Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268

http://directory.umm.ac.id/Data%20Elmu/jurnal/B/Biological%20Psichatry/Vol48.Issue8.2000/6889.pdf

Neuroimaging studies of mood disorders.

Background While depression is known to involve a disturbance of mood, movement and cognition, its associated cognitive deficits are frequently viewed as simple epiphenomena of the disorder.

Aims To review the status of cognitive deficits in depression and their putative neurobiological underpinnings.

Method Selective computerised review of the literature examining cognitive deficits in depression and their brain correlates.

Results Recent studies report both mnemonic deficits and the presence of executive impairment — possibly selective for set-shifting tasks — in depression. Many studies suggest that these occur independent of age, depression severity and subtype, task ‘difficulty’, motivation and response bias: some persist upon clinical ‘ recovery’.

Conclusions Mnemonic and executive deficits do no appear to be epiphenomena of depressive disorder. A focus on the interactions between motivation, affect and cognitive function may allow greater understanding of the interplay between key aspects of the dorsal and ventral aspects of the prefrontal cortex in depression.

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Cognitive deficits in depression: possible implications for functional neuropathology.

http://directory.umm.ac.id/Data%20Elmu/jurnal/B/Biological%20Psichatry/Vol48.Issue8.2000/6901.pdf

Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response.

Event-related functional MRI and a version of the Stroop color naming task were used to test two conflicting theories of anterior cingulate cortex (ACC) function during executive processes of cognition. A response-related increase in ACC activity was present when strategic processes were less engaged, and conflict high, but not when strategic processes were engaged and conflict reduced. This is inconsistent with the widely held view that the ACC implements strategic processes to reduce cognitive conflicts, such as response competition. Instead, it suggests that the ACC serves an evaluative function, detecting cognitive states such as response competition, which may lead to poor performance, and representing the knowledge that strategic processes need to be engaged.

Parsing executive processes: strategic vs. evaluative functions of the anterior cingulate cortex.

The relationship between neuropsychological test performance and regional cerebral blood flow (rCBF) was examined in 29 patients meeting Research Diagnostic Criteria (RDC) for major depression. Following a comprehensive neuropsychological assessment two subsets of tests, comprising tests that discriminated between patients and controls or between patients with varying degrees of global cognitive impairment, were selected. These subtests were entered into a principal components analysis (PCA) which generated a two-factor solution, accounting for 50% of the overall variance in test scores. Individual patient loadings on each of these factors were subsequently correlated with regional cerebral blood flow (rCBF), as measured by positron emission tomography (PET). Both factors demonstrated significant correlations with rCBF in the medial prefrontal cortex and frontal polar cortex while for each factor there were also unique patterns of correlations with posterior brain regions. The findings provide additional evidence that neuropsychological deficits in depression are associated with abnormalities in regional brain function and in particular with the function of the medial prefrontal cortex.

/pdf/neuropsychological-dysfunction-in-depression-the-1zhh3n8vuw.pdf

Neuropsychological dysfunction in depression : the relationship to regional cerebral blood flow

Purpose Raf kinase inhibitor protein (RKIP) inhibits the Raf and nuclear factor kappa B signaling pathways, and suppresses metastasis in animal models. We examined whether RKIP expression in primary colorectal cancers (CRCs) correlates with the risk of metastasis and overall survival. Patients and Methods RKIP expression was examined immunohistochemically in three separate cohorts: a tissue microarray containing 276 samples from human tumors and normal tissues, and retrospective studies of 268 CRC patients and 65 early-stage CRCs. Overall and metastasis-free survival rates were measured. Results RKIP was expressed in normal epithelia but was reduced in metastatic tumors. RKIP expression in primary CRC was an independent prognostic marker for survival using multivariate Cox regression analysis (hazard ratio, 2.808; 95% CI, 1.58 to 4.96; P .0002), independent of Dukes’ stage. Patients with Dukes’ C RKIP-positive tumors had similar 5-year survival rates as early-stage patients if tumors had equivalent RKIP expression levels. An independent study of early-stage CRCs confirmed that reduced RKIP expression predicted metastatic recurrence and reduced disease-free survival (hazard ratio, 4.5; 95% CI, 1.7 to 12.3; P .003). RKIP expression was independent of sex, age, mitotic index, lymphatic and vascular invasion, depth of invasion, and tumor site, but correlated positively with apoptotic index (P .024). Weak or loss of RKIP expression was the most significant and independent prognostic marker using a multivariate regression equation (hazard ratio, 4.5; 95% CI, 1.7 to 12.3; P .003). Conclusion RKIP expression in primary CRCs correlates with overall and disease-free survival, and can be useful for identifying early-stage CRC patients at risk of relapse.

https://ascopubs.org/doi/pdfdirect/10.1200/JCO.2006.07.5499

Raf Kinase Inhibitor Protein Expression in a Survival Analysis of Colorectal Cancer Patients

Cognitive dysfunction is an integral feature of depression, in some cases of sufficient severity to warrant a diagnosis of dementia. There has been little systematic investigation of whether cognitive dysfunction is an inevitable consequence of depression, or is specific to a subgroup of depressed patients. Related to this is the distribution of cognitive dysfunction, whether there is a continuum of impairment or a distinct demented subgroup. Finally, there is the question of which aspects of cognitive function are most sensitive to the intellectual decline seen in depression. A study is described which addresses these issues. The distribution of global cognition was found to be normally distributed in the sample of 29 patients assessed. Based on this distribution and the scores of a control sample, the patients were classified as unimpaired, borderline or impaired. Two sets of independent comparisons were carried out. First, the unimpaired depressed patients were compared to matched non-depressed controls. Significant deficits were found on a range of neuropsychological measures covering aspects of language function, memory, both recall and recognition, attention and behavioural regulation. These same patients were also compared with two groups of matched depressed patients, with varying degrees of global cognitive impairment. In general, the cognitive measures showed a gradient of dysfunction across the three patient groups. Significant differences between the depressed groups were shown on measures of immediate recall, attention and behavioural regulation. The possible significance of attentional factors for the observed memory dysfunction is discussed.

/pdf/cognitive-function-in-depression-its-relationship-to-the-ocdev8uloo.pdf

Cognitive function in depression: its relationship to the presence and severity of intellectual decline

Plasma biomarkers may be particularly useful as a predictor or early marker of clinical response to treatment in addition to radiological imaging. Cytokeratin 18 (CK18) is an epithelial-specific cytokeratin that undergoes cleavage by caspases during apoptosis. Measurement of caspase-cleaved (CK18–Asp396) or total cytokeratin 18 (CK18) from epithelial-derived tumours could be a simple, non-invasive way to monitor or predict responses to treatment. Soluble plasma CK18–Asp396 and CK18 were measured by ELISA from 73 patients with advanced gastrointestinal adenocarcinomas before treatment and during chemotherapy, as well as 100 healthy volunteers. Both CK18–Asp396 and total CK18 plasma levels were significantly higher in patients compared with the healthy volunteers (P=0.015, P<0.001). The total CK18 baseline plasma levels before treatment were significantly higher (P=0.009) in patients who develop progressive disease than those who achieve partial response or stable disease and this correlation was confirmed in an independent validation set. The peak plasma levels of CK18 occurring in any cycle following treatment were also found to be associated with tumour response, but peak levels of CK18–Asp396 did not reach significance (P=0.01, and P=0.07, respectively). Plasma levels CK18 are a potential marker of tumour response in patients with advanced gastrointestinal malignancy.

/pdf/cytokeratin-18-in-plasma-of-patients-with-gastrointestinal-299ffnsxwt.pdf

Cytokeratin 18 in plasma of patients with gastrointestinal adenocarcinoma as a biomarker of tumour response

Skin toxicity is a common side-effect of treatment with imatinib mesylate (STI571, Glivectrade mark) in advanced gastrointestinal stromal tumours (GIST) and chronic myeloid leukaemia. The optimal duration of treatment with imatinib mesylate in GIST has not yet been established, as durable remissions have been observed in patients. It is, therefore, important to develop strategies to deal with common side-effects of what may be a long-term treatment. Here we report the case of a patient with advanced GIST who developed a cutaneous drug reaction secondary to imatinib mesylate and the various management options that may be employed depending upon the severity of the toxicity. The case and literature are discussed.

/pdf/management-of-skin-toxicity-related-to-the-use-of-imatinib-3b3o102meb.pdf

Lucy C. Scott

Papers

Neuropsychological dysfunction in depression : the relationship to regional cerebral blood flow

Raf Kinase Inhibitor Protein Expression in a Survival Analysis of Colorectal Cancer Patients

Cognitive function in depression: its relationship to the presence and severity of intellectual decline

Cytokeratin 18 in plasma of patients with gastrointestinal adenocarcinoma as a biomarker of tumour response

Management of Skin Toxicity Related to the Use of Imatinib Mesylate (STI571, Glivectrade mark) for Advanced Stage Gastrointestinal Stromal Tumours.