blood-cancer: August 2008

ZusammenfassungHintergrund Die präoperative Eigenblutspende (EBS) ist eine effektive Methode zur Reduzierung des Fremdblutverbrauches. Dennoch findet sie nur vereinzelt Anwendung in der Herzchirurgie. Ein wesentliches Argument gegen die EBS ist die fehlende Zeit zur Durchführung. Ziel der Studie war die Untersuchung der Effektivität der präoperativen EBS bei kardiochirurgischen Routineeingriffen an einem Herzzentrum ohne längere präoperative Wartezeiten.

Transport von Blutgasproben

ZusammenfassungHintergrund Der Transport von Proben zur Blutgasanalyse mit einem Rohrpostsystem in ein Zentrallabor kann im Vergleich zur unmittelbaren Messung vor Ort Kosten und Fehler vermeiden. In dieser Studie sollte eine moderne pneumatische Rohrpostanlage auf Tauglichkeit für diese Aufgabe untersucht werden.

AB0-Blutgruppenexpression in Hornh?uten mit Transplantatversagen

ZusammenfassungHintergrund AB0-Blutgruppenantigene werden in der gesunden Hornhaut lediglich von Epithelzellen exprimiert. Diese Antigene können aber unter entzündlichen Rahmenbedingungen auch im Hornhautstroma oder -endothel gefunden werden. In dieser immunhistochemischen Studie untersuchten wir das Ausmaß der AB0-Blutgruppenantigenexpression in Hornhäuten mit Allotransplantatversagen.

Eigenblutspende in der Dysgnathiechirurgie

ZusammenfassungFragestellung Zur Minimierung des perioperativen Risikos transfusionsassoziierter Komplikationen wird im Rahmen von Dysgnathieeingriffen in der Regel eine präoperative Eigenblutspende durchgeführt. Mit der vorliegenden Studie wurde die Notwendigkeit dieser Maßnahme kritisch hinsichtlich gesundheitlicher, ökonomischer und juristischer Fragestellung untersucht.

Verletzungen der gro?en Gef??e

Zusammenfassung Zwar gilt die Angiographie heute noch als Referenzmethode für die Diagnostik von Verletzungen der Aorta und der großen Gefäße, in zunehmendem Maße wird sie jedoch durch die Mehrschichtspiralcomputertomographie unter Kontrastmittelgabe, dem sog. Angio-CT, ersetzt. Penetrierende Verletzungen der großen Gefäße werden unter den derzeitigen Bedingungen in Westeuropa selten beobachtet. Stumpfe Traumen der großen Gefäße sind Folge von Hochrasanztraumen, die traumatische Aortenruptur kommt häufig mit der Anamnese eines erheblichen Dezelerationstraumas vor. Als etablierter bisheriger Therapiestandard gilt die offene chirurgische Versorgung der Rupturstelle, bei aufgeschobener Dringlichkeit unter Protektion eines Linksbypasses oder als Notfalleingriff nach dem Prinzip des clamp and repair. Als neuere Technik bietet sich heute die endovaskuläre Therapie an, die eine rasche und vor allem schonende Ausschaltung der Rupturstelle gewährleistet. Stumpfe Traumen der abdominellen und pelvinen Gefäße werden in mehr als 90% mit intestinalen Begleitläsionen gesehen. Entsprechend ist für die Gefäßversorgung die mediane Laparatomie als transperitonealer Zugang erste Wahl.

Molekulare Bildgebung der Tumorgef??e

Zusammenfassung In den letzten 3 Dekaden wurden gro?e Anstrengungen unternommen, um die Mechanismen der Tumorvaskularisierung zu verstehen. Erst in den letzten Jahren wurden Erkenntnisse aus diesem Gebiet in die Klinik übertragen. Die Einführung neuer anti-angiogenetischer Substanzen in die Tumortherapie und die Notwendigkeit zur Evaluation ihrer Effizienz macht es klar, dass neue Methoden insbesondere im Bereich der Bildgebung durch CT, MRT und Ultraschall dringend ben?tigt werden. Die herk?mmlichen Kriterien, wie die Bestimmung der Tumorgr??e und des Durchmessers, sind nicht geeignet, die Wirksamkeit dieser Substanzen zu beurteilen. Denn die unter anti-angiogenetischer Therapie ausgeweitete Tumornekrose resultiert beispielsweise nicht in einer nachweisbaren Ver?nderung der Tumorgr??e. Daher sind molekulare Marker, die spezifisch das Endothel der Tumorgef??e erkennen und an Signalstoffe für die Bildgebung gekoppelt sind, notwendig, um das Remodeling der Tumorgef??e darstellen zu k?nnen.

Lebensqualit?t in der Blutstammzelltransplantation

Zusammenfassung Für die Bewertung einer Therapiemaßnahme ist die Lebensqualität (LQ) ein wesentlicher Maßstab. Die Blutstammzelltransplantation (BSZT) stellt für viele schwere onkologische und hämatologische sowie einige Immundefekt- und Stoffwechselerkrankungen die einzige Heilungsmöglichkeit dar. Schwere akute Toxizität und erhebliche Spätfolgen können die LQ nach BSZT deutlich einschränken. Die wenigen vorliegenden Studien zur LQ von Kindern nach BSZT beziehen sich ausschließlich auf die Auswirkungen von körperlichen Einschränkungen auf die körperlichen, psychischen und sozialen Funktionen, die so genannte gesundheitsbezogene LQ (HRQOL), Daten zur individuellen LQ fehlen. Die meisten Untersuchungen beschränken sich zudem auf einen Querschnitt einige Monate nach BSZT oder beschäftigen sich mit der späten Adaptation und Wiedereingliederung. Die LQ während der Phase intensiver Therapie und weitgehender Isolation wurde bisher nur selten untersucht, Daten zur LQ von Patienten, die an der Therapietoxizität oder an einem frühen Rezidiv verstarben, fehlen bisher.

Fremdblutsparende Ma?nahmen bei orthop?dischen Eingriffen

Zusammenfassung Durch Planung, Routine und enge Zusammenarbeit der einzelnen Fachdisziplinen mit multimodalen fremdbluteinsparenden Strategien können heute selbst große orthopädische Operationen nahezu ohne Fremdblutgabe durchgeführt werden. Da die meisten fremdbluteinsparenden Maßnahmen den Blutbedarf nur um 1–2 Einheiten verringern, müssen möglichst viele prä-, intra- und postoperative Maßnahmen kombiniert werden. Hierzu zählen u. a. die Eigenblutspende, die Gabe von Erythropoetin, die akute normovolämische Hämodilution, die intraoperative maschinelle Autotransfusion, blutsparende Operations- und Anästhesietechniken, Pharmaka um den Blutverlust zu verringern und die Herabsetzung des Transfusionstriggers. Die postoperative Rücktransfusion von Drainageblut empfehlen wir nicht. Dieser Artikel beschreibt die verschiedenen Methoden und unterzieht sie einer kritischen Würdigung.

Gesundheits?konomische Aspekte der Anwendung von Blut- und Plasmaprodukten

Zusammenfassung Die Versorgung von Patienten mit Blutkomponenten ist auf die Spendebereitschaft der Bevölkerung und ein gut organisiertes Blutspendewesen angewiesen. Zur Gewährleistung der Blutsicherheit sind hohe finanzielle Aufwendungen erforderlich. Der vorliegende Beitrag beschreibt 2 Anwendungsgebiete von Blut- und Blutprodukten. Zunächst werden Aspekte des Einsatzes von Gerinnungsfaktorkonzentraten bei Hämophiliepatienten (ca. 3000–4000 Patienten sind regelmäßig behandlungsbedürftig) diskutiert. Die geschätzten jährlichen Ausgaben der Kostenträger für Gerinnungsfaktorkonzentrate liegen in Deutschland bei rund 450 Mio. Euro, die mittleren Kosten pro Patient und Jahr schwanken, abhängig vom Behandlungszentrum, zwischen 40.903 Euro und 117.597 Euro. Die Behandlungskosten für eine Immuntoleranztherapie (ITT) bei Patienten mit Hemmkörpern, einer schwerwiegenden Komplikation der Therapie mit Gerinnungsfaktoren, werden z. B. für Kinder je nach Therapiedauer und Schweregrad auf rund 70.300 Euro bis 3.800.000 Euro geschätzt. Im zweiten Teil des Beitrages wird der Status quo der ökonomischen Evaluation für die Anwendung zellulärer Blutprodukte skizziert, und es werden ausgewählte Ergebnisse einer deutschen Querschnittserhebung zur Anwendung von Erythrozytenkonzentraten (EK) bei elektiven orthopädischen Operationen dargestellt. Diese Hämotherapiestudie zeigte, dass die Transfusionsraten innerhalb der teilnehmenden Zentren erheblich variierten [Transfusionsraten beim Eingriff elektiver Hüftgelenksersatz (THR): 17–94%]. Dies galt ebenso für den durchschnittlichen Blutverlust bei einer THR (Median [ml] Blutverlust: Zentrum mit niedrigstem/Zentrum mit höchstem Blutverlust: 883 ml/2975 ml). Die Akzeptanz niedriger intraoperativer Hämoglobinwerte war in den Kliniken unterschiedlich hoch. Aus diesen Unterschieden im Transfusionsverhalten der einzelnen Zentren wird deutlich, dass breite Qualitätssicherungsmaßnahmen (z. B. Benchmarkanalysen) erforderlich sind, um das vorhandene Einsparpotenzial für Erythrozytenkonzentrate von bis zu 350.000 Einheiten allein bei der Indikation Hüftgelenksersatz vollständig nutzen zu können. Transparenz hinsichtlich der Versorgungsprozesse ist eine grundlegende Voraussetzung für die ökonomische Beurteilung und optimale Ressourcenallokation

Infektionen bei Blutspendern

Zusammenfassung Die Verhinderung von transfusionsassoziierten Infektionenstellt eine der größten Herausforderungen derTransfusionsmedizin dar. Die Kombination von konsequenterSpenderauswahl und strikter Testung jeder Blutspende aufInfektionserreger mit validierten Testverfahren konnte dasÜbertragungsrisiko deutlich verringern. Durch die systematischeAuswertung von infektionsepidemiologischen Daten können neueRisikogruppen identifiziert, neue Infektionen und unbekannteInfektionswege erkannt werden. Die engmaschige Surveillance vonBlutspendern im Hinblick auf HIV-, Hepatitis-C-Virus-,Hepatitis- B-Virus- und Syphilisinfektionen, die gemäß § 22Transfusionsgesetz vom Robert Koch-Institut (RKI) durchgeführtwird, trägt zur Aufrechterhaltung des sehr hohenSicherheitsstandards bei Transfusionen in Deutschland bei. Diehierbei gewonnenen Daten helfen, Kriterien für dieSpenderselektion anzupassen und die Notwendigkeit vonetablierten und neuen Testverfahren zu prüfen. Darüber hinausermöglicht die Surveillance eine Abschätzung des verbleibendenInfektionsrisikos bei Bluttransfusionen. Über die bekanntentransfusionsrelevanten Infektionen hinaus müssen zunehmend auchandere Infektionskrankheiten, beispielsweiseWest-Nil-Virusinfektionen oder die variante Creutzfeldt-Jakob-Erkrankung (vCJK), im Hinblick auf ihreTransfusionsrelevanz infektionsepidemiologisch bewertetwerden.

Obere Einflussstauung

Zusammenfassung Die obere Einflussstauung entsteht durch Kompression oder Obstruktion der V. cava superior. Bei der Mehrzahl der Patienten sind dafür maligne Tumoren verantwortlich, in erster Linie Bronchialkarzinome oder Non-Hodgkin-Lymphome, bei den seltenen benignen Ursachen überwiegt die Cava-Thrombose. Die Symptomatik kann sehr unterschiedlich ausgeprägt sein. Ein Großteil der Patienten fällt durch eine Halsvenenstauung oder eine Schwellung des Gesichtes bzw. der oberen Extremität auf. Seltener sind schwerwiegende zentralnervöse Beschwerden. Das Ausmaß der Beschwerden ist abhängig vom Grad der Abflussbehinderung und der Dynamik des zugrunde liegenden Prozesses. Im Zentrum der Diagnostik stehen die Computertomographie des Thorax und die histologische Diagnosesicherung. Die Therapie ist abhängig von der Grunderkrankung. Bei malignen Erkrankungen ist eine Radio- und/oder Chemotherapie indiziert. Vor jeder Therapieeinleitung ist eine definitive Diagnosesicherung wünschenswert. Nur bei perakuter Symptomatik mit respiratorischer Insuffizienz oder Hirnödem ist eine Therapie ohne vorherige Diagnosestellung gerechtfertigt. Zur akuten Beschwerdelinderung kann dann durch Implantation eines expandierenden Stents in die V. cava superior Zeit gewonnen werden.

überwindung der Blut-Hirn-Schranke

Zusammenfassung Die Blut-Hirn-Schranke hemmt die Penetration von Zytostatika in das Hirnparenchym. Aufgrund des Fehlens dieser Schranke sind Hirnmetastasen jedoch grunds?tzlich einer systemischen Chemotherapie zug?nglich. Lediglich kleinere Tumorzellabsiedelungen mit wahrscheinlich intakter Blut-Hirn-Schranke sind als relativ geschützt anzusehen. Zus?tzlich ist die Behandlung von Hirnmetastasen durch die Chemoresistenz des Tumors und einen h?ufig schlechten Allgemeinzustand der betroffenen Patienten limitiert. Neue Zytostatika sind durch ihre biochemischen Eigenschaften oft besser in der Lage, in das Hirngewebe vorzudringen. „Targeted drugs“, wie beispielsweise Tyrosinkinaseinhibitoren, besitzen zudem selektivere Wirkmechanismen, potenziell eine synergistische Aktivit?t in Kombination mit Chemotherapie und h?ufig einen besseren therapeutischen Index. Ihre Wirksamkeit wird derzeit in klinischen Studien überprüft.

Risikomanagement bei Typ-2-Diabetes durch Blutzuckerselbstkontrolle

Zusammenfassung Der medizinische Nutzen einer Blutzuckerselbstkontrolle bei Typ-2-Diabetes wird seit Jahren sehr intensiv diskutiert. Insbesondere bei Personen mit Typ-2-Diabetes, die keine Insulintherapie erhalten, wird der therapeutische Nutzen in Frage gestellt. Während man in den vergangenen Jahren davon ausging, den Typ-2-Diabetes durch eine Intensivierung der pharmakologischen Maßnahmen therapieren zu können, erkennt man aktuell, dass die nichtmedikamentösen Maßnahmen im Therapiekonzept eine größere Rolle spielen müssen. Da der Typ-2-Diabetes in der Regel keine Symptome verursacht, spielt die Kontrolle der Blutglukose im Zusammenhang mit Lebensstiländerungen eine ganz wichtige Rolle bei der Stärkung der Eigenverantwortung des Betroffenen. Diese Überlegungen werden durch Metaanalysen wie auch ein Review der Cochrane Library bestätigt, die einen positiven Einfluss der Blutzuckerselbstkontrolle auf den HbA1c nachweisen. Die kürzlich publizierte ROSSO-Studie zeigt sogar eine Assoziation von Blutzuckerselbstkontrolle und reduzierter Mortalität bzw. Morbidität. Die im Jahr 2005 veröffentlichten globalen Konsensusleitlinien der Internationale Diabetes Federation (IDF) fordern daher, dass die Selbstmessung der Blutglukose allen Menschen mit neu diagnostiziertem Typ-2-Diabetes als integraler Teil des Selbstmanagements zu Verfügung gestellt wird.

Simulation des Blutflusses in der abdominellen Aorta

Zusammenfassung Das Ziel der numerischen Simulation des Blutflusses in der Aorta ist, die Mechanik der Entstehung von Aortenaneurysmen im Hinblick auf das Rupturrisiko zu untersuchen und die Wirkungen interventioneller Ma?nahmen zu beschreiben. Die Grundlage der numerischen Simulation sind virtuelle Modelle von Gef??en und die physikalischen Eigenschaften der Gef??bestandteile, des Blutes und der Str?mung. Basierend auf diesen Angaben werden mit Hilfe numerischer Methoden die str?mungsmechanischen Probleme des Blutflusses n?herungsweise gel?st. Die Ergebnisse k?nnen dann quantitativ und qualitativ dargestellt werden.

Perioperative Bluttransfusion

Zusammenfassung Chirurgisch und traumatisch bedingte Blutverluste sind die häufigsten Ursachen von allogenen Bluttransfusionen, welche nach wie vor mit beträchtlichen Risiken verbunden sind. Nach Korrektur der Hypovolämie ist der Anästhesist häufig mit einer normovolämischen Anämie konfrontiert. Die klinische Relevanz dieses isolierten Hämoglobinabfalls besteht darin, dass die globale und/oder regionale Sauerstoffversorgung über eine kritische Schwelle hinaus beeinträchtigt sein kann, wonach sich eine Gewebshypoxie einstellt. Diese kritische Schwelle ist von Patient zu Patient verschieden und abhängig von dessen Kapazität, den Abfall des Sauerstoffgehaltes zu kompensieren. Aus diesem Grunde sollten primär physiologische Transfusionskriterien angewandt werden und nicht rigide nummerische Transfusionskriterien wie die Hämoglobinkonzentration, welche die individuelle Reserve eines Patienten weitgehend außer Acht lassen.

Neonatale Stammzellen

Zusammenfassung Angesichts der großen gesellschaftlichen Relevanz und derethischen Akzeptanz der neonatalen Stammzellforschung widmetsich dieser Aufsatz grundlegenden rechtlichen Fragen, die imUmgang mit Nabelschnurblut auftreten. Es wird die ursprünglicham Nabelschnurblut bestehende Rechtslage in der Weise geklärt,dass dem Kind Eigentum und Persönlichkeitsrechte amNabelschnurblut zustehen. Da die Neugeborenen alsgeschäftsunfähige Personen keine Rechtsgeschäfte vornehmenkönnen, werden ihre persönlichkeits- und vermögensrechtlichenInteressen von ihren Eltern als ihren gesetzlichen Vertreternwahrgenommen und geschützt. Die Eltern können in Ausübung ihreselterlichen Sorgerechts über die Verwendung desNabelschnurblutes gemeinsam entscheiden und sind dabei nur durchdas Kindeswohl gebunden. Deshalb bedürfen die Spende desNabelschnurblutes, die Erhebung persönlicher Daten und dieDurchführung verschiedener Tests der Einwilligung durch dieEltern. Aus dem Arzneimittelrecht folgen die Pflichten für dieEntbindungskliniken und die Nabelschnurblutbanken, eineHerstellungserlaubnis für die jeweils ausgeführten Gewinnungs-und Verarbeitungsschritte einzuholen.Zusätzlich müssendiejenigen Blutbanken, die ungerichtete Spenden vorrätig halten,eine Zulassung gem. § 21 AMG besitzen, da derartige Spenden dieMerkmale eines Fertigarzneimittels erfüllen.

Role of the Brain Renin-angiotensin System in Blood Pressure Regulation

Varoni, M.V., Palomba, D., Demontis, M.P., Gianorso, S., Pais, G.L. and Anania, V., 2007. Role of the brain renin-angiotensin system in blood pressure regulation. Veterinary Research Communications, 31(Suppl. 1), 343–346

Gliadin Peptides Activate Blood Monocytes from Patients with Celiac Disease

To elucidate the role of innate immune responses in celiac disease, we investigated the effect of gliadin on blood monocytes from patients with celiac disease. Gliadin induced substantial TNF-α and IL-8 production by monocytes from patients with active celiac disease, lower levels by monocytes from patients with inactive celiac disease, and even lower levels by monocytes from healthy donors. In healthy donor monocytes gliadin induced IL-8 from monocytes expressing HLA-DQ2 and increased monocyte expression of the costimulatory molecules CD80 and CD86, the dendritic cell marker CD83, and the activation marker CD40. Gliadin also increased DNA binding activity of NF-κB p50 and p65 subunits in monocytes from celiac patients, and NF-κB inhibitors reduced both DNA binding activity and cytokine production. Thus, gliadin activation of HLA-DQ2+ monocytes leading to chemokine and proinflammatory cytokine production may contribute to the host innate immune response in celiac disease.

Effect of 30% Oxygen Administration on Verbal Cognitive Performance, Blood Oxygen Saturation and Heart Rate

This study investigated the effect of 30% oxygen administration on verbal cognitive performance, blood oxygen saturation, and heart rate. Five male (24.6(±0.9) years) and five female (22.2(±1.9) years) college students were selected as the subjects for this study. Two psychological tests were developed to measure the performance level of verbal cognition. The experiment consisted of two runs: one was a verbal cognition task, with normal air (21% oxygen) administered and the other was with hyperoxic air (30% oxygen) administered. The experimental sequence in each run consisted of Rest 1 (1 min), Control (1 min), Task (4 min), and Rest 2 (4 min). Blood oxygen saturation and heart rate were measured throughout the four phases. The results of the verbal behavioural analysis reveal that accuracy rates were enhanced with 30% oxygen administration compared to 21% oxygen. When 30% oxygen was supplied, blood oxygen saturation was increased significantly compared to that with 21% oxygen administration, whereas heart rate showed no significant difference. Significant positive correlations were found between changes in oxygen saturation and cognitive performance. This result supports the hypothesis that 30% oxygen administration would lead to increases in verbal cognitive performance.

Near-Wall Deposition Probability of Blood Elements as A New Hemodynamic Wall Parameter

The present study was performed to investigate deposition probability of blood particles on the vessel walls. To track dynamics of movement and adhesion of blood particles in the near wall region, two models such as the particle rolling model (PR-model) and the near wall force model (NWF-model) were employed in the present study. Simulations of the present models for the pre-activated platelets in the stagnated point flow chamber and for the pre-activated monocytes in the stenotic perfusion tube resulted in significant correlations with the experimental data. The proposed near wall deposition probability (NWDP) index exhibited good fits with the experimental data of the stagnation point flow chamber for the platelet. As for the monocyte, the NWDP index exhibited the best fit with the experimental data of the stenotic tube. The new hemodynamic index, NWDP, is different from the wall shear stress (WSS)-based hemodynamic parameters, such as MWSS (Mean Wall Shear Stress), AWSS (Amplitude of Wall Shear Stress), and OSI (Oscillatory Shear Index) in that it locates regions of both the high and low WSS. The proposed NWDP index needs to be tested and compared in real geometries for its effectiveness in locating regions of lesion-prone sites.

High prevalence of hepatitis B, C and delta virus infections among blood donors in Mongolia

Summary. Serum samples obtained from 289 first-time and 114 repeat donors at the Blood Center of Mongolia (MBC) were tested for serological and molecular markers of hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis delta virus (HDV) infections. Among the 403 blood donors, 33 (8.2%), 21 (5.2%), and 27 (6.7%) tested positive for hepatitis B surface antigen (HBsAg) and/or HBV DNA, HCV RNA, and HDV RNA, respectively. Collectively, 55 donors were viremic for one or more of these viruses, and included 54 first-time donors (18.7%) and 1 repeat donor (0.9%) (P < 0.0001). One discrepant case with HBsAg detectable only at MBC was negative for HBsAg, HBV DNA and anti-HBc in this study. Four donors who were HCV-viremic in this study were negative for anti-HCV by the MBC method. Further efforts to increase the sensitivity and specificity of the currently-used tests are urgently required in Mongolia. Three donors who were positive for anti-HBc and anti-HDV but negative for HBsAg, had both HBV DNA and HDV RNA. This suggests that introduction of a new anti-HDV serological test is useful for not only HDV screening but also HBV screening of anti-HBc-positive, HBsAg negative donors, considering a possibility of viral interference by coexisting HDV.

Binding activity of norovirus and sapovirus to histo-blood group antigens

Summary. Noroviruses (NoVs) and sapoviruses (SaVs) are causative agents of human gastroenteritis. There is increasing evidence that certain human NoV strains bind to histo-blood group antigens (HBGAs). We found that several NoV virus-like particles (VLPs) showed binding activity to HBGAs, while neither SaV genogroup I (GI) VLP nor SaV GV VLP showed such activity.

Saturday, August 16, 2008

Blood–brain barrier dysfunction and recovery

Summary. In this paper we discuss the importance of the blood–brain barrier (BBB) as an interface between blood and brain. Many (brain) diseases change the functionality and integrity of the BBB. Mostly this results in increased BBB permeability. Therefore we have studied de various signal transduction routes that are influenced by inflammatory stimuli. The radical scavenger N-acetylcysteine was able to protect the BBB against inflammatory stimuli. Similar results were found following application of glucocorticoids. In addition, it was observed that glucocorticoids and interferon-α,β increased the tightness of the in vitro BBB and when given together a potentiating effect was seen.

Molecular mechanisms involved in T cell migration across the blood–brain barrier

Summary. In the healthy individuum lymphocyte traffic into the central nervous system (CNS) is very low and tightly controlled by the highly specialized blood–brain barrier (BBB). In contrast, under inflammatory conditions of the CNS such as in multiple sclerosis or in its animal model experimental autoimmune encephalomyelitis (EAE) circulating lymphocytes and monocytes/macrophages readily cross the BBB and gain access to the CNS leading to edema, inflammation and demyelination. Interaction of circulating leukocytes with the endothelium of the blood–spinal cord and blood–brain barrier therefore is a critical step in the pathogenesis of inflammatory diseases of the CNS. Leukocyte/endothelial interactions are mediated by adhesion molecules and chemokines and their respective chemokine receptors. We have developed a novel spinal cord window preparation, which enables us to directly visualize CNS white matter microcirculation by intravital fluorescence videomicroscopy. Applying this technique of intravital fluorescence videomicroscopy we could provide direct in vivo evidence that encephalitogenic T cell blasts interact with the spinal cord white matter microvasculature without rolling and that α4-integrin mediates the G-protein independent capture and subsequently the G-protein dependent adhesion strengthening of T cell blasts to microvascular VCAM-1. LFA-1 was found to neither mediate the G-protein independent capture nor the G- protein dependent initial adhesion strengthening of encephalitogenic T cell blasts within spinal cord microvessel, but was rather involved in T cell extravasation across the vascular wall into the spinal cord parenchyme. Our observation that G-protein mediated signalling is required to promote adhesion strengthening of encephalitogenic T cells on BBB endothelium in vivo suggested the involvement of chemokines in this process. We found functional expression of the lymphoid chemokines CCL19/ELC and CCL21/SLC in CNS venules surrounded by inflammatory cells in brain and spinal cord sections of mice afflicted with EAE suggesting that the lymphoid chemokines CCL19 and CCL21 besides regulating lymphocyte homing to secondary lymphoid tissue might be involved in T lymphocyte migration into the immuneprivileged CNS during immunosurveillance and chronic inflammation. Here, I summarize our current knowledge on the sequence of traffic signals involved in T lymphocyte recruitment across the healthy and inflamed blood–brain and blood–spinal cord barrier based on our in vitro and in vivo investigations.

Hoe 140 abolishes the blood pressure lowering effect of taurine in high fructose-fed rats

Summary. High fructose feeding induces moderate increases in blood pressure of normal rats, associated with hyperinsulinemia, insulin resistance and impaired glucose tolerance. Increased vascular resistance, and sodium retention have been proposed to contribute to the blood pressure elevation in this model. Taurine, a sulphur-containing amino acid has been reported to have antihypertensive and antinatriuretic actions. In addition, taurine is shown to increase the excretion of nitrite and kinin availability and hence would be expected to improve the vascular tone. In the present study, the involvement of kinins in the blood pressure lowering effect of taurine was investigated by coadministration of Hoe 140, a kinin B2 receptor antagonist along with taurine. The effects of taurine on plasma and urinary concentrations of sodium and tissue kallikrein activity were studied in high fructose-fed rats. Fructose-fed rats had elevated blood pressure and decreased levels of sodium in urine. Treatment with 2% taurine in drinking water prevented the blood pressure elevation and coadministration of Hoe 140 abolished this effect of taurine in high fructose-fed rats. The findings confirm the antinatriuretic action of taurine and also suggest a role for the kinins in the mechanism of taurine action in diet-induced hypertension.

Replication of feline coronaviruses in peripheral blood monocytes

Summary. Feline infectious peritonitis virus (FIPV) (Coronaviridae) causes the most lethal viral infection in cats: FIP. The related feline enteric coronavirus (FECV) causes mild enteritis. Why these feline coronaviruses manifest so differently in vivo is not known. In this study, infection kinetics (titres and antigen expression) of FIPV 79-1146, and FECV 79-1683, were determined in peripheral blood monocytes from 3 donor cats and compared to those in Crandell feline kidney (CrFK) cells. The infection kinetics in monocytes were host dependent. Monocytes from 1 cat were resistant to both FIPV- and FECV-infection. Monocytes from the other 2 cats could initially be infected by both FIPV and FECV but FIPV infection was sustained in monocytes of only one cat. FECV-infection was never sustained and viral production was up to 100 times lower than in FIPV-infected monocytes. In CrFK cells, FIPV and FECV infection kinetics did not differ. In monocytes of a larger cat population (n = 19) the 3 infection patterns were also found. Considering all 22 investigated cats, 3/22 were not susceptible for FIPV and FECV. The rest could be infected with FECV and FIPV but 10/22 cats had monocytes that only sustained FIPV infection and 9/22 sustained neither FIPV nor FECV infection.

Inverse relationship between central serotonergic neurotransmission and blood pressure in alcohol-dependent male subjects

Summary. Data has accumulated indicating an inverse relation between central serotonergic (5-HT) neurotransmission and blood pressure in hypertensive rats and in healthy individuals. The present study aimed to elucidate whether an inverse relation exists between systolic (SBP) and diastolic (DBP) blood pressure levels and central 5-HT neurotransmission also in a group of alcohol-dependent individuals. Central 5-HT neurotransmission was assessed by using the maximum prolactin (PRL) responses to the 5-HT probe DL-fenfluramine (DL-FEN; 60 mg po) in 17 alcohol-dependent male subjects investigated during a period of on-going alcohol intake. BP was measured immediately before all time points for blood sampling, and readings before DL-FEN administration were used as the subjects resting BP. Results showed that there were inverse correlations between the maximum PRL responses to DL-FEN and the SBP levels (r = −0.57, p < 0.002) and with the DBP levels (r = −0.52, p < 0.05), respectively. The present study suggests the existence of an association between central 5-HT neurotransmission and blood pressure regulation also in alcohol-dependent individuals.

Two familial cases of high blood galactose of unknown aetiology

Summary We report two male siblings presenting as newborns with increased blood galactose, urinary excretion of galactitol, and normal galactose 1-phosphate on a breast milk diet. A lactose-free diet led to normalization of all metabolites, while reintroduction of galactose in the diet resulted in an accumulation of metabolites. Potential causes of galactosaemia include: (1) activities of three enzymes of galactose metabolism: galactokinase (GALK), galactose-1-phosphate uridyltransferase (GALT), and uridine diphosphate galactose 4'-epimerase (GALE), (2) portosystemic shunting, (3) Fanconi-Bickel syndrome, (4) tyrosinaemia. Each was excluded with appropriate tests. These two familial cases may represent a novel autosomal or X-linked recessive disorder of galactose metabolism, possibly due to a novel defect in the transport of galactose across the plasma membrane.

The theory–practice problem of blood pressure assessment

Summary The theoretical basis for assessment of blood pressure described in the guidelines of the ISH-ESC and in JNC 7 ignores the variability of blood pressure and is therefore not applicable in general practice. Although the guidelines do not meet the daily requirements, they are not questioned by the physician and are therefore confusing both physicians and millions of patients taking self-recordings. The unsolved problems are: The confidence interval for the single readings and the mean values are ignored. For this reason, the assignment of the patient to the different categories of hypertension is variable and dependent on pure chance. The effects of therapy cannot be detected in a reliable way. Judging the quality of self-recorded data, the blood pressure variability is interpreted as an error of measurement. The problem can be avoided if, instead of single values, mean values out of a sufficient number of measurements and their confidence intervals are assessed.

CD4+CD25high regulatory cells in peripheral blood of NSCLC patients

Summary The proportion and changes of CD4+CD25high regulatory T cells (Trs) in peripheral blood of non-small cell lung cancer (NSCLC) patients were analyzed and their clinical significance explored. The peripheral blood was collected from 61 patients with NSCLC and 15 healthy controls. By using monoclonal antibodies, the blood samples were evaluated with the flow cytometry for lymphocyte subsets (CD3+, CD4+ and CD8+) and CD4+CD25high Tr cells. The results showed that the proportion of CD4+CD25high Tr cells in NSCLC group was significantly higher than in control group [(4.36±2.07) % vs (2.04±1.03) %, P<0.01]. The proportion of CD4+CD25high Tr cells in late stage was higher than that in early stage [stages: + II (2.26±0.6) %; stage III (3.28±1.38) %; stage IV (6.06±4.08) %] (P<0.05). Kaplan-Meier survival analysis revealed that the prognosis of the patients who had higher proportion of CD4+CD25high Tr cells in peripheral blood was worse (P=0.0026). In conclusion, the relative increase in CD4+CD25high Tr cells in peripheral blood may be related to immunosuppression and tumor progression in patients with NSCLC. This finding suggests that CD4+CD25+high Tr cells in peripheral blood of NSCLC may be positive for prognosis analysis. The use of depletion of the CD4+CD25high Tr cell therapy to treat NSCLC patients may be an effective strategy.

Osmotic blood–brain barrier disruption chemotherapy for diffuse pontine gliomas

Summary The prognosis for patients with diffuse pontine gliomas (DPG) remains poor. New aggressive innovative treatments are necessary to treat this disease. From 1984 to 1998, eight patients (4M/4F), median age 11 years, with DPG were treated with monthly osmotic blood–brain barrier disruption (BBBD) chemotherapy using intraarterial carboplatin or methotrexate and intravenous cytoxan and etoposide. Patients presented for a median duration of 6 weeks with increased intracranial pressure, long tract signs, diplopia, ataxia, and nausea/vomiting. DPG was demonstrated on magnetic resonance (MR) imaging in seven patients and on CT in one. Two patients had biopsies that showed an astrocytoma and an anaplastic astrocytoma. Three tumors enhanced on MR imaging after contrast administration. Three patients had radiation therapy before BBBD chemotherapy and four afterwards. Two patients had chemotherapy (tamoxifen, topotecan) before BBBD chemotherapy and two afterwards. In general, patients were evaluated with MR imaging every 3 months to monitor for a response to treatment. The median number of chemotherapy cycles that were administered by BBBD was 10, mean 10. Three patients also received one, two, or three cycles of intraarterial chemotherapy without BBBD. One patient that was started on carboplatin was converted to methotrexate, and five that were started on the methotrexate protocol were later converted over to carboplatin. One patient received monthly methotrexate followed by 14 days of procarbazine and one patient started on methotrexate was switched to navelbine. MR imaging demonstrated two partial responses, five patients with stable disease, and one with disease progression. The median time to tumor progression was 15 months with the range from <1 to 40 months. The median survival from the time of diagnosis was 27 months, ranging from 7 to 80 months. The median survival time from the first BBBD or intraarterial treatment was 16.5 months, ranging from 5 to 69 months. One patient was lost to follow-up with an unknown date of death. Although the sample size is small, the TTP and survival times are longer than those previously reported in other DPG series. In addition, the ability to demonstrate stable disease or partial responses in DPG on MR imaging argues for the therapeutic benefit of BBBD chemotherapy. The enhanced delivery of chemotherapy afforded by osmotic BBBD supports the further examination of this treatment modality for patients with DPG.

The aetiology of neurological complications of organic acidaemias—A role for the blood–brain barrier

Summary The blood–brain barrier (BBB) metabolically isolates the central nervous system (CNS) from the circulation and protects it against fluctuations of hydrophilic nutrients in plasma and from intoxication. Recent studies have shown that dicarboxylic acids (DCAs) are transported across the blood–brain barrier at very low rates. In organic acidaemias, neurological complications are common. We hypothesize that, as a result of the very limited efflux, in certain organic acidaemias there is pathological accumulation of DCAs (e.g. glutarate, 3-hydroxyglutarate, D-2- and L-2-hydroxyglutarate, methylmalonate) in the brain secondary to the metabolic block. At high concentrations some of these compounds may become neurotoxic. Treatment should be aimed at preventing the accumulation of these compounds using our understanding of the properties of the BBB.

Dopamine and N-methyl-D-aspartate receptor expression in peripheral blood of patients undergoing alcohol withdrawal

Summary The aim of the present pilot study was to explore whether a change in cerebral receptors can be demonstrated in human peripheral blood lymphocytes during alcohol withdrawal. Dopamine (D1 and D2) and NMDA (1 and 2B) receptor expressions of 14 male patients suffering from alcohol-dependency were assessed through quantitative RT-PCR. A significant difference in D1 receptor expression (T = 2.361; p = 0.035) in terms of up-regulation could be shown, though there were no significant changes concerning D2, NMDA1 or NMDA2B receptor expression.

Importance of blood cellular genomic profile in coronary heart disease

Summary Since receptor/transcription factor family especially peroxisome proliferator-activated receptors PPARs (α,␣γ) and liver X receptor α (LXRα) have been recognized to play crucial role in both lipid metabolism and inflammation, the present study was addressed to explore the interrelationship between blood cellular genomic expression profile, serum lipid levels and severity of coronary heart disease (CHD) in human subjects. Based upon the demographic and laboratory data, the human subjects were divided into 4 groups. Genomic expression profile in the subjects belonging to these groups was determined by measuring the transcriptional expression of genes coding for PPARs (α, γ), CD36, LXRα and low density lipoprotein receptor (LDLR) in their blood mononuclear cells. This genomic expression profile was correlated with serum lipid profile as well as with the severity of CHD (revealed by coronary angiography coupled with modified Gensini score) using standard statistical analytical methods. Further in vitro and in vivo effect of statins on such genomic profile was also explored. Although genes coding for PPARs (α, γ), CD36, LDLR showed correlation with the severity of coronary atherosclerosis , blood cellular LXRα genomic profile showed conspicuous negative correlation with the severity of coronary atherosclerosis in subjects with or without hypercholesterolemia. This view was further confirmed in experiments directed to understand the effect of statins on the cellular genomic profile of PPARs (α, γ) and LXRα. Based on these reported findings, we propose that blood cellular LXRα genomic profile has a protective effect against the development of CHD and hence may be of importance in devising synthetic therapeutic drugs for CHD in future.

Disturbances of electrolytes and blood chemistry in acute alcohol intoxication

Summary Prevalence of electrolyte disturbances and biochemical changes were determined in patients admitted to the emergency room of the Department of Internal Medicine in Innsbruck, Austria during a six-month period. The value of biochemical parameters for the detection of chronic alcohol abuse was also investigated. The most frequent electrolyte disturbances found were hypernatremia (41%), hyperchloremia (21%), hypermagnesemia (17%) and hypocalcemia (15%), whereas hypokalemia and hypophosphatemia were observed quite rarely (5% and 3.4%, respectively). The most frequent biochemical changes observed were consistent with signs of cellular toxicity i.e. increased liver enzymes (elevated gamma-glutamyltransferase (GGT), aspartate aminotransferase, alanine aminotransferase and lactic dehydrogenase) as well as signs of pancreatitis (elevated serum lipase and amylase) and muscle damage (elevated creatine kinase). The most frequent changes in blood counts were leucocytosis (23%), thrombocytopenia (14%), and anemia (12%). C-reactive protein showed only minimal elevation. Male sex and level of blood alcohol were detected as major risk factors for the diagnosis of chronic alcohol abuse in the patient sample investigated. When testing the value of routinely measured parameters for predicting the presence of chronic alcohol abuse, GGT and mean corpuscular volume of red blood cells (MCV) appeared to be of equal value. A combination of elevated blood alcohol with an increase in either of these markers may be interpreted as high risk for chronic alcohol abuse in this particular group of patients.

Dopamine transporter immunoreactivity in peripheral blood lymphocytes discriminates Parkinson’s disease from essential tremor

Summary Peripheral blood lymphocytes (PBL) provide a model to study the changes of neurotransmitter-receptor systems in neurodegenerative disorders, including Parkinson’s disease (PD). In this study, densitometric analysis was applied to measure dopamine transporter (DAT) immunoreactivity in PBL from dopaminergic drug-free patients suffering PD or essential tremor (ET) with respect to healthy subjects. The results showed a significant reduction of DAT immunoreactivity in PBL in PD but not in ET. These finding suggests that DAT immunoreactivity in PBL may discriminate between PD and ET in the early clinical stages.

Identification and characterization of peptide mimics of blood group A antigen

Summary In order to investigate peptide mimics of carbohydrate blood group A antigen, a phage display 12-mer peptide library was screened with a monoclonal antibody against blood group A antigen, NaM87-1F6. The antibody-binding properties of the selected phage peptides were evaluated by phage ELISA and phage capture assay. The peptides were co-expressed as glutathione S-transferase (GST) fusion proteins. RBC agglutination inhibition assay was performed to assess the natural blood group A antigen-mimicking ability of the fusion proteins. The results showed that seven phage clones selected bound to NaM87-1F6 specifically, among which, 6 clones bore the same peptide sequence, EYWYCGMNRTGC and another harbored a different one QIWYERTLPFTF. The two peptides were successfully expressed at the N terminal of GST protein. Both of the fusion proteins inhibited the RBC agglutination mediated by anti-A serum in a concentration-dependent manner. These results suggested that the fusion proteins based on the selected peptides could mimic the blood group A antigen and might be used as anti-A antibody-adsorbing materials when immunoabsorption was applied in ABO incompatible transplantation.

Globoid cell leukodystrophy (Krabbe disease): Normal umbilical cord blood galactocerebrosidase activity and polymorphic mutations

Summary Globoid cell leukodystrophy is an inherited metabolic disorder of the central nervous system caused by deficiency of the lysosomal enzyme galactocerebrosidase. Haematopoietic stem cell transplantation is the only available effective treatment. The engraftment from normal donors provides competent cells able to correct the metabolic defect. Umbilical cord blood cells have proved to significantly decrease complications and improve engraftment rate compared to adult marrow cells in haematopoietic stem cell transplantation. Umbilical cord blood cells must be of sufficient activity to provide central nervous system recovery after engraftment is obtained. Galactocerebrosidase activity is known to be affected by two polymorphic alleles found at nucleotides 502 and 1637 of the cDNA for this gene. This enzyme activity and the polymorphic alleles noted above were analysed in 83 random samples of umbilical cord blood. The activity, assayed with the fluorogenic substrate 6-hexadecanoylamino-4-methylumbelliferyl-β-galactopyranoside, in those with neither polymorphic allele was 4.6 ± 1.7 units (nmol/h per mg protein). This optimal choice of cord blood was found in only 24% of specimens. Homozygotes for 1637T > C with activity of only 1.5 ± 0.4 units represented 16% of the samples. Those heterozygous for 1637T > C with slightly better activity (2.3 ± 0.7 units) represented 52% of the samples. Choice of umbilical cord blood for haematopoietic stem cell transplantation, therefore, requires consideration not only of cell quantity and HLA compatibility but also selection for normal alleles to obtain maximal enzymatic activity for central nervous system correction.

Skin plugs in phlebotomy puncture for blood donation

Summary Contamination at the site of the donors skin may occur despite proper disinfection, because pathogens in deeper regions (such as pores) may not be eliminated by skin disinfection. It is suspected that the cannula detaches fragments of tissue when it penetrates the skin; the tissue fragments may reach blood products and release pathogens there. In the present study we punctured piglet skin with cannulas commonly used for blood donation and performed histological as well as cytological investigations of the lavage fluid in the cannula to identify superficial skin cells and skin plugs. Histological specimens of the pierced skin showed frayed puncture sites with loosely attached tissue fragments. In the lavage fluid of the cannula, a collection of epidermal cells was found in one of 150 punctures. Our results confirm that the phlebotomy cannula may cause superficial tissue fragments to be punched out of the donors skin during blood donation. This fact should be taken into account when devising methods to reduce bacterial contamination in blood products.

Cerebral blood oxygenation changes induced by bypass blood flow in moyamoya disease and non-moyamoya cerebral ischaemic disease

Summary Background. Superficial temporal artery–middle cerebral artery (STA–MCA) anastomosis has been used to prevent stroke in patients with moyamoya disease (MD) and non-moyamoya ischaemic disease (non-MD). However, little is yet known regarding the difference between these groups of patients in the extent to which the bypass contributes to maintaining adequate cerebral blood oxygenation (CBO), or the temporal changes after surgery. In the present study, we evaluated the CBO changes induced by bypass blood flow in patients with MD and non-MD during the peri-operative periods employing optical spectroscopy. Methods. We investigated 13 patients who underwent STA–MCA anastomosis, including 5 MD and 8 non-MD patients. We evaluated the effects of STA blood flow on the CBO in the MCA territory on the anastomosis side, employing visual light spectroscopy during surgery and near infrared spectroscopy (NIRS) at one week after surgery.

Cervical spinal cord stimulation increases cerebral cortical blood flow in an experimental cerebral vasospasm model

Summary Background. Cerebral microcirculatory changes during cerebral vasospasm after aneurysmal subarachnoid haemorrhage (SAH) are still controversial and uncertain. The aim of our study is to demonstrate that spinal cord stimulation (SCS) augments cerebral cortical microcirculatory blood flow in an experimental cerebral vasospasm model by using Laser Doppler Flowmetry (LDF).Method. The experiments were carried out on 24 New Zealand rabbits. Three experimental groups were designed. In group 1, Cerebral cortical blood flow (CCoBF) was evaluated by LDF in 8 rabbits. In group 2, Intracisternal saline injection and cervical epidural electrode placement without SCS were performed in 8 animals before LDF. In group 3, LDF was performed before and after SCS on the 4th day of SAH in 8 rabbits. CCoBF parameters obtained from LDF data were compared.

Effect of awake Carotid Endarterectomy under local anaesthesia on peri-operative blood pressure: blood pressure is normalised when carotid stenosis is treated under local anaesthesia

Summary Background. Carotid Endarterectomy can be performed under local, regional or general anaesthesia. One of the most important effects of the type of anaesthetic used is on the systemic blood pressure. Although variations in blood pressure during and following carotid endarterectomy have been studied previously, the effects of awake carotid endarterectomy under local anaesthesia on blood pressure and its comparison with similar procedures under similar types of anaesthesia have not.Methods. Peri-operative blood pressure measurements were collected from the records of 25 consecutive patients for each of the following five procedures; Carotid Endarterectomy under general anaesthesia (CEAGA), Anterior Cervical Discectomy and Fusion under general anaesthesia (ACDF), Cerebral Angiography under local anaesthesia (ANG), Carotid Endarterectomy patients under local anaesthesia who were symptomatic (CEALAS) and Carotid Endarterectomy patients under local anaesthesia who were asymptomatic (CEALAA). The recordings were then analysed to find out if there were any clinically significant variations in peri-operative blood pressure.

A recursive-partitioning model for blood–brain barrier permeation

Summary A series of bagged recursive partitioning models for log(BB) is presented. Using a LGO-CV, three sets of physical property descriptors are evaluated and found to have Q2 values of 0.51 (CPSA), 0.53 (Ro5x) and 0.53 (MOE). Extrapolating these models to Pfizer chemical space is difficult due to P-glycoprotein (P-gp) mediated efflux. Low correlation coefficients for this test set are improved (R 2=0.39) when compounds known to be P-gp substrates or statistical extrapolations are removed. The use of simple linear models for specific chemical series is also found to improve the correlation over a limited chemical space.

Mechanisms of the Blood–Brain Barrier Disruption in HIV-1 Infection

Summary 1. Alterations of brain microvasculature and the disruption of the blood–brain barrier (BBB) integrity are commonly associated with human immunodeficiency virus type 1 (HIV-1) infection. These changes are most frequently found in human immunodeficiency virus-related encephalitis (HIVE) and in human immunodeficiency virus-associated dementia (HAD).2. It has been hypothesized that the disruption of the BBB occurs early in the course of HIV-1 infection and can be responsible for HIV-1 entry into the CNS.

Adrenomedullin Improves the Blood–Brain Barrier Function Through the Expression of Claudin-5

Summary 1. Aims: Brain vascular endothelial cells secret Adrenomedullin (AM) has multifunctional biological properties. AM affects cerebral blood flow and blood–brain barrier (BBB) function. We studied the role of AM on the permeability and tight junction proteins of brain microvascular endothelial cells (BMEC).2. Methods: BMEC were isolated from rats and a BBB in vitro model was generated. The barrier functions were studied by measuring the transendothelial electrical resistance (TEER) and the permeability of sodium fluorescein and Evans’ blue albumin. The expressions of tight junction proteins were analyzed using immunocytochemistry and immunoblotting.

Recovery of the blood pressure – cerebral flow relation after carotid stenting in elderly patients

Summary Background. As a sensitive and convenient means for the cerebral hemodynamic monitoring, dynamic cerebral autoregulation testing could be especially useful in medical conditions where less invasive diagnostics and therapies are preferred. This study analysed the effect of carotid stenting on dynamic autoregulation in elderly patients focussing on the relation between blood pressure and cerebral blood flow velocity. Methods. We examined 20 patients age 69 ± 8 years with coexisting cerebrovascular and medical risk factors before and at least six month after stenting of severe carotid stenoses. Data were compared to 24 age-matched healthy controls. Slow spontaneous oscillations were studied in continuous recordings of Transcranial Doppler and beat-to-beat blood pressure. Analysis was based on the “high-pass filter model”, which predicts a positive phase relationship between these oscillations.

Effects of a monoclonal anti-αvβ3 integrin antibody on blood vessels—A pharmacodynamic study

Summary Purpose: The integrin αvβ3 is an adhesion molecule expressed by proliferating endothelial cells and antibodies blocking this integrin inhibit angiogenesis in preclinical models. MEDI-522 is a second generation humanized anti-αvβ3 antibody designed for antiangiogenic therapy. The purpose of this study was to examine potential effects of this agent on blood vessels. Experimental design: In a phase I dose escalation study, MEDI-522 was administered by weekly infusions to 25 adult patients with advanced solid organ malignancies. As a surrogate angiogenesis assay, a wound was created by punch biopsy of the arm skin. This wound site was re-biopsied after a 7-day interval. Dual-label immunofluorescence experiments followed by computer-assisted image analysis were conducted to analyze the vasculature.

Racial Differences in Blood Pressure Control: Potential Explanatory Factors

Summary Objective The objective of the study was to identify potential explanatory factors for racial differences in blood pressure (BP) control.

First ISNS Reference Preparation for Neonatal Screening for thyrotropin, phenylalanine and 17α-hydroxyprogesterone in blood spots

Summary Background Neonatal screening for congenital disorders like phenylketonuria (PKU), congenital hypothyroidism (CH) and congenital adrenal hyperplasia (CAH) is generally performed in dried blood spots on filter paper. The analytes of interest for testing for PKU, CH and CAH are phenylalanine, thyrotropin (TSH) and 17α-hydroxyprogesterone (17OHP), respectively. The International Society for Neonatal Screening (ISNS) decided to prepare a combined reference preparation for the three analytes on filter paper Schleicher & Schuell #903, Whatman BFC180 and Toyo Roshi 545. This ‘First ISNS Reference Preparation for Neonatal Screening for TSH, phenylalanine and 17OHP in blood spots’ (1st ISNS-RPNS) has been prepared by the RIVM (Bilthoven).

A new subdural probe for combined intracranial pressure (ICP) and cerebral blood flow (CBF) monitoring

Summaey We report the development of a new subdural probe for combined intracranial pressure (ICP) and cerebral blood flow (CBF) monitoring with near infrared spectroscopy (NIRS) and indocyanine green (ICG) dye dilution. For NIRS a conventional subdural ICP monitoring probe was supplied with two fiber bundles and 90-degree prisms. Injections of 25mg ICG were performed. Regional values for the mean transit time of ICG (rmttICG), cerebral blood flow (rCBF) and cerebral blood volume (rCBV) were calculated. With prototypes of the probe in two patients with intracerebral haemorrhage 18 comparative measurements obtained simultaneously with conventional NIRS (optodes placed on the skin) and the subdural NIRS probe were performed. The new subdural NIRS probe allows combined monitoring of ICP and cerebral hemodynamics in the brain directly, without the influence of extracerebral tissue.

Ketamine Levels in Plasma and Red Blood Cells after Intravenous Administration in the Horse

Roncada, P., Romagnoli, N., Spadari, A., di Fabio, P., Nigro, V. and Zaghini, A., 2007. Ketamine levels in plasma and red blood cells after intravenous administration in the horse. Veterinary Research Communications, 31(Suppl. 1), 327–329

Blood Serum Proteome for Welfare Evaluation in Pigs

Roncada, P., Begni, B., Amadori, M., Cristoni, S., Archetti, I.L., Boldetti, C., Fortin, R., Deriu, F. and Greppi, G.F., 2007. Blood serum proteome for welfare evaluation in pigs. Veterinary Research Communications, 31(Suppl. 1), 321–325

Estimating Blood Volume in Obese and Morbidly Obese Patients

Preoperative assessment of blood volume (BV) is important for patients undergoing surgery. The mean value for indexed blood volume (InBV) in normal weight adults is 70 mL/kg. Since InBV decreases in a non-linear manner with increasing weight, this value cannot be used for obese and morbidly obese patients. We present an equation that allows estimation of InBV over the entire range of body weights.

The importance of systolic blood pressure control and cardiovascular disease prevention

Opinion statement Hypertension affects up to 75% of individuals 60 years of age and older. Cardiovascular risk is related to increases in systolic blood pressure and pulse pressure and to decreases in diastolic blood pressure, but systolic blood pressure reduction is the major target for improving outcomes in the elderly patient. Hypertension therapy in older individuals should include lifestyle modification, especially weight loss and sodium restriction, which may decrease the need for antihypertensive medication. The starting dose of medication should be one half that used in younger patients. If low initial doses are used, significant attention must be paid to adequate titration; combination therapy is usually required for optimal blood pressure control. The initial agent chosen is rarely the final agent used to achieve the recommended minimal systolic blood pressure goal of less than 140 mm Hg. If more than one agent is required, a diuretic should be included as one of the agents chosen. Although the reduction of blood pressure should occur more gradually in the older patient, the treatment goals should be similar and determined by the underlying concomitant disorder. The minimum goal should remain less than 140/90 mm Hg, with lower goals in diabetic patients and those with renal disease. Patients with isolated systolic hypertension should have a minimum systolic blood pressure goal of less than 140 mm Hg.

Antiradical effects of antihistamines in human blood. Structure-activity relationship.

No Abstract. .

H1- antihistamines and activated blood platelets

No Abstract. .

Thallium in Whole Blood Samples from College Students in Taiwan

No abstract available.

Blood pressure and diabetic nephropathyss

Conclusions: Baseline SBP is a stronger predictor than DBP of renal outcomes in those with nephropathy resulting from type 2 diabetes. Those with the highest baseline PP have the highest risk for nephropathy progression but also garner the greatest risk reduction with SBP lowered to less than 140 mm Hg.

Exertional rhabdomyolysis: Does elevated blood creatine kinase foretell renal failure?

Conclusions Recreational activity frequently produces large increases in circulating CK activity without consequence. Thus, high CK levels alone do not portend renal failure. Most cases of exertional rhabdomyolysis can, and probably do, resolve on their own without treatment. When taking a blood sample during a routine check, for example in monitoring patients on statin therapy, a high blood CK activity may indicate that strenuous exercise was performed in the previous 10 days. Patients should be queried as to their exercise history during this time. Snow shoveling, dirt shoveling, lifting and lowering heavy boxes, strenuous resistance training, and excessive calisthenics (such as push-ups and pull-ups) are exercises that may dramatically increase circulating CK activity for several days due to forceful eccentric contractions. In addition to elevated CK, factors such as underlying disease, dehydration, environmental heat stress, or genetic predisposition (eg, sickle cell trait) are likely required for exertional rhabdomyolysis to result in acute renal failure [8]. Persons who present to the emergency room with painful, swollen muscles about 2 days after a bout of strenuous exercise should be monitored for kidney function (BUN and creatinine), evidence of myoglobinuria and dehydration, and be queried regarding hydration, heat stress during the exercise, and possible trauma. In cases of exertional rhabdomyolysis, especially in laboratory situations, CK levels up to 100,000 U/L in the absence of nephrotoxic factors have been found to resolve without consequence when no treatment is provided. However, because few data confirm this in a clinical situation in which there may be comorbidities, it remains conservative and prudent in the emergency room to hydrate intravenously and monitor closely to help avoid hyperkalemia and/or acute renal failure in the face of fulminant exertional rhabdomyolysis.

Clinic versus home blood pressure measurements in patients with CKD

Conclusions In patients with CKD, BPs obtained at home are a stronger predictor of ESRD or death compared with BPs obtained in the clinic. Systolic home BP is an independent predictor for ESRD.

Diagnosis of high blood pressure in children by means of ambulatory blood pressure monitoring

Conclusions In conclusion, ambulatory BP monitoring has become a useful tool for the proper assessment of hypertension and should be performed as part of the initial evaluation in older children with persistent mild hypertension. The accurate diagnosis of whether or not hypertension is present in children may both prevent unnecessary diagnostic evaluation as well as allow early intervention so as to prevent the development of persistent hypertension and its sequelae.

Prospective trials of angiotensin receptor blockers: Beyond blood pressure control

Conclusions Current knowledge implicating the involvement of angiotensin II in both the development of hypertension and the pathophysiology of congestive heart failure, myocardial infarction, atherosclerosis, and vascular disease will open the door for more clinical trials involving angiotensin receptor blockers. Current and future studies should clearly answer the question of whether these drugs will play a major role in reducing morbidity and mortality from these diseases. If possible, these studies should attempt to further explain the role of angiotensin II and its receptors in the development of cardiovascular diseases.

Ambulatory and self-monitoring of blood pressure: Coming of age

Conclusions Both ABPM and SBPM seem to be useful tools to employ in clinical practice. They may help in identifying patients who are at lower risk, and in monitoring the effects of treatment. Although the cost-effectiveness of these methods is still being scrutinized, it is to be expected that SBPM, and to a lesser degree ABPM, will in the long run prove to reduce costs of hypertension treatment.

Alterations in T-Cell Subset Frequency in Peripheral Blood in Obesity

Background: Obesity affects the regulation of immune and inflammatory responses. This study characterizes differences in peripheral blood lymphocyte phenotype in obese humans. Methods: Frequencies of lymphocyte subsets among peripheral blood mononuclear cells were compared between 10 obese (BMI ≥35) and 10 lean subjects, as determined by antibodies directed against cluster differentiation (CD) markers. Results: Obese patients demonstrated an increased frequency of CD3+CD4+ T-cells (mean difference 12%, P=0.004), a decreased frequency of CD3+CD8+ T-cells (mean difference 9.4%, P=0.016) and an increased frequency of CD3+CD8+CD95+ T-cells (mean difference 13.3%, P=0.032). No other differences among T-cell or monocyte subsets were noted. Conclusions: Obesity is associated with alterations in frequencies of peripheral CD4+ and CD8+ T-cells and aberrations in the expression of CD95 among CD8+ T-cells. These data suggest both CD4+ and CD8+ T-cell compartments, as well as the regulation of CD95 expression on CD8+ T-cells, as targets for further study into obesity's effects on the immune system.

Predeposit Autologous Blood Donation: a survey of patient attitudes

Attitudes to autologous blood donation have been surveyed in a group of 38 postoperative bariatric patients. Only two patients (5%) declined to participate. Twenty-eight of 38 (70%) successfully predeposited autologous blood. Twenty-five of 28 donors (90%) had done so at the suggestion of their surgeon. Concern about contracting AIDS was the motivating factor in the majority of patients (21 patients, = 55%). Lack of infectious complications in general was cited by an additional four (11%). All respondents would donate autologous blood in the future, and would recommend the procedure to others who were about to undergo elective surgery. There was an increase from 29% to 50% who stated that, following their autologous donation experience, they would consider being homologous volunteer blood donors in the future.

Randomized Controlled Clinical Trial of Blood Glucose Awareness Training (BGAT III) in Switzerland and Germany

Although both diabetes and the efficacy of medical management are international issues, psycho-educational interventions might be culturally bound. Blood Glucose Awareness Training (BGAT) is a psycho-educational program for patients with type 1 diabetes mellitus. It is focused on improving recognition and management of extreme blood glucose levels, and is the best documented American psycho-educational program for this purpose. A randomized controlled clinical trial of BGAT's long-term benefits in a non-American setting has been lacking. One hundred and eleven adults with type 1 diabetes mellitus from Switzerland and Germany participated. After a 6 months baseline assessment, subjects were randomly assigned to receive either 2 months of BGAT (n = 56) or a physician-guided self-help control intervention (n = 55). BGAT improved recognition of low (p = 0.008), high (p = .03), and overall blood glucose (p = 0.001), and reduced frequency of severe hypoglycemia (p = 0.04), without compromising metabolic control. BGAT reduced both the external locus of control (p < 0.02) and fear of hypoglycemia (p < 0.02). BGAT was efficacious in reducing adverse clinical events and achieving clinically desirable goals in a European, as well as American setting.

Reduction of retinal blood flow in high myopia

AbstractPurpose To investigate changes in retinal vessel diameter and blood velocity in high myopia using laser Doppler velocimetry.

Friday, August 15, 2008

Associations between environmental exposure and blood pressure among participants in the Oslo Health Study (HUBRO)

AbstractBackground It is well known that environmental conditions are related to the risk of developing cardiovascular diseases and events. However, the mechanisms behind these relations are␣not well understood. One mechanism could be elevation of blood pressure. In this study we assessed associations between blood pressure and environmental conditions among citizens in Oslo, Norway.

Effects of body temperature on blood gases

AbstractBackground Changes in body temperature have important impact on measurements of blood gases. In blood gas analyzers the samples are always kept constant at a temperature of exactly 37°C during the measurements, and therefore results are not correct if body temperature differs from 37°C.

Whole-Blood Assay to Measure Oxidative Burst and Degranulation of Neutrophils for Monitoring Trauma Patients

AbstractBackground and Purpose: Polymorphonuclear neutrophils (PMNs) protect the host from invading microorganisms, but excessive PMN activation after trauma causes tissue injury. Rapid monitoring of PMN function is critical for the assessment of the inflammatory state of trauma patients. Here, the authors adapted two simple and rapid methods to measure oxidative burst and degranulation of human PMNs in whole blood to avoid potential interference of cell isolation procedures with the assessment of PMN function.

Perioperative blood transfusions increase infectious complications after ileoanal pouch procedures (IPAA)

AbstractBackground and purpose Assessment of risk factors associated with the use of perioperative allogeneic blood transfusion and the effect of transfusion on infectious complications after ileal pouch-anal anastomosis (IPAA).

Effect of increasing cardiac preload, sympathetic antagonism, or vasodilation on visceral blood flow during pneumoperitoneum

AbstractBackground and aims An impaired visceral perfusion caused by pneumoperitoneum may contribute to morbidity after laparoscopic surgery. The following three therapeutic concepts: increasing cardiac preload, controlled vasodilation, or selective sympathetic antagonism, were evaluated regarding a possible increase of visceral blood flow during pneumoperitoneum with carbon dioxide.

Fasting blood glucose and cancer risk in a cohort of more than 140,000 adults in Austria

AbstractAims/hypothesis We investigated relations between fasting blood glucose and the incidence of cancer.

Cost-utility analyses of intensive blood glucose and tight blood pressure control in type 2 diabetes (UKPDS 72)

AbstractAims/hypothesis This study estimated the economic efficiency (1) of intensive blood glucose control and tight blood pressure control in patients with type 2 diabetes who also had hypertension, and (2) of metformin therapy in type 2 diabetic patients who were overweight.

Thursday, August 14, 2008

Home blood glucose prediction: clinical feasibility and validation in islet cell transplantation candidates

AbstractAims/hypothesis Diabetic subjects do home monitoring to substantiate their success (or failure) in meeting blood glucose targets set by their providers. To succeed, patients require decision support, which, until now, has not included knowledge of future blood glucose levels or of hypoglycaemia. To remedy this, we devised a glucose prediction engine. This study validates its predictions.

Blood pressure and heart rate variability in patients with essential hyperhidrosis

Abstract.Introduction Essentialhyperhidrosis (EH) is often consideredto be related to an increasedactivity of sympathetic nervoussystem (SNS). However, there is alack of studies comparing autonomicnervous system (ANS) activityin controls and in EH patients.The aim of the present study was tosimultaneously investigate in patientswith severe EH, blood pressure,heart rate variability andplasma catecholamine levels incomparison with controls.

Blood Culture Sampling Rates at a German Pediatric University Hospital and Incidence of Invasive Pneumococcal Disease

Abstract.Background: Recent pediatric surveillance studies suggest theincidence of pneumococcal bacteremia, but not meningitis, islower in Germany than in most developed countries. Suboptimalcase assessment in routine clinical practice has been suspectedof contributing to this apparent discrepancy.

Interaction between cardiac beat-to-beat interval changes and systolic blood pressure changes

Abstract. This study assessed the interaction between cardiacbeat-to-beat interval changes and systolic pressure (SP)changes. Twenty subjects breathed regularly following displayedbreathing signals at 4, 6, 8, 10, 12 and 14 breaths per minute,each for 5 minutes. ECG, non-invasive blood pressure (Finapres)and respiration waveforms were recorded. Time offsets betweenthe cyclic patterns of RR-interval and SP changes werecalculated. Displayed breathing signals were well followed; themean correlation between displayed and recorded breathingsignals ranged from 0.72 to 0.86. The time offset betweenRR-interval peaks and subsequent SP troughs decreased withincreasing respiration rate, 3.8 ± 1.7 s, 3.5 ± 0.7 s, 3.1 ± 0.6s, 2.6 ± 0.4 s, 2.3 ± 0.4 s and 2.0 ± 0.4 s mean ± SD at 4, 6,8, 10, 12 and 14 breaths per minute respectively. Therelationship between mean time offset and frequency wassignificant (p < 0.001), with a 95% prediction interval of ±0.24 s. Published data showed no relationship between timeoffset and frequency, with a 95% prediction interval of ± 2.8 s.However, when the offset definition proposed in this researchwas applied to these data, a significant relationship (p <0.01) was evident, with a 95% prediction interval of ± 1.5 s. Inconclusion, apparently contradictory previous findings achievegood consensus when a standardized method for presenting resultsis applied. A delay exists between RR-interval and bloodpressure changes, and this delay varies with breathingfrequency.

Blood-brain barrier changesduring invasion of thecentral nervous system by HIV-1

Abstract. The mechanism underlyingthe early invasion of thecentral nervous system by HIV-1 isunclear. Here, we summarize oldand new findings supportingblood-brain barrier changes duringHIV and experimental simianimmunodeficiency virus (SIV) infection.The effect of inflammatoryand toxic molecules secreted bymonocytes and microglia on thefunctional integrity of tight junctionsof brain endothelium is highlighted.Furthermore, recent findingson a possible direct role of theenvelope and regulatory HIV-1proteins (gp120, Tat, Nef) in causingthe blood-brain barrierchanges are reviewed. The possibilitythat these proteins, as circulatingmolecules, may bind to microvesselendothelial cells andcause blood-brain changes with nodirect participation of the virus israised. Several issues deserve furtherinvestigation and answers tothese questions may provide keysfor new therapeutic strategies inHIV-1 infection of the central nervoussystem.

Sympathetic co-activation of skin blood vessels and sweat glands

Abstract. Skin blood vessels and sweat glands are both innervated bysympathetic C fibers. We investigated whether during diverserespiratory maneuvers the vasomotor responses (VRs) and thesympathetic skin responses (SSRs) were frequently oroccasionally co-activated. We simultaneously recorded theamplitude of the vasomotor responses and the sympathetic skinresponses, the ECG and the respiratory movements in 30 healthysubjects during natural breathing at rest, rhythmic respirationsat 6 per minute, sudden deep inspiration and Valsalva maneuver.We found: 1) The SSR habituates with all respiratory maneuverswhereas the VRs do not habituate. 2) There was slightco-activation between the SSRs and VRs during natural defaultbreathing (56 percent). 3) During rhythmic breathing at 6 perminute the VRs and the SSRs were frequently co-activated (97percent). The SSR appeared at the end of the inspirationcoinciding with the end of the decreased blood flow. However theSSR habituated after few rhythmic respirations. 4) During suddendeep inspiration one hundred percent of co-activations werebetween the initial phase of the VRs and the SSR. The SSR islarge in amplitude and longer in duration than during rhythmicbreathing. 5) During the Valsalva maneuver there was a strongco-activation (100 percent) particularly during the phases IIand III that are characterized by vaso-constriction but alsoduring phase IV. The SSR is the longest of duration in all ofthe maneuvers. The sympathetic innervation to the sweat glandsof the palm of the hand and to the skin blood vessels of thefingertips is differentiated. Under normothermic conditionssudden deep inspiration and Valsalva maneuver induced a largesympathetic simultaneous outflow to the skin blood vessels andsweat glands. The simultaneous recording of skin blood flow andthe SSRs provides a more complete assessment of the sympatheticoutflow to the skin than either one alone.

Riluzole and blood pressure in multiple system atrophy

Abstract. Riluzole is a neuroprotectiveagent that is currently testedfor the treatment of multiple systematrophy (MSA). Riluzole mayinfluence afferent and efferentparts ofthe baroreflex due to glutamateantagonistic effects. The effectof riluzole on the efferent partmay be unmasked in MSA patientswith dysfunction of afferent structuresofthe baroreflex. We comparedthe effect of a single dose of200 mg riluzole with placebo in 10patients with probable MSA.Brachial blood pressure and heartrate were recorded at baseline andfor 120 minutes every 5 minutes afteringestion ofr iluzole. For determinationof spontaneous baroreflexsensitivity, continuous fingerblood pressure and ECG wererecorded. Cardiac stroke volumewas monitored using impedancecardiography. The change in bloodpressure over a two hour periodwas significantly greater withriluzole than with placebo(5 ± 5/2 ± 3 mmHg with placebo,16 ± 6/10 ± 2mmHg with riluzole,p < 0.001 by ANOVA). Systemic vascularresistance increased 32 ± 6%with riluzole. Baroreflex sensitivity,the high and low frequency componentsof heart rate variability, andthe low frequency component ofsystolic blood pressure variabilitywere not different between placeboand riluzole treatment. We concludethat in MSA patients, manipulationof glutamatergic transmissionwith riluzole elicits amoderate pressor response. The responseis explained by a markedincrease in systemic vascular resistance.We propose that decreasedinhibition ofef ferent sympatheticneurons may contribute to the response.

Cancer and blood coagulation

Abstract. In human patients, blood coagulation disorders often associate with cancer, even in its early stages. Recently, in vitro and in vivo experimental models have shown that oncogene expression, or inactivation of tumour suppressor genes, upregulate genes that control blood coagulation. These studies suggest that activation of blood clotting, leading to peritumoral fibrin deposition, is instrumental in cancer development. Fibrin can indeed build up a provisional matrix, supporting the invasive growth of neoplastic tissues and blood vessels. Interference with blood coagulation can thus be considered as part of a multifaceted therapeutic approach to cancer.

Reduced cerebral blood flow velocity and impaired cerebral autoregulation in patients with Fabry disease

Abstract. In Fabry disease, there is glycosphingolipid storage in vascular endothelial and smooth muscle cells and neurons of the autonomic nervous system. Vascular or autonomic dysfunction is likely to compromise cerebral blood flow velocities and cerebral autoregulation. This study was performed to evaluate cerebral blood flow velocities and cerebral autoregulation in Fabry patients. In 22 Fabry patients and 24 controls, we monitored resting respiratory frequency, electrocardiographic RR-intervals, blood pressure, and cerebral blood flow velocities (CBFV) in the middle cerebral artery using transcranial Doppler sonography. We assessed the Resistance Index, Pulsatility Index, Cerebrovascular Resistance, and spectral powers of oscillations in RR-intervals, mean blood pressure and mean CBFV in the high (0.15–0.5 Hz) and sympathetically mediated low frequency (0.04–0.15 Hz) ranges using autoregressive analysis. Cerebral autoregulation was determined from the transfer function gain between the low frequency oscillations in mean blood pressure and mean CBFV. Mean CBFV (P < 0.05) and the powers of mean blood pressure (P < 0.01) and mean CBFV oscillations (P < 0.05) in the low frequency range were lower,while RR-intervals, Resistance Index (P < 0.01), Pulsatility Index, Cerebrovascular Resistance (P < 0.05), and the transfer function gain between low frequency oscillations in mean blood pressure and mean CBFV (P < 0.01) were higher in patients than in controls. Mean blood pressure, respiratory frequency and spectral powers of RR-intervals did not differ between the two groups (P > 0.05). The decrease of CBFV might result from downstream stenoses of resistance vessels and dilatation of the insonated segment of the middle cerebral artery due to reduced sympathetic tone and vessel wall pathology with decreased elasticity. The augmented gain between blood pressure and CBFV oscillations indicates inability to dampen blood pressure fluctuations by cerebral autoregulation. Both, reduced CBFV and impaired cerebral autoregulation, are likely to be involved in the increased risk of stroke in patients with Fabry disease.

Arsenic Speciation in Urine and Blood Reference Materials

Abstract. Acute and chronic exposure to arsenic is a growing problem in the industrialized world. Arsenic is a potent carcinogen and toxin in humans. In the body, arsenic is metabolized to produce several species, including inorganic forms, such as trivalent (AsIII) and pentavalent (AsV), and the methylated metabolites such as monomethylarsonic acid, (MMAV), and dimethylarsinic acid (DMAV), in addition to arsenobetaine (AsB) which is ingested and excreted from the body in the same form. Each of these species has been reported to possess a specific but different degree of toxicity. Thus, not only is the measurement of total As required, but also quantification of the individual metabolites is necessary to evaluate the toxicity and risk assessment of this element. There are a large number of reference materials that are used to validate methodology for the analysis of As in blood and urine, but they are limited to total As concentrations. In this study, the speciation of five arsenic metabolites is reported in blood and urine from commercial available control materials certified for total arsenic levels. The separation was performed with an anion exchange column using inductively coupled plasma mass spectrometry as a detector. Baseline separation was achieved for AsIII, AsV, MMAV, DMAV, and AsB, allowing us to quantify all five species. Excellent agreement between the total arsenic levels and the sum of the speciated As levels was obtained.

The effects of low-frequency vibrations on hepatic profile of blood

Abstract. Body vibrations training has become popular in sports training, fitness activity, it is still a rare form of physical rehabilitation.. Vibrations are transmitted onto the whole body or some body parts of an exercising person via a vibration platform subjected to mechanical vertical vibrations. During the training session a participant has to maintain his body position or do exercises that engage specific muscles whilst vibrations of the platform are transmitted onto the person's body. This paper is the continuation of the earlier study covering the effects of low-frequency vibrations on selected physiological parameters of the human body. The experiments were conducted to find the answer to the question if vibration exposure (total duration of training sessions 6 hours 20 min) should produce any changes in hepatic profile of blood. Therefore a research program was undertaken at the University of Science and Technology AGH – UST to investigate the effects of low-frequency vibration on selected parameters of hepatic profile of human blood. Cyclic fluctuations of bone loading were induced by the applied harmonic vibration 3.5 Hz and amplitude 0.004 m. The experiments utilizing two vibrating platforms were performed in the Laboratory of Structural Acoustics and Biomedical Engineering AGH-UST. The applied vibrations were harmless and not annoying, in accordance with the standard PN-EN ISO 130901-1, 1998. 23 women volunteers had 19 sessions on subsequent working days, at the same time of day. during the tests the participants remained in the standing position, passive. The main hypothesis has it that short-term low-frequency vibration exposure might bring about the changes of the hepatic profile of blood, including: bilirubin (BILIRUBIN), alkaline phosphatase (Alp), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and albumin (ALBUMIN) levels. Research data indicate the low-frequency vibrations exposure produces statistically significant decrease of bilirubin level [umol/l] in blood serum from 14.05 to 9.70 for 82% of participants, the probability level being p = 0.000041.

E5564 (Eritoran) inhibits lipopolysaccharide-induced cytokine production in human blood monocytes

Abstract. Objective and design In this ex vivo laboratory study, we investigated the effects of E5564 (eritoran), a toll-like receptor 4-directed endotoxin antagonist, on intracellular expression of interleukin (IL)-6 and tumor necrosis factor (TNF)-α in lipopolysaccharide (LPS)-stimulated human monocytes assessed by flow cytometry.

Glucose transport in human peripheral blood lymphocytes influenced by type 2 diabetes mellitus

Abstract. Introduction: The objective of this study was to evaluate glucose transport into lymphocytes in healthy subjects and patients with type 2 diabetes mellitus (DM) treated either with diet only or with insulin and to propose peripheral blood lymphocytes as a convenient model for cellular glucose transport studies.

Increased whole blood chemiluminescence in patients with chronic renal failure independent of hemodialysis treatment

Abstract. Introduction: The luminol-enhanced whole blood chemiluminescence (LBCL) assay is a rapid assay for the measurement of reactive oxygen species (ROS) generation by circulating phagocytes. This study’s aim was to determine if patients on maintenance hemodialysis (HD) and non-dialyzed patients with chronic renal failure (CRF) have altered LBCL and if dialysis itself affects ROS production in the blood.

Successful treatment of Wolman disease by unrelated umbilical cord blood transplantation

Abstract Wolman disease is a rapidly fatal lysosomal storage disease caused by the complete absence of lysosomal acid lipase activity. We report the cure of an infant with Wolman disease following transplantation of unrelated HLA-mismatched umbilical cord blood-derived stem cells. Umbilical cord blood was chosen as the stem-cell source because of its immediate availability and reduced tendency to cause graft-versus-host disease. The transplantation resulted in restoration of normal acid lipase levels before the onset of permanent end-organ damage. Four years after transplantation, the patient is thriving and has normal levels of acid lipase in peripheral blood cells. To our knowledge, this is the first report of a successful unrelated cord blood transplant in a patient with Wolman disease. Umbilical cord stem cells transplantation can restore acid lipase levels in Wolman disease, and if performed early, can cure the disease.

Leukocyte orchestration in blood and tumour tissue following interleukin-2 based immunotherapy in metastatic renal cell carcinoma

Abstract With the objective of evaluating leukocyte orchestration in situ, serial blood samples and tumour tissue core needle biopsies were obtained at baseline and repeated after 1 month of therapy, among 49 consecutive single-institution patients with metastatic renal cell carcinoma (mRCC). Patients were treated with outpatient low-dose subcutaneous interleukin 2 (IL-2) and interferon (IFN-) alone (n=23) or in combination with histamine dihydrochloride (n=26). Objective responses were achieved in ten of 49 patients (20%) with an overall median survival of 14 months and an estimated 1- to 4-year survival rate of 57, 35, 24 and 22%, respectively. Toxicity was mild to moderate with no treatment-related deaths. High numbers of blood monocytes and neutrophils were significantly correlated to short survival. By contrast, high numbers of intratumoural CD3+, CD4+, CD8+ and CD57+ lymphocytes were positively correlated to objective response and/or long-term survival. Intratumoural lymphocytes showed low expression, whereas blood lymphocytes showed almost normal levels of expression. Neutrophils, the most frequent peripheral blood leukocyte subset, were scarce within the tumour tissue. Intratumoural eosinophils were not observed. In progressing patients, both the absolute number and the relative composition of leukocyte subsets in blood and tumour tissue remained unaffected by cytokine therapy. However, in responding patients, cytokine therapy was followed by an absolute and relative increase in T cells in blood as well as tumour tissue, an absolute and relative reduction in neutrophils in peripheral blood and a relative reduction of intratumoural macrophages. Histamine did not influence levels of intratumoural or blood leukocyte numbers, -chain expression or cytotoxicity. In conclusion, the present regimen of outpatient low-dose subcutaneous IL-2 and IFN- in mRCC should attract interest based on response, survival and toxicity. In responding patients, cytokine therapy was followed by substantial changes in the blood and tumour tissue leukocyte composition, correlated to response and survival. No discernable differences in immunologic parameters studied could be detected between histamine- and nonhistamine-treated patients.

A novel formulation for blood trauma prediction by a modified power-law mathematical model

Abstract With the increasing use of artificial organs, blood damage has been raising ever more clinical concern. Blood trauma is in fact a major complication resulting from the implantation of medical devices and the use of life support apparatuses. Red blood cells damage predictive models furnish critical information on both the design and the evaluation of artificial organs, because their correct usage and implementation are thought to provide clear and rational guidance for the improvement of safety and efficacy. The currently adopted power-law shear-induced haemolysis prediction model lacks sensitivity with respect to the cumulative effect of previously applied stress magnitudes. An alternative model is proposed where a mechanical quantity was defined, able to describe the blood damage sustained by red cells under unsteady stress conditions, taking into account the load history. The proposed formulation predicted the same trend as the available experimental data. The obtained results have to be considered a preliminary validation of the basic hypothesis of this modified red blood cell damage prediction model. To date, the necessity to design further experiments to validate the proposed damage function clashes with the limitations inherent to current systems to get the time-varying shear stress completely under control.

Hepatocyte differentiation from embryonic stem cells and umbilical cord blood cells

Abstract With the development of regeneration medicine, many researchers have attempted hepatic differentiation from nonhepatic-origin cell sources. The differentiation of embryonic stem (ES) cells into hepatocyte-like cells has been reported in several papers. Mouse ES cells have shown a potential to develop into hepatocyte-like cells in vitro on the basis of hepatic gene expression after adding several growth factors. We transplanted cultured embryoid body (EB) cells (male) into female mice. A liver specimen of the recipient was examined by immunohistochemical staining for albumin and fluorescence in situ hybridization for the Y chromosome after transplantation. Both Y chromosome- and albumin-positive cells were recognized in the recipient female liver, and were considered to be hepatocyte-like cells derived from ES cells containing the Y chromosome. Many groups, including ourselves, have studied hepatocyte-like cell differentiation from umbilical cord blood cells (UBCs). We cultured nucleated cells isolated from UBCs. Using immunostaining, ALB-positive and CK-19-positive cells were recognized in the culture. Dual staining of ALB and CK-19 demonstrated that ALB was coexpresed with CK-19, suggesting the existence of hepatic progenitors. In this review, we consider recent studies of the differentiation of hepatocytes from nonhepatic origins, especially ES cells and umbilical cord blood.

Does cyclooxygenase-2 affect blood pressure?

Abstract With the development and clinical implementation of the new cyclooxygenase (COX)-2 inhibitors, their safety, including the effects on renal function and blood pressure, is attracting increasing attention. In the kidney, COX-2 is constitutively expressed and is highly regulated in response to alterations in intravascular volume. COX-2 metabolites have been implicated in mediation of renin release, regulation of sodium excretion, and maintenance of renal blood flow. Similar to conventional nonsteroidal anti-inflammatory drugs, inhibition of COX-2 may cause modest elevations in blood pressure in a minority of subjects. COX-2 inhibitors may also exacerbate pre-existing hypertension or interfere with other antihypertensive drugs. Special caution should be taken in patients with volume depletion or decreased organ perfusion.

Spectral-luminescent manifestation of the damaging action of brain ischemia on blood serum components

Abstract With the aid of spectral-luminescent analysis, our hypothesis on the determining role of free-radical oxidation in damage of blood serum components (low-density lipoproteins) in ischemia has been confirmed. An increase in the luminescence intensity of the blood serum of animals that suffered from brain ischemia as against that of healthy animals is registered. Lipoperoxide free-radical damage of phospholipids of the amphipathic layer of low-density lipoproteins after an ischemic procedure has also been confirmed by fluorescent probes (rhodamine 6G and Nile Blue).

Peripheral blood gene expression profiling for cardiovascular disease assessment

Abstract Whole blood gene expression profiling has the potential to be informative about dynamic changes in disease states and to provide information on underlying disease mechanisms. Having demonstrated proof of concept in animal models, a number of studies have now tried to tackle the complexity of cardiovascular disease in human hosts to develop better diagnostic and prognostic indicators. These studies show that genomic signatures are capable of classifying patients with cardiovascular diseases into finer categories based on the molecular architecture of a patient’s disease and more accurately predict the likelihood of a cardiovascular event than current techniques. To highlight the spectrum of potential applications of whole blood gene expression profiling approach in cardiovascular science, we have chosen to review the findings in a number of complex cardiovascular diseases such as atherosclerosis, hypertension and myocardial infarction as well as thromboembolism, aortic aneurysm, and heart transplant.

Temporo-spatial distribution of blood vessels in human lumbar intervertebral discs

Abstract While there is consensus in the literature that blood vessels are confined to the outer anulus fibrosus of normal adult intervertebral disc, debate continues whether there is a vascular in-growths into inner parts of the intervertebral disc during degeneration. We therefore tested the hypothesis that vascular in-growth is not a distinct feature of disc degeneration. The specific endothelial cell marker CD 31 (PECAM) was used to immunohistochemically investigate 42 paraffin-embedded complete mid-sagittal human intervertebral disc sections of various ages (0–86 years) and varying extent of histomorphological degeneration. Additionally, 20 surgical disc samples from individuals (26–69 years) were included in this study. In discs of fetal to infantile age, blood vessels perforated the cartilaginous end plate and extended into the inner and outer anulus fibrosus, but not into the nucleus pulposus. In adolescents and adults, no blood vessels were seen except for the outer zone of the anulus fibrosus adjacent to the insertion to ligaments. The cartilaginous end plate remained free of vessels, except for areas with circumscribed destruction of the end plate. In advanced disc degeneration, no vessels were observed except for those few cases with complete, scar-like disc destruction. However, some rim lesions and occasionally major clefts were surrounded by a small network of capillary blood vessels extending into deeper zones of the anulus fibrosus. A subsequent morphometric analysis, revealed slightly “deeper” blood vessel extension in juvenile/adolescent discs when compared to young, mature and senile adult individuals with significantly “deeper” extension in the posterior than anterior anulus. The analysis of the surgical specimens showed that only sparse capillary blood vessels which did not extend into the nucleus pulposus even in major disc disruption. Our results show that vascular invasion deeper than the periphery was not observed during disc degeneration, which supports the hypothesis that vascular in-growth is not a distinct feature of disc degeneration.

Effect of a low-frequency magnetic field on the structure of globular blood proteins

Abstract We used IR Fourier absorption spectra of blood to study changes in the structure of globular blood proteins with extracorporeal autohemomagnetotherapy, used to treat ischemic heart disease. We compare the spectra of blood before and after magnetotherapy in the regions: amide I (1655 cm−1), amide II (1545 cm−1), amide III (1230–1350 cm−1), amide IV and amide V (400–700 cm−1). We have shown that pronounced changes in the spectra in the indicated regions on direct exposure of blood in vivo to a low-frequency pulsed magnetic field are connected with conformational changes in the secondary structure of globular blood proteins, which are apparent in the increase in the contribution of the α-helix conformation. We discuss the magnetotherapy-initiated appearance of new IR absorption bands at 1018 and 1038 cm−1 and an increase in the intensity of a number of other bands located in the 1000–1200 cm−1 region, which suggests a change in the concentration of some blood components.

Leg blood flow measurements using venous occlusion plethysmography during head-up tilt

Abstract We tested whether venous occlusion plethysmography (VOP) is an appropriate method to measure calf blood flow (CBF) during head-up tilt (HUT). CBF measured with VOP was compared with superficial femoral artery blood flow as measured by Doppler ultrasound during incremental tilt angles. Measurements of both methods correlated well (r = 0.86). Reproducibility of VOP was fair in supine position and 30° HUT (CV: 11%–15%). This indicates that VOP is an applicable tool to measure leg blood flow during HUT, especially up to 30° HUT.

Umbilical cord blood mesenchymal stem cells

Abstract We studied umbilical cord blood mesenchymal stem cells and compared mesenchymal stem cells derived from umbilical cord blood, adipose tissue, and skin. Umbilical cord blood mesenchymal stem cells were characterized morphologically, cytofluorometrically, and by their differentiation potential. Umbilical cord blood mesenchymal stem cells did not differ from cells isolated from adipose tissue and skin by the main parameters (by morphology, expression of surface markers, and differentiation potential). A specific feature of umbilical cord blood mesenchymal stem cells is their low count per volume of the initial material and very low proliferative activity.

Relationship between Blood Cortisol Level and Blood Parameters in Animals with Experimental Bile Peritonitis

Abstract We studied the relationship between blood cortisol level and hemogram parameters in animals with bile peritonitis. A strong correlation was revealed between variations in cortisol concentration and leukocyte count. We found differences in the hormonal regulation of individual cell populations in the peripheral blood.

Phenotype of peripheral blood lymphocytes and serum immunoglobulin concentration in patients with early rheumatoid arthritis

Abstract We studied the phenotype of peripheral blood lymphocytes and serum immunoglobulin concentration in patients with early rheumatoid arthritis and rheumatoid arthritis of more than 12 months duration. Subpopulations of CDIgM+, CD25+, and HLA-DR+ lymphocytes and IgA concentration differed in these groups of patients with rheumatoid arthritis. The count of lymphocytes carrying CDIgM+ and HLA-DR+ receptors correlated with activity of rheumatoid arthritis.

The oxidative status of blood cells in a murine model of graft-versus-host disease

Abstract We studied the oxidative status of red and white blood cells during the development of graft vs host disease (GVHD) as well as the effects of treatment with antioxidants, both in vitro and in vivo. (BALB/c X C57BL/6) F1 mice were conditioned by total body radiation and, 1 day later, transplanted with semi-allogeneic C57BL/6 spleen cells. GVHD was followed by its clinical manifestations. Oxidative stress in red blood cells (RBC), neutrophils, and lymphocytes was assessed by measuring generation of reactive oxygen species and the content of reduced glutathione by flow cytometry after gating of the specific populations. Oxidative stress was noticed 3 weeks after transplantation. It was higher in mice receiving allogeneic spleen cells as compared with mice transplanted with syngeneic cells, suggesting that it was associated with GVHD. The results also demonstrated that treatment with the antioxidants N-acetylcysteine and a derivative of vitamin E (tocopherol succinate, propofol), both in vitro and in vivo, reduced the oxidative stress. The results indicate that various blood cells, including RBC, neutrophils, and lymphocytes, are under oxidative stress and that treatment with antioxidants reduced the stress and, thus, may be useful in ameliorating the severe consequences of GVHD.

Effect of plant extracts on trans -sialidase activity in human blood plasma

Abstract We studied the effects of plant extracts and products of their biological treatment on trans-sialidase activity in human blood plasma. Extracts of kelp, fucus, yarrow, Saint John’s wort, onion, and honey in vitro decreased trans-sialidase activity. Extracts of pollen (beebread) and garlic powder produced the maximum inhibitory effect. trans-Sialidase activity of blood plasma ex vivo decreased 2-fold after peroral administration of pollen and garlic powder. A correlation was found between the decrease in trans-sialidase activity in blood plasma and ability of blood plasma to induce cholesterol accumulation in cultured cells from the intact human aortic intima.

Effect of Licorice Root on Peripheral Blood Indexes upon Vibration Exposure

Abstract We studied the effect of continuous vibration and treatment with licorice root (Glycyrrhiza glabra L.) on peripheral blood red cells in rabbits. Active substances of licorice root accelerated metabolism in cells of the bone marrow erythroid stem, enhanced compensatory reserve of the organism, and increased animal's resistance to stress.