Pulmonary findings in Churg–Strauss syndrome in chest X-rays and high resolution computed tomography at the time of initial diagnosis

Churg–Strauss syndrome (CSS) is a rare, systemic, necrotizing, small- and middle-sized vessel vasculitis which is accompanied by blood eosinophilia, eosinophil infiltration of various tissues, and bronchial asthma. The lungs are the organs most often involved in CSS. The aim of this study was a retrospective evaluation of the pulmonary findings in chest X-rays and high resolution computed tomography (HRCT) in CSS patients at the time of initial diagnosis and to determine their frequency, character, and location. Seventeen CSS patients were studied (12 women; 5 men; aged 29–56 years). In all patients at the time of initial diagnosis, chest X-rays were performed, and in 15 patients, HRCT was performed additionally. The radiological images were evaluated independently by two radiologists who reached a decision by consensus. Out of 17 patients studied, chest X-rays revealed parenchymal abnormalities in 11, pleural effusion in three, and bronchial wall thickening in one. In five patients, no abnormalities in chest X-rays were found. In HRCT, abnormalities were found in all patients (15 patients, 100%). Predominant HRCT findings consisted of: ground-glass opacities and consolidations found in 13 patients (86.7%). Additionally, in four patients, pulmonary micronodules were described; in ten, interlobular septal thickening; in three, linear opacities; in ten, bronchial wall thickening and/or bronchial dilatation; and in three, pleural effusions. Ground-glass opacities and consolidation abnormalities distribution pattern were peripheral in seven and random in six patients. In patients with CSS, the most common pulmonary radiological findings are parenchymal opacities, which may be peripheral or random in distribution. Pathologic changes were found in 70.6% of patient in chest X-rays, and in 100%, when HRCT was performed. These changes are nonspecific; however, they should be not overlooked, as they may help in establishing the diagnosis and suggest the prognosis.     

Differential effects of serotonin (5‐HT)2 receptor‐targeting ligands on locomotor responses to nicotine‐repeated treatment

We verified the hypothesis that serotonin (5‐HT)₂ receptors control the locomotor effects of nicotine (0.4 mg kg⁻¹) in rats by using the 5‐HT_2A receptor antagonist M100907, the preferential 5‐HT_2A receptor agonist DOI, the 5‐HT_2C receptor antagonist SB 242084, and the 5‐HT_2C receptor agonists Ro 60‐0175 and WAY 163909. Repeated pairings of a test environment with nicotine for 5 days, on Day 10 significantly augmented the locomotor activity following nicotine administration. Of the investigated 5‐HT₂ receptor ligands, M100907 (2 mg kg⁻¹) or DOI (1 mg kg⁻¹) administered during the first 5 days in combination with nicotine attenuated or enhanced, respectively, the development of nicotine sensitization. Given acutely on Day 10, M100907 (2 mg kg⁻¹), Ro 60‐0175 (1 mg kg⁻¹), and WAY 163909 (1.5 mg kg⁻¹) decreased the expression of nicotine sensitization. In another set of experiments, where the nicotine challenge test was performed on Day 15 in animals treated repeatedly (Days: 1–5, 10) with nicotine, none of 5‐HT₂ receptor ligands administered during the second withdrawal period (Days: 11–14) to nicotine‐treated rats altered the sensitizing effect of nicotine given on Day 15. Our data indicate that 5‐HT_2A receptors (but not 5‐HT_2C receptors) play a permissive role in the sensitizing effects of nicotine, while stimulation of 5‐HT_2A receptors enhances the development of nicotine sensitization and activation of 5‐HT_2C receptors is essential for the expression of nicotine sensitization. Repeated treatment with the 5‐HT₂ receptor ligands within the second nicotine withdrawal does not inhibit previously established sensitization. Synapse 64:511–519, 2010. © 2010 Wiley‐Liss, Inc.     

Migrants' health and access to healthcare in the Czech Republic

The article is dealing with current state of Czech health policy in relation to migration. Overall migration information, available data on migrants' health status as well as accessibility of healthcare are provided. Some health risks connected with migration are mentioned and discussed. Authors concluded that the most urgent problem of Czech health policy in relation to migrants remains the insufficient guarantee of legal entitlement to health care. This concerns a large group of migrants with long-term residence, since the current legal regulation is disadvantageous to migrants coming from countries outside the EU.     

Protein kinase Cε as a cancer marker and target for anticancer therapy

Protein kinase Cε (PKCε) is a representative member of a family of novel PKC isoforms that are independent of calcium, but can be activated by phorbol esters, diacylglycerol (DAG) and phosphatidylserine (PS). This kinase is capable of modulating crucial cell functions, including proliferation, differentiation and survival. These activities depend on enzyme translocation to subcellular compartments upon binding DAG, PS or exogenous stimulators. PKCε initiates malignant transformation of cells through its effects on the Ras/Raf/MAPK pathway and displays the greatest carcinogenic potential of all PKC isoforms. PKCε also promotes tumor metastatic capacity and resistance to anti-cancer therapy. Overexpression of PKCε is found in numerous cancers including colon, breast, stomach, prostate, thyroid and lung and is considered an important marker of negative disease outcome. Although overexpression of PKCε is observed in tumors, it is not found in healthy tissues hence it has been suggested as a diagnostic marker or a putative target for specific inhibitors used for treatment of cancer. Research on selective inhibition of PKCε is under way and diverse approaches may become clinically applicable anti-tumor strategies. Suppression of the PKCε-encoding gene achieved through the antisense cDNA, suppression of PKCε with RNAi and inhibition achieved with translocation-inhibitory peptides may provide novel treatment strategies for cancer.     

Pharmacological adherence to oral anticoagulant and factors that influence the international normalized ratio stability

Cross-sectional study developed to relate the international normalized ratio (INR), used as a parameter to monitor the levels of blood clotting, stability to adherence, age, level of education, socioeconomic level, interaction with other drugs, comorbidities, vitamin K intake, anticoagulation time and drug cost. 156 patients were included, mean age 57 ± 13 years, (53.8%) male, 61 (39.1%) had high adherence, 91 (58.3%) medium and 4 (2.6%) low adherence to treatment, 117 (75%) had INR stability up to 50% and 39 (25%) > 75%, patients with shorter time of anticoagulation presented higher stability, those who spent less on the drug remained more stable and had better adherence. It was concluded that more than 90% of patients had high and medium adherence and that the anticoagulation time and drug cost were the factors related to the anticoagulation stability.     

An enzyme-linked immunosorbent assay for human cathepsin X, a potential new inflammatory marker

The human lysosomal cysteine-type carboxypeptidase cathepsin X is mainly present in monocytes and macrophages and may be released into the circulation due to constitutive and/or regulated secretion by (activated) immune cells. To define its potential diagnostic value as an inflammatory marker, we have developed a highly sensitive and specific sandwich-type immunoassay (ELISA) for cathepsin X permitting both intra- and extracellular detection and quantification. The dynamic range of the cathepsin X ELISA was determined to be 100 (detection limit) to 8000 pg/ml. Reproducibility of both within and between runs yielded coefficients of variation (CVs) of 2.7-3.5% and 6.3-7.3%, respectively. Cross-reactivity with other members (cathepsin B, L) of the thiol-dependent cathepsin family was not observed. The ELISA was used to quantify cathepsin X in leukocytes as well as in plasma of healthy volunteers and patients with multiple trauma. During the first 72 h after trauma, plasma levels of cathepsin X increased significantly, particularly in patients who died during the posttraumatic period. In comparison to the well-known inflammation marker neutrophil elastase, cathepsin X levels predicted survival with a higher significance in the later posttraumatic phase. In conclusion, this report provides the first evidence of cathepsin X immunoreactivity not only in cell lysates but also in plasma samples. We suggest that the newly developed highly reproducible ELISA will be of great value for further evaluation of this protease as a diagnostic and/or prognostic marker in inflammatory diseases.     

Survival of patients with colorectal cancer liver metastases treated by regional chemotherapy

BACKGROUND/AIMS: Liver is the most common site of metastatic disease in colorectal cancer. Superior response rate was demonstrated in trials comparing hepatic arterial administration of cytotoxic agents with systemic chemotherapy. METHODOLOGY: Records of 109 consecutive patients with colorectal carcinoma metastatic to the liver treated by regional chemotherapy, who underwent implantation of a port system into hepatic artery or portal vein tributaries between 1991 and 1999, were reviewed and survival was evaluated using the log-rank test and multivariate analysis (Cox's proportional hazard regression). RESULTS: The median survival from diagnosis was 24 months. Survival was significantly longer for patients treated by radical resection, and patients treated in 1997-1999. On multivariate analysis, treatment by 6 or more chemotherapy cycles, stage 1 liver metastases, treatment with irinotecan and radical resection were associated with better survival, while the presence of extrahepatic disease had an adverse effect on the risk of death. Extrahepatic spread was subsequently detected in almost half of the patients who had originally isolated liver metastases. CONCLUSIONS: Patients treated by liver resection had the best outcome, while patients with extrahepatic diseases had poor prognosis. The prognosis of patients treated by regional chemotherapy improved significantly with the advent of irinotecan and better selection.     

C-reactive protein, interleukin-6 and tumor necrosis factor alpha as predictors of incident coronary and cardiovascular events and total mortality. A population-based, prospective study

Previous studies have shown an association between serum C-reactive protein (CRP) and cardiovascular disease (CVD) risk. The roles of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFalpha) are less well established. The aim of the present study was to analyze the associations of CRP, IL-6 and TNFalpha with incident coronary heart disease (CHD) events, CVD events, and total mortality. A random population sample, including men and women aged 25-64 years was examined in Finland in 1992. The sample size was 7,927 and 6,051 (76%) participated. The cohort was followed up until the end of 2001. During the follow-up, 151 incident CHD events, 205 CVD events and 183 deaths from any cause were observed. A stratified random subsample (n=313) was used as the comparison group. After adjustment for conventional CVD risk factors, CRP showed a significant association with CHD risk in men (HR=2.39, 1.08-5.28, comparing fourth quartile to the first quartile). This association remained significant after further adjustment for TNFalpha. TNFalpha also was a significant predictor of CHD among men, but the association was nonlinear (HR=2.21, 1.18-4.14 comparing the three upper quartiles to the first quartile). Further adjustment for CRP did not change this association substantially. Both CRP and TNFalpha predicted also all CVD events and total mortality among men. Among women the findings were nonsignificant. In conclusion, CRP and TNFalpha were significant, independent predictors of CHD and CVD events and total mortality among men. These findings provide further support to the important role of inflammation in the pathogenesis of CVD.     

Pictet-Spengler reactions for the synthesis of pharmaceutically relevant heterocycles

The synthesis of biologically active heterocyclic scaffolds is one of the significant challenges of modern synthetic chemistry. The Pictet-Spengler (PS) reaction, known for approximately a century, remains a particularly popular cyclization method. This review describes recent applications of the PS reaction in the total synthesis of alkaloids and biologically active analogs of tetrahydroisoquinoline and tetrahydro-β-carboline. The utility of PS cyclization in the synthesis of a range of heterocyclic scaffolds is also described.