Julia Holler

Neuropeptide Y Is Expressed by Rat Mononuclear Blood Leukocytes and Strongly Down-Regulated during Inflammation

Neuropeptide Y (NPY), a classical sympathetic comediator, regulates immunological functions including T cell activation and migration of blood leukocytes. A NPY-mediated neuroimmune cross-talk is well conceivable in sympathetically innervated tissues. In denervated, e.g., transplanted organs, however, leukocyte function is not fundamentally disturbed. Thus, we hypothesized that NPY is expressed by blood leukocytes themselves and regulated during inflammation. NPY mRNA and peptide expression were analyzed in mononuclear leukocytes isolated from the blood vessels of healthy rat kidneys, as well as from the blood vessels of isogeneic and allogeneic renal grafts transplanted in the Dark Agouti to Lewis or in the Fischer 344 to Lewis rat strain combination. Depending on the donor strain, acute allograft rejection is either fatal or reversible but both experimental models are characterized by massive accumulation of intravascular leukocytes. Leukocytes, predominantly monocytes, isolated from the blood vessels of untreated kidneys and isografts expressed high amounts of NPY mRNA and peptide, similar to expression levels in sympathetic ganglia. During acute allograft rejection, leukocytic NPY expression drastically dropped to ∼1% of control levels in both rat strain combinations. In conclusion, NPY is an abundantly produced and tightly regulated cytokine of mononuclear blood leukocytes.

Peridural analgesia may affect long-term survival in patients with colorectal cancer after surgery (PACO-RAS-Study): an analysis of a cancer registry.

Objective: To determine the effect of peridural analgesia on long-term survival in patients who underwent surgical treatment of colorectal carcinoma. Background: Clinical and animal studies suggest a potential benefit of peridural analgesia on morbidity and mortality after cancer surgery. The effect of peridural analgesia on long-term outcome after surgery for colorectal cancer remains undefined. Methods: From 2003 to 2009, there were 749 patients who underwent surgery for colorectal carcinoma under general anesthesia with or without peridural analgesia. Clinical data were reviewed retrospectively and analyzed with multivariate analysis and Kaplan-Meier plots. Results: There were 442 patients who received peridural analgesia and 307 patients who did not receive peridural analgesia. A substantial survival benefit was observed in patients who received peridural analgesia (5-year survival rate: peridural analgesia, 62%; no peridural analgesia, 54%; P < 0.02). The hazard rate for death was decreased by 27% in patients who received peridural analgesia. When peridural analgesia was included simultaneously in a Cox model with the confounding factors age, American Society of Anesthesiologists classification, and stage, there was a significant survival benefit in patients who received peridural analgesia. In patients with America Society of Anesthesiologists classification 3 to 4, there was significantly greater survival with peridural analgesia than without peridural analgesia (P < 0.009). Conclusions: Peridural analgesia may improve survival in patients underwent surgery for colorectal carcinoma. The survival benefit with peridural analgesia was greater in patients who had greater medical morbidity.

Die Rolle von Biomarkern in der Diagnostik der akuten Mesenterialischämie

ZusammenfassungDie akute Mesenterialischämie stellt auch heutzutage aufgrund ihrer hohen Letalität den behandelnden Mediziner vor eine große Herausforderung. Unspezifische Symptome in der frühen Phase der Erkrankung erschweren eine rasche Diagnose der Mesenterialischämie und nur eine frühzeitige Diagnose und Therapie kann den Patienten vor irreversibler Darmischämie, ausgedehnten Darmresektionen, Sepsis und Tod bewahren. Im Gegensatz zu beispielsweise Troponin als frühem Marker für die kardiale Ischämie ist ein zuverlässiger Marker für die Mesenterialischämie bisher nicht im klinischen Alltag etabliert. Dieser würde eine Früherkennung der Patienten in der frühen, reversiblen Phase ermöglichen.Diese Übersichtsarbeit fasst die Pathophysiologie, Epidemiologie und klinische Symptomatik der akuten Mesenterialischämie zusammen und soll einen Überblick über mögliche Biomarker, allen voran das Serumlaktat, geben. Nur Serumlaktat wird bisher als Routineparameter zur Diagnostik der mesenterialen Ischämie verwendet.AbstractAcute mesenteric ischemia is a severe and challenging disease. Unspecific symptoms in the initial phase make a fast diagnosis difficult although it is of major importance to protect patients from irreversible ischemia, extended bowel resection, sepsis and death in the late phase. In contrast to troponin as an early biomarker for cardiac ischemia, a reliable biomarker for acute intestinal ischemia has not yet been identified in the current literature and clinical practice. This would allow the early identification of these critically ill patients in the initial reversible phase of acute intestinal ischemia.This review highlights the pathophysiology, epidemiology and clinical findings of acute mesenteric ischemia and gives an overview of biomarkers which have been investigated in mesenteric ischemia with a special focus on lactate, which is the only parameter routinely used in the diagnostic setting of acute mesenteric ischemia.

Expression of peptide YY by human blood leukocytes.

Peptide YY is produced by L cells in the mucosa of the distal ileum, colon, and rectum and may have systemic and paracrine functions. We hypothesized that peptide YY is expressed by peripheral blood mononuclear cells. The purpose of the present study was to evaluate the expression of peptide YY mRNA and peptide by peripheral blood mononuclear cells and differentiated THP-1 cells after lipopolysaccharide treatment as an in vitro model of inflammation. Blood was drawn by venipuncture from 18- to 63-year-old healthy male blood donors (n=63); peptide YY mRNA expression levels were detected in peripheral blood mononuclear cells from all healthy male subjects. In 3 subjects, peripheral blood mononuclear cells were cultured for 3 and 24h and peptide YY was detected in the cell culture supernatant. In human monocytic THP-1 cells treated with phorbol-12-myristate-13-acetate to induce differentiation to macrophages, treatment with lipopolysaccharide caused down-regulation of peptide YY mRNA levels. In summary, freshly isolated peripheral blood mononuclear cells from healthy humans expressed peptide YY. In vitro data suggested that peptide YY expression is down-regulated by differentiation of monocytes to macrophages and proinflammatory stimuli.

Increased expression of epidermal fatty acid‐binding protein by alveolar macrophages during acute rejection of rat lungs

Holler J, Zakrzewicz A, Garn H, Hirschburger M, Kummer W, Padberg W, Grau V. Increased expression of epidermal fatty acid‐binding protein by alveolar macrophages during acute rejection of rat lungs. APMIS 2010; 118: 791–800.

Bronchogenic Cyst in the Liver Mimicking Metastasis of Colorectal Carcinoma: A Case Report and Review

Introduction: Carcinomas of the colon and rectum are the third most common cancer entity in the world and bear a high risk of synchronous (25%) or metachronous (50%) hepatic tumor seeding. For therapeutic decisions the differential diagnosis between benign and malignant hepatic lesions in the computer tomography scan is of major importance. We herein discuss congenital hepatic cysts derived from the primitive foregut as potential differential diagnosis for hepatic metastases from a colorectal primary tumor. Case presentation: A caucasian, 56-year old female patient with the initial diagnosis of an adenocarcinoma of the rectum had initially been treated by an anterior rectum resection and hemihepatectomy due to synchronous hepatic metastases (pT3 pN1(2/13), G2, pM1(HEP), L1, V0, pR0) in a curative intention. The follow-up staging after 2 years showed recurrent liver metastases. A local resection of the hepatic foci was performed. One of three lesions was classified as a classical ventral foregut derived bronchogenic cyst located subcapsularly in the liver. A follow-up resection of pulmonary metastases was performed 13 months later. The patient is still alive and healthy 68 months after the primary operation. Conclusions: For the diagnosis and treatment of hepatic metastases of colorectal carcinomas it is very useful to know potential differential diagnoses in radiographic imaging. Foregut derived cysts can be histologically subclassified into Ciliated Hepatic Foregut Cysts and Bronchogenic Cysts. While Ciliated Hepatic Foregut Cysts are known to be located in the liver, we present the rare case of a Bronchogenic Cyst, which was located in the liver parenchyma.

The role of biomarkers in the diagnostics of acute mesenteric ischemia

ZusammenfassungDie akute Mesenterialischämie stellt auch heutzutage aufgrund ihrer hohen Letalität den behandelnden Mediziner vor eine große Herausforderung. Unspezifische Symptome in der frühen Phase der Erkrankung erschweren eine rasche Diagnose der Mesenterialischämie und nur eine frühzeitige Diagnose und Therapie kann den Patienten vor irreversibler Darmischämie, ausgedehnten Darmresektionen, Sepsis und Tod bewahren. Im Gegensatz zu beispielsweise Troponin als frühem Marker für die kardiale Ischämie ist ein zuverlässiger Marker für die Mesenterialischämie bisher nicht im klinischen Alltag etabliert. Dieser würde eine Früherkennung der Patienten in der frühen, reversiblen Phase ermöglichen.Diese Übersichtsarbeit fasst die Pathophysiologie, Epidemiologie und klinische Symptomatik der akuten Mesenterialischämie zusammen und soll einen Überblick über mögliche Biomarker, allen voran das Serumlaktat, geben. Nur Serumlaktat wird bisher als Routineparameter zur Diagnostik der mesenterialen Ischämie verwendet.AbstractAcute mesenteric ischemia is a severe and challenging disease. Unspecific symptoms in the initial phase make a fast diagnosis difficult although it is of major importance to protect patients from irreversible ischemia, extended bowel resection, sepsis and death in the late phase. In contrast to troponin as an early biomarker for cardiac ischemia, a reliable biomarker for acute intestinal ischemia has not yet been identified in the current literature and clinical practice. This would allow the early identification of these critically ill patients in the initial reversible phase of acute intestinal ischemia.This review highlights the pathophysiology, epidemiology and clinical findings of acute mesenteric ischemia and gives an overview of biomarkers which have been investigated in mesenteric ischemia with a special focus on lactate, which is the only parameter routinely used in the diagnostic setting of acute mesenteric ischemia.

Non-neuronal neuropeptide Y and its receptors during acute rejection of rat pulmonary allografts

This study tested the hypothesis that neuropeptide Y (NPY) and NPY receptors 1 (Y1) and 2 (Y2) participate in lung allograft rejection. Inflammation in grafts may include interaction between blood leukocytes and graft endothelial cells and marked accumulation of intravascular blood leukocytes. Fewer leukocytes accumulate in lung than in kidney allografts. Lung transplantion was performed in the Dark Agouti to Lewis rat strain combination. Intravascular and intraalveolar leukocytes were isolated from the grafts, and we evaluated the mRNA expression of NPY, Y1, and Y2 by real-time RT-PCR as well as the peptide expression of NPY by radioimmunoassay and immunohistochemistry. NPY and Y1 were expressed by pulmonary intravascular and intraalveolar leukocytes. Y1 was up-regulated by pulmonary intravascular and intraalveolar leukocytes during allograft rejection while Y2 could not be detected. Higher NPY expression levels in intravascular leukocytes were observed in lung compared to kidney allografts, which were investigated previously. Our findings suggest that an increased leukocytic expression of NPY in lung compared to kidney allografts results in a reduced accumulation of leukocytes in allograft vessels.

Die Rolle von Biomarkern in der Diagnostik der akuten Mesenterialischämie@@@The role of biomarkers in the diagnostics of acute mesenteric ischemia

ZusammenfassungDie akute Mesenterialischämie stellt auch heutzutage aufgrund ihrer hohen Letalität den behandelnden Mediziner vor eine große Herausforderung. Unspezifische Symptome in der frühen Phase der Erkrankung erschweren eine rasche Diagnose der Mesenterialischämie und nur eine frühzeitige Diagnose und Therapie kann den Patienten vor irreversibler Darmischämie, ausgedehnten Darmresektionen, Sepsis und Tod bewahren. Im Gegensatz zu beispielsweise Troponin als frühem Marker für die kardiale Ischämie ist ein zuverlässiger Marker für die Mesenterialischämie bisher nicht im klinischen Alltag etabliert. Dieser würde eine Früherkennung der Patienten in der frühen, reversiblen Phase ermöglichen.Diese Übersichtsarbeit fasst die Pathophysiologie, Epidemiologie und klinische Symptomatik der akuten Mesenterialischämie zusammen und soll einen Überblick über mögliche Biomarker, allen voran das Serumlaktat, geben. Nur Serumlaktat wird bisher als Routineparameter zur Diagnostik der mesenterialen Ischämie verwendet.AbstractAcute mesenteric ischemia is a severe and challenging disease. Unspecific symptoms in the initial phase make a fast diagnosis difficult although it is of major importance to protect patients from irreversible ischemia, extended bowel resection, sepsis and death in the late phase. In contrast to troponin as an early biomarker for cardiac ischemia, a reliable biomarker for acute intestinal ischemia has not yet been identified in the current literature and clinical practice. This would allow the early identification of these critically ill patients in the initial reversible phase of acute intestinal ischemia.This review highlights the pathophysiology, epidemiology and clinical findings of acute mesenteric ischemia and gives an overview of biomarkers which have been investigated in mesenteric ischemia with a special focus on lactate, which is the only parameter routinely used in the diagnostic setting of acute mesenteric ischemia.

[The effect of peridural analgesia on long-term survival after surgery in patients with colorectal cancer : A systematic meta-analysis].

BACKGROUND The results of recent clinical studies suggest a potential benefit of peridural analgesia (PDA) during general anesthesia on long-term survival in patients after surgery for colorectal cancer. In order to test the hypothesis a meta-analysis was performed. OBJECTIVES To determine the prognostic impact of perioperative PDA on long-term survival in patients with colorectal cancer who underwent surgical resection. MATERIAL AND METHODS By searching the relevant literature (up to May 2014) a total of 5 studies were identified from a total of 608 publications and a meta-analysis was carried out. Adjusted hazard ratios (HR) with 95 % confidence intervals (CI) were used to assess the strength of associations. The random effects model was used to analyze the data and a modified forest plot was applied. Additionally, a potential publication bias was visually examined in a funnel plot. RESULTS A positive association between PDA and improved long-term survival was observed in patients who underwent surgery for colorectal cancer without metastases (HR = 0.81, 95 % CI 0.68-0.96, p = 0.055). CONCLUSION Despite a publication bias the use of PDA in patients who underwent surgery for colorectal cancer without metastases seemed to be advantageous. Randomized controlled trials are warranted to confirm the positive effects of additional PDA. The exact mechanisms of tumor suppressive effects of PDA have not yet been elucidated.ZusammenfassungHintergrundIn mehreren klinischen Studien zeigt sich eine Verbesserung der Langzeitprognose für Patienten, die unter perioperativer periduraler Schmerztherapie zusätzlich zur Allgemeinnarkose an einem kolorektalen Karzinom operiert wurden.FragestellungHat eine zusätzlich verwendete perioperative peridurale Analgesie (PDA) einen Effekt auf das Langzeitüberleben von Patienten nach chirurgischer Resektion eines kolorektalen Karzinoms?Material und MethodenEs erfolgten eine systematische Literaturrecherche (bis 5/2014) in Medline sowie eine Metaanalyse des Einflusses einer PDA auf das Langzeitüberleben von Patienten nach Resektion eines kolorektalen Karzinoms in den UICC-Stadien I bis IV. Die korrigierten Hazard Ratios (HR) mit einem 95 %-Konfidenzintervall (KI) wurden als Maß für den statistischen Effekt auf das Langzeitüberleben zugrunde gelegt. Für die Analyse wurde ein Modell mit zufälligen Effekten verwendet und auf einen potenziell publikationsbezogenen Fehler überprüft (Forest-/Funnel-Plot).ErgebnisseVon 608 identifizierten Publikationen wurden 5 Studien eingeschlossen. Im Modell mit zufälligen Effekten zeigte sich ein verbessertes Langzeitüberleben für Patienten, die perioperativ zusätzlich zur Allgemeinnarkose eine PDA erhielten (HR = 0,81, 95 %-KI 0,68–0,97, p = 0,055). Die Analyse der Einflussfaktoren zeigte einen statistisch robusten Effekt. Damit verminderte sich das Sterblichkeitsrisiko in den analysierten Studien durch die Verwendung einer PDA im Mittel um 19 % gegenüber einer alleinigen Allgemeinanästhesie.DiskussionDiese Metaanalyse zeigt trotz eines Publikationsbias, dass eine zusätzliche perioperative peridurale Analgesie das Langzeitüberleben von Patienten mit einem nicht fernmetastisierten kolorektalen Karzinom nach chirurgischer Resektion verbessern kann.AbstractBackgroundThe results of recent clinical studies suggest a potential benefit of peridural analgesia (PDA) during general anesthesia on long-term survival in patients after surgery for colorectal cancer. In order to test the hypothesis a meta-analysis was performed.ObjectivesTo determine the prognostic impact of perioperative PDA on long-term survival in patients with colorectal cancer who underwent surgical resection.Material and methodsBy searching the relevant literature (up to May 2014) a total of 5 studies were identified from a total of 608 publications and a meta-analysis was carried out. Adjusted hazard ratios (HR) with 95 % confidence intervals (CI) were used to assess the strength of associations. The random effects model was used to analyze the data and a modified forest plot was applied. Additionally, a potential publication bias was visually examined in a funnel plot.ResultsA positive association between PDA and improved long-term survival was observed in patients who underwent surgery for colorectal cancer without metastases (HR = 0.81, 95 % CI 0.68–0.96, p = 0.055).ConclusionDespite a publication bias the use of PDA in patients who underwent surgery for colorectal cancer without metastases seemed to be advantageous. Randomized controlled trials are warranted to confirm the positive effects of additional PDA. The exact mechanisms of tumor suppressive effects of PDA have not yet been elucidated.