Comparative analysis of clinicopathological correlations of cyclooxygenase-2 expression in resectable pancreatic cancer

AIM:To perform a comparative analysis of clinicopathological correlations of cyclooxygenase2 (COX2) expression in pancreatic cancer, examined by monoclonal and polyclonal antibodies.METHODS: The COX2 expression in 85 resection specimens of pancreatic ductal adenocarcinoma was immunohistochemically examined using both monoclonal and polyclonal antibodies. The final immunoscores were obtained by multiplying the percentage of positive cells with the numeric score reflecting the staining intensity.COX2 expressi...     

Ofatumumab Combined With Fludarabine and Cyclophosphamide (O-FC) Shows High Activity in Patients With Previously Untreated Chronic Lymphocytic Leukemia: Results From a Randomized,Multicenter, International,Two-Dose,Parallel-Group Phase II Trial

IntroductionChemoimmunotherapy regimens are the treatment standard for fit patients with chronic lymphocytic leukemia (CLL). Ofatumumab is a human monoclonal antibody that binds to a unique membrane-proximal epitope composed of both the large- and small-loop domains of CD20. Overall response rates (ORRs) of 47%-58% have been observed with single-agent ofatumumab in patients with fludarabine-refractory CLL. We evaluated the efficacy and tolerability of 2 doses of ofatumumab combined with fludarabine and cyclophosphamide (O-FC) in previously untreated patients with CLL in an international, randomized, parallel-group phase II trial.Patients and MethodsPatients with active CLL were randomized to ofatumumab 500 mg (group A) or 1000 mg (group B) day 1, with fludarabine 25 mg/m² and cyclophosphamide 250 mg/m² days 2-4, course 1; days 1-3, courses 2-6; administered every 4 weeks for 6 courses. For both groups, first dose of ofatumumab was 300 mg. The primary endpoint was complete response (CR) rate (1996 NCI-WG criteria) assessed by an Independent Review Committee (IRC), measured from the start of treatment up to 3 months after the last course.ResultsThere were 61 patients enrolled and randomized on this study (Table 1). Seventy-one percent and 57% of patients in groups A (n = 31) and B (n = 30), respectively, completed all 6 courses of O-FC treatment. The CR rate by IRC evaluation was 32% (95% CI, 17%-51%) for group A and 50% (95% CI, 31%-69%) for group B; the ORR was 77% (95% CI, 59%-90%) and 73% (95% CI, 54%-88%), respectively (Table 1). The CR rate and ORR for patients who received all 6 courses of O-FC were 56% and 92%, respectively. Follow-up is ongoing for progression-free and overall survival. No grade 3-4 infusion-related reactions on the day of ofatumumab infusion were reported. During treatment and up to 30 days following the last dose, the most common (> 10% of patients) grade 3-4 adverse events (AEs) reported by investigators were infections in 11 patients (group A, n = 4; group B, n = 7), including febrile neutropenia in 3 patients in each group, and hematologic AEs, including neutropenia in 29 patients (group A, n = 11; group B, n = 18), anemia in 8 patients (group A, n = 2; group B, n = 6), and thrombocytopenia in 9 patients (group A, n = 2; group B, n = 7). Grade 3-4 hemolytic anemia occurred in 2 patients in group A and 1 in group B. In group A, a patient died 50 days from last dose during follow-up (febrile neutropenia). In group B, a patient died 19 days from last dose during treatment (dyspnea; etiology unknown), and another patient died 186 days from last dose (neutropenia following alternative treatment for progressive CLL).ConclusionsThe O-FC regimen is active in previously untreated patients with CLL at the ofatumumab doses investigated. AEs with the O-FC regimen were manageable with no unexpected toxicities. The 1000 mg dose of ofatumumab is currently being evaluated in combination with chemotherapy in other studies for patients with CLL. Abstract 8 - Table 1. Patient Characteristics and Response

Clinical and demographic characteristics predicting QOL in patients with epilepsy in the Czech Republic: How this can influence practice

ObjectiveThe aim of our study was to assess the influence of different clinical and demographic variables on quality of life (QOL) in patients with epilepsy in the Czech Republic.MethodsOutpatients with epilepsy (n = 268) who visited two neurology departments between 2005 and 2006 were included. Clinical and demographic characteristics were retrieved from medical records. Quality of life was measured by the Quality of Life in Epilepsy Inventory (QOLIE-31). Using multiple regression analysis, we determined which variables were associated with QOLIE-31 overall and subscale scores.ResultsSeizure frequency, employability and psychiatric comorbidity were found to be risk factors for QOLIE-31 overall score, accounting for 33% of the variance in the regression model. Seizure frequency was strong predictor for all seven subscales. Employability explained 10% of the variance in the QOLIE overall score and was the strongest predictor for Overall QOL, Emotional Well-being, Energy/Fatigue and Cognitive Function. Gender, type of seizures, age at onset of seizures, and systemic comorbidity had no significant association in this study.ConclusionsThe present study confirms that besides seizure frequency, employability and comorbid psychiatric conditions are strong predictors of QOL in patients with epilepsy. Interventions focusing on psychosocial problems and identification of factors that hamper employment in patients with epilepsy are necessary for improving QOL in these patients.     

Four cases of venous thromboembolism associated with olanzapine

Aims:  Psychiatric disorders and treatment with conventional antipsychotic medications have been associated with venous thromboembolism, but only a few data on recent antipsychotics such as olanzapine are available.
Methods:  We describe four subjects treated with olanzapine who developed venous thromboembolism, and were hospitalized at the University Hospital in Hradec Kralove during the period 2004–2006.
Results:  We found a combination of several clinical and laboratory risk factors in our patients.
Conclusions:  A cohort study or case–control studies are needed to better elucidate the possible role of olanzapine in etiopathogenesis of venous thromboembolism.     

Murine Typhus and Leptospirosis as Causes of Acute Undifferentiated Fever, Indonesia

To investigate rickettsioses and leptospirosis among urban residents of Semarang, Indonesia, we tested the blood of 137 patients with fever. Evidence of Rickettsia typhi, the agent of murine typhus, was found in 9 patients. Another 9 patients showed inconclusive serologic results. Thirteen patients received a diagnosis of leptospirosis. No dual infections were detected.     

Proteomics in aquatic amphipods: can it be used to determine mechanisms of toxicity and interspecies responses after exposure to atrazine?

Proteomics has gained popularity in the field of ecotoxicology as a holistic tool for unraveling novel mechanisms of toxicity and elucidating subtle effects of contaminant exposure. The holoarctic amphipod Diporeia spp. is declining at precipitous rates in the Great Lakes, and we are evaluating the use of the well-studied amphipod model Hyalella azteca as a surrogate for Diporeia spp. This article presents proteomics data from both amphipod species exposed to atrazine (ATZ) and one of its metabolites, desethylatrazine (DEA; 3 and 30 μg/L for 21 and 42 d). We used a proteomics approach to determine whether these two species of amphipods responded similarly to the same chemicals and to understand better the mechanisms of toxicity of ATZ and DEA in aquatic invertebrates. We observed disruption in energy production and mitochondrial function as well as hormesis in exposed organisms. In addition, we identified a two proteins (GAPDH and HSP 90 kDa) that have been linked to hormonal disruptions, suggesting potential endocrine disruption. Finally, we found that H. azteca and Diporeia spp. responded with similar proteomic profiles after ATZ and DEA exposure, suggesting that H. azteca may be used as a surrogate model organism for Diporeia spp.