Contrasting patterns of deficits in visuospatial memory and executive function in patients with major depression with and without ECT referral.

BACKGROUND: The pretreatment neuropsychological profile of drug-resistant patients with major depressive disorder (MDD) referred for electroconvulsive therapy (ECT) may differ from that of their drug-respondent MDD counterparts. Such differences could help in identifying distinct MDD subtypes, thus offering insights into the neuropathology underlying differential treatment responses. METHOD: Depressed patients with ECT referral (ECTs), depressed patients with no ECT referral (NECTs) and non-psychiatric Controls (matched groups, n=15) were assessed with memory and executive function tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB). RESULTS: ECTs scored significantly lower than NECTs in the Mini-Mental State Examination (MMSE; p=0.01). NECTs performed worse than Controls in the Paired Associates Learning (PAL) task (p<0.03; Control/NECT p<0.01) and the Spatial Recognition Memory (SRM) task (p<0.05; Controls/NECTs p<0.05); ECTs performed between Controls and NECTs, not differing from either. In the Intra/Extradimensional (IED) set-shifting task, ECTs performed worse that Controls and NECTS (IED: p<0.01; Controls/ECTs p<0.01), particularly in the shift phases, which suggests reduced attentional flexibility. In Stockings of Cambridge (SOC), ECTs abandoned the test early more often than Controls and NECTs (H=11, p<0.01) but ECTs who completed SOC performed comparably to the other two groups. CONCLUSIONS: A double dissociation emerged from the comparison of cognitive profiles of ECT and NECT patients. ECTs showed executive deficits, particularly in attentional flexibility, but mild deficits in tests of visuospatial memory. NECTs presented the opposite pattern. This suggests predominantly frontostriatal involvement in ECT versus temporal involvement in NECT depressives.

The hamster model of sequential oral oncogenesis.

Oral squamous cell carcinoma (OSCC) is a common cancer characterised by low survival rate and poor prognosis. The multistep process of oral carcinogenesis is affected by multiple genetic events such as alterations of oncogenes and tumour suppressor genes. The use of appropriate experimental animal models that accurately represent the cellular and molecular changes which are associated with the initiation and progression of human oral cancer is of crucial importance. The Syrian golden hamster cheek pouch oral carcinogenesis model is the best known animal system that closely correlates events involved in the development of premalignant and malignant human oral cancers. Therefore, we established an experimental system of chemically induced oral carcinogenesis in hamsters, in order to study different stages of tumour formation: normal mucosa, hyperkeratosis, hyperplasia, dysplasia, early invasion, well differentiated OSCC and moderately differentiated OSCC. We investigated the expression of oncogenes EGFR, erbB2, erbB3, FGFR-2, FGFR-3, c-myc, N-ras, ets-1, H-ras, c-fos and c-jun, apoptosis markers Bax and Bcl-2, tumour suppressor genes p53 and p16, and cell proliferation marker Ki-67 in the sequential stages of hamster oral oncogenesis. Here, we describe the findings of the experimental model in regard to the involvement of signal transduction pathways in every stage of cancer development. Increased apoptosis and cell proliferation were observed in early stages of oral oncogenesis. Furthermore, the increased expression of transmembrane receptors (EGFR, erbB2, FGFR-2 and FGFR-3) as well as the increased expression of nuclear transcriptional factors in early stages of oral cancer indicates that these molecules may be used as early prognostic factors for the progression of OSCC. Since the expression of both H-ras and N-ras do not seem to affect signal transduction during oral oncogenesis, it can be assumed that a different signalling pathway, such as the PI3K and/or PLCgamma pathway, may be implicated in the pathogenesis of OSCC.

Abundance and localization of skeletal muscle-related erbB2 may stimulate tumour growth during initial stages of oral oncogenesis.

ErbB2 and erbB3 transmembrane receptors, known to be associated with neuronal and skeletal muscle developmental function, seem to play an important role in human oral oncogenesis. This study was designed to determine gradual erbB2 and erbB3 expression in an experimental animal system of induced oral carcinogenesis in Syrian golden hamsters. Thirty-seven animals were divided into one control group (N=7) and three experimental groups (N=10 each one), which were treated with carcinogen 9,10-dimethyl-1,2-benzanthracene and sacrificed at 10, 14 and 19 weeks after treatment. The histological status of observed lesions in the three experimental groups corresponded well with tumour advancement (from oral mucosal dysplasia to moderately differentiated squamous cell carcinoma). Tissue sections ranging from normal mucosa to squamous cell carcinoma were studied using monoclonal antibodies against erbB2 and erbB3 proteins. Cytoplasmic erbB2 expression was gradually increased in pre-cancerous stages, remained stable in initial tumour stages and substantially decreased in moderately-differentiated carcinomas, suggesting that it may be useful as an early prognostic factor. On the contrary, erbB3 was not expressed at all either in normal or tumour tissue.

Cell proliferation and apoptosis culminate in early stages of oral oncogenesis.

Markers of cell proliferation (Ki-67 antigen) and apoptosis (Bax, Bcl-2) were studied in an experimental system of induced oral carcinogenesis in Syrian golden hamsters. Thirty-seven animals were divided into one control group and three experimental groups, which were treated with a carcinogen and sacrificed at 10, 14 and 19 weeks after treatment. The histological status of the lesions in the three experimental groups corresponded well with tumour advancement (from oral mucosal dysplasia to moderately differentiated squamous cell carcinoma). Tumour sections were studied using monoclonal antibodies against Bax, Bcl-2 and Ki-67 proteins. Pro-apoptotic Bax expression maintained high levels during all stages of oral carcinogenesis. Anti-apoptotic Bcl-2 expression decreased significantly in dysplastic and early invasion lesions and consequently increased almost to normal tissue level in consequent stages. Finally, Ki-67 expression increased sharply in initial stages of oral carcinogenesis, but significantly decreased in later stages.

Set shifting deficits in melancholic vs. non-melancholic depression: preliminary findings.

Twenty-two patients with major depressive disorder, 11 of them with melancholic features, and 11 controls were investigated with CANTAB subtests focusing in visual memory/learning and executive functions. Melancholic patients performed worse than the other groups in all tasks and manifested a significant impairment in set shifting. The results are discussed in association with prefrontal dysfunction.

Embolization for the treatment of pseudoaneurysm and transection of facial vessels.

Transection of the facial and the internal maxillary arteries while routine operations were performed was the cause of uncontrolled bleeding and a pseudoaneurysm. We present a study of the mechanisms that create and the means that control hemorrhage and pseudoaneurysms in the maxillofacial region.

Acquired competence in cognitive therapy following a two level course.

The objective of this study was to examine the predictive value of trainees' previous experience and performance at an introductory course in Cognitive Therapy for their subsequent success in an advanced course. From 203 completers of an introductory course during seven consecutive years 32 participated in an advanced course. In a linear regression analysis previous clinical and psychotherapeutic experience as well as performance at the introductory course were studied as predictors for trainees' success in the advanced course. Performance at the introductory course was the only significant predictor of trainees' successful completion of the advanced course. An introductory course might help to select those trainees who have the desired qualities to succeed in a formal psychotherapeutic training program.

The notion of "Sisyphus task" in medicine: A reconstruction.

In medicine, along with the other domains of our life, the myth of Sisyphus is frequently evoked upon confronting a task conceived as laborious, endless and for some futile or even purposeless and meaningless. In this paper, we explore the origin of the myth of Sisyphus so that its connotations and symbolizations will hopefully emerge clearer. It is suggested that the natural background of the myth might be related to the seismologic history of Greece, and Corinth in particular, a city ruined and rebuilt several times. The natural component might symbolically echo in the personified myth of Sisyphus, Corinth's founder and might explain the peculiar labor he was condemned to execute eternally, as well as the meanings the myth carries. Like his own city, Sisyphus also suffered the same "ups and downs" of fate, either as a public figure -patron of several big achievements- or as a punished hero condemned to role a stone in the underworld. His persistent efforts led to temporary successes, even though he could not find permanent solutions to the labors he undertook alive or dead. Thus, the myth of Sisyphus is related to human efforts and its limitations, the feasible and infeasible the two main poles between which the myth functions. Conceptualizing with Sisyphean terms their function, physicians can celebrate their transient victories, and by realizing their limitations, reconstruct their aspirations without decreasing their efforts.