Combination of the human anti-CD30 antibody 5F11 with cytostatic drugs enhances its antitumor activity against Hodgkin and anaplastic large cell lymphoma cell lines

Due to its selective overexpression on the malignant cells of Hodgkin's lymphoma (HL) and large cell anaplastic lymphoma (ALCL), CD30 is an excellent target for immunotherapy of these diseases. The fully human monoclonal anti-CD30-antibody 5F11 has been shown to be effective against CD30-expressing cell lines both in vitro and in vivo. In addition, 5F11 shows promising antitumor activity in phase 1/2 clinical trials. To extend these promising results, the authors evaluated combinations of 5F11 with conventional cytostatic drugs against a variety of lymphoma cell lines in vitro. Most combinations tested showed at least additive cytotoxic effects on the HL-derived cell lines L428, L540, and L1236 and the ALCL-derived cell line Karpas 299 as measured by proliferation assays (XTT) and the induction of apoptosis (annexin-V FACS analysis). The most impressive results were detected with the combination of 5F11 and gemcitabine or etoposide. The data suggest that the combination of the human antibody 5F11 with conventional chemotherapy might be beneficial in the combined chemo-immunotherapy of CD30-positive lymphomas.     

Pregnancy is not a risk factor for gallstone disease： Results of a randomly selected population sample

AIM: To investigate the prevalence, risk factors, and selection of the study population for cholecystolithiasis in an urban population in Germany, in relation to our own findings and to the results in the international literature. METHODS: A total of 2 147 persons (1 111 females, age 42.8±12.7 years; 1 036 males, age 42.3±13.1 years) participating in an investigation on the prevalence of Echinococcus multilocularis were studied for risk factors and prevalence of gallbladder stone disease. Risk factors were assessed by means of a standardized interview and calculation of body mass index (BMI). A diagnostic ultrasound examination of the gallbladder was performed. Data were analyzed by multiple logistic regression, using the SAS statistical software package. RESULTS: Gallbladder stones were detected in 171 study participants (8.0%, n = 2 147). Risk factors for the development of gallbladder stone disease included age, sex, BMI, and positive family history. In a separate analysis of female study participants, pregnancy (yes/no) and number of pregnancies did not exert any influence. CONCLUSION: Findings of the present study confirm that age, female sex, BMI, and positive family history are risk factors for the development of gallbladder stone disease. Pregnancy and the number of pregnancies, however, could not be shown to be risk factors. There seem to be no differences in the respective prevalence for gallbladder stone disease in urban and rural populations.     

Assessment of RTG-W1, RTL-W1, and PLHC-1 fish cell lines for genotoxicity testing of environmental pollutants by means of a Fpg-modified comet assay

In a context of growing awareness of aquatic pollution impacts, there is an increasing need to develop methods for hazard and risk assessment of pollutants. For this purpose, in vitro models such as fish cell lines warrant to be evaluated as possible alternative to in vivo fish testing, and new toxicity endpoints such as genotoxicity deserve to be considered. This study assesses the interest of the formamido pyrimidine glycosylase (Fpg)-modified comet assay applied to three fish cell lines (RTL-W1, RTG-W1, and PLHC-1) regarding the sensitivity of the system for measuring genotoxicity of various classes of pollutants. Cytochrome P450-dependent EROD activity has also been measured to evaluate the importance of the biotransformation capacity of the cell lines in genotoxicity assessment. For all cell lines and chemicals tested, a concentration dependent genotoxic effect was observed with a 10- to 1000-fold increased sensitivity when using the Fpg-protocol compared to the standard comet assay. Such a modified assay led in particular to improve the detection threshold of oxidative and alkylating DNA damages following exposure at environmentally relevant contaminant concentrations and could partly compensate for the lower sensitivity of cell lines versus whole organism testing often cited as a limit of in vitro testing.     

Causal attributions among patients undergoing coronary artery bypass surgery: gender aspects and relation to depressive symptomatology

Causal attributions made by patients for their coronary heart disease may contribute to gender differences in emotional adjustment. The purpose of this study was to determine gender differences in causal attributions and to analyze the associations between causal attributions and depressive symptomatology in patients undergoing coronary artery bypass graft (CABG) surgery. Nine hundred and seventy-nine patients (mean age 66.8 years, 19.9% women) completed a modified version of the Illness Perception Questionnaire (IPQ) and the depression module of the Patient Health Questionnaire (PHQ-9) 1–3 days before CABG-surgery and 1 year after surgery. Men were more likely to name their health behavior (men: 40.2%, women: 26.9%, P < .001) as a cause of disease, whereas women were more likely to cite destiny (women: 34.7%, men: 25.7%, P = .012). Regression analyses showed cross-sectional and longitudinal associations of attributions with depressive symptomatology which were independent of gender, sociodemographic and clinical variables. Attribution to personality and stress were associated with an increase in depressive symptomatology. Causal attributions may present a valuable approach for identifying patients at risk for depression and the implementation of targeted interventions.     

Event-related desynchronization of sensorimotor EEG rhythms in hemiparetic patients with acute stroke

Previous neuroimaging studies based on neurovascular coupling have shown that stroke affects both, strength and spatial extent of brain activation during upper limb movements. Here, we investigated the sub-second amplitude dynamics of a direct neuronal measure, i.e., event-related desynchronization (ERD) of EEG oscillations during finger movements, in patients with acute cortical and subcortical stroke. Acute cortical strokes were found to decrease the ERD of alpha oscillations for the affected pericentral sensorimotor areas compared to a control group. Within the cortical stroke group, the affected hemisphere showed a smaller alpha-ERD compared to the unaffected hemisphere when each was contralateral to the acting hand. Furthermore, when cortical stroke patients moved their paretic hand, the ipsilateral (i.e., contralesional) alpha-ERD was stronger than the contralateral (ipsilesional) ERD. Interestingly, the alpha-ERD amplitude in a hemisphere with a cortical stroke was relatively well preserved for non-paretic hand movements compared to alpha-ERD amplitude for paretic hand movements. This finding provides a new perspective for assessing the rehabilitative potential, which could be utilized through training of the still responsive cortical network, e.g., via enforced use of the paretic hand.