeiten bilden eigene Untersuchungen an 30 Patienten der Klinik für Herz-, Thorax-und Gefäβchirurgie der Universität Münster die Diskussions-basis. Herzchirurgische Eingriffe mit CPB lösen eine systemische Entzündungsreaktion aus, bei der die Bildung von Zytokinen, wie TNF-oc, IL-2, IL-6 und IL-8, eine dominierende Rolle spielt. Die Zytokinsynthese wird dabei in erster Linie durch aktivierte Komplementfaktoren und durch die aus dem Darm in die Zirkulation gelangenden Endotoxine getriggert. Das Aus-maβ der Zytokinbildung korreliert mit der Schwere des operati-ven Eingriffs und der Dauer des CPB. Zytokine sind unter anderem wichtige Mediatoren der Leukozyten-Endothel-Inter-aktion, die vor allem bei der Abstoβungsreaktion nach Herztransplantation zu einem wichtigen Pathomechanismus wird. Das zeitliche Erscheinen und der Konzentrationsverlauf proin-flammatorischer Zytokine in der Zirkulation spiegeln das Aus-maβ der systemischen Entzündungsreaktion wider und können Hinweise auf mögliche Komplikationen geben. Abstoβungsre-aktionen nach Herztransplantationen werden hingegen nicht durch typische Muster zirkulierender Zytokine oder ihrer Re-zeptoren angezeigt, sondern durch die gesteigerte lokale Expression der Adhäsionsmoleküle ICAM-1 und VCAM-1 im Transplantat.
Activating Transcription Factor 3 Constitutes a Negative Feedback Mechanism That Attenuates Saturated Fatty Acid/Toll-Like Receptor 4 Signaling and Macrophage Activation in Obese Adipose Tissue
Authors: Suganami Takayoshi , Yuan Xunmei , Shimoda Yuri , Uchio-Yamada Kozue , Nakagawa Nobutaka , Shirakawa Ibuki , Usami Takako , Tsukahara Takamitsu , Nakayama Keizo , Miyamoto Yoshihiro , Yasuda Kazuki , Matsuda Junichiro , Kamei Yasutomi , Kitajima Shigetaka , Ogawa Yoshihiro
Published: May 2009

Obese adipose tissue is markedly infiltrated by macrophages, suggesting that they may participate in the inflammatory pathways that are activated in obese adipose tissue. Evidence has suggested that saturated fatty acids released via adipocyte lipolysis serve as a naturally occurring ligand that stimulates Toll-like receptor (TLR)4 signaling, thereby inducing the inflammatory responses in macrophages in obese adipose tissue. Through a combination of cDNA microarray analyses of saturated fatty acid-stimulated macrophages in vitro and obese adipose tissue in vivo, here we identified activating transcription factor (ATF)3, a member of the ATF/cAMP response element-binding protein family of basic leucine zipper-type transcription factors, as a target gene of saturated fatty acids/TLR4 signaling in macrophages in obese adipose tissue. Importantly, ATF3, when induced by saturated fatty acids, can transcriptionally repress tumor necrosis factor-α production in macrophages in vitro. Chromatin immunoprecipitation assay revealed that ATF3 is recruited to the region containing the activator protein-1 site of the endogenous tumor necrosis factor-α promoter. Furthermore, transgenic overexpression of ATF3 specifically in macrophages results in the marked attenuation of proinflammatory M1 macrophage activation in the adipose tissue from genetically obese KK
A

y

mice fed high-fat diet. This study provides evidence that ATF3, which is induced in obese adipose tissue, acts as a transcriptional repressor of saturated fatty acids/TLR4 signaling, thereby revealing the negative feedback mechanism that attenuates obesity-induced macrophage activation. Our data also suggest that activation of ATF3 in macrophages offers a novel therapeutic strategy to prevent or treat obesity-induced adipose tissue inflammation.
Atheroprotective Effects of Alum Are Associated With Capture of Oxidized LDL Antigens and Activation of Regulatory T Cells
Authors: Wigren Maria , Bengtsson Daniel , Dunér Pontus , Olofsson Katarina , Björkbacka Harry , Bengtsson Eva , Fredrikson Gunilla Nordin , Nilsson Jan
Published: May 2009

The immune system represents a promising novel target for prevention of atherosclerosis. Several pilot vaccines that reduce atherosclerosis in experimental animals have been developed. The aluminum hydroxide adjuvant Alum has been shown to have antiatherogenic properties in itself, suggesting that it may be a suitable adjuvant in possible future atherosclerosis vaccines. To characterize the immune pathways mediating this protection, we treated wild-type C57BL/6 and
Apoe
−
/
−
mice with Alum or PBS. Analyses of splenocytes isolated from 12-week-old mice demonstrated that Alum increased the presence of CD4
+
CD25
+
FoxP3
+
regulatory T cells and downregulated the expression of T cell activation markers CD28 and ICOS in
Apoe
−
/
−
mice but not in C57BL/6 wild-type mice. A similar immunosuppressive phenotype was found also in 25-week-old
Apoe
−
/
−
mice and was associated with reduced atherosclerosis. Alum precipitates recovered from the injection site of
Apoe
−
/
−
mice contained antigens derived from oxidized LDL. These findings demonstrate that treatment of
Apoe
−
/
−
mice with Alum results in an increase of regulatory T cells and suggest that these are activated by tolerogenic antigen-presenting cells presenting oxidized LDL antigens. Our findings provide improved mechanistic understanding of the atheroprotective properties of aluminum hydroxide adjuvants but also point to the importance of determining if hypercholesterolemia may compromise the efficacy of Alum-containing vaccines used clinically today.
Normobaric Hyperoxia Reduces the Neurovascular Complications Associated With Delayed Tissue Plasminogen Activator Treatment in a Rat Model of Focal Cerebral Ischemia
Authors: Liu Wenlan , Hendren Jill , Qin Xu-Jun , Liu Ke Jian
Published: May 2009

Background and Purpose—

A major limitation of tissue plasminogen activator (tPA) thrombolysis for ischemic stroke is the narrow time window for safe and effective therapy. Delayed tPA thrombolysis increases the risk of cerebral hemorrhage and mortality, which, in part, is related to neurovascular proteolysis mediated by matrix metalloproteinases (MMPs). We recently showed that normobaric hyperoxia treatment reduces MMP-9 expression and blood–brain barrier disruption in the ischemic brain. Therefore, we hypothesized that normobaric hyperoxia could increase the safety of delayed tPA thrombolysis in stroke.

Methods—

Male Sprague-Dawley rats were exposed to normobaric hyperoxia (95% O
2
) or normoxia (21% O
2
) during 5-hour filament occlusion of the middle cerebral artery followed by 19-hour reperfusion. Thirty minutes before reperfusion, saline or tPA was continuously infused to rats over 1 hour. Outcome parameters were neurological score, mortality rate, brain edema, hemorrhage volume, and MMP-9. Hemorrhage was quantified with a hemoglobin spectrophotometry method. Edema was evaluated as hemispheric enlargement. MMP-9 was measured by gelatin zymography.

Results—

In normoxic rats, delayed tPA treatment at 4.5 hours after stroke onset resulted in high mortality, more severe neurological deficits, increased hemorrhage volumes, and augmented MMP-9 induction compared with saline. Rats treated with combined normobaric hyperoxia and tPA showed significantly reduced tPA-associated mortality, brain edema, hemorrhage, and MMP-9 augmentation as compared with tPA alone.

Conclusions—

Our results suggest that early normobaric hyperoxia treatment may represent an important strategy to increase the safety of delayed tPA thrombolysis in ischemic stroke.
4D Radial Acquisition Contrast-Enhanced MR Angiography and Intracranial Arteriovenous Malformations
Authors: Eddleman Christopher S. , Jeong Hyun J. , Hurley Michael C. , Zuehlsdorff Sven , Dabus Guilherme , Getch Christopher G. , Batjer H. Hunt , Bendok Bernard R. , Carroll Timothy J.
Published: May 2009

Background and Purpose—

The current gold standard for imaging intracranial AVMs involves catheter-based techniques, namely cerebral digital subtraction angiography (DSA). However, DSA presents some procedural risks to the patient. Unfortunately, AVM patients usually undergo multiple DSA exams throughout their diagnostic and therapeutic course, significantly increasing their procedural risk exposure. As such, high-quality noninvasive imaging is desired. We hypothesize that 4D radial acquisition contrast-enhanced MRA approximates the vascular architecture and hemodynamics of AVMs compared to conventional angiography.

Methods—

Thirteen consecutive AVM patients were assessed by 4D radial acquisition contrast-enhanced MRA and DSA. The 4D rCE-MRA images were independently assessed regarding the location, nidal size, Spetzler–Martin grade, and identification of arterial feeders, drainage pattern, and any other vascular anomalies.

Results—

4D rCE-MRA correctly depicted the size, venous drainage pattern, and prominent arterial feeders in all cases. Spetzler–Martin grade was correctly determined between reviewers and between the different imaging modalities in all cases except 1. The nidus size was in good correlation between the reviewers, where
r
=0.99,
P
<0.000001. There was very good agreement between reviewers regarding the individual scans (κ=0.63 to 1), whereas the agreement between the DSA and 4D rCE-MRA images was also good (κ=0.61 to 0.85).

Conclusions—

We have developed a 4D radial acquisition contrast-enhanced MRA sequence capable of imaging intracranial AVMs approximating that of DSA. Image analysis demonstrates equivalency in terms of grading AVMs using the Spetzler–Martin grading scale. This 4D rCE-MRA sequence has the potential to avoid some applications of DSA, thus saving patients from potential procedural risks.
Stroke Therapy Academic Industry Roundtable (STAIR) Recommendations for Extended Window Acute Stroke Therapy Trials
Authors: Saver Jeffrey L. , Albers Gregory W. , Dunn Billy , Johnston Karen C. , Fisher Marc
Published: May 2009

The Stroke Therapy Academic Industry Roundtable (STAIR) meetings focus on helping to advance the development of acute stroke therapies. Further extending the time window for acute stroke therapies is an important endeavor for increasing the number of stroke patients who might benefit from treatment. The STAIR group recommends that future extended time window trials initially should focus on selected patient groups most likely to respond to investigational therapies and that penumbral imaging is one tool that may identify such patients. The control group in these trials should receive best locally available medical care; if regulatory approval for intravenous (i.v.) tPA is extended to 4.5 hours, then tPA will become the most appropriate comparator in trials conducted within this time window. In future well-designed extended window clinical trials randomization is appropriate and should not be precluded by using unproven treatment with intraarterial (i.a.) thrombolysis or mechanical devices. For proof of concept, extended time window, phase II trials of i.v. thrombolysis, or mechanical devices in which early recanalization/reperfusion is the primary end point, rescue therapy/bailout treatment with i.a. thrombolysis or devices may be acceptable. Statistical considerations and definitions of successful recanalization/reperfusion are suggested for these trials.
Property law and Imperial and British titles: the Dukes of Marlborough and the Principality of Mindelheim
Authors: Cox Noel
Published: May 2009

The title of prince of the Holy Roman Empire was conferred in 1704 upon all the children heirs and lawful descendants, male and female, of John Churchill, the first duke of Marlborough. The title of prince of Mindelheim was granted in 1705 to all male descendants and daughters of the first duke. But following the Treaty of Utrecht in 1713 and the Treaty of Rastatt in 1714 the principality passed to Bavaria. The right of the dukes of Marlborough to use the style and title was thus lost, and any residual rights would have expired in 1722 on the death of the duke, as they could not pass to a daughter (unlike his British titles). Despite this it is still common practice to describe the Duke of Marlborough as a Prince of the Holy Roman Empire and Prince of Mindelheim. This paper considers the differences in the treatment of the descent of the British and imperial titles.
The effect of nicotine on visuospatial attention in chronic spatial neglect depends upon lesion location
Authors: Vossel S. , Kukolja J. , Thimm M. , Thiel CM , Fink GR
Published: May 2009

The deficit to reorient attention from ipsilesional to contralesional space is one key feature of the spatial neglect syndrome. As previous studies suggest that reorienting of visuospatial attention is modulated by cholinergic neurotransmission, we investigated whether cholinergic stimulation with nicotine (Nicorette® 2 mg, Pharmacia/Pfizer, Helsingborg, Sweden) facilitates attentional reorienting in spatial neglect patients. Nine nonsmoking patients with stable neglect symptoms were investigated in a within-subject cross-over design. We used a location-cueing paradigm and analysed reaction time (RT) differences between validly and invalidly cued, as well as between neutrally cued and uncued targets as a function of hemifield and drug. Moreover, since the nicotine effect is mediated by parietal brain areas in healthy subjects, we tested whether lesion location influences the pharmacological effect. Nicotine speeded RTs in valid and invalid trials nonspecifically, without modulating the validity effect in the location-cueing task in the whole group of patients. Lesion-symptom mapping revealed a relationship between lesion site and the pharmacological effect on reorienting to contralesional space in right parietal and temporal brain regions. We conclude that in patients with chronic spatial neglect the performance in the location-cueing paradigm can be modulated by a cholinergic stimulant provided that the lesion spares right parietal and temporal cortex.
Implementation of the Enteral Nutrition Practice Recommendations
Authors: Brantley Susan L.
Published: May 2009

In developing the evidence‐based Enteral Nutrition Practice Recommendations, the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) formed a task force to address the many aspects of safety in the delivery and provision of enteral nutrition support. This recently published document provides healthcare professionals with recommendations that are derived from evidence‐based practice. The development and use of clinical practice guidelines (CPGs) is a recent, significant contribution for the dissemination of evidence‐based medicine. This involves the review of scientific literature along with clinical skill and knowledge to generate specific recommendations assisting healthcare providers and patients with decisions regarding appropriate healthcare. A primary opportunity to improve patient outcomes will come from the effective delivery of existing therapies rather than from the new development of treatment modalities. Compliance with CPGs is challenging because it depends on a variety of factors. Both general and specific strategies have been devised with the expansion of the new discipline of implementation science. The high degree of evidence now available in medicine gives clinicians more opportunity to improve patient outcomes and quality of care. It remains for clinicians to evaluate their institutional mission and goals, and to investigate those CPGs appropriate to improve patient care in that setting.
A Unified Solution for an Anisotropic Functionally Graded Piezoelectric Beam Subject to Sinusoidal Transverse Loads
Authors: Huang D.J. , Ding H.J. , Chen W.Q.
Published: May 2009

The behavior of anisotropic functionally graded piezoelectric beams subject to sinusoidal transverse loads is investigated based on the equations for a generalized plane stress problem. Both the stress function and electric displacement function are assumed to consist of two parts. One corresponds to a product of a trigonometric function of the longitudinal coordinate (x) and an undetermined function of the thickness coordinate (z). The other is represented by a linear polynomial of x with unknown coefficients also depending on z. The equations governing these z-dependent functions are presented. The expressions for stresses, electric displacements, resultant forces, displacements, and electric potential are then deduced, in which the integral constants are determined from the boundary conditions. Analytical solution is derived in the case that material coefficients vary exponentially along the thickness of the beam. Semi-analytical solution is also suggested along with the sub-layer approximation when the material properties vary in an arbitrary fashion along the thickness. Various boundary conditions at the two ends of the beam can be taken into consideration. Numerical results and the associated discussions are finally presented.
Google stemming mechanisms
Authors: Uyar Ahmet
Published: May 2009

In this study we investigated the stemming mechanisms of Google. We used its web interface and submitted many queries via a program. Stemming is the process of correlating morphologically similar words with one another. Search engines use stemming to match documents having one form of a word with queries having another form of the same word. We investigated the stemming mechanism of Google for three classes of words: singulars/plurals, combined words, and verbs with many postfixes. Our results indicate that Google uses a document-based algorithm for stemming. It evaluates each document separately and makes a decision to index or not for the conflated forms of the words it has. It indexes documents only for word forms that are semantically strongly correlated. While it indexes documents for singulars and plurals frequently, it rarely indexes documents for word forms with the postfixes of -able or -tively.
Treatment of a 7-Year Old Girl With Long-standing Disordered Eating Behaviors Since Infancy
Authors: Tremblay Line , Lariviere Michel
Published: May 2009

The authors present the case of a 7-year-old girl with disordered eating secondary to severe symptoms of gastroesophageal reflux (GER) experienced during infancy. Symptoms include deficits in interpreting signs of hunger and refusals to eat, leading to latent physical development. Methods of assessment include parent and child interviews, child eating behaviors and parental feeding strategies questionnaires, a 2-week food record, and mealtime behavioral observations. The objective of treatment was weight gain through decreasing problematic eating behaviors: dawdling eating, excessive talking at mealtime, and frequently leaving the table during meals. Cognitive-behavioral approaches (eg, using reinforcements and consequences, increasing food intake by small portion sizes, and increasing the child's awareness of signs of hunger through direct prompts and parental modeling) were successful, and parents reported physical growth weight gain at 6-month follow-up.
Excessive Cow's Milk Consumption and Iron Deficiency in Toddlers
Authors: Bondi Steven A. , Lieuw Kenneth
Published: May 2009

Elimination of iron deficiency and iron deficiency anemia in children is a crucial public health concern because these conditions have been linked to cognitive and behavioral deficits. In the infant age group, great strides have been made to reduce iron deficiency and iron deficiency anemia significantly. However, similar progress has not yet been made with toddlers. Cow's milk consumption has long been associated with iron deficiency and iron deficiency anemia in children. Because cow's milk is a staple in the diet of most toddlers, they are at particular risk for these conditions. Two unusual presentations of anemia in toddlers caused by excessive cow's milk consumption are described: one in a child with congestive heart failure, the other in a child with profound eosinophilia. The role of cow's milk in iron deficiency and iron deficiency anemia is also examined.
Cell-nonautonomous function of Id1 in the hematopoietic progenitor cell niche
Authors: Suh Hyung Chan , Ji Ming , Gooya John , Lee Michael , Klarmann Kimberly D. , Keller Jonathan R.
Published: May 2009

Development of hematopoietic stem cells (HSCs) and their immediate progeny is maintained by the interaction with cells in the microenvironment. We found that hematopoiesis was dysregulated in Id1−/− mice. Although the frequency of HSCs in Id1−/− bone marrow was increased, their total numbers remained unchanged as the result of decreased bone marrow cellularity. In addition, the ability of Id1−/− HSCs to self-renew was normal, suggesting Id1 does not affect HSC function. Id1−/− progenitors showed increased cycling in vivo but not in vitro, suggesting cell nonautonomous mechanisms for the increased cycling. Id1−/− HSCs developed normally when transplanted into Id1+/+ mice, whereas the development of Id1+/+ HSCs was impaired in Id1−/− recipients undergoing transplantation and reproduced the hematologic features of Id1−/− mice, indicating that the Id1−/− microenvironment cannot support normal hematopoietic development. Id1−/− stromal cells showed altered production of cytokines in vitro, and cytokine levels were deregulated in vivo, which could account for the Id1−/− hematopoietic phenotypes. Thus, Id1 is required for regulating the hematopoietic progenitor cell niche but is dispensable for maintaining HSCs.
An in vivo chemical library screen in Xenopus tadpoles reveals novel pathways involved in angiogenesis and lymphangiogenesis
Authors: Kälin Roland E. , Bänziger-Tobler Nadja E. , Detmar Michael , Brändli André W.
Published: May 2009

Angiogenesis and lymphangiogenesis are essential for organogenesis but also play important roles in tissue regeneration, chronic inflammation, and tumor progression. Here we applied in vivo forward chemical genetics to identify novel compounds and biologic mechanisms involved in (lymph)angiogenesis in Xenopus tadpoles. A novel 2-step screening strategy involving a simple phenotypic read-out (edema formation or larval lethality) followed by semiautomated in situ hybridization was devised and used to screen an annotated chemical library of 1280 bioactive compounds. We identified 32 active compounds interfering with blood vascular and/or lymphatic development in Xenopus. Selected compounds were also tested for activities in a variety of endothelial in vitro assays. Finally, in a proof-of-principle study, the adenosine A1 receptor antagonist 7-chloro-4-hydroxy-2-phenyl-1,8-naphthyridine, an inhibitor of blood vascular and lymphatic development in Xenopus, was shown to act also as a potent antagonist of VEGFA-induced adult neovascularization in mice. Taken together, the present chemical library screening strategy in Xenopus tadpoles represents a rapid and highly efficient approach to identify novel pathways involved in (lymph)angiogenesis. In addition, the recovered compounds represent a rich resource for in-depth analysis, and their drug-like features will facilitate further evaluation in preclinical models of inflammation and cancer metastasis.
Epoxyeicosatrienoates are the dominant eicosanoids in human lungs upon microbial challenge
Authors: Kiss L. , Schütte H. , Padberg W. , Weissmann N. , Mayer K. , Gessler T. , Voswinckel R. , Seeger W. , Grimminger F.
Published: May 2009

Lipoxygenase, cyclo-oxygenase and cytochrome P450 (CYP) products of arachidonic acid (AA) are implicated in pulmonary vasoregulation. The CYP-mediated epoxyeicosatrienoates (EETs) have been described previously as the predominant eicosanoids in human lungs upon stimulation with the Ca2+ionophore A23187. In this study, we challenged perfused human lungs with two microbial agents:Escherichia colihaemolysin (ECH) and formyl-methionyl-leucyl-phenylalanine (fMLP).

Both stimuli elicited pronounced generation of leukotrienes (LTs), hydroxyeicosatetraenoic acids (HETEs), prostanoids (PTs) and EETs/dihydroxyeicosatrienoic acids (DHETs), as assessed by liquid chromatography–mass spectrometry, paralleled by pulmonary artery pressor response and lung oedema formation. The maximum buffer concentrations of EETs/DHETs surpassed those of LTs plus HETEs and PTs by a factor of four (ECH) or three (AA/fMLP). Dual 5-lipoxygenase/cyclo-oxygenase inhibition caused pronounced reduction of AA/fMLP-induced LT/PT synthesis and oedema formation but only limited attenuation of pulmonary vasoconstriction, while inhibition of CYP epoxygenase clearly attenuated AA/fMLP-induced EET/DHET synthesis and vasoconstriction but not oedema formation, suggesting a major contribution of LTs/PTs to vascular leakage and of EETs/DHETs to pressor response.

Consequently, generation of EETs/DHETs is greater than that of LTs plus HETEs and PTs inex vivoperfused human lungs upon microbial challenge suggesting a substantial contribution of these mediators to inflammatory–infectious pulmonary injury.
Tbx1 and Brn4regulate retinoic acid metabolic genes during cochlear morphogenesis
Authors: Braunstein Evan M , Monks Dennis C , Aggarwal Vimla S , Arnold Jelena S , Morrow Bernice E
Published: May 2009

Background

In vertebrates, the inner ear is comprised of the cochlea and vestibular system, which develop from the otic vesicle. This process is regulated via inductive interactions from surrounding tissues. Tbx1, the gene responsible for velo-cardio-facial syndrome/DiGeorge syndrome in humans, is required for ear development in mice. Tbx1 is expressed in the otic epithelium and adjacent periotic mesenchyme (POM), and both of these domains are required for inner ear formation. To study the function of Tbx1 in the POM, we have conditionally inactivated Tbx1 in the mesoderm while keeping expression in the otic vesicle intact.

Results

Conditional mutants (TCre-KO) displayed malformed inner ears, including a hypoplastic otic vesicle and a severely shortened cochlear duct, indicating that Tbx1 expression in the POM is necessary for proper inner ear formation. Expression of the mesenchyme marker Brn4 was also lost in the TCre-KO. Brn4
-;Tbx1
+/-embryos displayed defects in growth of the distal cochlea. To identify a potential signal from the POM to the otic epithelium, expression of retinoic acid (RA) catabolizing genes was examined in both mutants. Cyp26a1 expression was altered in the TCre-KO, while Cyp26c1 showed reduced expression in both TCre-KO and Brn4
-;Tbx1
+/- embryos.

Conclusion

These results indicate that Tbx1 expression in the POM regulates cochlear outgrowth potentially via control of local retinoic acid activity.
Gene expression in lungs of mice lacking the 5-hydroxytryptamine transporter gene
Authors: Crona Daniel , Harral Julie , Adnot Serge , Eddahibi Saadia , West James
Published: May 2009

Background

While modulation of the serotonin transporter (5HTT) has shown to be a risk factor for pulmonary arterial hypertension for almost 40 years, there is a lack of in vivo data about the broad molecular effects of pulmonary inhibition of 5HTT. Previous studies have suggested effects on inflammation, proliferation, and vasoconstriction. The goal of this study was to determine which of these were supported by alterations in gene expression in serotonin transporter knockout mice.

Methods

Eight week old normoxic mice with a 5-HTT knock-out (5HTT-/-) and their heterozygote(5HTT+/-) or wild-type(5HTT+/+) littermates had right ventricular systolic pressure(RVSP) assessed, lungs collected for RNA, pooled, and used in duplicate in Affymetrix array analysis. Representative genes were confirmed by quantitative RT-PCR and western blot.

Results

RVSP was normal in all groups. Only 124 genes were reliably changed between 5HTT-/- and 5HTT+/+ mice. More than half of these were either involved in inflammatory response or muscle function and organization; in addition, some matrix, heme oxygenase, developmental, and energy metabolism genes showed altered expression. Quantitative RT-PCR for examples from each major group confirmed changes seen by array, with an intermediate level in 5HTT +/- mice.

Conclusion

These results for the first time show the in vivo effects of 5HTT knockout in lungs, and show that many of the downstream mechanisms suggested by cell culture and ex vivo experiments are also operational in vivo. This suggests that the effect of 5HTT on pulmonary vascular function arises from its impact on several systems, including vasoreactivity, proliferation, and immune function.
Co-ordinated stage-dependent enhancement of Plasmodium falciparum antioxidant enzymes and heat shock protein expression in parasites growing in oxidatively stressed or G6PD-deficient red blood cells
Authors: Akide-Ndunge Oscar Bate , Tambini Elisa , Giribaldi Giuliana , McMillan Paul J , Müller Sylke , Arese Paolo , Turrini Francesco
Published: May 2009

Background

Plasmodium falciparum-parasitized red blood cells (RBCs) are equipped with protective antioxidant enzymes and heat shock proteins (HSPs). The latter are only considered to protect against thermal stress. Important issues are poorly explored: first, it is insufficiently known how both systems are expressed in relation to the parasite developmental stage; secondly, it is unknown whether P. falciparum HSPs are redox-responsive, in view of redox sensitivity of HSP in eukaryotic cells; thirdly, it is poorly known how the antioxidant defense machinery would respond to increased oxidative stress or inhibited antioxidant defense. Those issues are interesting as several antimalarials increase the oxidative stress or block antioxidant defense in the parasitized RBC. In addition, numerous inhibitors of HSPs are currently developed for cancer therapy and might be tested as anti-malarials. Thus, the joint disruption of the parasite antioxidant enzymes/HSP system would interfere with parasite growth and open new perspectives for anti-malaria therapy.

Methods

Stage-dependent mRNA expression of ten representative P. falciparum antioxidant enzymes and hsp 60/70–2/70–3/75/90 was studied by quantitative real-time RT-PCR in parasites growing in normal RBCs, in RBCs oxidatively-stressed by moderate H2O2 generation and in G6PD-deficient RBCs. Protein expression of antioxidant enzymes was assayed by Western blotting. The pentosephosphate-pathway flux was measured in isolated parasites after Sendai-virus lysis of RBC membrane.

Results

In parasites growing in normal RBCs, mRNA expression of antioxidant enzymes and HSPs displayed co-ordinated stage-dependent modulation, being low at ring, highest at early trophozoite and again very low at schizont stage. Additional exogenous oxidative stress or growth in antioxidant blunted G6PD-deficient RBCs indicated remarkable flexibility of both systems, manifested by enhanced, co-ordinated mRNA expression of antioxidant enzymes and HSPs. Protein expression of antioxidant enzymes was also increased in oxidatively-stressed trophozoites.

Conclusion

Results indicated that mRNA expression of parasite antioxidant enzymes and HSPs was co-ordinated and stage-dependent. Secondly, both systems were redox-responsive and showed remarkably increased and co-ordinated expression in oxidatively-stressed parasites and in parasites growing in antioxidant blunted G6PD-deficient RBCs. Lastly, as important anti-malarials either increase oxidant stress or impair antioxidant defense, results may encourage the inclusion of anti-HSP molecules in anti-malarial combined drugs.