Carsten Schmidt

Universitätsklinikum Jena, Jena, Thuringia, Germany

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Publications (30)187.81 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: To detect high risk patients with a progressive disease course of ulcerative colitis (UC) requiring immunosuppressive therapy (IT).
    World journal of gastroenterology : WJG. 09/2014; 20(35):12574-80.
  • Harald Farnik, Marlene Driller, Thomas Kratt, Carsten Schmidt, Martin Faehndrich, Mireen Friedrich-Rust, Natalie Filmann, Alfred KöNigsrainer, Andreas Stallmach, Michael Heike, Stefan Zeuzem, Joerg G. Albert
    Gastrointestinal Endoscopy 05/2014; 79(5):AB335. · 4.90 Impact Factor
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    ABSTRACT: Inflammatory bowel disease (IBD) is a frequently occurring disease in young people, which is characterized by a chronic inflammation of the gastrointestinal tract. The therapy of IBD is dominated by the administration of anti-inflammatory and immunosuppressive drugs, which suppress the intestinal inflammatory burden and improve the disease-related symptoms. Established treatment strategies are characterized by a limited therapeutical efficacy and the occurrence of adverse drug reactions. Thus, the development of novel disease-targeted drug delivery strategies is intended for a more effective therapy and demonstrates the potential to address unmet medical needs. This review gives an overview about the established as well as future-oriented drug targeting strategies, including intestine targeting by conventional drug delivery systems (DDS), disease targeted drug delivery by synthetic DDS and disease targeted drug delivery by biological DDS. Furthermore, this review analyzes the targeting mechanisms of the respective DDS and discusses the possible field of utilization in IBD.
    Advanced drug delivery reviews 10/2013; · 11.96 Impact Factor
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    ABSTRACT: The systemic therapy of inflammatory bowel diseases (IBD) by oral administration of anti-inflammatory and immunosuppressive agents is characterized by an increased probability of adverse drug reactions. A successful treatment with a simultaneous reduction of adverse events may be achieved by the administration of micro- and nanosized targeted drug delivery systems, which accumulate selectively in inflamed mucosal areas without systemic absorption. We described in a first in vivo study in IBD patients a significantly enhanced, but minor accumulation of non-functionalized poly(lactic-co-glycolic acid) (PLGA) microparticles in ulcerous lesions very recently. The aim of this study was therefore the assessment of an increased targeting potential of different non-, chitosan- and polyethylene glycol (PEG)-functionalized PLGA micro- and nanoparticles to inflamed intestinal mucosa compared to healthy mucosa. For the quantification of nano- and microparticles, fluoresceinamine-labeled-PLGA was synthesized by carbodiimide reaction. Fluorescent chitosan-, PEG-, and non-functionalized PLGA micro- and nanoparticles with mean hydrodynamic diameters of 3000 nm and 300 nm were prepared by solvent evaporation technique. The targeting efficiencies in terms of particle translocation and deposition were investigated in Ussing chamber experiments. Healthy and inflamed macrobiopsies were received from routine endoscopic examinations of patients with IBD as well as control patients. 101 Ussing chamber experiments of patients with IBD (Crohńs disease: n = 7 and ulcerative colitis: n = 9) as well as healthy control patients (n=5) were performed. Histomorphological and electrophysiological investigations of inflamed mucosal tissues confirmed a significant alteration of mucosal barrier integrity in IBD patients (TER: healthy: 34.1 Ω x cm(2); inflamed: 21.6 Ω x cm(2); p=0.034). In summary, nanoparticles showed an increased translocation and deposition compared to microparticles in healthy and in inflamed mucosa. Chitosan-functionalized particles adhered onto the tissue surface and thus showed the lowest particle translocation and deposition in healthy and inflamed tissues. PEG-functionalized nanoparticles showed the highest translocation through healthy (2.31%) and inflamed mucosa (5.27%). Moreover, PEG-functionalized microparticles showed a significantly increased translocation through inflamed mucosa (3.33%) compared to healthy mucosa (0.55%; p=0.045). Notably, the particle deposition of PEG-functionalized microparticles was significantly increased in inflamed mucosa (10.8%) compared to healthy mucosa (4.1%; p=0.041). Based on the targeted translocation and deposition to inflamed intestinal mucosa, PEG-functionalized PLGA microparticles were qualified as an innovative drug delivery system. These particles may serve as a selective treatment strategy to inflamed mucosal areas in IBD with the potential to improve therapeutic efficacy and to reduce adverse events.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 09/2013; · 3.15 Impact Factor
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    ABSTRACT: BACKGROUND:: The correlation between noninvasive markers with endoscopic activity according to the modified Baron Index in patients with ulcerative colitis (UC) is unknown. We aimed to evaluate the correlation between endoscopic activity and fecal calprotectin (FC), C-reactive protein (CRP), hemoglobin, platelets, blood leukocytes, and the Lichtiger Index (clinical score). METHODS:: UC patients undergoing complete colonoscopy were prospectively enrolled and scored clinically and endoscopically. Samples from feces and blood were analyzed in UC patients and controls. RESULTS:: We enrolled 228 UC patients and 52 healthy controls. Endoscopic disease activity correlated best with FC (Spearman's rank correlation coefficient r = 0.821), followed by the Lichtiger Index (r = 0.682), CRP (r = 0.556), platelets (r = 0.488), blood leukocytes (r = 0.401), and hemoglobin (r = -0.388). FC was the only marker that could discriminate between different grades of endoscopic activity (grade 0, 16 [10-30] μg/g; grade 1, 35 [25-48] μg/g; grade 2, 102 [44-159] μg/g; grade 3, 235 [176-319] μg/g; grade 4, 611 [406-868] μg/g; P < 0.001 for discriminating the different grades). FC with a cutoff of 57 μg/g had a sensitivity of 91% and a specificity of 90% to detect endoscopically active disease (modified Baron Index ≥2). CONCLUSIONS:: FC correlated better with endoscopic disease activity than clinical activity, CRP, platelets, hemoglobin, and blood leukocytes. The strong correlation with endoscopic disease activity suggests that FC represents a useful biomarker for noninvasive monitoring of disease activity in UC patients.
    Inflammatory Bowel Diseases 01/2013; · 5.12 Impact Factor
  • Proceedings of the 17th Annual Conference in Medical Image Understanding and Analysis (MIUA); 01/2013
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    ABSTRACT: Most of the drugs used in the treatment of inflammatory bowel disease (IBD) become systemically bioavailable and potentially bear strong adverse effects. Targeting inflamed areas of the intestine and keeping the drug localised at its site of action can reduce adverse effects. In animal studies, luminal uptake into inflamed mucosal areas has been shown to be size dependent. We investigated the potential of nano- and microparticle uptake into the rectal mucosa of human IBD patients. Fluorescently labelled placebo nanoparticles (NP) 250nm in size and microparticles (MP) 3.0μm in size were prepared. Two hours after rectal application to patients with Crohn´s disease (CD) or ulcerative colitis (UC), confocal laser endomicroscopy was performed to visualize particles in inflamed mucosal areas. In biopsies, ex vivo mucosal transport processes were investigated in miniaturised Ussing chambers. We examined 33 patients with IBD (19 patients with CD, 14 patients with UC) and 6 healthy controls. A significantly enhanced accumulation of MP in ulcerous lesions was observed (covered area=1.28% (range 0.83% - 3.45%) vs. 0% in controls; p=0.011), while NP were visible only in traces on mucosal surfaces of all patients. Ussing chamber experiments suggest persorption of particles through cellular voids; statistical significance was only reached for NP. Drug-containing particles may have great potential to more specifically target intestinal lesions to maximise therapeutic efficacy and minimise potential side effects. Nanoparticles may not be required for local drug delivery to intestinal lesions in humans, thereby minimizing the risk of unintended translocation into the blood system.
    Journal of Controlled Release 11/2012; · 7.63 Impact Factor
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    ABSTRACT: The clinical course of Crohn's disease (CD) is highly variable with a subgroup of patients developing a progressive disease course necessitating immunosuppressive therapy (IT). However, reliable, stable and non-invasive individual clinical parameters in order to identify patients at risk for undergoing subsequent IT have not been sufficiently established. We therefore aimed to identify such clinical parameters. A retrospective, multicenter analysis of CD patients from 6 German tertiary IBD centers was performed. Patients were classified into two groups depending on requiring IT or not. Personal data, clinical and laboratory parameters during the first 3 months after CD diagnosis and effects of initial medical therapy were compared between these two groups. In 218 (61.8%) of the 353 patients the CD course necessitated IT. Those patients were significantly younger at symptom onset and diagnosis, and required significantly more often a systemic corticosteroid therapy. Furthermore, significant differences in serological markers of inflammation were observed. Age, gender and the effect of initial steroid therapy were used to develop a prognostic model predicting the individual probability of necessitating IT. The simple clinical items age at diagnosis, gender, and need for systemic steroid therapy can predict a progressive disease course in early CD. Our model based on these parameters allows an individualized estimation of each patient's risk to develop a progressive disease course. Thereby, our model can help in deciding if patients will need immunosuppressive drugs early in the disease course or if a careful watch and wait strategy is justified.
    Journal of Crohn s and Colitis 02/2012; 6(1):21-8. · 3.56 Impact Factor
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    ABSTRACT: Recent studies demonstrated that depression was associated with mucosal inflammation in patients with ulcerative colitis (UC). This association had not been studied in patients with UC with ileal pouch-anal anastomosis (IPAA) after restorative proctocolectomy. We hypothesized that depression and mucosal proinflammatory cytokines in UC-patients with pouchitis were associated. We assessed 18 IPAA-UC-patients with pouchitis and 19 IPAA-UC-patients without pouchitis. Mucosal biopsies were taken from the areas with maximal inflammation in the pouch or from the posterior wall of the pouch if the pouch had a normal endoscopic appearance. Disease activity was assessed by the Pouch Disease Activity Index. The expression of mucosal proinflammatory gene transcripts (interleukin-8 [IL-8] and interleukin-1ß [IL-1b]) was quantified by real-time polymerase chain reaction. Depression was assessed by the Hospital Anxiety and Depression Scale (HADS). Pearson correlations between depression and cytokine transcripts were calculated. The correlation of HADS depression scores of patients with pouchitis with IL-8 was r=0.51 (p=0.03) and with IL-1ß was r=0.47 (p=0.04). The correlation between the HADS depression scores of patients without pouchitis with IL-8 was r=-0.19; (p=0.21) and with IL-1ß was r=-0.12 (p=0.30). Depression is associated with mucosal proinflammatory cytokines in patients with pouchitis after restorative proctocolectomy in patients with UC.
    Journal of Crohn s and Colitis 09/2011; 5(4):350-3. · 3.56 Impact Factor
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    ABSTRACT: Gastrointestinal cancer is a major public health problem worldwide. Detection of early neoplastic lesions in gastrointestinal tract is essential for cure, because prognosis and survival are related to the size and stage of malignant lesions. Endoscopic screening and treatment of polyps could prevent approximately 80% of colorectal cancer (CRC). However, white-light endoscopy is an imperfect technology since miss rates of up to 25% have been reported and polyps without malignant potential were treated without benefit but with additional costs and risks to the patient. There are several known "human" predictors of an inadequate colonoscopy. These include patient characteristics such as poor bowel preparation, female gender, or inpatient status. Skills of the endoscopists are also an important issue. Therefore, a variety of advanced technologies has been attempted to overcome these issues. These new endoscopic imaging techniques allow a more precise classification of mucosal alterations with selection of patients for invasive therapy or surveillance. Further, molecular and functional imaging techniques could identify novel targets for therapies and new prospects to access response to therapies. However, at the "end of the day" a better endoscopic approach for CRC screening and surveillance depends on a good bowel preparation, a trained endoscopist spending sufficient time on a detailed examination together with an advanced endoscope.
    Journal of Biophotonics 06/2011; 4(7-8):482-9. · 3.86 Impact Factor
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    ABSTRACT: Population ageing is a global phenomenon. People aged 65 years and older comprise approximately 16% of the population of Europe. The medical management of elderly patients with inflammatory bowel disease (IBD) is challenging with respect to diagnosis, pharmaceutical and surgical treatment, and complications. IBD has a late onset in 10%-15% of patients, with the first flare occurring at 60 to 70 years of age; others suffer from the disease for several decades. Even though the natural course of the disease in geriatric populations and the diagnostic options may not differ much from those in younger patients, distinct problems exist in the choice of medical therapy. Recommended clinical practise has been rapidly evolving towards an intensified initial treatment in IBD. However, in patients older than 65 years, a gentler approach should be used, and a combination of immunosuppressive agents should be avoided because of increased risk of infectious and neoplastic complications. Furthermore, elderly patients with severe IBD show prolonged, complicated post-operative clinical courses with worse hospital outcomes, so early surgical intervention for elderly patients is recommended. This article provides an overview of elderly IBD patient care, including medical and surgical therapeutic considerations and emphasises the necessity of close collaborations between gastroenterologists and surgeons.
    Journal of Crohn s and Colitis 06/2011; 5(3):177-88. · 3.56 Impact Factor
  • Carsten Schmidt, Juliane Kaden, Andreas Stallmach
    Gastrointestinal Endoscopy 04/2011; 73(4). · 4.90 Impact Factor
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    ABSTRACT: Complementary therapies are frequently used by patients with inflammatory bowel disease (IBD). The aim of this study was to evaluate the efficacy and safety of long-term therapy with a new Boswellia serrata extract (Boswelan, PS0201Bo) in maintaining remission in patients with Crohn's disease (CD). In 22 German centers a double-blind, placebo-controlled, randomized, parallel study was performed. In all, 108 outpatients with CD in clinical remission were included. Patients were randomized to Boswelan (3×2 capsules/day; 400 mg each) or placebo for 52 weeks. The primary endpoint was the proportion of patients in whom remission was maintained throughout the 52 weeks. Secondary endpoints were time to relapse, changes of Crohn's Disease Activity Index (CDAI), and IBD Questionnaire (IBDQ) scores. The trial was prematurely terminated due to insufficient discrimination of drug and placebo with regard to the primary efficacy endpoint. A total of 82 patients were randomized to Boswelan (n=42) or placebo (n=40). Sixty-six patients could be analyzed for efficacy. 59.9% of the actively treated patients and 55.3% of the placebo group stayed in remission (P=0.85). The mean time to diagnosis of relapse was 171 days for the active group and 185 days for the placebo group (P=0.69). With respect to CDAI, IBDQ, and laboratory measurements of inflammation, no advantages in favor of active treatment were detected. Regarding safety concerns, no disadvantages of taking the drug compared to placebo were observed. The trial confirmed good tolerability of a new Boswellia serrata extract, Boswelan, in long-term treatment of CD. However, superiority versus placebo in maintenance therapy of remission could not be demonstrated.
    Inflammatory Bowel Diseases 02/2011; 17(2):573-82. · 5.12 Impact Factor
  • Carsten Schmidt, Utz Settmacher, Andreas Stallmach
    Gastroenterology 01/2011; 140(5). · 12.82 Impact Factor
  • Gastroenterology 05/2010; 138(5). · 12.82 Impact Factor
  • Gastroenterology 05/2010; 138(5). · 12.82 Impact Factor
  • Carsten Schmidt, Andreas Stallmach
    Gastroenterology 01/2009; 136(5). · 12.82 Impact Factor
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    ABSTRACT: Nowadays, it is considered as an established fact that patients with long-standing ulcerative colitis (UC) are at an increased risk of developing colorectal cancer (CRC). Although data for CRC risk in Crohn's disease (CD) are not as extensive, it has been suggested that the risks are comparable to UC. Current strategies for the prevention and early detection of cancer in this high-risk population are grounded in the concept of an inflammation-neoplasia-carcinoma sequence. To reduce CRC mortality in inflammatory bowel disease, colonoscopic surveillance with random and targeted biopsies were recommended to detect early neoplasia. The introduction of novel endoscopic techniques such as chromoendoscopy, narrow band imaging or confocal endomicroscopy to facilitate targeted biopsy has become increasingly associated with enhanced neoplasia detection. However, there is only indirect evidence that such surveillance strategies are likely to be effective at reducing the risk of death from inflammatory bowel disease-associated CRC. Further, new data revealed that surveillance strategies largely based upon disease duration delayed or missed a substantial number of patients with early CRC. Therefore, actual surveillance guidelines seem to be insufficient and need to be restructured.
    Digestive Diseases 01/2009; 27(4):584-90. · 2.73 Impact Factor
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    ABSTRACT: Inflammatory bowel diseases (IBDs; ulcerative colitis, UC, and Crohn's disease, CD) show familial clustering suggestive of a genetic background. A linkage susceptibility region for these diseases (IBD9) lies on chromosome 3p and includes the DNA mismatch repair gene MLH1. Loss of MLH1 confers the characteristic microsatellite instability (MSI) phenotype which is also frequently found in the mucosa of IBD patients. A common germline alteration of MLH1 (655A>G) results in the amino acid exchange MLH1 I219V. Conflicting data exist on its effect on the function of the protein and it has recently been reported to cosegregate with refractory UC, suggesting that this alteration may impair mismatch repair activity and thereby contribute to certain forms of UC. We analyzed the MLH1 I219V alteration using in silico and biochemical analyses and assessed its appearance in 67 well-classified UC patients in comparison to 40 healthy individuals. The analyses showed that I219 is a conserved, buried hydrophobic residue, and that I219V is unlikely to abolish MLH1 function but may modulate it. Quantitative biochemical evaluation showed identical stability and activity of the protein. Furthermore, the alteration occurred equally frequently in analyzed patients and healthy volunteers. The MLH1 I219V alteration does not directly contribute to the etiology of UC through an impairment of mismatch repair. A putative linkage disequilibrium of MLH1 I219V with the causative gene(s) of the IBD9 locus is rather distant.
    Inflammatory Bowel Diseases 05/2008; 14(5):605-11. · 5.48 Impact Factor
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    ABSTRACT: Pouchitis and irritable pouch syndrome (IPS) are 2 of the most frequent sequelae of ileal pouch-anal anastomosis (IPAA) after restorative proctocolectomy in patients with ulcerative colitis. These complications can compromise the gain in health-related quality of life (HRQOL) substantially. The pathophysiological mechanisms underlying IPS and the predictors of HRQOL in IPS have not been studied so far. In IPAA patients in remission (n = 10), patients with pouchitis (n = 18) and patients with IPS (n = 15) symptoms, endoscopical and histological patterns, anxiety and depressiveness (Hospital Anxiety and Depression Scale HADS), and HRQOL scores (Inflammatory Bowel Disease Questionnaire, IBDQ-D) were assessed. Mucosal expression of 5 proinflammatory gene transcripts (MRP-14, IL-1beta, IL-8, MIP-2alpha, and MMP-1) were quantified using real-time polymerase chain reaction. Clinical symptoms and HRQOL differed significantly (P < 0.01) between patients in remission on the one hand and those with pouchitis or IPS on the other. However, between IPS and pouchitis no such differences could be found. Depressiveness scores differed between IPS and patients in remission (P = 0.05). HRQOL in IPS was predicted by depressiveness (P < 0.001). Cytokine transcripts discriminated between pouchitis and IPS (P < 0.01), whereas between IPS patients and asymptomatic patients no such differences were observed. Patients with IPS and pouchitis cannot be differentiated by clinical symptoms or HRQOL, which is associated with depressiveness in IPS patients. IPS is a noninflammatory sequela in IPAA patients that shares clinical features with IBD. Quantification of mucosal proinflammatory gene transcripts differentiates objectively and simply between IPS and pouchitis.
    Inflammatory Bowel Diseases 01/2008; 13(12):1502-8. · 5.48 Impact Factor

Publication Stats

508 Citations
187.81 Total Impact Points

Institutions

  • 2012–2013
    • Universitätsklinikum Jena
      Jena, Thuringia, Germany
  • 2007–2013
    • Friedrich-Schiller-University Jena
      • Clinic of Internal Medicine III
      Jena, Thuringia, Germany
  • 2011
    • Klinikum Saarbrücken
      Saarbrücken, Saarland, Germany
  • 2008
    • Goethe-Universität Frankfurt am Main
      • Center for Internal Medicine
      Frankfurt, Hesse, Germany
  • 2002–2005
    • Universität des Saarlandes
      Saarbrücken, Saarland, Germany