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Biomedical subjects

M Zeitz

Publications and source records attributed to M Zeitz.

At least 19 recordsLinked to original sources
PubMed2006

Cyclophosphamide pulse therapy followed by azathioprine or methotrexate induces long-term remission in patients with steroid-refractory Crohn's disease.

BACKGROUND: In patients with steroid-refractory Crohn's disease, the therapeutic goal is to achieve both rapid remission and maintenance of clinical response. AIM: To evaluate the long-term benefit in patients treated with cyclophosphamide pulse therapy and azathioprine or methotrexate, a combination shown to be effective in a recent pilot study. METHODS: Sixteen patients with acute steroid-refractory Crohn's disease participated in a prospective open-labelled uncontrolled pilot study between December 1998 and June 2003. All had a median number of 4 monthly pulses of intravenous cyclophosphamide (750 mg) and were followed until relapse of the disease. RESULTS: Thirteen of 16 patients (81%) achieved remission within 8 weeks after two pulses of cyclophosphamide in combination with azathioprine or methotrexate, with a Crohn's Disease Activity Index decrease from 294 to 111 (median). Remission sustained for 19 months (median, range: 1-45). Moreover, eight patients with pyoderma gangrenosum and erythema nodosum who responded to cyclophosphamide have maintained their remission for up to 30 months. CONCLUSIONS: In steroid refractory patients with Crohn's disease, cyclophosphamide is highly effective to induce remission. This uncontrolled study indicates that cyclophosphamide-induced remission is long-lasting under standard immunosuppressive therapy.

Adult↗
PubMed2006

Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn's disease.

BACKGROUND: Epithelial barrier function is impaired in Crohn's disease. AIM: To define the underlying cellular mechanisms with special attention to tight junctions. METHODS: Biopsy specimens from the sigmoid colon of patients with mild to moderately active or inactive Crohn's disease were studied in Ussing chambers, and barrier function was determined by impedance analysis and conductance scanning. Tight junction structure was analysed by freeze fracture electron microscopy, and tight junction proteins were investigated immunohistochemically by confocal laser scanning microscopy and quantified in immunoblots. Epithelial apoptosis was analysed in terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling and 4',6-diamidino-2-phenylindole staining. RESULTS: Patients with active Crohn's disease showed an impaired intestinal barrier function as indicated by a distinct reduction in epithelial resistance. As distribution of conductivity was even, focal epithelial lesions (eg, microerosions) did not contribute to barrier dysfunction. Instead, freeze fracture electron microscopy analysis showed reduced and discontinuous tight junction strands. Occludin and the sealing tight junction proteins claudin 5 and claudin 8 were downregulated and redistributed off the tight junction, whereas the pore-forming tight junctions protein claudin 2 was strongly upregulated, which constitute the molecular basis of tight junction changes. Other claudins were unchanged (claudins 1, 4 and 7) or not detectable in sigmoid colon (claudins 11, 12, 14, 15 and 16). Claudin 2 upregulation was less pronounced in active Crohn's disease compared with active ulcerative colitis and was inducible by tumour necrosis factor alpha. As a second source of impaired barrier function, epithelial apoptosis was distinctly increased in active Crohn's disease (mean (SD) 5.2 (0.5)% v 1.9 (0.2)% in control). By contrast, barrier function, tight junction proteins and apoptosis were unaffected in Crohn's disease in remission. CONCLUSION: Upregulation of pore-forming claudin 2 and downregulation and redistribution of sealing claudins 5 and 8 lead to altered tight junction structure and pronounced barrier dysfunction already in mild to moderately active Crohn's disease.

Adult↗
PubMed2006

Critical comment: analyzing the effect of novel therapies on cytokine expression in inflammatory bowel disease: do cytokine levels reflect clinical response?

Over the past several years, research in the field of cytokine production and function has become indispensable to understand the immunopathology of chronic intestinal inflammation. Thereupon, clinical studies analyzing cytokine production have generated a tremendous amount of data. In patients with inflammatory bowel disease, several studies examined pro-inflammatory cytokines in gut tissue and plasma, but a clear interpretation of the results with respect to disease activity or therapeutic response has been hampered by patient- and sample-related pitfalls.

Biomarkers↗
PubMed2006

Equivalent effect of DNA damage-induced apoptotic cell death or long-term cell cycle arrest on colon carcinoma cell proliferation and tumour growth.

Knowledge of the type of biological reaction to chemotherapy is a prerequisite for its rational enhancement. We previously showed that irinotecan-induced DNA damage triggers in the HCT116p53(wt) colon carcinoma cell line a long-term cell cycle arrest and in HCT116p53(-/-) cells apoptosis (Magrini et al., 2002). To compare the contribution of long-term cell cycle arrest and that of apoptosis to inhibition of cell proliferation after irinotecan-induced DNA damage, we used this isogenic system as well as the cell lines LS174T (p53(wt)) and HT-29 (p53(mut)). Both p53(wt) cell lines responded to damage by undergoing a long-term tetraploid G1 arrest, whereas the p53(mut) cell lines underwent apoptosis. Cell cycle arrest as well as apoptosis caused a similar delay in cell proliferation. Irinotecan treatment also induced in mouse tumours derived from the p53(wt) cell lines a tetraploid G1 arrest and in those derived from the p53-deficient cell lines a transient G2/M arrest and apoptosis. The delay of tumour growth was in the same range in both groups, that is, arrest- and apoptosis-mediated tumour growth inhibition was comparable. In conclusion, cell cycle arrest as well as apoptosis may be equipotent mechanisms mediating the chemotherapeutic effects of irinotecan.

Animals↗
PubMed2006

[27-year-old man with high fever and septic shock after returning from vacation].

A 27-year-old man was admitted with high fever and shivers eleven days after returning from vacation in Indonesia. Physical examination, laboratory values, abdominal ultrasound, and chest x-ray were not conclusive. All blood cultures yielded growth of Salmonella enterica serovar Typhi, and typhoid fever was diagnosed. Subsequently, the patient developed septic shock and pulmonary edema. In this case report epidemiological, clinical, and therapeutic aspects of typhoid fever are discussed with special emphasis on criteria for severe typhoid fever, which is treated with additional glucocorticoids.

Adult↗
PubMed2006

Autochthonous hepatitis E virus infection in Germany with sequence similarities to other European isolates.

Hepatitis E virus (HEV) is a common cause of acute hepatitis in endemic areas. Yet reports on autochthonous cases in other areas such as middle Europe are increasing. Here we report on a patient, who obviously acquired his HEV infection in Germany. Sequence analysis of the virus gained from his serum revealed homologies to other European isolates and swine isolates.

Communicable Diseases↗
PubMed2006

[An unusual case of upper GI bleeding: esophageal cancer metastasis at a percutaneous endoscopic gastrostomy site--case report and review of the literature].

We present the case of a patient with an esophageal squamous cell carcinoma, who was treated primarily by radiotherapy. Due to dysphagia, the patient received a percutaneous endoscopic gastrostomy (PEG) without any sign of tumour at that time. Five months later the patient presented with an upper GI bleeding from a gastric ulcer, which histologically turned out to be a metastasis of the previously diagnosed squamous cell carcinoma. So-called "implantation metastases" at the percutaneous endoscopic gastrostomy site are rare and most of the cases have been described in patients with head and neck tumours. Moreover, the presentation as an upper GI bleed is very uncommon and needs the attention of both endoscopists as well as gastrointestinal oncologists. Clinicopathological features of this case with a brief review of the literature are presented.

Carcinoma, Squamous Cell↗
PubMed2006

Cine magnetic resonance imaging of the small bowel: comparison of different oral contrast media.

PURPOSE: To evaluate several substances regarding small bowel distension and contrast on balanced steady-state free precession (bSSFP) cine magnetic resonance (MR) images. MATERIAL AND METHODS: Luminal contrast was evaluated in 24 volunteers after oral application of two different contrast agent groups leading to either bright lumen (pineapple, blueberry juice) or dark lumen (tap water, orange juice) on T1-weighted images. Bowel distension was evaluated in 30 patients ingesting either methylcellulose or mannitol solution for limiting intestinal absorption. Fifteen patients with duodeno-jejunal intubation served as the control. Quantitative evaluation included measurement of luminal signal intensities and diameters of four bowel segments, qualitative evaluation assessed luminal contrast and distension on a five-point scale. RESULTS: Quantitative and qualitative evaluation of the four contrast agents revealed no significant differences regarding luminal contrast on bSSFP images. Quantitative evaluation revealed significantly lower (P<0.05) small bowel distension for three out of four segments (qualitative evaluation: two out of four segments) for methylcellulose in comparison to the control. Mannitol was found to be equal to the control. CONCLUSION: Oral ingestion of tap water or orange juice in combination with mannitol is recommended for cine MR imaging of the small bowel regarding luminal contrast and small bowel distension on bSSFP sequences.

Administration, Oral↗
PubMed2005

[Fever of unknown origin in the 21st century: infectious diseases].

Fever of unknown origin (FUO) is a rare but important disease. The definition of FUO has not changed in the last 50 years. Classical FUO is defined by an illness of at least 3 weeks duration with fever greater than 38 masculine C, and no established diagnosis after 1 week of hospital investigation. The causes of FUO can be divided in four categories: infectious diseases, noninfectious inflammatory diseases, neoplasms, and others (miscellaneous). Recent studies have surprisingly shown that despite improved diagnostic procedures the percentage of patients with FUO, in which no diagnosis after intensive investigations in specialized centres can be found, has increased. However, finding the correct diagnosis in FUO is essential for these patients for psychological and vital reasons. Therefore and because of economic reasons patients with FUO should be investigated in specialized centres with a department for rheumatology and infectious diseases.

Aged↗
PubMed2005

[Ulcerative colitis? Guidelines 2004].

Ulcerative colitis was first described in 1859 from Samuel Wilks, a physician at Guy's hospital in London. The prevalence in the high incidence areas ranges from 80 to 120/100.000/year. Ulcerative colitis is a chronic relapsing or chronic active disease which starts at the rectum and presents with a continuous inflammation. Primarily young adults are affected (20 to 40 years of age) but the disease may present at all ages, from younger than 1 year of life to the 80s. Many series show a secondary peak in incidence in the elderly. In the present review we will focus on the basic principles of the therapy with regard to the variety of disease manifestations. The therapeutic algorithms will be described separately for the induction of remission and the maintenance of remission. The localization of inflammation and disease activity represent crucial factors which have to be considered. With regard to these factors, the therapeutic regimens range from simple local therapy with aminosalicylates to systemic immunosuppressive therapy, which will in extreme cases require the administration of ciclosporin. Since ulcerative colitis is associated with an increased risk in developing colon carcinoma, medical therapy as well as endoscopic surveillance are fundamental in the prevention of carcinoma. In the end an outlook to future therapeutic targets and strategies will be provided.

Adrenal Cortex Hormones↗
PubMed2005

Decreased levels of interleukin-12p40 in the serum of patients with Whipple's disease.

BACKGROUND: An impaired production of interleukin (IL)-12 and T cell interferon-gamma (IFN-gamma) of in vitro stimulated monocytes has been discussed as a pathogenic factor in Whipple's disease (WD). It is unclear whether this defect of cellular immunity is translated to the humoral immune system and to serum correlates. METHODS: We analyzed the serum of 40 patients with Whipple's disease in various degrees of disease activity by sandwich enzyme-linked immunosorbent assay for differences in cytokine and cell adhesion molecule concentrations compared with age- and sex-matched controls. RESULTS: We observed a highly significant reduction of IL-12p40 levels (patients, 0.18+/-0.05 ng/ml (mean+/-SEM); controls, 3.19+/-0.39 ng/ml; p<0.01) in all stages of disease activity, whereas the concentration of IL-12p70 was comparable with controls. Furthermore, we observed a slight decrease in tumour necrosis factor alpha (TNF-alpha) concentrations in the serum of patients (patients, 6.36+/-0.90 pg/ml; controls, 10.5+/-1.23 pg/ml; p<0,05). The levels of other cytokines such as IFN-gamma, IL-2, IL-13 and transforming growth factor beta, as well as soluble cell adhesion molecules lymphocyte function-associated antigen 3 and intercellular adhesion molecule 1, were not significantly different compared with controls. Levels of immunoglobulin G2 (IgG2) measured in the serum of WD patients were below normal in 24 of 29 patients and were even below the 95% confidence interval in 10 patients. CONCLUSION: Our data demonstrate a persistent defect of the cellular immune response with decreased serum concentrations of IL-12p40 and TNF-alpha and decreased IgG2 levels in a large group of WD patients. These data support as in vivo finding the results obtained in previous investigations with stimulated monocytes/lymphocytes. The isolated decrease in IL-12p40 may hint at possible defects in the IL-12/IFN-gamma promoter system.

Biomarkers↗
PubMed2005

[The role of leptin in the immune system--a linking of endocrinology and immunology].

Leptin is primarily known as a hormone regulating food intake and the adjustment to a distinct state of nutrition. In the present work a new function of leptin will be described, namely the role of leptin in the immune system. Structural characteristics of leptin and the leptin receptor already suggest an immune modulatory function. The effect of leptin on the various populations of immune cells in vitro will be described. These data are supported by findings obtained in in vivo animal models as well as descriptive and functional data from leptin-deficient humans which will be outlined in detail. In conclusion, the chimeric function of leptin as hormone and a cytokine/adipokine represents a unique link between the immune and the endocrine system thus opening a new field of research and therapeutic options.

Animals↗