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  • 1
    Article
    Article
    BMJ Publishing Group Ltd and British Society of Gastroenterology
    Language: English
    In: Gut February 2010, Vol.59(2), p.275
    Description: In a retrospective analysis of 93 patients, Seifert et al1 investigated the role of transluminal endoscopic necrosectomy after acute pancreatitis. From the authors' point of view, the mortality rate of only 7.5% and a good long-term outcome appear to make this relatively new approach look favourable when compared with the results of published studies on surgical debridement in necrotising pancreatitis. However, a detailed look at the characteristics of the patients in the GEPARD study shows that this is like comparing apples and oranges. Surgical series on acute pancreatitis predominantly investigate the subset of patients with infected necrosis and severe organ dysfunction. Data on the severity of the disease are regularly presented, usually as severity scores (eg, Ranson, APACHE II, SOFA), the incidence of single or multiple organ failure or the extent of pancreatic necrosis.2 3 However, severity data are missing in the GEPARD study. Importantly, the patients in the GEPARD study appear to be much healthier. Their predominant symptoms were abdominal pain and gastric obstruction/vomiting. The majority of patients with so-called sepsis (defined as fever alone, C-reactive protein levels raised to eight times normal, bacteraemia or positive FNA culture) probably would not fit the well-established international definition of sepsis. Only 20% of the patients analysed had been treated in the ICU after admission, only 4.3% showed signs of septic shock and all endoscopic interventions had been possible under sedation. Importantly, infected necrosis was only present in 54% of patients. Indeed, what the GEPARD study investigated is endoscopic therapy of postnecrotic collections. Typically, this cohort of patients is reasonably healthy and only exhibits infrequently severe complications.4 Regarding the data from this perspective, the mortality rate of 7.5% does not appear particularly low and the two patients who died during surgery are to be taken seriously. In addition, the authors noted that 22 patients were withdrawn from the current report due to a previous publication, but that study included only 11 patients with acute pancreatitis.5
    Keywords: Acute Pancreatitis
    ISSN: 0017-5749
    ISSN: 00175749
    E-ISSN: 1468-3288
    E-ISSN: 14683288
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  • 2
    Language: English
    In: Gastroenterology, November 2013, Vol.145(5), pp.1026-1034
    Description: Infection with hepatitis B virus (HBV) can be prevented by vaccination with HB surface (HBs) antigen, which induces HBs-specific antibodies and T cells. However, the duration of vaccine-induced protective immunity is poorly defined for health care workers who were vaccinated as adults. We investigated the immune mechanisms (antibody and T-cell responses) of long-term protection by the HBV vaccine in 90 health care workers with or without occupational exposure to HBV, 10−28 years after vaccination. Fifty-nine of 90 health care workers (65%) had levels of antibodies to HBs antigen above the cut-off (〉12 mIU/mL) and 30 of 90 (33%) had HBs-specific T cells that produced interferon-gamma. Titers of antibodies to HBs antigen correlated with numbers of HBs-specific interferon-gamma−producing T cells, but not with time after vaccination. Although occupational exposure to HBV after vaccination did not induce antibodies to the HBV core protein (HBcore), the standard biomarker for HBV infection, CD4 and CD8 T cells against HBcore and polymerase antigens were detected. Similar numbers of HBcore- and polymerase-specific CD4  and CD8 T cells were detected in health care workers with occupational exposure to HBV and in patients who acquired immunity via HBV infection. Most of the HBcore- and polymerase-specific T cells were CD45RO CCR7 CD127 effector memory cells in exposed health care workers and in patients with acquired immunity. In contrast, most of the vaccine-induced HBs-specific T cells were CD45RO CCR7 CD127 terminally differentiated cells. HBs antigen vaccine-induced immunity protects against future infection but does not provide sterilizing immunity, as evidenced by HBcore- and polymerase-specific CD8 T cells in vaccinated health care workers with occupational exposure to HBV. The presence of HBcore- and HBV polymerase-specific T-cell responses is a more sensitive indicator of HBV exposure than detection of HBcore-specific antibodies.
    Keywords: Immunization ; Immune Response ; T Cell ; Virus ; Medicine
    ISSN: 0016-5085
    E-ISSN: 1528-0012
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  • 3
    In: Transplantation, 2016, Vol.100(2), pp.260-261
    Keywords: Liver Transplantation ; Antiviral Agents -- Therapeutic Use ; End Stage Liver Disease -- Surgery ; Hepatitis C, Chronic -- Drug Therapy;
    ISSN: 0041-1337
    E-ISSN: 15346080
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  • 4
    In: Transplantation, 2016, Vol.100(6), pp.1173-1174
    Keywords: Access to Information ; Donor Selection ; Internet ; Liver Transplantation -- Methods ; Living Donors -- Supply & Distribution;
    ISSN: 0041-1337
    E-ISSN: 15346080
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  • 5
    Language: English
    In: European Journal of Cancer, 2015, Vol.51, p.S1
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ejca.2015.01.014 Byline: Karakhanova Svetlana, Werner Jens, Bazhin V. Alexandr Abstract: Pancreatic ductal adenocarcinoma (PDAC) represents one of the deadliest cancers in the world. PDAC cells activate tumour-specific immune responses but simultaneously trigger a strong immunosuppression. We showed that PDAC cells produce high amount of chronic inflammatory mediators and PDAC tumours build an immunosuppressive cytokine milieu, which correlates with tumour progression. On the cellular level, we found that tumours from the murine Panc02 orthotopic model of PDAC were infiltrated with high numbers of regulatory T cells (Treg). Remarkably, these cells exhibited the effector/memory phenotype, suggesting their enhanced suppressive activity and higher proliferation capacity. With regard to the innative immune cells, we observed a pronounced accumulation of macrophages and myeloid-derived suppressor cells (MDSC) in murine PDAC tumours. Whilst macrophages seem not to play a significant role in this PDAC model in the context of immunosuppression, MDSC are highly suppressive, and their accumulation is associated with an increase in intratumoural vascular endothelial growth factor (VEGF) concentration during the PDAC progression. Thus, Treg and MDSC are strongly involved in the PDAC-associated immunosuppression and their depletion could provide the base for new approaches for therapy of PDAC.
    Keywords: Vascular Endothelial Growth Factor ; Adenocarcinoma ; Immunotherapy ; Pancreatic Cancer
    ISSN: 0959-8049
    Source: Cengage Learning, Inc.
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  • 6
    Language: English
    In: European Journal of Cancer, March, 2015, Vol.51, p.S1
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ejca.2015.01.014 Byline: Karakhanova Svetlana, Werner Jens, Bazhin V. Alexandr Abstract: Pancreatic ductal adenocarcinoma (PDAC) represents one of the deadliest cancers in the world. PDAC cells activate tumour-specific immune responses but simultaneously trigger a strong immunosuppression. We showed that PDAC cells produce high amount of chronic inflammatory mediators and PDAC tumours build an immunosuppressive cytokine milieu, which correlates with tumour progression. On the cellular level, we found that tumours from the murine Panc02 orthotopic model of PDAC were infiltrated with high numbers of regulatory T cells (Treg). Remarkably, these cells exhibited the effector/memory phenotype, suggesting their enhanced suppressive activity and higher proliferation capacity. With regard to the innative immune cells, we observed a pronounced accumulation of macrophages and myeloid-derived suppressor cells (MDSC) in murine PDAC tumours. Whilst macrophages seem not to play a significant role in this PDAC model in the context of immunosuppression, MDSC are highly suppressive, and their accumulation is associated with an increase in intratumoural vascular endothelial growth factor (VEGF) concentration during the PDAC progression. Thus, Treg and MDSC are strongly involved in the PDAC-associated immunosuppression and their depletion could provide the base for new approaches for therapy of PDAC.
    Keywords: Vascular Endothelial Growth Factor ; Adenocarcinoma ; Immunotherapy ; Pancreatic Cancer
    ISSN: 0959-8049
    Source: Cengage Learning, Inc.
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  • 7
    Language: English
    In: European Journal of Cancer, 2015, Vol.51, p.S12
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ejca.2015.01.047 Byline: Karakhanova Svetlana, Werner Jens, Bazhin V. Alexandr Abstract: Prognosis of patients with carcinoma of the exocrine pancreas is particularly poor. A combination of chemotherapy with immunotherapy could be an option for treatment of pancreatic cancer. The aim of this study was to perform an immunomonitoring of the CapRI-2 patients, and tumour-bearing mice treated with combination of chemo (radio) therapies with interferon-2[alpha]. Low doses of interferon-2[alpha] led to a decrease in total leucocyte and an increase in monocyte counts. Furthermore, we observed a positive effect of interferon-2[alpha] therapy on the dendritic cells and NK cell activation immediately after the first injection. In addition, we recorded an increased amount of interferon-[gamma] and interleukin-10 (IL-10) in the serum following the interferon-2[alpha] therapy. These data clearly demonstrate that pancreatic carcinoma patients show an immunomodulatory response to interferon-2[alpha] therapy. Analysis of immunosuppressive cells in the Panc02 orthotopic mouse model of pancreatic cancer revealed an accumulation of the myeloid-derived suppressor cells in spleens and tumours of the mice treated with interferon-2[alpha] and 5-fluorouracil. The direct effect of the drugs on myeloid-derived suppressor cells was also registered in vitro. These data expose the importance of both immunoactivating and immunosuppressive mechanisms induced by combined chemo-immunotherapy.
    Keywords: Biological Response Modifiers – Analysis ; Pancreatic Cancer – Analysis ; Interferon – Analysis ; Chemotherapy – Analysis
    ISSN: 0959-8049
    Source: Cengage Learning, Inc.
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  • 8
    Language: English
    In: European Journal of Cancer, March, 2015, Vol.51, p.S12
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ejca.2015.01.047 Byline: Karakhanova Svetlana, Werner Jens, Bazhin V. Alexandr Abstract: Prognosis of patients with carcinoma of the exocrine pancreas is particularly poor. A combination of chemotherapy with immunotherapy could be an option for treatment of pancreatic cancer. The aim of this study was to perform an immunomonitoring of the CapRI-2 patients, and tumour-bearing mice treated with combination of chemo (radio) therapies with interferon-2[alpha]. Low doses of interferon-2[alpha] led to a decrease in total leucocyte and an increase in monocyte counts. Furthermore, we observed a positive effect of interferon-2[alpha] therapy on the dendritic cells and NK cell activation immediately after the first injection. In addition, we recorded an increased amount of interferon-[gamma] and interleukin-10 (IL-10) in the serum following the interferon-2[alpha] therapy. These data clearly demonstrate that pancreatic carcinoma patients show an immunomodulatory response to interferon-2[alpha] therapy. Analysis of immunosuppressive cells in the Panc02 orthotopic mouse model of pancreatic cancer revealed an accumulation of the myeloid-derived suppressor cells in spleens and tumours of the mice treated with interferon-2[alpha] and 5-fluorouracil. The direct effect of the drugs on myeloid-derived suppressor cells was also registered in vitro. These data expose the importance of both immunoactivating and immunosuppressive mechanisms induced by combined chemo-immunotherapy.
    Keywords: Biological Response Modifiers -- Analysis ; Pancreatic Cancer -- Analysis ; Interferon -- Analysis ; Chemotherapy -- Analysis
    ISSN: 0959-8049
    Source: Cengage Learning, Inc.
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  • 9
    In: PLoS ONE, 2014, Vol.9(6)
    Description: CSPG4 marks pericytes, undifferentiated precursors and tumor cells. We assessed whether the shed ectodomain of CSPG4 (s CSPG4 ) might circulate and reflect potential changes in CSPG4 tissue expression (p CSPG4 ) due to desmoplastic and malignant aberrations occurring in pancreatic tumors. Serum s CSPG4 was measured using ELISA in test (n = 83) and validation (n = 221) cohorts comprising donors (n = 11+26) and patients with chronic pancreatitis (n = 11+20) or neoplasms: benign (serous cystadenoma SCA, n = 13+20), premalignant (intraductal dysplastic IPMNs, n = 9+55), and malignant (IPMN-associated invasive carcinomas, n = 4+14; ductal adenocarcinomas, n = 35+86). Pancreatic p CSPG4 expression was evaluated using qRT-PCR (n = 139), western blot analysis and immunohistochemistry. s CSPG4 was found in circulation, but its level was significantly lower in pancreatic patients than in donors. Selective maintenance was observed in advanced IPMNs and PDACs and showed a nodal association while lacking prognostic relevance. Pancreatic p CSPG4 expression was preserved or elevated, whereby neoplastic cells lacked p CSPG4 or tended to overexpress without shedding. Extreme pancreatic overexpression, membranous exposure and tissue high /sera low -discordance highlighted stroma-poor benign cystic neoplasm. SCA is known to display hypoxic markers and coincide with von-Hippel-Lindau and Peutz-Jeghers syndromes, in which p VHL and LBK1 mutations affect hypoxic signaling pathways. In vitro testing confined p CSPG4 overexpression to normal mesenchymal but not epithelial cells, and a third of tested carcinoma cell lines; however, only the latter showed p CSPG4 -responsiveness to chronic hypoxia. siRNA-based knockdowns failed to reduce the malignant potential of either normoxic or hypoxic cells. Thus, overexpression of the newly established conditional hypoxic indicator, CSPG4 , is apparently non-pathogenic in pancreatic malignancies but might mark distinct epithelial lineage and contribute to cell polarity disorders. Surficial retention on tumor cells renders CSPG4 an attractive therapeutic target. Systemic ‘drop and restoration’ alterations accompanying IPMN and PDAC progression indicate that the interference of pancreatic diseases with local and remote shedding/release of sCSPG4 into circulation deserves broad diagnostic exploration.
    Keywords: Research Article ; Medicine And Health Sciences
    E-ISSN: 1932-6203
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  • 10
    Language: English
    In: Disability and Rehabilitation, 03 July 2018, Vol.40(14), pp.1639-1645
    Description: Background: People with cervical spinal cord injury have impaired function of the respiratory muscles, which results in reduced ventilation. Glossopharyngeal insufflation/breathing increases total lung capacity and improves cough function, however, knowledge of the experiences regarding learning...
    Keywords: Breathing Exercise ; Experiences ; Glossopharyngeal Insufflation ; Lung Function ; Physiotherapy ; Qualitative Method ; Social Welfare & Social Work ; Occupational Therapy & Rehabilitation ; Physical Therapy
    ISSN: 0963-8288
    E-ISSN: 1464-5165
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