Executive cognitive deficits in primary dystonia.

Primary dystonia is a disorder of movement for which no consistent pathophysiology has been identified; in the absence of evidence to the contrary, it is assumed to be cognitively benign. We have studied a clinically heterogeneous group of 14 patients with primary dystonia on a battery of neuropsychological tests. Despite well-preserved speed of information processing, language, spatial, memory and general intellectual skills relative to normal controls, we have identified a constellation of attentional-executive cognitive deficits on the Cambridge Neuropsychological Test Automated Battery (CANTAB). Specifically, patients demonstrated significant difficulties negotiating the extra-dimensional set-shifting phase of the IED task. The implications of these findings for the pathophysiology of primary dystonia are discussed. This is, to the best of our knowledge, the first report of a significant cognitive deficit in patients with primary dystonia.     

Tuimorigenic activity of fluoranthene, 2-methylfluoranthene and 3-methylfluoranthene in newborn CD-I mice

Fluoranthene (FA) is frequently among the more abundant componentsdetected in environmental mixtures of polycyclic aromatic hydrocarbons.Several methylated fluoranthenes, although less prevalent thanFA, have also been detected as environmental pollutants. WhileFA is inactive as a tumorigenic agent on mouse skin, it doesinduce lung and liver tumors in newborn mice. Among the fiveisomers of methylfluoranthene, only 2-methylfluoranthene (2-MeFA)and 3-methylfluoranthene (3-MeFA) are active as tumor initiatorson mouse skin. A comparative bioassay was performed to determinethe relative tumorigenic activity of FA, 2-MeFA and 3-MeFA innewborn CD-1 mice. All three compounds were assayed at dosesof 3.46 and 17.3 µmol. The bioassay was terminated whenmice were 1 year old. At a dose of 17.3 µmol, FA and 2-MeFAinduced a similar incidence of lung tumors (65–96%) inboth male and female mice. However, tumor multiplicity in thelung was different between FA and 2-MeFA. At a dose of 17.3µmol, the multiplicity of lung tumors observed for miceadministered 2-MeFA ranged from 3.04 to 3.94 tumors per mouse.In contrast, animals treated with FA developed only an averageof 1.12–2.45 tumors per mouse. 3-MeFA did not induce astatistically significant incidence of lung tumors in eithermale or female mice. All three compounds when administered tonewborn mice did induce a significant incidence of liver tumorsamong male mice. The relative tumorigenic potency observed wasFA 5     

Spontaneous reports of most distressing concerns in patients with inoperable lung cancer: at present,in retrospect and in comparison with EORTC-QLQ-C30+LC13

Patients with lung cancer experience considerable distress. Therefore, accurate methods for assessing distress and quality of life over time may play a key role for managing and evaluating palliative care. Alternatives to commonly used standardized questionnaires are individual measures. This study prospectively and retrospectively explored the concerns that 46 patients with inoperable lung cancer spontaneously reported as causing most distress close to diagnosis and 6 months later. Changes in content individually generated through a structured inductive freelisting were compared with EORTC-QLQ-C30+LC13 ratings. The results showed that patients perceived a wide variety of concerns as most distressing and that their concerns changed over time. Between 56 and 62% of these concerns were assessed by items included in the EORTC-QLQ-C30+LC13 questionnaires. Furthermore, patients’ reports of most distress from fatigue, pain and dyspnea were not always reflected in intensity ratings of comparable EORTC-QLQ-C30+LC13 items. These results indicate that items included in standardized measures are not always adequate to assess patients’ concerns, priorities and changes over time. In addition to standardized questionnaires, individualized measures may be useful in the clinical palliative setting for providing detailed information about the individual’s problems and prioritizations.     

Evidence-based medicine for nutrition support: an overview of the process.

On a daily basis, clinicians make decisions regarding therapies to result in the best outcome for their patients. These decisions should be based on the evidence in the literature, indicating a therapy will cause the best outcome. To facilitate this, many professional societies and scientific journals have published technical and scientific reviews, as well as evidence-based standards of care focused on many issues of nutrition support practice. This paper provides an overview of how these reviews and standards of care are derived to promote both the understanding of what they can and cannot do to enhance clinical practice.     

Effects of IFN-gamma and interleukin-1beta on major histocompatibility complex antigen and intercellular adhesion molecule-1 expression by 9L gliosarcoma: relevance to its cytolysis by alloreactive cytotoxic T lymphocytes.

To enhance the efficacy of cellular immunotherapy for gliomas, we tested the concept of using proinflammatory cytokine treatment with interferon-gamma (IFN-gamma) or interleukin-1beta (IL-1beta) or both to render glioma cells more susceptible to cytolysis by alloreactive cytotoxic T lymphocytes (aCTL). The cytokines, separately or in combination, were able to upregulate major histocompatibility complex (MHC) class I antigen or intercellular adhesion molecule-1 (ICAM-1) on Fischer rat 9L gliosarcoma cells. 9L cells were incubated in vitro for 24, 48, or 72 h with varying concentrations of rat IFN-gamma (0-2000 U/ml) or recombinant human IL-1 (rHUIL-1) (0-1000 U/ml) or both. By 48 h, IFN-gamma (500 U/ml) maximally induced the percentage of positive expressing cells and the relative antigen density of MHC class I and ICAM-1 on 9L cells, whereas IL-1 induced only ICAM-1 expression. Simultaneous incubation of IL-1 with IFN-gamma did not further affect the induction of class I on 9L cells more than that achieved with IFN-gamma alone. 9L cells with upregulated MHC class I and ICAM-1 expression were more sensitive to lysis by aCTL in in vitro cytotoxicity assays, regardless of whether the precursor aCTL came from naive or from 9L-immunized rats. Furthermore, inhibition of 9L cytotoxicity in assays that included blocking antibodies to MHC class I or to ICAM-1 revealed that T cell receptor (TCR) interactions with MHC class I and that ICAM-1 interactions with lymphocyte function-associated-1 (LFA-1) antigen account for a portion of the glioma lysis by aCTL.