W Padberg

Justus-Liebig-Universität Gießen, Gieben, Hesse, Germany

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Publications (139)306.42 Total impact

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    ABSTRACT: In addition to its well-described role in lipid metabolism, apolipoprotein E (ApoE) exerts immunomodulatory functions. A protective role of ApoE and ApoE-mimetic peptide (ApoE(133-149)) application was documented in several inflammatory disorders. In this study, we test the hypothesis that ApoE(133-149) promotes renal allograft survival. Dark Agouti, Brown Norway, and Fischer 344 kidneys were transplanted to Lewis rats to investigate fatal and reversible acute rejection. Apolipoprotein E expression was assessed in intravascular leukocytes of renal grafts, in graft tissue and in recipient blood plasma. Recipients of Brown Norway kidneys were treated with ApoE(133-149), and graft survival was monitored until day 100. Graft infiltration, cytokine, and chemokine production were analyzed. Intravascular graft leukocytes and renal tissue obtained from animals undergoing reversible acute rejection expressed increased levels of ApoE mRNA, whereas during fatal rejection, ApoE expression was reduced or remained unchanged. Animals treated with ApoE(133-149) showed prolonged allograft survival, which was associated with a reduced infiltration of CD8 and α/β T-cell receptor-expressing cells, diminished Granzyme B mRNA expression, and decreased caspase-3 activation. Endogenous ApoE overexpression and exogenous application of ApoE(133-149) seem to protect renal allografts from fatal acute rejection. This effect was associated with a reduced influx of cytotoxic T cells.
    Transplantation 02/2015; · 3.78 Impact Factor
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    ABSTRACT: Acute 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.
    10/2014; 86(1).
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    ABSTRACT: 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.
    10/2014;
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    ABSTRACT: Adrenomedullin-2/intermedin stabilizes the pulmonary microvascular barrier challenged by application of thrombin ex vivo and by experimental ventilation in vivo. Here, we test the hypothesis that adrenomedullin-2/intermedin(8-47) protects mouse lungs from ischemia/reperfusion injury in vivo. C57BL/6 mice were anesthetized, intubated, ventilated, and heparinized. Blood vessels and the main bronchus of the left lung were clamped for 90 min. Thereafter, lungs were reperfused for 120 min. Five min before clamping and before reperfusion, mice obtained intravenous injections of adrenomedullin-2/intermedin(8-47). After reperfusion, mice were sacrificed and bronchoalveolar lavage of the left and the right lung was performed separately. The integrity of the blood-air barrier was investigated by electron microscopy using stereological methods. In response to ischemia/reperfusion injury, intraalveolar leukocytes accumulated in the ischemic lung. Two applications of 10 ng/kg body weight adrenomedullin-2/intermedin(8-47) dramatically reduced leukocyte infiltration to about 15% (p ≤ 0.001). Also the proportion of the subpopulation of neutrophil granulocytes decreased (12% vs 5%, p = 0.013). Electron microscopy revealed a protection of the blood-air barrier by adrenomedullin-2/intermedin(8-47). Adrenomedullin-2/intermedin(8-47) ameliorates early ischemia/reperfusion injury in mouse lungs by protecting the integrity of the blood-air barrier and by potently reducing leukocyte influx into the alveolar space. Adrenomedullin-2/intermedin(8-47) might be of therapeutic interest in lung transplantation and cardiopulmonary bypass. “Take home” message: Adrenomedullin-2/intermedin(8-47) ameliorates ischemia/reperfusion injury in mouse lungs and reduces leukocyte influx.
    Peptides 10/2014; · 2.61 Impact Factor
  • Medizinische Klinik, Intensivmedizin und Notfallmedizin. 10/2014; 109(7):554.
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    ABSTRACT: Rectovaginal fistulas (RVF) are rare but represent a challenge for both patients and surgeons. The most common cause of RVF is obstetric trauma, and treatment is based on fistula classification and localization of the fistula in relation to the vagina and rectum. Conventional therapy frequently fails, making surgery the most viable approach for fistula repair. One surgical procedure which offers adequate repair of lower and middle rectovaginal fistulas consists of interposition of a bulbocavernosus fat flap also called modified Martius flap. First described by Heinrich Martius in 1928, this approach has been continuously modified and adjusted over time and is used in the repair of various pelvic floor disorders. Overall success rates reported in the literature of the interposition of a Martius flap as an adjunct procedure in the surgical management of RVF are 65-100 %. We present a detailed description of the operation technique together with a discussion of the use of a dorsal-flapped modified Martius flap in the treatment of RVF.
    Geburtshilfe und Frauenheilkunde 10/2014; 74(10):923-927. · 0.85 Impact Factor
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    ABSTRACT: Patients with signs of an acute abdomen continue to be a challenge for both the emergency physician and the intensivist. Clinical symptoms usually result from secondary peritonitis possibly progressing to intraabdominal sepsis. Critically ill patients need rapid diagnostic work-up and an interdisciplinary therapeutic approach. Among patients with secondary peritonitis, those with postoperative peritonitis (e.g., after anastomotic leakage) show a particularly high mortality because of unspecific symptoms. Beyond routine diagnostic procedures, patients with an acute abdomen often require a CT scan which helps to detect the septic focus, thereby often allowing an interventional source control. Therapy consists of three main elements: source control, broad-spectrum antimicrobial therapy, and supportive intensive care medicine.
    Medizinische Klinik, Intensivmedizin und Notfallmedizin. 09/2014;
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    ABSTRACT: Acute rejection and respiratory infections are major risk factors for chronic lung allograft dysfunction (CLAD) after lung transplantation. To shed light on the enigmatic aetiology of CLAD we test the following hypotheses using a new experimental model: 1) Alloimmune-independent pulmonary inflammation reactivates alloimmunity. 2) Alloimmunity enhances the susceptibility of the graft towards pathogen associated molecular patterns. Pulmonary Fischer 344 to Lewis rat allografts were treated with lipopolysaccharide (LPS), which consistently results in lesions typical for CLAD. Grafts, local lymph nodes, and spleens were harvested before (day 28) and after LPS application (days 29, 33, and 40) for real-time RT-PCR and immunohistochemistry. Mixed lymphocyte reactions were performed on day 33. Four weeks after transplantation, lung allografts displayed mononuclear infiltrates compatible with acute rejection and over-expressed most components of the Toll-like receptor system. Allografts but not secondary lymphoid organs expressed increased levels of Th1-type transcription factors and cytokines. LPS induced macrophage infiltration as well as mRNA expression of pro-inflammatory cytokines and effector molecules of innate immunity. Unexpectedly, T cell reactivity was not enhanced by LPS. We conclude that prevention of CLAD might be accomplished by local suppression of Th1 cells in stable grafts and by controlling innate immunity during alloimmune-independent pulmonary inflammation.This article is protected by copyright. All rights reserved.
    Transplant International 09/2014; · 3.16 Impact Factor
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    ABSTRACT: 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 24 h 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.
    Peptides 08/2014; · 2.61 Impact Factor
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    ABSTRACT: Chronic allograft injury (CAI) is a major cause for renal allograft dysfunction and characterized by vasculopathies, tubular atrophy, and fibrosis. We demonstrated that numerous leukocytes interact with vascular endothelial cells of allografts and produce acetylcholine, which contributes to vascular remodeling. The cholinergic system might be a promising target for the development of novel therapies. However, neither the cellular mechanisms nor the acetylcholine receptors involved in CAI are known. Kidney transplantation was performed in the Lewis to Lewis and in the Fischer-334 to Lewis rat strain combination, which is an established experimental model for CAI. Expression of nicotinic and muscarinic acetylcholine receptors mRNA was quantified in renal tissue by real-time RT-PCR on days 9 and 42 after surgery. We detected CHRNA2-7, CHRNA10, CHRNB2, CHRNB4, and CHRM1-3 mRNA in normal kidneys and in renal transplants. In contrast, CHRNA9, CHRM4, and CHRM5 mRNA remained below the threshold of detection. In renal allografts, CHRNA3 and CHRNB4 mRNA expression were dramatically reduced compared to isografts. In conclusion, we demonstrated that most acetylcholine receptor subtypes are expressed by normal and transplanted kidneys. Allograft rejection downmodulates CHRNA3 and CHRNB4 mRNA. The role of different acetylcholine receptor subtypes in the development of CAI remains to be established.
    BioMed Research International 07/2014; 2014:289656. · 2.71 Impact Factor
    This article is viewable in ResearchGate's enriched format
  • Peptides 06/2014; · 2.61 Impact Factor
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    ABSTRACT: Background and Methods We showed previously that rabbit ATG induction induces a strong decrease of CD4+ T cells together with impaired in-vitro IL-2 secretion up to 1 year post-transplant. To further characterize long-term immunological effects of ATG induction 2 and 5 years post-transplant, we used sensitive intracellular cytokine analysis in the same prospective study of 84 renal transplant recipients (ATG, n=44). Results A significantly increased frequency of severe infectious disease (HR=2.0, p=0.027) as well as suppressed T cell functions were found within 2 years after ATG induction but not beyond (logistic regression (logreg): CD4 cell IL-10 responses, p=0.064; T cell proliferation, p=0.038). Impaired T cell proliferation at 2 years was associated with occurrence of severe infection (p=0.017). Importantly, a strong and persistent decrease of CD4 cell counts (p<0.0005 at 5 years) was independently associated with ATG induction (logreg p=0.002) but not related to functional CD4 cell impairment (helper activity/ cytokine production) or an increased risk of infection. Conclusions Severe infection up to 2 years after ATG induction was associated with impaired T cell proliferative capacity but not with the profound decline in CD4 cell counts that occurred after ATG induction and persisted up to 5 years.
    Human immunology 06/2014; · 2.55 Impact Factor
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    ABSTRACT: Chronic allograft injury (CAI) limits the long-term success of renal transplantation. Nestin is a marker of progenitor cells, which probably contribute to its pathogenesis. We hypothesize that nestin is induced by ischemia/reperfusion injury and acute rejection, main risk factors for CAI. Syngeneic renal transplantation was performed in Lewis rats and allogeneic transplantation in the Fischer 344 to Lewis strain combination, which results in reversible acute rejection and in CAI in the long-run. The Dark Agouti to Lewis rat strain combination was used to study fatal acute rejection. In untreated kidneys, nestin immunoreactivity was detected in glomeruli and in very few interstitial or microvascular cells. Syngeneic transplantation induced nestin expression within 4 days, which decreased until day 9 and returned to control levels on day 42. Nestin expression was strong during acute rejection and still detected during the pathogenesis of CAI on day 42. Nestin-positive cells were identified as endothelial cells and interstitial fibroblast-like cells co-expressing alpha-smooth muscle actin. A sub-population of them expressed proliferating cell nuclear antigen. In conclusion, nestin is induced in renal grafts by ischemia/reperfusion injury and acute rejection. It is expressed by proliferating myofibroblasts and endothelial cells and probably contributes to the pathogenesis of CAI.
    Apmis 04/2014; · 1.92 Impact Factor
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    ABSTRACT: Hemangiomas of the gastrointestinal tract and mesentery are uncommon benign vascular lesions. While spontaneous bleeding is the hallmark of the gastrointestinal tumor variant, clinical signs of mesenteric hemangiomas are mostly unspecific. Despite the increasing imaging quality of computerized tomography (CT), in most cases the final diagnosis is established through surgery and histopathologic analysis of a macrobiopsy.We present a case report of a 20-year-old female patient who was admitted with progressive abdominal distension and suffered from persistent abdominal pain for 3 months. A large retroperitoneal tumor mass was detected on the CT scan. Due to radiographic signs of an intraabdominal liposarcoma, an explorative laparotomy was performed revealing a large hemangioma originating from the mesosigmoid.Although rare, gastrointestinal hemangiomas should be kept in mind by oncological visceral surgeons as one differential diagnosis of large intraabdominal tumorous masses, especially in young adults.
    World Journal of Surgical Oncology 03/2014; 12(1):79. · 1.20 Impact Factor
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    ABSTRACT: Acute pancreatitis is a potentially fatal disease with individually differing expression of systemic involvement. For this reason early diagnosis with subsequent risk stratification is essential in the clinical management of this frequent gastroenterological disorder. Severe forms of acute pancreatitis occur in approximately 20 % of cases often requiring intensive care monitoring and interdisciplinary therapeutic approaches. In the acute phase adequate fluid replacement and sufficient analgesic therapy is of major therapeutic importance. Concerning the administration of antibiotics and the nutritional support of patients with acute pancreatitis a change in paradigms could be observed in recent years. Furthermore, endoscopic, radiological or surgical interventions can be necessary depending on the severity of the disease and potential complications.
    Der Anaesthesist 03/2014; · 0.74 Impact Factor
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    ABSTRACT: We report the case of a 67 year old female patient with a multifocal colonic adenocarcinoma (pT3 N0 L0 V0 G2 R0 and pT1 N0 L0 V0 G2 R0) (Figure 1a) with classical histological morphology and immunohistochemical phenotype (CK7-, CK20+, CDX2+ TTF1-). During staging two lesions in the right and the left lung each suspicious of beeing primary/metastatic carcinomas were detected and after right-sided upper lobectomy an additional bronchopulmonary adenocarcinoma (pT1a N1a L1 V0 G2 R0) (Figure 1a) with expression of "lung-specific" immunomarkers (CK7+, CK20-, CDX2-, TTF1+) was identified. By contrast histological examination of the left-sided lung tumor revealed a biphenotypic adenocarcinoma with tubular and mucinous differentiation (Figures 1b-d), a "lung-specific" immunoprofile in tubular areas (CK7+, CK20-, CDX2-, TTF1+) (Figure 1e), and a pattern compatible with bronchopulmonary mucinous adenocarcinoma (CK7+, CK20+, TTF1-) in the mucinous tumor parts (Figure 1f), suggesting an intrapulmonal metastasis of the right-sided bronchopulmonary adenocarcoinoma. This article is protected by copyright. All rights reserved.
    Histopathology 12/2013; · 3.30 Impact Factor
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    ABSTRACT: The treatment of transsphincteric anal fistulas is a challenge between recurrence rate and incontinence. Many surgical and conservative procedures have been described in the treatment of anal fistulas. Fistulectomy and primary sphincter reconstruction (FPSR) has not gained great popularity in this field due to the risk of sphincter damage. The aim of this study is to evaluate FPSR in the treatment of transsphincteric fistulas. We retrospectively analyzed 50 patients with high transsphincteric fistulas of cryptoglandular origin that were treated with FPSR between 2005 and 2008. Preoperative assessment included physical and proctologic examination. Continence and pain scores were evaluated preoperatively and postoperatively. In our 50 patients, 22 patients (44 %) had a previous proctologic operation and 11 patients (22 %) presented with recurrent fistulas. The fistulas existed for an average of 8 months. The operation time was 28 ± 16 min. Mean follow-up was 22± months. The fistula healed in 44 patients (88 %) who developed no recurrence. In five patients (10 %), the fistula healed, but they developed a recurrence in the observation period. In one patient (2 %), the fistula did not heal. Three patients developed low-grade incontinence for flatus, and one patient with 2° incontinence improved. Preoperatively and postoperatively calculated continence and pain scores showed a slight but significant elevation in the Clinical Continence Score, the German Society of Coloproctology Score showed no significant difference, and preexisting pain was reduced significantly by surgery. FPSR is a safe surgical procedure for the treatment of high transsphincteric anal fistula. The primary healing rate is high with a low risk of recurrence or incontinence.
    International Journal of Colorectal Disease 12/2013; · 2.24 Impact Factor
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    ABSTRACT: In the perioperative phase, sepsis and sepsis-associated death are the most important problems for both the surgeon and the intensivist. Critically ill patients profit from an early identification and implementation of an interdisciplinary therapy. The purpose of this review on septic peritonitis is to give an update on the diagnosis and its evidence-based treatment. Rapid diagnosis of sepsis is essential for patient´s survival. A bundle of studies was performed on early recognition and on new diagnostic tools for abdominal sepsis. Although surgical intervention is considered as an essential therapeutic step in sepsis therapy the time-point of source control is still controversially discussed in the literature. Furthermore, the Surviving Sepsis Campaign (SSC) guidelines were updated in 2012 to facilitate evidence-based medicine for septic patients. Despite many efforts, the mortality of surgical septic patients remains unacceptably high. Permanent clinical education and further surgical trials are necessary to improve the outcome of critically ill patients.
    Langenbeck s Archives of Surgery 11/2013; · 1.89 Impact Factor
  • Autonomic Neuroscience 10/2013; 177(2):317. · 1.37 Impact Factor
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    ABSTRACT: The long-term success of human lung transplantation is limited by the development of bronchiolitis obliterans syndrome. Acute rejection episodes and infections are important risk factors and seem to play major pathogenic roles. We established a relevant experimental model that mimics important aspects of human bronchiolitis obliterans syndrome. The Fischer 344-to-Lewis rat strain combination was used for orthotopic left lung transplantation. Isogeneic transplantations were performed in the Lewis rat. Recipients were treated with ciclosporin for 10 days. Lipopolysaccharide or vehicle was instilled into the airways 28 days after transplantation. Grafts were monitored by computed tomography, and recipients were euthanized on Days 28-90. The messenger RNA expression of selected chemokines and their receptors was measured on Days 28, 29, 33, 40 after transplantation. Graft histopathology on Day 90 was compared with lungs from patients who underwent re-transplantation due to end-stage allograft dysfunction. Lung allografts treated with ciclosporin and vehicle only sporadically displayed tissue remodeling. In contrast, lipopolysaccharide treatment induced severe inflammation. In the long-term, severe vascular remodeling, lung fibrosis, and fibroproliferative remodeling of airways were found that closely resemble the histopathologic changes in grafts from human patients with bronchiolitis obliterans syndrome. Chronic damage was virtually absent from pulmonary isografts and native right lungs. Chemokine (C-C motif) ligand 5 and chemokine (C-X-C motif) ligand 9-11, and their receptors, were over-expressed in allografts. Our experimental model mirrors key aspects of human bronchiolitis obliterans syndrome. It will be useful to elucidate its pathogenesis and to develop therapeutic approaches improving the long-term outcome of human lung transplantation.
    The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 09/2013; · 5.61 Impact Factor

Publication Stats

742 Citations
306.42 Total Impact Points

Institutions

  • 1991–2014
    • Justus-Liebig-Universität Gießen
      • • Department of Internal Medicine
      • • Department of Anaesthesiology and Intensive Care Medicine
      Gieben, Hesse, Germany
  • 2006–2011
    • Universitätsklinikum Gießen und Marburg
      Marburg, Hesse, Germany
  • 1987
    • Harvard Medical School
      • Department of Surgery
      Boston, Massachusetts, United States