C Loddenkemper

Publications (42)89.59 Total impact

• Source

  Available from: Anja A Kühl

  Article: Mesenteric fat - control site for bacterial translocation in colitis?

  A Batra, M M Heimesaat, S Bereswill, A Fischer, R Glauben, D Kunkel, A Scheffold, U Erben, A Kühl, C Loddenkemper, H-A Lehr, M Schumann, J-D Schulzke, M Zeitz, B Siegmund
  [show abstract] [hide abstract]
  ABSTRACT: In Crohn's disease bacteria could be detected in the adjacent mesenteric fat characterized by hypertrophy of unknown function. This study aimed to define effector responses of this compartment induced by bacterial translocation during intestinal inflammation. Dextran sulfate sodium-induced colitis served as a model of intestinal inflammation. Translocation of peptides and bacteria into mesenteric fat was evaluated. Innate functions of mesenteric fat and epithelium were characterized at whole tissue, cellular, and effector molecule levels. Orally applied peptides translocated in healthy wild-type (WT) mice. Bacterial translocation was not detected in healthy and acute but increased in chronic colitis. Mesenteric fat from colitic mice released elevated levels of cytokines and was infiltrated by immune cells. In MyD88(-/-) mice bacterial translocation occurred in health and increased in colitis. The exaggerated cytokine production in mesenteric fat accompanying colonic inflammation in WT mice was less distinct in MyD88(-/-) mice. In vitro studies revealed that fat not only increases cytokine production following contact with bacterial products, but also that preadipocytes are potent phagocytes. Colonic inflammation is accompanied by massive cytokine production and immune cell infiltration in adjacent adipose tissue. These effects can be considered as protective mechanisms of the mesenteric fat in the defense of bacterial translocation.
  Mucosal Immunology 05/2012; 5(5):580-91. · 6.96 Impact Factor
• Article: Immunpathologie bei der ankylosierenden Spondylitis und anderen Spondyloarthritiden

  H. Appel, C. Loddenkemper, J. Sieper
  [show abstract] [hide abstract]
  ABSTRACT: Bei der ankylosierenden Spondylitis liegen histomorphologisch mindestens 2verschiedene Stadien vor: (1) Die akuten entzündlichen Veränderungen zeichnen sich durch Knochenmarksödem, lymphozytäre Infiltrate, erhöhte Osteoklastendichte und hohe Gefäßdichte aus. (2) Bei der Knochenneubildung zeigt sich in den betroffenen Arealen fibröses Bindegewebe, Knorpelneubildung und eine anhaltend hohe Gefäßdichte, bevor sich trabekulärer Knochen neu ausbildet. Mechanismen der enchondralen Ossifikation können ebenfalls vermutet werden. Im Bereich der Wirbelsäule, der Sakroiliakalgelenke und der Hüftgelenke ist die Synovitis weniger ausgeprägt als beispielsweise in den Kniegelenken. Im Bereich der Sehnenansätze zeichnet sich die Enthesitis durch eine um Faserknorpel herum gelagerte lymphozytäre Infiltration aus, die ebenfalls zur Verknöcherung führt. Die molekularen Mechanismen, die bei den Übergängen von der Entzündung zur Knochenneubildung eine wichtige Rolle spielen, sind bisher nicht bekannt. Histomorphological analysis shows at least two different patterns in patients with ankylosing spondylitis. Bone marrow edema, lymphocytic infiltrates, increased osteoclast density and increased microvessel density are typical findings in acute inflammation. In areas of new bone formation newly formed trabecular bone shows formation of fibrous tissue in the bone marrow with new cartilage formation and persistently high microvessel density. Morphological changes reminiscent of endochondral ossification can also be observed. Compared to peripheral joints, such as the knee, synovitis is not a predominant finding in the spine, the sacroiliac joints and the hip. Enthesitis is characterised by lymphocytic infiltrates around fibrous cartilage followed by subsequent ankylosis. The molecular mechanisms which promote the transition from inflammation to new bone formation in patients with ankylosing spondylitis are not well understood.
  Zeitschrift für Rheumatologie 04/2012; 67(1):25-31. · 0.46 Impact Factor
• Article: Primäres duktales Adenokarzinom im Bereich der Orbita

  M. Grünbaum, J. Ervens, H. Stein, C. Loddenkemper
  [show abstract] [hide abstract]
  ABSTRACT: Vorgestellt wird der Fall eines 59-jährigen Patienten, der mit Druckgefühl in der linken Orbita und Exophthalmus mit Bulbushochstand linksseitig vorstellig wurde. Die eingeschränkte Bulbusmotilität führte zu Doppelbildern. Die präoperative MRT zeigte eine Raumforderung der linken medialen Orbita. Die morphologischen und immunhistologischen Befunde führten zu der Diagnose eines primären duktalen Karzinoms vom Speichelgangtyp (SDC). Der Tumor konnte unter Organerhaltung des Auges entfernt werden. Der Patient ist 12Monate nach der Behandlung beschwerde- und tumorfrei. The case of a 59-year-old patient is described who presented with a left-sided pressure sensation in the left orbit and exophthalmus with a proud bulbus. The limited bulbus motility led to double vision. A preoperative MRI showed a space-occupying lesion in the left medial orbit. The morphological and immunohistochemical findings led to the diagnosis of a primary ductal carcinoma resembling salivary duct carcinoma (SDC). The tumor could be removed without compromising the eye. The patient suffers no side-effects or recurrences 12 months later. SchlüsselwörterEpitheliale Neoplasie-Speichelgangkarzinom-Duktales Wachstumsmuster-Androgenrezeptor KeywordsEpithelial neoplasm-Salivary duct carcinoma-Ductal growth pattern-Androgen receptor
  Der Pathologe 04/2012; 31(4):279-282. · 0.67 Impact Factor
• Article: Orale Epstein-Barr-Virus-assoziierte diffuse großzellige B-Zell-Lymphome bei HIV-negativen immunsupprimierten Patienten

  K. Rhinow, I. Schirmer, C. Loddenkemper, I. Anagnostopoulos, H. Stein, P. A. Reichart
  [show abstract] [hide abstract]
  ABSTRACT: ProblemstellungDie diffusen grozelligen B-Zell-Lymphome (DLBCL) werden zu den Non-Hodgkin-Lymphomen (NHL) gezhlt und sind mit 30–40% die hufigsten NHL im Erwachsenenalter. Die tiologie ist ungeklrt, jedoch werden Viren, insbesondere das Epstein-Barr-Virus (EBV), mit der Entstehung von Lymphomen in Zusammenhang gebracht. Dies trifft insbesondere fr Patienten mit angeborener oder erworbener Immunschwche zu.Patient1Bei einer 39-jhrigen Patientin entwickelte sich nach 24Jahren immunsuppressiver Therapie mit Azathioprin wegen einer Myasthenia gravis ein EBV-assoziiertes DLBCL des plasmoblastischen Subtyps am Oberkieferalveolarfortsatz im Bereich der Zhne 11, 21. Das klinische Bild entsprach einer therapeutisch schwer beeinflussbaren, lokalisierten, akut nekrotisierenden Parodontitis. Nach einer Polychemotherapie befindet sich die Erkrankung gegenwrtig in vollstndiger Remission.Patient2Unter immunsuppressiver Therapie mit Azathioprin und CyclosporinA entwickelte sich bei einem 56-jhrigen Patienten sieben Wochen nach Herztransplantation ein EBV-assoziiertes DLBCL der immunoblastischen Variante im posterioren Bereich des rechten oberen zahnlosen Alveolarfortsatzes. Klinisch zeigte sich eine weiche, nicht druckdolente, 1,50,50,5cm groe Schwellung mit zentraler Ulzeration. Der Tumor wurde entfernt, eine Bestrahlung des entsprechenden Bereichs folgte. Innerhalb eines 15-jhrigen Beobachtungszeitraums zeigte sich kein Rezidiv.DiskussionDie Fallberichte zeigen, dass maligne B-Zell-Lymphome als gefrchtete Komplikationen einer Immunsuppression auch oral auftreten knnen und bei entsprechender Anamnese (HIV-Infektion oder immunsuppressive Therapie) an derartige Lsionen gedacht werden muss. Der Nachweis des Epstein-Barr-Virus in beiden Fllen weist auf einen mglichen Zusammenhang bei der Onkogenese der oralen DLBCL insbesondere bei Immundefekt hin.SchlussfolgerungenDas unterschiedliche, mitunter unspezifische Erscheinungsbild der oral auftretenden DLBCL erfordert eine schnelle grozgige Probeentnahme und bersendung an spezialisierte hmatopathologische Referenzzentren zur diagnostischen Abklrung, da diese Tumoren bereits in frhen Stadien disseminieren.BackgroundDiffuse large B-cell lymphomas (DLBCL) are non-Hodgkins lymphomas (NHL) and with a prevalence of 30–40% they comprise the most frequent NHL in adults. Although their etiology is still unknown, a virus induction, especially by the Epstein-Barr-virus (EBV), is the subject of discussion. Patients with congenital or acquired immunodeficiency are primarily afflicted.Patient1A 39-year-old female patient developed an EBV-associated DLBCL of the plasmablastic subtype in the maxillary alveolar ridge in the region of teeth 11 and 21 after 24years of immunosuppressive therapy with azathioprine due to myasthenia gravis. Clinically the lesion presented as a localized acute necrotizing periodontitis that was resistant to symptomatic therapy. After polychemotherapy the disease is in complete remission until today.Patient2A 56-year-old male patient developed an EBV-associated DLBCL of immunoblastic variant of the right maxillary edentulous alveolar ridge in the posterior region 7weeks after heart transplantation and immunosuppressive therapy with azathioprine and cyclosporineA. Clinically, a soft, nonpainful, swelling measuring 1.50.50.5cm with a central ulceration was evident. The tumor was excised followed by local radiation therapy. No recurrence was noted during a 15-year-follow-up.DiscussionThe presented clinical cases demonstrate the increased risk of occurrence of oral malignant B-cell lymphomas as adverse effects of immunosuppressive therapy. The demonstration of EBV in the tumor cells in both cases underlines the involvement of this virus in the pathogenesis of oral DLBCL arising in the setting of an immunodeficiency as has been shown previously in patients with HIV.ConclusionsDue to the varying and often nonspecific clinical appearance of oral DLBCL, an early biopsy and work-up by an institute specialized in hematopathology is essential for diagnosis, because these tumors may disseminate in early stages.
  Mund- Kiefer- und Gesichtschirurgie 04/2012; 10(3):155-161.
• Article: Hyperkeratotische invertierte seborrhoische Keratose des äußeren Gehörgangs

  P. Halleck, C. Loddenkemper, M. Hummel, H. Scherer, A. Haisch
  [show abstract] [hide abstract]
  ABSTRACT: Obwohl die seborrhoische Keratose eine der häufigsten gutartigen Neubildungen am Rumpf, Extremitäten, Kopf und Hals im Alter Obwohl die seborrhoische Keratose eine der häufigsten gutartigen Neubildungen am Rumpf, Extremitäten, Kopf und Hals im Alter ist, findet sich nur äußerst selten eine Manifestation im Gehörgang. Noch seltener ist das Auftreten einer invertierten bzw. ist, findet sich nur äußerst selten eine Manifestation im Gehörgang. Noch seltener ist das Auftreten einer invertierten bzw. hyperkeratotischen histologischen Variante an dieser Lokalisation. Wir stellen das Krankheitsbild eines 74-jährigen Mannes hyperkeratotischen histologischen Variante an dieser Lokalisation. Wir stellen das Krankheitsbild eines 74-jährigen Mannes mit einer rezidivierenden hyperkeratotischen, stellenweise invertierten seborrhoischen Keratose des linken äußeren Gehörgangs mit einer rezidivierenden hyperkeratotischen, stellenweise invertierten seborrhoischen Keratose des linken äußeren Gehörgangs vor. Gelegentlich bereitet diese Erkrankung diagnostische Schwierigkeiten, insbesondere in der Abgrenzung zu malignen Differenzialdiagnosen. vor. Gelegentlich bereitet diese Erkrankung diagnostische Schwierigkeiten, insbesondere in der Abgrenzung zu malignen Differenzialdiagnosen. Man sollte sich vor einer unkritischen Diagnosestellung in Acht nehmen, da diese Läsionen, vor allem der irritative Subtyp, Läsionen, vor allem der irritative Subtyp, histologisch wie Basalzellkarzinome imponieren und bewertet werden können. histologisch wie Basalzellkarzinome imponieren und bewertet werden können. Seborrheic keratosis is one of the most common benign neoplasms seen at the trunk, extremities, head and neck of older individuals Seborrheic keratosis is one of the most common benign neoplasms seen at the trunk, extremities, head and neck of older individuals which rarely occurs in the auditory canal. Even rarer is the occurrence of an inverted or hyperkeratotic variant in this localization. which rarely occurs in the auditory canal. Even rarer is the occurrence of an inverted or hyperkeratotic variant in this localization. We present the clinical picture of a 74-year-old man with a recurrent hyperkeratotic, partially inverted seborrheic keratosis We present the clinical picture of a 74-year-old man with a recurrent hyperkeratotic, partially inverted seborrheic keratosis of the right external auditory canal. This disease is sometimes difficult to diagnose, particulary to mark down malignant of the right external auditory canal. This disease is sometimes difficult to diagnose, particulary to mark down malignant lesions. An uncritical diagnosis must be avoided, since these lesions and especially the irritated subtype might be falsely lesions. An uncritical diagnosis must be avoided, since these lesions and especially the irritated subtype might be falsely assessed as basal cell carcinomas which they may resemble histologically. assessed as basal cell carcinomas which they may resemble histologically.
  HNO 04/2012; 57(5):480-483. · 0.40 Impact Factor
• Article: Fieber unklarer Genese in der Gastroenterologie

  T. Schneider, S. Daum, C. Loddenkemper, M. Zeitz
  [show abstract] [hide abstract]
  ABSTRACT: Der Gastrointestinaltrakt kann bei Patienten mit Fieber unklarer Genese klinisch oder diagnostisch im Vordergrund stehen. Wichtige Erkrankungen umfassen den Morbus Whipple, das Mittelmeerfieber, isoliert auf die mesenterialen Gefäße beschränkte Formen der Vaskulitis und Manifestationen des Immunrekonstitutionssyndroms. Gelegentlich präsentieren sich chronisch entzündliche Darmerkrankungen primär mit Fieber. Die enge interdisziplinäre Zusammenarbeit ist von entscheidender Bedeutung bei der Aufklärung dieser Erkrankungen. Endoskopische Verfahren zur Gewinnung von Probenmaterial sind häufig für die Diagnosestellung entscheidend. In manchen Fällen reicht aber das bioptische Material zur Diagnosesicherung nicht aus, und es müssen durch einen chirurgischen Eingriff größere Gewebeproben (z.B. intestinale Lymphknoten oder Darmresektate) gewonnen werden. Sonst symptomfreie gastrointestinale Malignome (insbesondere Kolon und Pankreas) sind eine wichtige Differenzialdiagnose. Letztendlich kann in den meisten Fällen die für die Prognose des Patienten entscheidende Diagnose gestellt werden. The gastrointestinal tract may be of major clinical or diagnostic importance in fever of unknown origin. To the classical diseases in this sense belong very different diseases as Whipple’s disease, Familiar Mediterranean Fever, isolated mesenterial vasculitis, and manifestations of immune reconstitution inflammatory disease, but also unusual manifestations of otherwise easily recognized diseases like special forms of celiac disease, or inflammatory bowel disease. Endoscopical techniques to obtain biopsies for diagnostic procedures are frequently crucial to solve the diagnostic puzzle. In some cases the bioptic material may not be sufficient to reach a diagnosis and further surgical intervention is necessary (intestinal lymph-nodes or bowel resections) to acquire enough tissue for a definite diagnosis. Nevertheless using these different approaches in most cases of fever of unknown origin the underlying cause can be identified which for many patients means not more or less than significant improvement or even survival.
  Der Internist 04/2012; 50(6):668-675. · 0.30 Impact Factor
• Article: Neurotuberkulose

  B.-M. Mackert, J. Conradi, C. Loddenkemper, F.K.H. van Landeghem, R. Loddenkemper, R. Ignatius, T. Schneider
  [show abstract] [hide abstract]
  ABSTRACT: Die Neurotuberkulose ist in Deutschland eine eher seltene Erkrankung. Wegen der therapeutischen Konsequenzen und einer Vielzahl von Differenzialdiagnosen ist die Kenntnis dieser Erkrankung trotzdem sehr wichtig. Die Diagnose der Neurotuberkulose wird in der Zusammenschau des klinischen Erscheinungsbildes, der Liquordiagnostik sowie der zerebralen Bildgebung gestellt. Eine frühzeitige Diagnosestellung, der unverzügliche Beginn einer adäquaten antituberkulotischen Therapie und das klinische Stadium sind die prognostisch wichtigen Faktoren für den langfristigen Heilungserfolg. Trotz der Verfügbarkeit von effektiven Chemotherapeutika lässt sich die Neurotuberkulose häufig nicht zufriedenstellend therapieren. In weniger als der Hälfte der Fälle kann eine bleibende Beeinträchtigung oder der Tod verhindert werden. Neuere Arbeiten belegen, dass eine rechtzeitige und adäquate adjuvante Kortikoidtherapie die Prognose hinsichtlich der Letalität und Morbidität verbessert. Resistenzentwicklungen des wichtigsten Erregers, Mycobacterium tuberculosis, erschweren die Therapie. Die neueren Erkenntnisse vor allem zur Diagnostik und Therapie werden zusammengefasst und anhand von Fallbeispielen dargestellt. In Germany neurotuberculosis is quite rare. Familiarity with the disease is nonetheless important because of many differential diagnoses and therapeutic implications. The diagnosis of neurotuberculosis is made by considering of clinical presentation, CSF, and cerebral imaging. Early diagnosis, prompt initiation of effective antitubercular therapy, and clinical staging are necessary for establishing a long-term treatment prognosis. The results of neurotuberculosis therapy are often unsatisfactory despite the availability of effective drugs. Lasting damage or death can be averted in fewer than half of the patients. Studies now confirm that early adjuvant corticoid therapy reduces lethality and morbidity. Resistant new strains of the pathogen, Mycobacterium tuberculosis, complicate therapy. Recent discoveries especially in diagnosis and therapy are explained using case evidence.
  Der Nervenarzt 04/2012; 79(2):153-166. · 0.68 Impact Factor
• Article: [Tropheryma whipplei infection. Colonization, self-limiting infection and Whipple's disease].

  V Moos, C Loddenkemper, T Schneider
  [show abstract] [hide abstract]
  ABSTRACT: Whipple's disease is a multisystemic infection caused by the ubiquitous bacterium Tropheryma whipplei. Immunological host factors enable classical Whipple's disease; however, T. whipplei can be found in three other clinical conditions: healthy colonization, self-limiting infections, and isolated endocarditis. The genetic predisposition of the host rather than the genotype of the bacterium influences the infection. Modern diagnostic methods elucidate the many facets of Whipple's disease. In particular, isolated T. whipplei-induced infective endocarditis can only be diagnosed after valve resection. The sole treatment of Whipple's disease evaluated prospectively comprises intravenous induction therapy with ceftriaxone or meropenem, followed by continuation therapy with oral TMP-SMX. In the case of Immune reconstitution inflammatory syndrome (IRIS) or inflammatory lesions of the CNS in the setting of Whipple's disease, additional treatment with corticosteroids should be considered to avoid severe tissue damage.
  Der Pathologe 06/2011; 32(5):362-70. · 0.67 Impact Factor
• Article: [Primary ductal adenocarcinoma near the orbit].

  M Grünbaum, J Ervens, H Stein, C Loddenkemper
  [show abstract] [hide abstract]
  ABSTRACT: The case of a 59-year-old patient is described who presented with a left-sided pressure sensation in the left orbit and exophthalmus with a proud bulbus. The limited bulbus motility led to double vision. A preoperative MRI showed a space-occupying lesion in the left medial orbit. The morphological and immunohistochemical findings led to the diagnosis of a primary ductal carcinoma resembling salivary duct carcinoma (SDC). The tumor could be removed without compromising the eye. The patient suffers no side-effects or recurrences 12 months later.
  Der Pathologe 07/2010; 31(4):279-82. · 0.67 Impact Factor
• Article: Diagnostic value of confocal endomicroscopy in celiac disease.

  U Günther, S Daum, F Heller, M Schumann, C Loddenkemper, M Grünbaum, M Zeitz, C Bojarski
  [show abstract] [hide abstract]
  ABSTRACT: Improved endoscopic screening with targeted biopsies might enhance diagnostic yield in celiac disease. Confocal endomicroscopy (CEM) allows high-resolution in vivo histological analysis. We compared the endomicroscopic findings during ongoing endoscopy with the histological findings graded according to the Marsh classification. Twenty-four patients with celiac disease and six patients with celiac disease that was refractory on a gluten-free diet were examined using CEM. The duodenal mucosa was evaluated by CEM and by conventional histological analysis in respect of villous atrophy, crypt hyperplasia, and increased numbers of intraepithelial lymphocytes (IELs > 40 / 100 enterocytes). The CEM results were assessed as to sensitivity, specificity, and interobserver variability. A Marsh classification score determined by CEM was compared to that obtained by histology. Thirty patients undergoing routine upper gastrointestinal endoscopy were used as controls. Conventional histology showed villous atrophy and crypt hyperplasia in 23 and increased numbers of IELs in 27 of the 30 patients with celiac disease. With CEM, villous atrophy, crypt hyperplasia, and increased IELs were respectively identified in 17, 12, and 22 of the 30 patients. The agreement of the findings on CEM with those of conventional histology was good in relation to villous atrophy (sensitivity 74 %) and increased numbers of IELs (sensitivity 81 %), but inadequate in relation to crypt hyperplasia (sensitivity 52 %). The kappa values for determination of interobserver variability were 0.90 for villous atrophy, 1.00 for crypt hyperplasia, and 0.84 for IEL detection. In the 30 control patients, normal duodenal architecture was found by both histology and endomicroscopy, indicating an overall specificity of 100 %. The assessment of duodenal histology by CEM in patients with celiac disease is sensitive and specific in determining increased numbers of IELs and villous atrophy, but insufficient in respect of crypt hyperplasia. For routine use of CEM in patients with celiac disease, the technique would need to be improved.
  Endoscopy 03/2010; 42(3):197-202. · 5.21 Impact Factor
• Article: Cytomegalovirus-esophagitis as initial presentation of HIV infection mimicking adenocarcinoma.

  G Weinberg, B Siegmund, M Grünbaum, C Loddenkemper, T Schneider
  Endoscopy 01/2010; 42 Suppl 2:E22-3. · 5.21 Impact Factor
• Article: [Fever of unknown origin in gastroenterology].

  T Schneider, S Daum, C Loddenkemper, M Zeitz
  [show abstract] [hide abstract]
  ABSTRACT: The gastrointestinal tract may be of major clinical or diagnostic importance in fever of unknown origin. To the classical diseases in this sense belong very different diseases as Whipple's disease, Familiar Mediterranean Fever, isolated mesenterial vasculitis, and manifestations of immune reconstitution inflammatory disease, but also unusual manifestations of otherwise easily recognized diseases like special forms of celiac disease, or inflammatory bowel disease. Endoscopical techniques to obtain biopsies for diagnostic procedures are frequently crucial to solve the diagnostic puzzle. In some cases the bioptic material may not be sufficient to reach a diagnosis and further surgical intervention is necessary (intestinal lymph-nodes or bowel resections) to acquire enough tissue for a definite diagnosis. Nevertheless using these different approaches in most cases of fever of unknown origin the underlying cause can be identified which for many patients means not more or less than significant improvement or even survival.
  Der Internist 07/2009; 50(6):668-75. · 0.30 Impact Factor
• Article: In vivo diagnosis of acute intestinal graft-versus-host disease by confocal endomicroscopy.

  C Bojarski, U Günther, K Rieger, F Heller, C Loddenkemper, M Grünbaum, L Uharek, M Zeitz, J C Hoffmann
  [show abstract] [hide abstract]
  ABSTRACT: Conventional histology with hematoxylin and eosin (H&E) staining is the accepted standard for diagnosing acute intestinal graft-versus-host disease (GvHD). Confocal endomicroscopy (CEM) is a noninvasive method that allows in vivo histology to be performed during endoscopy. The aim of this study was to evaluate CEM for the diagnosis of acute intestinal GvHD. This observational pilot study conducted between September 2006 and August 2008 included patients with acute diarrhea after stem cell transplantation, infectious diarrhea, or active ulcerative colitis. CEM (EC-3870CIFK, Pentax, Tokyo, Japan) was performed after intravenous injection of fluorescein 10% and topical application of acriflavine 0.05%. A total of 35 patients with acute diarrhea after stem cell transplantation were examined. In 16 patients, CEM and histology showed no evidence of GvHD. In 14/19 patients with histologically confirmed GvHD, the diagnosis could already be established by CEM during ongoing endoscopy. In GvHD grade IV, near complete destruction of the colonic crypts ("flat mucosa") was visible. Control patients with infectious colitis (N = 15) or ulcerative colitis (N = 15) displayed inflammatory changes but no evidence of GvHD. Altogether, sensitivity of CEM was 74% and specificity was 100 %. CEM improves rapid diagnosis of acute intestinal GvHD with high accuracy while performing endoscopy. Platelet transfusions and unnecessary biopsy acquisition can be avoided once acute intestinal GvHD has been diagnosed in vivo.
  Endoscopy 05/2009; 41(5):433-8. · 5.21 Impact Factor
• Article: Anti-CD30 human IL-2 fusion proteins display strong and specific cytotoxicity in vivo.

  B Hirsch, J Brauer, M Fischdick, C Loddenkemper, S Bulfone-Paus, H Stein, H Dürkop
  [show abstract] [hide abstract]
  ABSTRACT: Although therapy of CD30-positive lymphomas such as classical Hodgkin lymphoma and anaplastic large cell lymphoma has been improved considerably during the last decades, patients suffer from high toxicity of current therapeutic regimens. Since CD30 expression is very restricted, CD30-positive tumors are well suited for immunotherapeutic approaches. Several distinct immunotherapeutic approaches with chimeric, humanized, and bispecific antibodies as well as immunotoxins are already described. In this report, we give a short overview of CD30-targeting approaches in humans. Furthermore, we introduce two novel anti-CD30 fusion proteins consisting of the single chain variable fragment of the CD30 monoclonal antibody Ber-H2 and human interleukin-2, evaluate their biological activity in a human CD30-positive syngeneic murine model, and demonstrate the immunological mechanisms leading to tumor rejection by these reagents. The data indicate that there are several promising approaches in CD30-targeted immunotherapy. The findings of the anti-CD30 IL-2 constructs suggest that these fusion proteins are particularly useful to remove small, residual tumors.
  Current drug targets 03/2009; 10(2):110-7. · 3.93 Impact Factor
• Article: Comparative analysis of mononuclear cells isolated from mucosal lymphoid follicles of the human ileum and colon.

  Y Junker, H Bode, U Wahnschaffe, A Kroesen, C Loddenkemper, R Duchmann, M Zeitz, R Ullrich
  [show abstract] [hide abstract]
  ABSTRACT: Studies of human mucosal lymphoid follicles are rare and have been limited to children's Peyer's patches, which are visible at endoscopy. We investigated lymphoid follicles in ileum biopsies of 87 patients and surgical colon specimens from 66 cancer patients, and examined phenotype and function of isolated follicular immune cells. Two (0-10) and 12 (0-117) follicles per patient were found in ileum and colon samples respectively (P < 0.001). The number of lymphoid follicles mononuclear cells (LFMC) that could be isolated per patient was higher from colon compared with ileum specimens [725 000 (0-23 Mio) versus 100 000 (0-1.3 Mio), P < 0.001]. T cells were predominant in both LFMC and lamina propria mononuclear cells (LPMC), but B cells were more and plasma cells less frequent in LFMC. T cells from mucosal follicles were more frequently CD4-positive and CD62L-positive, but less frequently CD8-positive, CD103-positive and CD69-positive than lamina propria T cells. LFMC from ileum compared with colon showed no differences in mononuclear cell composition. Anti-CD3/CD28 stimulation induced similar proliferation of LFMC and LPMC from ileum and colon, as well as secretion of high levels of interferon-gamma, tumour necrosis factor-alpha and interleukin (IL)-2, but lower levels of IL-4, IL-6 and IL-10. LFMC from colon secreted more IL-2 than those from ileum. Our study shows that mucosal lymphoid follicles can be identified clearly in adult human colon and yield viable immune cells sufficient for phenotypical and functional analysis. The cellular composition of LFMC from ileum and colon is similar, and both secrete predominantly T helper type 1 cytokines.
  Clinical & Experimental Immunology 01/2009; 156(2):232-7. · 3.36 Impact Factor
• Article: [Nodular regenerative hyperplasia as a side effect of azathioprine in a patient with Crohn's disease].

  M Schumann, J C Preiss, C Loddenkemper, U Günther, R Somasundaram, B Siegmund, M Zeitz
  [show abstract] [hide abstract]
  ABSTRACT: A 48-year-old patient with Crohn's disease was admitted to our hospital with fatigue, icterus, hepatosplenomegaly and ascites. INVESTIGARTIOS: The whole blood count revealed a pancytopenia, hyperbilirubinemia and slightly elevated transaminases. Examination of the liver histology showed areas of enlarged hyperplastic hepatocytes adjacent to areas of atrophic hepatocytes and dilated sinusoids. Pancytopenia was most likely azathioprine-related. Analysis of the liver histology was highly suggestive of an azathioprine-related, nodular regenerative hyperplasia (NRH). After discontinuation of azathioprine the patient's condition improved substantially. NRH is a rare but potentially serious complication of azathioprine therapy. Other causes include various rheumatological, vascular and myeloproliferative diseases. When azathioprine is prescribed it must be borne in mind that it can cause NRH as a potential adverse effect, and liver enzymes should be measured at regular follow-up examinations.
  DMW - Deutsche Medizinische Wochenschrift 10/2008; 133(38):1897-900. · 0.53 Impact Factor
• Article: In vivo diagnosis of intestinal spirochaetosis by confocal endomicroscopy.

  U Günther, H-J Epple, F Heller, C Loddenkemper, M Grünbaum, T Schneider, M Zeitz, C Bojarski
  Gut 10/2008; 57(9):1331-3. · 10.11 Impact Factor
• Source

  Available from: Georg Cherepnev, MD/PhD

  Article: Correlation of T cell response and bacterial clearance in human volunteers challenged with Helicobacter pylori revealed by randomised controlled vaccination with Ty21a-based Salmonella vaccines.

  T Aebischer, D Bumann, H J Epple, W Metzger, T Schneider, G Cherepnev, A K Walduck, D Kunkel, V Moos, C Loddenkemper, I Jiadze, M Panasyuk, M Stolte, D Y Graham, M Zeitz, T F Meyer
  [show abstract] [hide abstract]
  ABSTRACT: Helicobacter pylori remains a global health hazard, and vaccination would be ideal for its control. Natural infection appears not to induce protective immunity. Thus, the feasibility of a vaccine for humans is doubtful. In two prospective, randomised, double-blind, controlled studies (Paul Ehrlich Institute application nos 0802/02 and 1097/01), live vaccines against H pylori were tested in human volunteers seronegative for, and without evidence of, active H pylori infection. Volunteers (n = 58) were immunised orally with Salmonella enterica serovar Typhi Ty21a expressing H pylori urease or HP0231, or solely with Ty21a, and then challenged with 2x10(5) cagPAI(-) H pylori. Adverse events, infection, humoral, cellular and mucosal immune response were monitored. Gastric biopsies were taken before and after vaccination, and postchallenge. Infection was terminated with antibiotics. Vaccines were well tolerated. Challenge infection induced transient, mild to moderate dyspeptic symptoms, and histological and transcriptional changes in the mucosa known from chronic infection. Vaccines did not show satisfactory protection. However, 13 of 58 volunteers, 8 vaccinees and 5 controls, became breath test negative and either cleared H pylori (5/13) completely or reduced the H pylori burden (8/13). H pylori-specific T helper cells were detected in 9 of these 13 (69%), but only in 6 of 45 (13%) breath test-positive volunteers (p = 0.0002; Fisher exact test). T cells were either vaccine induced or pre-existing, depending on the volunteer. Challenge infection offers a controlled model for vaccine testing. Importantly, it revealed evidence for T cell-mediated immunity against H pylori infection in humans.
  Gut 09/2008; 57(8):1065-72. · 10.11 Impact Factor
• Article: A 62-year-old woman with bilateral pleural effusions and pulmonary infiltrates caused by extramedullary hematopoiesis.

  C Schwarz, R Bittner, A Kirsch, C Loddenkemper, T Mairinger, N Schonfeld, M Serke, R Loddenkemper
  [show abstract] [hide abstract]
  ABSTRACT: A 62-year-old female presented with a 1-month history of irritating cough and increasing dyspnea. A chronic idiopathic myelofibrosis had been diagnosed 5 years ago. CT of the chest and abdomen showed bilateral pleural effusions with a thickened pleura, nodular infiltrations in both lungs, enlarged intraabdominal lymph nodes and splenomegaly. Pleuroscopy (medical thoracoscopy) on the left side revealed dense tumorous nodules mainly on the posterior chest wall pleura, but also on the diaphragm and the lung. Biopsies taken from the chest wall pleura revealed extramedullary hematopoiesis (EMH) with abnormal megakaryocytes as well as myeloid and erythroid precursors. After unsuccessful tetracycline pleurodesis, talcum slurry was instilled via the chest tube without recurrence of the pleural effusion. Furthermore, treatment with hydroxyurea was started, and the disease regressed and then remained stable over the next 24 months. In conclusion, the pleuropulmonary findings were caused by EMH due to chronic idiopathic myelofibrosis. The definite diagnosis was established by pleuroscopy followed by successful pleurodesis with talc slurry, after tetracycline pleurodesis had failed.
  Respiration 09/2008; 78(1):110-3. · 2.26 Impact Factor
• Article: [Immune reconstitution inflammatory syndrome (IRIS) of the small bowel in an immunocompromised patient suffering from systemic lupus erythematosus and non-tuberculous mycobacteriosis].

  S Daum, V Moos, C Loddenkemper, C Schürmann, E Märker-Hermann, H Stein, M Zeitz, T Schneider
  [show abstract] [hide abstract]
  ABSTRACT: An overwhelming immune reaction resulting in granulomatous inflammation after infection with opportunistic pathogens is termed immune reconstitution inflammatory syndrome (IRIS). It has mainly been described in patients with human immunodeficiency virus (HIV) infection on highly active antiretroviral therapy (HAART) who show a significant increase of low CD4 T cells (initially <50/microl). IRIS may lead to organ damage and differential diagnosis is often difficult. We report the case of a 38-year-old female patient who developed a Mycobacteria genavense infection of the liver and the bowel after several immunosuppressive therapies for systemic lupus erythematosus. CD4 T cell counts as low as 17/microl were found and immunosuppressive therapy was stopped. Despite several courses of antibiotic treatment and rising CD4 T cell counts, severe malabsorption persisted. Upper endoscopy revealed a continuous inflammation with pseudopolyps of the small bowel and histologically, a granulomatous infiltrate was detected. After exclusion of a persisting infection by Mycobacteria genavense, IRIS of the small bowel was suspected and treatment with prednisolone was started. The clinical and histological picture improved significantly, the number of CD25(+)CD4(+) cells decreased in the lamina propria of the duodenum under treatment with prednisolone and Foxp3+ regulatory T cells (Treg) accumulated around granulomas. This case shows that IRIS is not restricted to HIV patients but may also occur in otherwise immunosuppressed patients. Due to different treatment strategies, distinguishing IRIS from infectious diseases is essential. The role of Treg in IRIS has to be elucidated.
  Zeitschrift für Rheumatologie 07/2008; 67(4):277-8, 280-3. · 0.46 Impact Factor