New onset of diabetes mellitus and weight loss as a manifestation of pancreatic cancer.

The case report is about a 68-years-old man who developed a weight loss and diabetes mellitus as early symptoms of pancreatic cancer several months before the diagnosis. Unfortunately, the diagnosis was made too late, at the stage of generalized disease, when symptomatic treatment was the only possible way. The aim of the article is to warn about this possible way of pancreatic cancer manifestation, because only the diagnosis determined in time, when the tumor is localized, allows its resection - the only curative treatment method. For this reason, it is necessary to consider the presence of pancreatic cancer in the case of an atypical manifestation of diabetes.

Levels of endothelial substances in patients with newly identified hypertension compared with healthy controls.

INTRODUCTION: Endothelial dysfunction occurs at the very beginning of hypertension. The primary goal of our study was to determine plasmatic levels of multiple endothelial substances in otherwise healthy patients with primary hypertension and compare them to healthy individuals. Secondary goals were to determine the change in NOx levels after initiation of treatment and to compare the NOx levels in patients with established resistant hypertension. MATERIALS AND METHODS: 87 consecutive patients were enrolled. In the exploratory cohort of 22 healthy and 28 hypertensive individuals, plasmatic levels of big endotelin-1, asymmetric dimethylarginin, osteopontin, oxidized LDL, 3-nitro-L-tyrosine, growth/differentiation factor 15, intercellular adhesion molecule, vascular cell adhesion molecule, tumor necrosis factor-α, vascular endothelial growth factor, interleukins -1ß, -6 and nitric oxide levels (NO, expressed as NOx) were determined. The remaining 27 individuals were used as a validation cohort. Ten patients with established resistant hypertension were enrolled from our Hypertension Clinic. RESULTS: There was a statistically significant difference in NOx levels between healthy controls and hypertensive patients/resistant hypertensive patients: 45.164 µmol/L ± 48.627 vs 17.763 µmol/L ± 10.333 (P=0.00004)/14.36 µmol/L ± 7.194 (P=0.00007). CONCLUSION: We identified a decrease in total NOx plasmatic levels in otherwise healthy patients with primary hypertension that was more profound in patients with resistant hypertension. Plasmatic levels of other determined endothelial substances did not differ among the groups. However, due to the significant variability of plasmatic NOx levels even in healthy controls and many factors that affect it, we cannot recommend it to be used to assess endothelial function routinely.

[Relapsing autoimmune pancreatitis type 1: case report]. / Relabující autoimunitní pankreatitida 1. typu: kazuistika.

Autoimmune pancreatitis (AIP) is a rare form of chronic pancreatitis, classified into 2 subtypes - AIP type 1 and AIP type 2. We present a case of a 31-years-old female admitted to our institution with upper abdominal pain and obstructive jaundice. Endoscopic retrograde cholangiopancreatoscopy (ERCP) revealed stenosis of intrapancreatic distal bile duct. Diffuse parenchymal enlargement and typical features of AIP were shown by computed tomography (CT) and endoscopic ultrasonography (EUS). The patient´s serum IgG4 was elevated at 3.8 g/l (range 0.08-1.4 g/l). She was diagnosed with AIP type 1 and treated with prednisone (initial dose of 30 mg per day, then tapered by 5 mg/day every week). The maintenance dose of 5 mg per day was continued for 6 months. Despite clinical and radiological remission, serum levels of IgG4 remained elevated. The patient experienced disease relapse 25 months after first attack. Moreover, new finding of calcifications occured in pancreas. The relapse was managed with corticosteroids and maintenance immunosupression with azathioprin was started. Literature review on risk factor of relapse, long-term immunosupressive therapy indication and optimal follow-up of AIP type 1 patients are discussed.Key words: autoimmune pancreatitis type 1 - long-term follow-up - relapse - therapy.

Impact of cardiopulmonary bypass surgery on cytokines in epicardial adipose tissue: comparison with subcutaneous fat.

BACKGROUND: Cardiac surgery and cardiopulmonary bypass (CPB) have been shown to stimulate a systemic inflammatory response which has been associated with adverse postoperative outcomes. Adipose tissue, both epicardial (EAT) and subcutaneous (SAT), is a known source of inflammatory cytokines, but its role in the pathophysiology of surgery- and CPB-induced systemic inflammatory response has not been fully elucidated. Therefore, we conducted a study to establish levels of selected cytokines in EAT and SAT prior to and after surgery with CPB. METHODS: Adipose tissue samples were obtained from patients undergoing planned cardiac surgery on CPB. Samples from EAT and SAT were collected before and immediately after CPB. Levels of tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), adipocyte fatty acid-binding protein (AFABP), leptin and adiponectin were determined by ELISA, which were adjusted for a total concentration of proteins in the individual samples. RESULTS: Samples from 77 patients (mean age 67.68 ± 11.5 years) were obtained and analysed. Leptin, adiponectin, TNF-α and AFABP were shown to decrease their concentrations statistically significantly in the EAT after CPB while no statistically significant drop was observed in the SAT. On the contrary, IL-6 showed only a slight and statistically insignificant decrease in the EAT after CPB and it was in the SAT where a statistically significant drop was observed. DISCUSSION: One of the most relevant findings of this study was the marked decrease in EAT levels of TNF-α, AFABP, leptin and adiponectin after the CPB termination. Our results suggest that EAT might serve as a pool of cytokines which are released into the circulation in reaction to surgery with CPB. Should these novel findings be confirmed, new strategies to assess and possibly reduce EAT contribution on adverse outcomes of cardiac surgery may be developed.

[Symptomatic and asymptomatic primary hyperparathyroidism in outpatient care - current issues]. / Péce o nemocné se symptomatickou a asymptomatickou primární hyperparatyreózou v ambulantní praxi dnes.

OBJECTIVE: To assess the diagnostic and therapeutic options in the care of patients with primary hyperparathyreosis in outpatient practice.Cohort and methods: The study included all the patients with primary hyperparathyroidism treated at the 2nd Internal Medicine Department, Masaryk University and the University Hospital of St. Anne in Brno in the period from Jan 1, 2008 to Dec 31, 2013. The sample consisted of 218 patients, including 41 men and 177 women. Patients with secondary hyperparathyroidism, especially patients with underlying hypovitaminosis D, renal insufficiency and those taking medications with possible effects on parathyroid hormone levels, have not been included in the study. A special attention was paid to differences between the normocalcaemic and hypercalcaemic patients. Ultrasound scanning was performed in all patients, while scintigraphy was indicated in patients who are considered for possible surgical treatment. RESULTS: In the group of 218 patients, serum calcium levels at the baseline were pathologically elevated in 31 patients (14 %) and normal in 187 patients (86 %). One fifth of patients with normocalcaemic primary hyperparathyroidism developed long-term hypercalcaemia - within two years in two thirds of the patients from the onset of the disease and sporadically also after more than four years of follow-up. Parathyroid adenoma was found and removed in 30 hypercalcemic patients (in 97 % of all 31 hypercalcemic patients operated on) and in 2 normocalcemic patients (40 % of all 5 the normocalcemic patients operated on). Pharmacological treatment was administered to 22 patients, of which 9 patients received long-term treatment and 13 patients received pharmacotherapy only during the preoperative preparation for patients with very high serum calcium levels. CONCLUSION: The results support the opinion that primary hyperparathyroidism is a biphasic disease. The initial normocalcemic period is often asymptomatic or associated with symptoms of little importance. Severe complications, however, may already be present also in normocalcemic patients. The decision of when patients with normocalcemic primary hyperparathyroidism should be monitored and when initiation of treatment is needed should also require more detailed information.Key words: hypercalcaemia - hyperparathyroidism asymptomatic and primary - normocalcaemia - outpatient care - parathyroid hormone - surgery and pharmacotherapy.

Tobacco smoking and cytokine levels in human epicardial adipose tissue: Impact of smoking cessation.

BACKGROUND & AIMS: Epicardial adipose tissue (EAT) is a source of a number of cytokines which could act in the pathogenesis of coronary artery disease (CAD). The potential relationship between known cardiovascular risk factors, such as smoking, dyslipidaemia or diabetes mellitus and EAT humoral signalling, has not been fully elucidated. Therefore, we designed and conducted a cross-sectional study to determine whether selected cardiovascular risk factors are linked to levels of cytokines in epicardial and subcutaneous adipose tissue (SAT). METHODS: Samples of SAT and EAT were collected from consecutive patients undergoing scheduled cardiac surgery. Tissue concentrations of tumour necrosis factor-ɑ (TNF-α), interleukin-6 (IL-6), adipocyte fatty acid-binding protein, leptin, and adiponectin were determined by ELISA. RESULTS: We enrolled 140 patients. TNF-α and IL-6 concentrations in EAT and SAT were significantly higher in current smokers (CS) than in never smokers (NS) and former smokers (FS). There were no differences between FS and NS. No other clinical variables were associated with cytokine concentrations in a regression analysis. CONCLUSIONS: Smoking was independently associated with higher TNF-α and IL-6 concentrations in EAT and SAT. A novel observation that pro-inflammatory cytokines are elevated in EAT in smokers could contribute to identify potential mechanisms involved in the pathogenesis of adverse effects of tobacco smoking. There were no differences between EAT cytokine production in NS and FS, which support the importance of smoking cessation for cardiovascular risk reduction.

PRIMARY HYPERPARATHYROIDISM, WITH A FOCUS ON MANAGEMENT OF THE NORMOCALCEMIC FORM: TO TREAT OR NOT TO TREAT?

OBJECTIVE: The aim of this study was to determine reasonable care for normocalcemic primary hyperparathyroidism (NCPHPT) patients treated at the endocrine clinic. METHODS: The study is based on 218 outpatient cases of primary hyperparathyroidism (PHPT), 187 (86%) of whom were NCPHPT. Subjective complaints, biochemical tests, imaging, and treatment outcome for NCPHPT patients were monitored and compared with the same parameters in patients with hypercalcemic hyperparathyroidism. The number of patients with newly diagnosed NCPHPT who became hypercalcemic and the time period in which it happened were also recorded. RESULTS: Over 6 years of study, in total, 36 of 187 originally normocalcemic patients became hypercalcemic (19%); 24 of 36 within 2 years and 2 of 36 later than after 4 years. Sestamibi scintigraphy was performed in 103 normocalcemic patients (adenoma was detected in 5 cases) and in 46 hypercalcemic patients with pathologically elevated serum calcium levels at the time of assessment (adenoma was detected in 32 of 46 cases). Surgery was performed in 33 patients, 11 of whom were originally normocalcemic (i.e., 6% of all 187 originally normocalcemic patients), and 22 were hypercalcemic from the outset (i.e., 71% of all 31 originally hypercalcemic patients). CONCLUSION: Some NCPHPT patients converted to hypercalcemic, mostly within 2 years, but some after 4 years or later. Normocalcemic patients should be monitored on a long-term basis, as it is impossible to anticipate when and which normocalcemic patients will become hypercalcemic. Imaging is much less effective in normocalcemic than in hypercalcemic patients.

[The role of metabolic syndrome in gastroenterology]. / Role metabolického syndromu v gastroenterologii.

GOAL: Metabolic syndrome and its components play an important part in the development of not only cardiovascular conditions, but also digestive and pancreaticobiliary system diseases. The aim of our study is to present a comprehensive overview of the diseases where metabolic syndrome is an inducing risk factor, or where it affects the course of the disease. RESULTS: Metabolic syndrome is a significant risk factor of induction of gastroesophageal reflux and its complication, which is Barretts esophagus. Metabolic syndrome was described as the disease closely linked to idiopathic intestinal inflammations, diseases of the biliary tree and pancreas. Acute pancreatitis, both its development in obese individuals and the burden of its course, are in close correlation with metabolic syndrome, similarly as the course of chronic, mainly alcoholic pancreatitis. Study of non-alcoholic steatopancreatitis presents a challenge, most importantly with regard to the function of pancreatic B cells in obese individuals. Non-alcoholic hepatic steatosis and its forms may as much as lead to the stage of cirrhosis of the liver and they pose a risk of hepatocellular carcinoma. Metabolic syndrome was also described in a population study as a risk factor for carcinoma of the colon. SUMMARY: Metabolic syndrome and its components present an important risk factor in relation to inducing some benign as well as malignant gastrointestinal and pancreaticobiliary diseases. A systemic approach to influencing the metabolic syndrome and its components is therefore one of the important approaches to influencing the development and course of not only cardiovascular conditions.

[Akromegaly and pharmacotherapy]. / Akromegalie a medikamentózní lécba.

Acromegaly is a rare and serious disease. A successful and rational therapy of acromegaly ought to combine surgery, radiotherapy and pharmacotherapy. The submitted article presents a case of acromegaly that was only diagnosed at the stage when total pituitary adenoma removal was impossible. Even so, the long-term stabilisation of the disease was reached by way of repeated surgery through transfenoidal and transcranial approach, by linear accelerator radiation therapy and Leksell Gamma Knife radiotherapy and by pharmacotherapy with somatostatin analogon octreotide and growth hormone receptor antagonist pegvisomant. The octreotide and pegvisomant dosage has been repeatedly changed according to IGF1 levels. The contemporary somatostatin analogon Sandostatin LAR 30 mg is given once every 3 weeks and the growth hormone receptor antagonist Somavert 20 mg is applied daily. Despite this serious disease, the patient has already been living contentedly for 10 years. From the ethical point of view, the financials costingness of the therapy should be considered as reasonable.

Systemic AL amyloidosis with unusual cutaneous presentation unmasked by carotenoderma.

We present a case study of an elderly woman with systemic lambda-type AL amyloidosis that featured unusually extensive cutaneous involvement. The case initially presented with a sudden hyper ß-carotenemia with carotenoderma that instigated the clinical examination including skin biopsy. A diagnosis of systemic amyloidosis was made. Immunohistochemistry and Western-blot analysis indicated the presence of lambda light chain proteins in skin amyloid deposits. However, notable co-deposition of wild-type apoA-I and transthyretin was observed which caused initial diagnostic confusion. Proteomic analysis of microdissected skin amyloid deposits by mass spectrometry confirmed lambda light chain proteins in amyloid deposits and co-deposition of apolipoprotein A-IV and serum amyloid P-component. The patient died from renal failure caused by amyloid nephropathy combined with analgesic nephropathy. The autopsy disclosed vascular, cardiac, renal and pulmonary amyloid deposition. While all amyloid deposits were positive for lambda light chain proteins, the immunodetection of apoA-I and transthyretin varied significantly among the visceral amyloid deposits. Although the patient exhibited a 1000-fold increase in serum ß-carotene levels, only a mild increase in retinol and lutein concentrations was observed. Increased ß-carotene values were also found in the liver and the skin. The mechanisms underlying this hyper ß-carotenemia remain undetermined.

Main results of the ouabain and adducin for Specific Intervention on Sodium in Hypertension Trial (OASIS-HT): a randomized placebo-controlled phase-2 dose-finding study of rostafuroxin.

BACKGROUND: The Ouabain and Adducin for Specific Intervention on Sodium in Hypertension (OASIS-HT) Trial was a phase-2 dose-finding study of rostafuroxin, a digitoxygenin derivative, which selectively antagonizes the effects of endogenous ouabain (EO) on Na+,K+-ATPase and mutated adducin. Rostafuroxin lowered blood pressure (BP) in some animal models and in humans. METHODS: OASIS-HT consisted of 5 concurrently running double-blind cross-over studies. After 4 weeks without treatment, 435 patients with uncomplicated systolic hypertension (140-169 mm Hg) were randomized to rostafuroxin (0.05, 0.15, 0.5, 1.5 or 5.0 mg/d) or matching placebo, each treatment period lasting 5 weeks. The primary endpoint was the reduction in systolic office BP. Among the secondary endpoints were diastolic office BP, 24-h ambulatory BP, plasma EO concentration and renin activity, 24-h urinary sodium and aldosterone excretion, and safety. ANOVA considered treatment sequence (fixed effect), subjects nested within sequence (random), period (fixed), and treatment (fixed). RESULTS: Among 410 analyzable patients (40.5% women; mean age, 48.4 years), the differences in the primary endpoint (rostafuroxin minus placebo) ranged from -0.18 mm Hg (P = 0.90) on 0.15 mg/d rostafuroxin to 2.72 mm Hg (P = 0.04) on 0.05 mg/d. In the 5 dosage arms combined, the treatment effects averaged 1.30 mm Hg (P = 0.03) for systolic office BP; 0.70 mm Hg (P = 0.08) for diastolic office BP; 0.36 mm Hg (P = 0.49) for 24-h systolic BP; and 0.05 mm Hg (P = 0.88) for 24-h diastolic BP. In the 2 treatment groups combined, systolic (-1.36 mm Hg) and diastolic (-0.97 mm Hg) office BPs decreased from week 5 to 10 (P for period effect ≤ 0.028), but carry-over effects were not significant (P ≥ 0.11). All other endpoints were not different on rostafuroxin and placebo. Minor side-effects occurred with similarly low frequency on rostafuroxin and placebo. CONCLUSIONS: In 5 concurrently running double-blind cross-over studies rostafuroxin did not reduce BP at any dose. TRIAL REGISTRATION: ClinicalTrials (NCT): NCT00415038.

Polymorphism in the tumor necrosis factor-alpha gene promoter is associated with severity of rheumatoid arthritis in the Czech population.

Rheumatoid arthritis (RA) is a model of multigenic inflammatory disorder in which tumor necrosis factor-alpha (TNF-alpha) plays an important role. Genetic factors may be implicated in the susceptibility to disease initiation as well as in severity of disease course. Elevated levels of TNF-alpha in the plasma and synovial fluid from RA patients may be associated with polymorphisms in the promoter region of the TNF-alpha gene. The aim of this study was to elucidate putative association between the -308 G/A polymorphism in the promoter region of the TNF-alpha gene and susceptibility to onset and severity of RA. A total of 130 RA patients and a control group of 150 healthy subjects with similar age and sex distribution were available for the study. All patients fulfilled the American College of Rheumatology revised criteria for RA. RA patients had a disease duration of at least 2 years. Radiographs of both hands of all RA patients were scored with the Steinbrocker method. There were 15 patients of stage I (nonerosive form) of RA and 114 patients of stages II-IV (erosive form). To assess the RA patient's functional ability, the Health Assessment Questionnaire (HAQ) was used. The -308 G/A promoter polymorphism of the TNF-alpha gene was detected by polymerase chain reaction and restriction fragment length polymorphism analysis. No differences in genotype distribution and allelic frequences of -308 G/A TNF-alpha promoter polymorphism have been found between RA patients and the control group. Significant differences have been observed within the RA group divided according to the radiographic progression of disease based on the Steinbrocker radiographic score and functional ability (HAQ). These results suggest an association of the -308 G/A polymorphism of the TNF-alpha gene with the severity of RA.

Association of three polymorphisms in the gene coding for endothelin-1 with essential hypertension, overweight and smoking.

OBJECTIVE: To evaluate the association of three endothelin-1 (ET-1) gene polymorphisms with essential hypertension, as well as with two cardiovascular risk factors: body mass index (BMI) and smoking. DESIGN: Three gene polymorphisms and the genotype and allelic distributions were compared between normotensive healthy volunteers and patients with essential hypertension. The genetic association of the three genotypes with BMI and smoking status was calculated. PATIENTS AND METHODS: CA/CT dinucleotide repeat polymorphism, G(8002)A polymorphism and -3A/-4A polymorphism (-138 insertion/deletion) were examined in the gene coding for ET-1 (6p21.3) in 398 subjects: 192 normotensives (healthy volunteers) and 206 patients with essential hypertension. Normotension was verified by 24 h ambulatory blood pressure monitoring. RESULTS: Significant inner associations were observed between all three polymorphisms, which suggests possible complex interactions inside the gene. The only significant difference in a single gene case control study was in the lengths of allelic variants of CA/CT dinucleotide repeat polymorphism. In hypertensive patients, the alleles of G(8002)A and -3A/-4A ET-1 polymorphisms were found to be significantly associated (G with -3A and A with -4A). None of the ET-1 gene polymorphisms was associated with BMI. A highly significant increase of the -3A allele of the -3A/-4A ET-1 polymorphism was found in hypertensive men who were current smokers or had smoked at least seven cigarettes a week for at least one year at any time in their life compared with hypertensive men who had never smoked (odds ratio 1.54, 95% CI 1.03 to 2.32, P=0.009). CONCLUSIONS: Smoking seems to be an independent cardiovascular risk factor genetically codetermined by the ET-1 gene variant.