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Brno, Czech Republic

Bojkova M.,University of Ostrava | Dite P.,University of Ostrava | Dvorackova J.,University of Ostrava | Novotny I.,Masaryk Oncological Institute | And 5 more authors.
Digestive Diseases | Year: 2014

Background: Immunoglobulin G4 (IgG4)-related diseases are a group of diseases characterized by enlargement of the affected organs, elevation of serum IgG4, massive infiltration of affected organs with lymphocytes and plasma cells with IgG4 positivity and tissue fibrosis. Type I autoimmune pancreatitis is one form of IgG4-related disease. For IgG4-related diseases, various localizations are described for up to 10% of malignancies. The aim of our study was to examine IgG4 serum levels and pancreatic tissue with respect to the simultaneous presence of autoimmune pancreatitis in patients with pancreatic cancer. Methods: IgG4 serum levels were examined In 106 patients with histologically confirmed pancreatic cancer. The level of 135 mg/dl was considered as the normal value. Pancreatic tissue was histologically examined with respect to the presence of markers of autoimmune pancreatitis. Results: A higher IgG4 level than the cut-off value of 135 mg/dl was proven in 11 patients with pancreatic cancer. Of these 11 patients, 7 had levels twice the normal limit (65.6%). Autoimmune pancreatitis was diagnosed in these individuals. In the case of 1 patient, it was basically an unexpected finding; another patient was initially diagnosed with autoimmune pancreatitis. Repeated biopsy of the pancreas at the time of diagnosis did not confirm the presence of tumour structures, therefore steroid therapy was started. At a check-up 6 months after starting steroid therapy, the condition of the patient improved subjectively and IgG4 levels decreased. However, endosonographically, malignancy was suspected, which was subsequently confirmed histologically. This patient also demonstrated an IgG4 level twice the normal limit. Conclusion: IgG4-related diseases can be accompanied by the simultaneous occurrence of malignancies, which also applies to autoimmune pancreatitis. Chronic pancreatitis is considered a risk factor for pancreatic cancer. It cannot be reliably confirmed whether this also applies to autoimmune pancreatitis. In accordance with other works, however, it is evident that, despite the described high sensitivity and specificity for IgG4 elevation in the case of autoimmune pancreatitis, even levels twice the normal limit are demonstrable in some individuals with pancreatic cancer, without the presence of autoimmune pancreatitis. We believe that patients with IgG4-related disease, including autoimmune pancreatitis, must be systematically monitored with respect to the potential presence of malignancy. © 2014 S. Karger AG, Basel.


Constantine R.J.,University of South Florida | Jentz S.,University of South Florida | Bengtson M.,University of South Florida | Mcpherson M.,University of South Florida | And 3 more authors.
Pharmacoepidemiology and Drug Safety | Year: 2012

Purpose: This study aims the following: (i) to describe the exposure to antipsychotic medications over a 4-year period experienced by a cohort of children who initiated antipsychotic treatment before their sixth birthday; and (ii) to identify variables associated with the risk of antipsychotic exposure. Methods: Children were identified who initiated an index episode of antipsychotic treatment before their sixth birthday in Florida's fee for service Medicaid program. With the use of claims data, the medication utilization of these children was tracked during the year before and the 4years following the start of their index episodes (pre-index and four post-index periods). Generalized estimating equations were used to identify variables associated with the risk of additional days of antipsychotic exposure. Results: Five hundred twenty-eight children were included in the cohort. The mean total number of days of exposure was 821.9 (±431.9), representing 56.3% of all days during the four post-index periods. The mean days of exposure to combinations of antipsychotics and other classes of psychotherapeutic medications were 623.8±447.6days. Children with primary diagnoses of pervasive developmental disorders and affective disorders were at greater risk of additional days of exposure than children with attention deficit/hyperactivity disorder. Exposure tended to be greater among children with indicators of clinical complexity including the presence of secondary diagnoses and the use of other classes of psychotherapeutic medications in addition to antipsychotics. Conclusions: Exposure to antipsychotic mediations was extensive. Although these children may have had complex and severe problems, additional research is urgently needed on the benefits and risks of long-term antipsychotic exposure among very young children. © 2011 John Wiley & Sons, Ltd.


Wohlfahrt P.,Charles University | Wohlfahrt P.,Institute for Clinical and Experimental Medicine | Wohlfahrt P.,St Anns University Hospital | Krajcoviechova A.,Charles University | And 7 more authors.
Atherosclerosis | Year: 2013

Background: Carotid-femoral pulse wave velocity (PWV), as a parameter of aortic stiffness, is an established marker of cardiovascular risk. There has been increasing use of arterial stiffness parameters combining aortic and muscular stiffness or a parameter derived from PWV - the stiffness index beta (BETA=ln(systolic/diastolic pressure)×2 blood viscosity/pulse pressure×PWV2). The aim of this study was to compare different arterial stiffness parameters in a general population random sample. Methods and results: In 809 individuals from the Czech post-MONICA study (aged 54±13.5 years, 47% men), we compared the association of carotid-femoral PWV (cfPWV), carotid-ankle PWV (caPWV), and BETA with cardiovascular risk factors, parameters of subclinical organ damage, and presence of manifest cardiovascular disease.Both cfPWV and caPWV were similarly associated with blood pressure and glucose level, while cfPWV was more strongly associated with age, cholesterol level and glomerular filtration rate whereas caPWV with Sokolow-Lyon index. BETA derived from cfPWV and caPWV was less dependent on blood pressure, while it showed a closer association with coronary heart disease presence, as compared to cfPWV and caPWV. Conclusions: Addition of lower extremity to aortic stiffness has an effect on the association with cardiovascular risk factors while having no effect on the association with manifest cardiovascular disease. Beta transformation of PWV decreases its dependence on blood pressure and may increase its power in cardiovascular risk prediction. © 2013 Elsevier Ireland Ltd.


Wohlfahrt P.,Charles University | Wohlfahrt P.,St Anns University Hospital | Wohlfahrt P.,Institute for Clinical and Experimental Medicine | Krajcoviechova A.,Charles University | And 6 more authors.
Journal of Hypertension | Year: 2015

Objectives: There is no agreement on optimal blood pressure (BP) level during the acute phase of stroke, because studies on the relation between BP and stroke outcome have shown contradicting results. The aim of this study was to compare the relationship of admission, maximal, discharge BP and its components during hospitalization for the first-ever acute ischemic stroke with total mortality after stroke. Methods: In 532 consecutive patients (mean age 66 ± 10 years, 59% of men) hospitalized for their first-ever ischemic stroke, the association between BP and total mortality during a median follow-up of 66 weeks (interquartile range 33-119 weeks) was analyzed. Results: In multivariate analysis, both admission mean BP (MBP) and discharge SBP quartiles were independent predictors of mortality and outperformed other parameters of BP. After multivariate adjustments, patients with admission MBP below 100 mmHg had a higher risk of death than those with MBP between 100-110 and 110-121 mmHg, whereas the risk of mortality did not differ from the group with admission MBP above 122 mmHg. Similarly, patients with discharge SBP below 120 mmHg had an increased risk of death as compared to groups with SBP between 120-130 and 130-141 mmHg, whereas the risk of death was similar to that with discharge SBP above 141 mmHg. Conclusion: Among patients hospitalized for their first-ever ischemic stroke, the risk of all-cause death is significantly increased in those with admission MBP below 100 mmHg and discharge SBP below 120 mmHg, even after adjustments for other confounders. © 2015 Wolters Kluwer Health, Inc.


Jelinkova I.,Academy of Sciences of the Czech Republic | Jelinkova I.,Masaryk University | Safarikova B.,Academy of Sciences of the Czech Republic | Safarikova B.,Masaryk University | And 13 more authors.
Biochemical Pharmacology | Year: 2014

In search for novel strategies in colon cancer treatment, we investigated the unique ability of platinum(IV) complex LA-12 to efficiently enhance the killing effects of tumor necrosis factor-related apoptosis inducing ligand (TRAIL), and compared it with the sensitizing action of cisplatin. We provide the first evidence that LA-12 primes human colon cancer cells for TRAIL-induced cytotoxicity by p53-independent activation of the mitochondrial apoptotic pathway. The cooperative action of LA-12 and TRAIL was associated with stimulation of Bax/Bak activation, drop of mitochondrial membrane potential, caspase-9 activation, and a shift of the balance among Bcl-2 family proteins in favor of the pro- apoptotic members. In contrast to cisplatin, LA-12 was a potent inducer of ERK-mediated Noxa and BimL protein upregulation, and more effectively enhanced TRAIL-induced apoptosis in the absence of Bax. The cooperative action of LA-12 and TRAIL was augmented following the siRNA-mediated silencing of Mcl-1 in both Bax proficient/deficient cells. We newly demonstrated that LA-12 induced ERK-mediated c-Myc upregulation, and proved that c-Myc silencing inhibited the mitochondrial activation and apoptosis in colon cancer cells treated with LA-12 and TRAIL. The LA-12-mediated sensitization to TRAIL-induced apoptosis was demonstrated in several colon cancer cell lines, further underscoring the general relevance of our findings. The selective action of LA-12 was documented by preferential priming of cancer but not normal colon cancer cells to TRAIL killing effects. Our work highlights the promising potential of LA-12 over cisplatin to enhance the colon cancer cell sensitivity to TRAIL-induced apoptosis, and provides new mechanistic insights into their cooperative action. © 2014 Elsevier Inc. All rights reserved.

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