Angiotensin II type 1 receptor antibodies in childhood kidney transplantation

Angiotensin II type 1 receptor antibodies (AT1 RAb) have emerged as non-HLA Ab present in patients with acute AMR and risk of graft loss. Furthermore, AT1 RAb have been shown to increase angiotensin II sensitivity which may play a role in the development of CVD and hypertension. Data on AT1 RAb in stable transplant recipients are lacking. The aim of this study was to analyze the levels of AT1 RAb in a cohort of stable patients after kidney transplantation (tx) in childhood. A cross-sectional study of 30 children (median age 14, range 3-19 yr, median time since tx five yr) and 28 adults who were transplanted in childhood (median age 26, range 20-40 yr, median time since tx 18 yr) transplanted between 1993-2006 and 1983-2002, respectively, was performed. Healthy controls were 51 healthy children (5-8 yr) and 199 healthy donors (median age 56.5 yr, range 42-83 yr). Plasma AT1 RAb were analyzed by immunoassay. Median total AT1 RAb IgG concentration was significantly higher in the pediatric-tx group as compared to the adult-tx group (40.0 and 10.95 U/mL, p < 0.0001). For both groups, the tx group showed higher levels: the pediatric-tx group vs. control group (40.0 vs. 13.3 U/mL, p = 0.0006) and the adult-tx group vs. adult control group (10.95 vs. 6.5 U/mL, p < 0.0001). Age was the strongest indicator of high levels of AT1 RAb IgG (p = 0.0003). AT1 RAb total IgG levels are significantly higher in a stable pediatric-tx cohort as compared to adult-tx patients and healthy controls of comparable age groups. The relevance of our findings in relation to age, time since tx, previous or future rejection, and CVD risk merits future studies

Postoperative Immune Suppression in Visceral Surgery: Characterisation of an Intestinal Mouse Model

Background: Postoperatively acquired immune dysfunction is associated with a higher mortality rate in case of septic complications. As details of this severe clinical problem are still unknown, animal models are essential to characterise the mechanisms involved. Methods: Mice were laparotomised and the small intestine was pressed smoothly in antegrade direction. For extension of trauma, the intestine was manipulated three times consecutively. Following this, the ex vivo cytokine release of splenocytes was determined. The degree of surgical trauma was analysed by detection of HMGB1 and IL-6 in serum and by neutrophil staining in the muscularis mucosae. Results: We adapted the previously described animal model of intestinal manipulation to provide a model of surgically induced immune dysfunction. Following intestinal manipulation, the mice showed elevated serum levels of HMGB1 and IL-6 and increased infiltration of granulocytes into the muscularis mucosae. Ex vivo cytokine release by splenocytes was suppressed in the postoperative period. The degree of suppression correlated with the extent of surgical trauma. Conclusions: In this study, we describe a surgically induced immune dysfunction animal model, in which a significant surgical trauma is followed by an immune dysfunction. This model may be ideal for the characterisation of the postoperative immune dysfunction syndrome

A retrospective of the GREGOR solar telescope in scientific literature

In this review, we look back upon the literature, which had the GREGOR solar telescope project as its subject including science cases, telescope subsystems, and post-focus instruments. The articles date back to the year 2000, when the initial concepts for a new solar telescope on Tenerife were first presented at scientific meetings. This comprehensive bibliography contains literature until the year 2012, i.e., the final stages of commissioning and science verification. Taking stock of the various publications in peer-reviewed journals and conference proceedings also provides the "historical" context for the reference articles in this special issue of Astronomische Nachrichten/Astronomical Notes.Comment: 6 pages, 2 color figures, this is the pre-peer reviewed version of Denker et al. 2012, Astron. Nachr. 333, 81

Surgical Trauma and Postoperative Immune Dysfunction

Background: In postoperative sepsis, mortality is increased due to the surgically induced immune dysfunction. Further causes of this traumatic effect on the immune system include burn injuries and polytrauma, as well as endogenous traumata like stroke. Several animal models have been defined to analyse the characteristics of trauma-induced immune suppression. This article will correlate our results from animal studies and clinical observations with the recent literature on postoperative immune suppression. Methods: The previously described model of surgically induced immune dysfunction (SID) was performed in mice by laparotomy and manipulation of the small intestine in the antegrade direction. Blood samples were collected 6 and 72 h following SID to analyse the white blood cell count and corticosterone levels. To assess the postoperative immune status in humans, we analysed expression of HLA-DR on monocytes of 118 patients by flow cytometry prior to and 24, 48 and 72 h after surgery. Results: The postoperative immune suppression in our SID model is characterised by lymphocytopenia and significantly increased corticosterone levels in mice dependent on the degree of surgical trauma. This is comparable to the postoperative situation in humans: major and especially long-lasting surgery results in a significantly reduced expression of HLA-DR on circulating monocytes. Previous studies describe a similar situation following burn injury and endogenous trauma, i.e. stroke. Conclusions: We suggest the completion of our previously published sepsis classification due to the immune status at the onset of sepsis: type A as the spontaneously acquired sepsis and type B as sepsis in trauma-induced pre-existing immune suppression

Compensatory upregulation of anti-beta-adrenergic receptor antibody levels might prevent heart failure presentation in pediatric myocarditis

BACKGROUND: Myocarditis can be associated with severe heart failure and is caused by different inflammatory and autoimmune responses. The aim of this study was to describe the immunological response in children with myocarditis by analyzing anti-beta-adrenergic receptor antibodies (anti-β-AR Abs). METHODS: Sera of children who were hospitalized with biopsy-proven myocarditis were prospectively collected between April 2017 and March 2019. Anti-β1-AR Ab, anti-β2-AR Ab, and anti-β3-AR Ab were quantified by a CE-certified ELISA kit. According to normal values for immunoglobulin G (IgG), three age groups, 5–17 years, were defined. Children without inflammatory cardiac pathology and no heart failure signs were served as a control group. RESULTS: We compared 22 patients with biopsy-proven myocarditis and 28 controls. The median age (interquartile range) of the myocarditis group (MYC) was 12.1 (2.7–16.4) years, 13 men, left ventricular ejection fraction (LVEF) 51% and for control group, the median age was 5.0 (3.0–6.8) years, nine men, LVEF 64%. Myocarditis patients in the age group >5–17 years showed significantly higher anti-β3-AR Ab levels as compared to controls (p = 0.014). Lower anti-β2-AR Ab and anti-β3-AR Ab levels were significantly correlated with higher left ventricular diameters in myocarditis patients. The event-free survival using a combined endpoint (mechanical circulatory support [MCS], transplantation, and/or death) was significantly lower in myocarditis patients with antibody levels below the median as compared to myocarditis patients with antibody levels ≥ the median. CONCLUSION: Anti-β-AR Ab levels are increased in children with myocarditis and >5 years of age. These antibodies might be upregulated compensatory to prevent further cardiac deterioration. A worse event-free survival in patients with lower anti-β-AR Ab levels might be a therapeutic target for immunoglobulin substitution

The Wave-Front Correction System for the Sunrise Balloon-Borne Solar Observatory

This paper describes the wave-front correction system developed for the Sunrise balloon telescope, and it provides information about its in-flight performance. For the correction of low-order aberrations, a Correlating Wave-Front Sensor (CWS) was used. It consisted of a six-element Shack - Hartmann wave-front sensor (WFS), a fast tip-tilt mirror for the compensation of image motion, and an active telescope secondary mirror for focus correction. The CWS delivered a stabilized image with a precision of 0.04 arcsec (rms), whenever the coarse pointing was better than ± 45 arcsec peak-to-peak. The automatic focus adjustment maintained a focus stability of 0.01 waves in the focal plane of the CWS. During the 5.5 day flight, good image quality and stability were achieved during 33 hours, containing 45 sequences, which lasted between 10 and 45 min. © 2010 The Author(s)

Bacterial migration through punctured surgical gloves under real surgical conditions

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to confirm recent results from a previous study focussing on the development of a method to measure the bacterial translocation through puncture holes in surgical gloves under real surgical conditions.</p> <p>Methods</p> <p>An established method was applied to detect bacterial migration from the operating site through the punctured glove. Biogel™ double-gloving surgical gloves were used during visceral surgeries over a 6-month period. A modified Gaschen-bag method was used to retrieve organisms from the inner glove, and thus-obtained bacteria were compared with micro-organisms detected by an intra-operative swab.</p> <p>Results</p> <p>In 20 consecutive procedures, 194 gloves (98 outer gloves, 96 inner gloves) were examined. The rate of micro-perforations of the outer surgical glove was 10% with a median wearing time of 100 minutes (range: 20-175 minutes). Perforations occurred in 81% on the non-dominant hand, with the index finger most frequently (25%) punctured. In six cases, bacterial migration could be demonstrated microbiologically. In 5% (5/98) of outer gloves and in 1% (1/96) of the inner gloves, bacterial migration through micro-perforations was observed. For gloves with detected micro-perforations (n = 10 outer layers), the calculated migration was 50% (n = 5). The minimum wearing time was 62 minutes, with a calculated median wearing time of 71 minutes.</p> <p>Conclusions</p> <p>This study confirms previous results that bacterial migration through unnoticed micro-perforations in surgical gloves does occur under real practical surgical conditions. Undetected perforation of surgical gloves occurs frequently. Bacterial migration from the patient through micro-perforations on the hand of surgeons was confirmed, limiting the protective barrier function of gloves if worn over longer periods.</p

Rapid induction of autoantibodies during ARDS and septic shock

<p>Abstract</p> <p>Background</p> <p>Little is known about the induction of humoral responses directed against human autoantigens during acute inflammation. We utilized a highly sensitive antibody profiling technology to study autoantibodies in patients with acute respiratory distress syndrome (ARDS) and severe sepsis, conditions characterized by intensive immune activation leading to multiple organ dysfunction.</p> <p>Methods</p> <p>Using Luciferase Immunoprecipitation Systems (LIPS), a cohort of control, ARDS and sepsis patients were tested for antibodies to a panel of autoantigens. Autoantibody titers greater than the mean plus 3 SD of the 24 control samples were used to identify seropositive samples. Available longitudinal samples from different seropositive ARDS and sepsis patient samples, starting from within the first two days after admission to the intensive care, were then analyzed for changes in autoantibody over time.</p> <p>Results</p> <p>From screening patient plasma, 57% of ARDS and 46% of septic patients without ARDS demonstrated at least one statistically significant elevated autoantibody compared to the controls. Frequent high titer antibodies were detected against a spectrum of autoantigens including potassium channel regulator, gastric ATPase, glutamic decarboxylase-65 and several cytokines. Analysis of serial samples revealed that several seropositive patients had low autoantibodies at early time points that often rose precipitously and peaked between days 7-14. Further, the use of therapeutic doses of corticosteroids did not diminish the rise in autoantibody titers. In some cases, the patient autoantibody titers remained elevated through the last serum sample collected.</p> <p>Conclusion</p> <p>The rapid induction of autoantibodies in ARDS and severe sepsis suggests that ongoing systemic inflammation and associated tissue destruction mediate the break in tolerance against these self proteins.</p

Hantaviren und Nagetiere in Deutschland: Das Netzwerk „Nagetier-übertragene Pathogene”

ZusammenfassungHantavirus-Infektionen sind in Deutschland seit etwa 25 Jahren bekannt. Die durchschnittliche Antikörperprävalenz in der Bevölkerung liegt bei ca. 1 bis 2%. Nach Einführung der Meldepflicht im Jahr 2001 sind jährlich durchschnittlich etwa 70 bis 240 Fälle gemeldet worden. Im Jahr 2005 und insbesondere im Jahr 2007 ist jedoch ein deutlicher Anstieg der Zahl der gemeldeten Fälle registriert worden. Die am meisten betroffenen Regionen lagen in den Bundesländern Baden-Württemberg, Bayern, Nordrhein-Westfalen und Niedersachsen. Im Gegensatz zur gut dokumentierten Situation beim Menschen ist die Kenntnis der geografischen Verbreitung und Häufigkeit von Hantavirus-Infektionen in den Nagetier-Reservoiren und deren Schwankungen sehr begrenzt. Aus diesem Grund wurde in Deutschland das Netzwerk „Nagetier-übertragene Pathogene“ etabliert, das interdisziplinäre Untersuchungen zur Nagetier-Populationsdynamik, Prävalenz und Evolution von Hantaviren und anderen Nagetier-assoziierten Zoonoseerregern und den zugrunde liegenden Mechanismen sowie deren Auswirkungen auf die Häufigkeit humaner Infektionen erlaubt. Ein Monitoring von Hantaviren in Nagetieren wurde in Endemiegebieten (Baden-Württemberg, Bayern, Nordrhein-Westfalen, Niedersachsen) und Regionen mit einer geringen Zahl humaner Fälle (Mecklenburg-Vorpommern, Brandenburg, Sachsen, Sachsen-Anhalt, Thüringen, Schleswig-Holstein, Hessen, Rheinland-Pfalz) initiiert. Insgesamt wurde eine breite geographische Verbreitung des Puumalavirus (PUUV) in Rötelmäusen und des Tulavirus in Microtus-Mäusen dokumentiert. Dobrava-Belgrad-Virus-positive Apodemus-Mäuse wurden bisher ausschließlich in Brandenburg, Mecklenburg-Vorpommern und Niedersachsen gefunden. In den Hantavirus-Ausbruchsgebieten in Baden-Württemberg, Bayern, Nordrhein-Westfalen und Niedersachsen wurde bei Rötelmäusen eine hohe PUUV-Prävalenz beobachtet. Initiale Longitudinalstudien in Nordrhein-Westfalen (Stadt Köln), Bayern (Niederbayern) und Niedersachsen (ländliche Region bei Osnabrück) zeigten ein stabiles Vorkommen des PUUV in den Rötelmaus-Populationen. Neben den Untersuchungen zu Hantaviren ist auch mit Studien zum Vorkommen von anderen Nagetier-assoziierten Zoonoseerregern begonnen worden. Die begonnenen Longitudinalstudien werden Schlussfolgerungen zur Evolution von Hantaviren und anderen Nagetierassoziierten Erregern und zu Veränderungen in deren Häufigkeit und Verbreitung ermöglichen. Diese Untersuchungen werden zukünftig eine verbesserte Risikoabschätzung für die Gefährdung der Bevölkerung ermöglichen, die auch die möglichen zukünftigen Klimawandel-bedingten Veränderungen in der Epidemiologie Nagetier-assoziierter Zoonoseerreger berücksichtigt