Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Keywords: SAFETY ; INFECTIONS ; NONMELANOMA SKIN CANCERS ; ULCERATIVE-COLITIS ; CROHNS-DISEASE ; T-CELL LYMPHOMA ; RHEUMATOID-ARTHRITIS ; RETROSPECTIVE COHORT ; INFLIXIMAB ; AZATHIOPRINE
    Abstract: PURPOSE: We aimed to analyse malignancy rates and predictors for the development of malignancies in a large German inflammatory bowel disease (IBD) cohort treated with thiopurines and/or anti-tumour necrosis factor (TNF) antibodies. METHODS: De novo malignancies in 666 thiopurine-treated and/or anti-TNF-treated IBD patients were analysed. Patients (n = 262) were treated with thiopurines alone and never exposed to anti-TNF antibodies (TP group). In addition, patients (n = 404) were exposed to anti-TNF antibodies (TNF+ group) with no (7.4%), discontinued (80.4%) or continued (12.1%) thiopurine therapy. RESULTS: In the TP group, 20 malignancies were observed in 18 patients compared with 8 malignancies in 7 patients in the TNF+ group (hazard ratio 4.15; 95% CI 1.82-9.44; p = 0.0007; univariate Cox regression). Moreover, 18.2% of all patients in the TP group 〉/=50 years of age developed a malignancy, compared with 3.8% of all patients 〈50 years of age (p = 0.0008). In the TNF+ group, 6.5% of all patients 〉/=50 years of age developed malignancies compared with 0.3% of all patients 〈50 years of age (p = 0.0007). In both groups combined, thiopurine treatment duration 〉/=4 years was associated with the risk for skin cancer (p = 0.0024) and lymphoma (p = 0.0005). CONCLUSIONS: Our data demonstrate an increased risk for the development of malignancies in IBD patients treated with thiopurines in comparison with patients treated with anti-TNF antibodies with or without thiopurines.
    Type of Publication: Journal article published
    PubMed ID: 24788825
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    facet.materialart.
    facet.materialart.
    German Medical Science; Düsseldorf, Köln
    In:  27. Deutscher Krebskongress; 20060322-20060326; Berlin; DOCOP487 /20060320/
    Publication Date: 2006-04-21
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    ISSN: 1432-5233
    Keywords: Glucagon-like-peptide-1 ; Prediabetes ; NOD mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of the insulinotropic gut hormone glucagon-like-peptide-1 (GLP-1) was studied on the residual insulin capacity of prediabetic nonobese diabetic (NOD) mice, a model of insulin-dependent diabetes mellitus (type 1). This was done using isolated pancreas perfusion and dynamic islet perifusion. Prediabetes was defined by insulitis and fasting normoglycemia. Insultis occurred in 100% of NOD mice beyond the age of 12 weeks. K values in the intravenous glucose tolerance test were reduced in 20-week-old NOD mice compared with agematched non-diabetes-prone NOR (nonobese resistant) mice (2.4±1.1 vs 3.8±1.5% min−1,P〈0.05). Prediabetic NOD pancreases were characterized by a complete loss of the glucose-induced first-phase insulin release. In perifused NOD islets GLP-1, at concentrations already effective in normal islets, left the insulin release unaltered. However, a significant rise of glucose-dependent insulin secretion occurred for GLP-1 concentrations〉0.1 nM. This was obtained with both techniques, dynamic islet perifusion and isolated pancreas perfusion, indicating a direct effect of GLP-1 on the beta-cell. Analysis of glucose-insulin dose-response curves revealed a marked improvement of glucose sensitivity of the NOD endocrine pancreas in the presence of GLP-1 (half-maximal insulin output without GLP-1 15.2 mM and with GLP-1 9.4 mM,P〈0.002). We conclude that GLP-1 can successfully reverse the glucose sensing defect of islets affected by insulitis.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    ISSN: 1432-5233
    Keywords: Insulin ; Glucagon ; Somatostatin ; Glucagon-like peptide-I ; Galanin ; Incretin ; Decretin ; Adenylate cyclase ; Cyclic adenosine monophosphate ; Protein kinase A
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The interaction of glucagon-like peptide-I (GLP-I) and galanin in clonal endocrine pancreatic cells was characterized. By Northern blot analysis the presence of GLP-I receptor mRNA was shown in B (\TC-1 cells) and D (RIN 1048-38) cells but not in A (INR1 G9) cells, thus confirming functional data demonstrating the absence of active GLP-I receptors on glucagon-producing cells. Galanin receptors were detected on B and D cells but not on A cells. In B and D cells galanin inhibited the GLP-I stimulated adenylate cyclase activity. Treatment of insulin-and somatostatin-producing cells with GLP-I increased intracellular cAMP levels, and this was dampened by galanin. GLP-I stimulated the activity of protein kinase A in B and D cells, which was also inhibited by galanin. Galanin alone did not influence B- and D-cell function. These data show that in the endocrine pancreas B and D cells but not A cells express GLP-I and galanin receptors. The interaction of GLP-I and galanin occurs at the level of adenylate cyclase. Galanin might act in the endocrine pancreas as a physiological inhibitor of the potent incretin hormone GLP-I. Therefore, we suggest galanin is a ‘decretin’.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    ISSN: 1432-5233
    Keywords: Key words  Glucagon-like-peptide-1 ; Prediabetes ; NOD mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract   The effect of the insulinotropic gut hormone glucagon-like-peptide-1 (GLP-1) was studied on the residual insulin capacity of prediabetic nonobese diabetic (NOD) mice, a model of insulin-dependent diabetes mellitus (type 1). This was done using isolated pancreas perfusion and dynamic islet perifusion. Prediabetes was defined by insulitis and fasting normoglycemia. Insulitis occurred in 100% of NOD mice beyond the age of 12 weeks. K values in the intravenous glucose tolerance test were reduced in 20-week-old NOD mice compared with age-matched non-diabetes-prone NOR (nonobese resistant) mice (2.4±1.1 vs 3.8±1.5% min–1, P〈0.05). Prediabetic NOD pancreases were characterized by a complete loss of the glucose-induced first-phase insulin release. In perifused NOD islets GLP-1, at concentrations already effective in normal islets, left the insulin release unaltered. However, a significant rise of glucose-dependent insulin secretion occurred for GLP-1 concentrations 〉0.1 nM. This was obtained with both techniques, dynamic islet perifusion and isolated pancreas perfusion, indicating a direct effect of GLP-1 on the beta-cell. Analysis of glucose-insulin dose-response curves revealed a marked improvement of glucose sensitivity of the NOD endocrine pancreas in the presence of GLP-1 (half-maximal insulin output without GLP-1 15.2 mM and with GLP-1 9.4 mM, P〈0.002). We conclude that GLP-1 can successfully reverse the glucose sensing defect of islets affected by insulitis.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    ISSN: 1432-5233
    Keywords: Key words Leptin ; Insulin secretion ; Endocrine pancreas ; β-cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Leptin is a hormone produced and secreted from the adipose tissue. Its physiological actions include the regulation of satiety, food intake and energy balance. The production of leptin is increased by high insulin levels. Here, we demonstrate that leptin acts as an inhibitor of glucose-induced (20 mM) insulin secretion from isolated human islets. No effect was observed in the presence of lower glucose levels (2.8 and 10 mM glucose). The pancreatic β-cell might represent a target of a direct physiological action of leptin. We suggest the presence of an “adipo-insular axis” in which leptin mediates negative feedback from the adipose tissue to the endocrine pancreas.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    ISSN: 1432-2277
    Keywords: Key words Pancreas-specific protein ; pancreas transplantation ; Neopterin ; pancreas transplantation ; Serum amyloid A ; pancreas transplantation ; Pancreas transplantation ; rejection parameters ; Rejection ; pancreas transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A reliable, noninvasive indicator of pancreatic allograft rejection is urgently needed. In this study, serum (S), plasma (P), and urine (U) levels of pancreas-specific protein (P-PASP, U-PASP), neopterin (S-NEOP, U-NEOP), amylase (U-AMYL), and amyloid A (SAA) were measured daily in ten type I diabetic patients following simultaneous pancreas and kidney transplantation (SPK). Rejection episodes occurred in three isolated pancreas, nine isolated kidney, and five simultaneous pancreas and kidney transplants. In the case of the eight pancreas rejections, SAA was the rejection marker with the highest diagnostic accuracy (94 %). Using P-PASP and U-PASP, an accuracy of 81 % and 79 %, respectively, was achieved. During viral infections, U-NEOP levels increased to a maximum level of 1904 μmol/mol creatinine, whereas during bacterial infections, SAA levels increased to a maximum value of 43 mg/dl. SAA, measured for the first time in SPK, appears to be a valuable rejection parameter. In combination with U-NEOP and U-AMYL, a differential diagnosis between rejection, bacterial infection, and viral infection was possible. Neither U-PASP nor P-PASP monitoring led to a significant improvement in the results.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    ISSN: 1432-0428
    Keywords: Keywords Insulin secretion, protein kinase, insulin secreting cells, human CaMK II, cloning of new subtypes.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. The Ca2+/calmodulin-dependent protein kinase II (CaMK II) is highly expressed in pancreatic islets and associated with insulin secretion vesicles. The suppression of CaMK II disturbs insulin secretion and insulin gene expression. There are four isoforms of CaMK II, α to δ, that are expressed from different genes in mammals. Our aim was to identify the isoforms of CaMK II expressed in human beta cells by molecular cloning from a human insulinoma cDNA library and to assess its distribution in humans.¶Methods. The previously unknown complete coding sequences of human CaMK II β and the kinase domain of CaMK II δ were cloned from a human insulinoma cDNA library. Quantitative determination of CaMK II isoform mRNA was carried out in several tissues and beta cells purified by fluorescence activated cell sorting and compared to the housekeeping enzyme pyruvate dehydrogenase.¶Results. We found CaMK IIβ occurred in three splice variants and was highly expressed in endocrine tissues such as adrenals, pituitary and beta cells. Liver showed moderate expression but adipose tissue or lymphocytes had very low levels of CaMK II β-mRNA. In human beta cells CaMK II β and δ were expressed equally with pyruvate dehydrogenase whereas tenfold lower expression of CaMK II γ and no expression of CaMK IIα were found.¶Conclusion/interpretation. Although CaMK II δ is ubiquitously expressed, CaMK II β shows preferential expression in neuroendocrine tissues. In comparison with the expression of a key regulatory enzyme in glucose oxidation, pyruvate dehydrogenase, two of the four CaM kinases investigated are expressed at equally high levels, which supports an important role in beta-cell physiology. These results provide the basis for exploring the pathophysiological relevance of CaMK IIβ in human diabetes. [Diabetologia (2000) 43: 465–473]
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 9
    ISSN: 1433-8580
    Keywords: Camostate ; Adipocyte ; Lipolysis ; Adrenaline ; Theophylline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of the ε-guanidino acid derivate camostate (FOY 305) on lipolysis of isolated adipocytes was evaluated to test its supposed influence on the reactions of lipid metabolism in experimental shock. Isoprenaline (10−6 M) and theophylline (10−3 M) significantly stimulated lipolysis in vitro. The basal submaximal (isoprenaline 10−6–10−9 M) and maximal (isoprenaline 10−6 M) catecholamine-stimulated lipolysis were not affected by camostate (10−6 M). Furthermore, camostate (0.1–100 × 10−6 M) did not influence half-maximal theophylline-induced lipolysis of the adipocytes. Our findings do not support the suggestion that ε-guanidino acid derivates diminish in shock the increase of free fatty acids in blood via an influence on lipolysis in the peripheral adipose tissue.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 10
    ISSN: 1433-8580
    Keywords: Feedback regulation ; Pancreatic enzymes ; Camostate ; Atropine ; Cholecystokinin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the present study the effect of atropine on feedback regulation of pancreatic function was investigated in male rats. Orogastric tube feeding of a single dose of the protease inhibitor camostate (100 mg) caused a 6-fold increase in plasma CCK. This was accompanied by a 50% decrease in pancreatic enzyme content for up to 6h. The effect of i.v. infusion of atropine (100 µg · kg−1 · h−1) was studied 60 and 180 min after camostate feeding. Atropine completely abolished the decrease in enzyme content 180 min after camostate feeding. The stimulated CCK plasma levels were significantly lowered by the infusion of atropine 60 min, but not 180 min, after feeding of camostate. It is discussed that a cholinergic pathway mediates CCK release in the early phase of feedback regulation of pancreatic function.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...