Manfred Wehrmann

Universitätsklinikum Tübingen, Tübingen, Baden-Württemberg, Germany

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Publications (129)400.25 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Although the prognosis of differentiated thyroid carcinoma (DTC) is excellent, with 10-year survival rates of about 90%, about one-third of patients experiences recurrent disease. We aimed to identify novel histological prognostic factors to optimize treatment and follow-up of patients at risks. Retrospective analysis of patients diagnosed from January 1990 to March 2004. A total of 93 patients diagnosed with DTC of which 67 with papillary and 26 with follicular histology. Analysis of immunohistochemical expression of somatostatin receptor (sst) subtypes 1-5, glucose transporter-1 (GLUT-1), receptor tyrosine kinase c-KIT, oestrogen and progesterone receptors, and proliferation marker Ki-67 and correlation with the patients' clinical outcome. DTC showed immunohistochemical expression of GLUT-1, C-KIT and progesterone receptor in a high percentage of cases (range: 57-80%). In contrast, the oestrogen receptor as well as the sst subtypes 1-5 was less frequently detected (range: 15-29%). Mean staining of the proliferation marker Ki-67 was 6% positive cells (range 0-20%). Ki-67 expression was significantly associated with tumour staging (ρ = 0·2076, P = 0·0459), whereas the other histopathological markers were not associated with gender, age, tumour entity, or tumour classification. Tumour staging and expression of Ki-67, oestrogen receptor and sst2, but of none of the other histopathological factors, independently predicted the clinical outcome 5 years after definitive treatment (P < 0·0001, P < 0·0001, P = 0·0004 and P = 0·0206, respectively). In patients with DTC, Ki-67 expression associates with tumour staging and clinical outcome.
    Clinical Endocrinology 01/2012; 77(1):139-45. DOI:10.1111/j.1365-2265.2012.04343.x · 3.35 Impact Factor
  • DMW - Deutsche Medizinische Wochenschrift 07/2011; 136(28-29):1476. DOI:10.1055/s-0030-1247626 · 0.55 Impact Factor
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    ABSTRACT: To report the safety and diagnostic performance of magnetic resonance (MRI)--guided core biopsy of osseous lesions in children with chronic recurrent multifocal osteomyelitis (CRMO) that were visible on MRI but were occult on radiography and computed tomography (CT). A retrospective analysis of MRI-guided osseous biopsy performed in seven children (four girls and three boys; mean age 13 years (range 11 to 14) with CRMO was performed. Indication for using MRI guidance was visibility of lesions by MRI only. MRI-guided procedures were performed with 0.2-Tesla (Magnetom Concerto; Siemens, Erlangen, Germany; n = 5) or 1.5-T (Magnetom Espree; Siemens; n = 2) open MRI systems. Core needle biopsy was obtained using an MRI-compatible 4-mm drill system. Conscious sedation or general anesthesia was used. Parameters evaluated were lesion visibility, technical success, procedure time, complications and microbiology, cytology, and histopathology findings. Seven of seven (100%) targeted lesions were successfully visualized and sampled. All obtained specimens were sufficient for histopathological analysis. Length of time of the procedures was 77 min (range 64 to 107). No complications occurred. Histopathology showed no evidence of malignancy, which was confirmed at mean follow-up of 50 months (range 28 to 78). Chronic nonspecific inflammation characteristic for CRMO was present in four of seven (58%) patients, and edema with no inflammatory cells was found in three of seven (42%) patients. There was no evidence of infection in any patient. MRI-guided osseous biopsy is a safe and accurate technique for the diagnosis of pediatric CRMO lesions that are visible on MRI only.
    CardioVascular and Interventional Radiology 02/2011; 35(1):146-53. DOI:10.1007/s00270-011-0119-9 · 1.97 Impact Factor
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    ABSTRACT: Chronic sinusitis is almost invariably a feature of cystic fibrosis. However, data on the endoscopically confirmed prevalence of chronic polypoid sinusitis (CPS) and its histological features are limited. Single centre prospective observational study. Unselected pediatric CF patients (n=81; ≤ 18 years) were endoscopically assessed for the prevalence of CPS. Sixteen of these underwent sinus surgery. The surgically obtained sinus specimens were compared to sinus specimen of non-CF-patients undergoing sinus surgery (n=61), using conventional histology and immunohistochemistry. The prevalence of endoscopically confirmed CPS increased with age from 19% in infants younger than six years reaching 45% in adolescents. In CF patients, histology typically showed dilated glandular ducts and a predominance of mucous glands. The number of plasma cells and mast cells but not of eosinophils was significantly elevated compared to non-CF patients. Prevalence of CPS in pediatric CF patients increases with age. Our findings indicate that chronic bacterial infection rather than allergic mechanisms may forward this pathology.
    Journal of cystic fibrosis: official journal of the European Cystic Fibrosis Society 02/2011; 10(3):181-6. DOI:10.1016/j.jcf.2011.01.003 · 3.82 Impact Factor
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    ABSTRACT: Up to 8% of patients with gluten sensitivity (GS) develop neurological symptoms such as ataxia, dementia, seizures or peripheral neuropathy. The underlying immunological mechanisms still remain to be elucidated. We here report the case of a 68-year-old male patient suffering from progressive ataxia and dementia associated with chronic diarrhea and both elevated IgG and IgA antigliadin-antibodies. At autopsy, frequent argyrophilic glial and neuronal inclusions within the basal nucleus of Meynert were considered as the structural correlative for the cognitive decline. Significant neuronal loss in the cerebellar cortex and the inferior olives was accompanied by infiltrating CD8(+)/perforin(+)/granzyme B(+) cells as well as reactive astrogliosis and microglial activation. These CD8(+) cytotoxic T and NK cells are likely to act as effector cells responsible for neuronal cell death in patients with gluten sensitivity and neurological disease and might therefore at least partly be responsible for cerebellar symptoms in gluten ataxia. In conclusion, our results, showing an absence of B- or plasma cells but multiple CD8(+) as well as granzyme B and perforin expressing cells in ataxia-associated brain areas, suggest that there are also prominent cytotoxic effects in neuropathogenesis of GS.
    Neuropathology 08/2009; 30(1):92-6. DOI:10.1111/j.1440-1789.2009.01042.x · 1.80 Impact Factor
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    ABSTRACT: Availability of an individualized preselection of oncolytic viruses to be used for virotherapy of tumor patients would be of great help. Using primary liver tumor resection specimens we evaluated the precision-cut liver slice (PCLS) technology as a novel in vitro test system for characterization of paramount tumor infection parameters of individual patients. PCLS slices from resection specimens of 20 liver tumor patients were cultivated in vitro for up to 5 days and infected with 5 different oncolytic measles vaccine virus (MeV) strains. Effectiveness of tumor infection was monitored by viral nucleocapsid (N) protein detection in immunofluorescence staining or Western blot analysis or by detection of GFP marker gene expression. MeV spreading in PCLS cultures was visualized by confocal microscopy. Oncolytic MeV vaccine particles were demonstrated to efficiently infect PCLS slices originating from different primary and secondary tumors of the liver with MeV strains Moraten/Edmonston Zagreb and AIK-C showing highest infection rates (75% of all tested tumor specimens). Employing mixed liver tissue slices (exhibiting both tumorous and non-tumorous tissue areas on one and the same sample) a distinct tumor area favouring pattern of MeV infections was observed being in accordance with our finding that primary human hepatocytes are also permissive to MeV particles, albeit at a much lower rate and with a much less pronounced cytopathic effect. Furthermore, confocal microscopy demonstrated virus penetration throughout tumor tissues into deep cell layers. In conclusion, the PCLS technology is suitable to perform a tumor-patient individualized preselection of oncolytic agents prior to clinical virotherapeutic applications.
    International Journal of Oncology 06/2009; 34(5):1247-56. DOI:10.3892/ijo_00000253 · 3.03 Impact Factor
  • Gastroenterology 05/2009; 136(5). DOI:10.1016/S0016-5085(09)62862-6 · 13.93 Impact Factor
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    ABSTRACT: Sacrococcygeal teratomas (SCTs) are benign tumours of the newborn with absolute indication for surgery directly after birth. We recently described the presence of stem cells positive for the stem cell markers nanog and Oct4 in SCTs. Here we report the isolation of three stem cell lines from three different SCTs. Cells were propagated in mesenchymal or in embryonic stem cell medium. Non-clonal homogeneous stem cell lines were obtained after two to three passages and characterized in vitro by immunocytochemistry, RT-PCR, western blot, FACS analysis, and metaphase spreads. The differentiation potential was tested in vitro and in vivo. The isolated cell lines, which we refer to as human sacrococcygeal teratoma stem cells (hSctSCs), express nanog, Oct4 and stella, and are negative for malignancy markers alpha-fetoprotein and carcinoembryonic antigen. They can be induced in vitro to express neuronal, osteogenic, and chondrogenic traits. After grafting in vivo, spontaneous integration into the neural crest of the chick embryo and teratoma formation in the nude mouse were obtained. Our results indicate that SCTs are derived from remnants of the epiblast-derived primitive streak, which in the human embryo normally regresses but forms teratomas in children affected with SCT. The hSctSCs therefore may be comparable to mouse epiblast-derived stem cells (EpiSCs) and share characteristic features with human embryonic stem (hES) cells. Thus, SCT tissue obtained after surgery appears to be a novel source for the generation of human stem cells without the ethical implications associated with hES cells.
    The Journal of Pathology 03/2009; 217(4):589-96. DOI:10.1002/path.2486 · 7.43 Impact Factor
  • Karsten Müssig · Manfred Wehrmann · Marius Horger
    Fertility and sterility 02/2009; 91(2):656. DOI:10.1016/j.fertnstert.2008.01.033 · 4.59 Impact Factor
  • C Busch · M Oppitz · M Wehrmann · P Schweizer · U Drews
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    ABSTRACT: To study the range of differentiation and presence of cells positive for stem cell markers in 20 sacrococcygeal teratomas (SCTs) which were consecutively operated on between 1990 and 2000 in the Department of Paediatric Surgery in Tübingen, Germany. Preserved paraffin-embedded material was re-evaluated. In addition to tissues of various organs, caudal organ structures not described before were identified, such as colon with pancreas originating from colonic crypts, Fallopian tube and vaginal epithelia. The derivation of the latter was confirmed by Müllerian duct specific CA125 and CA19-9 antibodies. The expression of stem cell markers was studied with antibodies against nanog, Oct4, SSEA-4, nestin and subtype M3 muscarinic receptors. Cells positive for these markers were encountered in immature end buds and capillary sprouts, and as single cells in neural tissue, gonadal structures, hairs and in the stem cell niches of differentiated epithelia. Our data indicate that SCTs of the newborn arise from remnants of the epiblast-like tail bud blastema and demonstrate that they contain cells positive for embryonic stem cell markers and may represent a novel source for human embryonic stem cells.
    Histopathology 06/2008; 52(6):717-30. DOI:10.1111/j.1365-2559.2008.03017.x · 3.30 Impact Factor
  • Emergency Medicine Journal 05/2008; 25(4):242. DOI:10.1136/emj.2007.052076 · 1.78 Impact Factor
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    ABSTRACT: OBJECTIVE: Our objective was to describe the spectrum of MRI features in patients with deep and generalized morphea. CONCLUSION: Imaging features of morphea are not specific and usually overlap with those of other disorders involving the skin, fascia, and musculature, such as some types of fasciitis, myositis, and so forth. Nevertheless, the imaging features of morphea reflect pathomorphologic changes of this rare disorder and enable a complete assessment of the disease extent, including depth of infiltration and disease activity.
    American Journal of Roentgenology 02/2008; 190(1):32-9. DOI:10.2214/AJR.07.2163 · 2.74 Impact Factor
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    Brain Pathology 02/2008; 18(1):100-2, 141. DOI:10.1111/j.1750-3639.2007.00115_3.x · 4.35 Impact Factor
  • Pancreas 02/2008; 36(1):92-5. DOI:10.1097/MPA.0b013e318149f536 · 3.01 Impact Factor
  • Raimund Kottke · Marius Horger · Heiko Schimmel · Manfred Wehrmann
    American Journal of Roentgenology 12/2007; 189(5):W247-50. DOI:10.2214/AJR.05.1455 · 2.74 Impact Factor
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    ABSTRACT: A 54-year-old woman with voiding difficulties was referred to our department. She complained about a slow urine stream, hesitancy, straining when voiding and the feeling of incomplete emptying. The gynaecological examination revealed a 4x3 cm pelvic tumour. The tumour was well circumscribed in the retropubic space between the symphysis and the bladder neck sonographically and by magnetic resonance imaging and was closed off from neighbouring structures. After removal of the tumour, the voiding problems were reversed, and the patient has remained asymptomatic. The histological examination showed a leiomyoma with high vascularisation. This case report showed that retropubic tumours can obstruct the urethra and cause voiding dysfunctions. Consequently, this needs to be considered in the differential diagnosis.
    International Urogynecology Journal 11/2007; 18(10):1229-31. DOI:10.1007/s00192-007-0337-5 · 2.16 Impact Factor
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    ABSTRACT: Humoral hypercalcaemia is a common complication of malignancy with parathyroid hormone-related protein (PTHrP) as a major cause. Breast and lung cancer are relatively common sources of ectopic PTHrP secretion leading to increased osteoclastic bone resorption. We report the rare case of a 40-year-old man with severe hypercalcaemia due to a PTHrP-secreting poorly differentiated endocrine carcinoma of the pancreas. On immunohistochemistry, the tumour was positive for PTHrP and somatostatin receptors sst1, sst2, and sst3, whereas sst4 and sst5 were not detected. We demonstrate the transient improvement of hypercalcaemia after adding octreotide to the treatment mainstays in hypercalcaemia of malignancy (fluid repletion, administration of bisphosphonates, loop diuretics, and glucocorticoids). To the best of our knowledge, this is the first report showing somatostatin receptor expression in a PTHrP-secreting pancreatic neuroendocrine tumour.
    European Journal of Gastroenterology & Hepatology 09/2007; 19(8):719-23. DOI:10.1097/01.meg.0000223908.00987.18 · 2.15 Impact Factor
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    ABSTRACT: Small cell lung carcinoma (SCLC) is frequently associated with a paraneoplastic syndrome. We report on a rare case of SCLC presenting with syndrome of inappropriate antidiuretic hormone (SIADH) secretion and ectopic ACTH production. In accordance with the endocrine evaluation, immunohistochemical staining of the tumour was positive for ADH and ACTH. Chemotherapy with etoposide and carboplatin induced a nearly complete remission. Simultaneous secretion of ADH and ACTH is infrequently reported with only five cases described in the literature. SIADH in patients with ectopic ACTH syndrome may be underdiagnosed due to the antagonistic hormone actions of cortisol and ADH on renal sodium excretion.
    Lung Cancer 08/2007; 57(1):120-2. DOI:10.1016/j.lungcan.2007.03.003 · 3.74 Impact Factor
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    ABSTRACT: Acute lung injury (ALI), such as that which occurs with mechanical ventilation, contributes to morbidity and mortality of critical illness. Nonetheless, in many instances, ALI resolves spontaneously through unknown mechanisms. Therefore, we hypothesized the presence of innate adaptive pathways to protect the lungs during mechanical ventilation. In this study, we used ventilator-induced lung injury as a model to identify endogenous mechanisms of lung protection. Initial in vitro studies revealed that supernatants from stretch-induced injury contained a stable factor which diminished endothelial leakage. This factor was subsequently identified as adenosine. Additional studies in vivo revealed prominent increases in pulmonary adenosine levels with mechanical ventilation. Because ectoapyrase (CD39) and ecto-5'-nucleotidase (CD73) are rate limiting for extracellular adenosine generation, we examined their contribution to ALI. In fact, both pulmonary CD39 and CD73 are induced by mechanical ventilation. Moreover, we observed pressure- and time-dependent increases in pulmonary edema and inflammation in ventilated cd39(-/-) mice. Similarly, pharmacological inhibition or targeted gene deletion of cd73 was associated with increased symptom severity of ventilator-induced ALI. Reconstitution of cd39(-/-) or cd73(-/-) mice with soluble apyrase or 5'-nucleotidase, respectively, reversed such increases. In addition, ALI was significantly attenuated and survival improved after i.p. treatment of wild-type mice with soluble apyrase or 5'-nucleotidase. Taken together, these data reveal a previously unrecognized role for CD39 and CD73 in lung protection and suggest treatment with their soluble compounds as a therapeutic strategy for noninfectious ALI.
    The Journal of Immunology 07/2007; 178(12):8127-37. DOI:10.4049/jimmunol.178.12.8127 · 5.36 Impact Factor
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    ABSTRACT: Innovative epigenetic therapeutics comprise histone deacetylase inhibitors (HDAC-I) and demethylating agents (DA). It was recently found that HDAC-I compounds exhibit profound therapeutic activities against hepatocellular carcinoma (HCC). A comprehensive preclinical investigation was performed on the potential of a combined HDAC-I/DA epigenetic regimen for the highly chemotherapy-resistant HCC entity. Human HCC-derived cell lines or primary human hepatocytes (PHH) were treated with HDAC-I compound suberoylanilide hydroxamic acid (SAHA) or DA compound 5-aza-2'-deoxycytidine (5-aza-dC) or both and examined for cellular damage, proliferation, histone acetylation pattern, and DNA methylation. In vivo activities were investigated in a xenograft hepatoma model. Monotherapeutic application of SAHA or 5-aza-dC was found to induce substantial antiproliferative effects in HCC-derived cells, strongly enhanced by combined SAHA and 5-aza-dC treatment. PHH from different human donors did not exhibit any relevant cellular damage even when applying high doses of the combination regimen, whereas HCC-derived cell lines showed a dose-dependent damage. In vivo testing demonstrated a statistical significant inhibition of hepatoma cell growth for the combined treatment regime. Because the combined HDAC-I/DA epigenetic approach was found to produce significant antitumor effects in HCC model systems and did not impair cellular integrity of untransformed hepatocytes, this combination therapy is now considered for further investigation in clinical trials.
    Cancer 05/2007; 109(10):2132-41. DOI:10.1002/cncr.22652 · 4.90 Impact Factor

Publication Stats

2k Citations
400.25 Total Impact Points

Institutions

  • 2002–2012
    • Universitätsklinikum Tübingen
      • • Department of General, Visceral and Transplant Surgery
      • • Department of Anesthesiology and Intensive Care Medicine
      Tübingen, Baden-Württemberg, Germany
  • 1989–2011
    • University of Tuebingen
      • • Institute of Pathology and Neuropathology
      • • Department of Internal Medicine
      • • Department of Orthopaedic Surgery
      • • Department of Ethnology
      Tübingen, Baden-Württemberg, Germany