Functional specialization and dynamic resource allocation in visual cortex

We studied the spatiotemporal characteristics of cortical activity in early visual areas and the fusiform gyri (FG) by means of magnetoencephalography (MEG). Subjects performed a visual classification task, in which letters and visually similar pseudoletters were presented in different surrounds and under different task demands. The stimuli appeared in a cued half of the visual field (VF). We observed prestimulus effects on amplitudes in V1 and Cuneus relating to VF and task demands, suggesting a combination of active anticipation and specialized routing of activity in visual processing. Amplitudes in the right FG between 150 and 350 ms after stimulus onset reflected task demands, while those in the left FG between 300 and 400 ms showed selectivity for graphemes. The contrasting stimulus‐evoked effects in the right and left FG show that the former area is sensitive to task demands irrespective of stimulus content, whereas the left FG is sensitive to stimulus content irrespectively of task demand. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.     

Professionalism beyond medical school: An educational continuum?

Given the changes in society we are experiencing, the increasing focus on patient centred care and acknowledgment that medical education needs to continue not only in the residency programmes but throughout the doctors career, is not surprising. This article describes the attention currently paid to professionalism in the residency programmes, differences in perception of professionalism between patients, faculty, students and residents, differences in professionalism issues in the different educational phases, as well as their consequences for training and assessment regarding professionalism. Continuous medical education in professionalism is thereafter briefly discussed.     

Expression of cd44 splice variants in human cutaneous melanoma and melanoma cell lines is related to tumor progression and metastatic potential

Expression of CD44, particularly of certain splice variants, has been linked to tumor progression and metastasis formation in a number of different animal and human cancers. Because human cutaneous melanoma is among the most aggressive human cancers, we explored expression of CD44 isoforms (CD44v) in lesions of melanocytic tumor progression. In addition, by RT-PCR and FACS analysis we assessed CD44v RNA species and cell surface expression of CD44v in cultured melanocytes isolated from human foreskin and in a panel of 2 non-, 2 sporadically and 2 highly metastatic human melanoma cell lines. We observed that all melanocytic lesions examined showed strong uniform expression of standard CD44 (CD44s) epitopes. We did not detect CD44v6 expression in the melanocytic lesions. However, CD44 isoforms containing v5 or v10 were differentially expressed. V5 was expressed in 16%, 0%, 20%, 67% and 58% of common nevi, atypical nevi, early primary melanomas (± 1.5 mm), advanced primary melanomas (> 1.5 mm) and metastases, respectively, and hence was related to tumor progression. In contrast, CD44vl0 was expressed in all common nevi, whereas part of the atypical nevi and most primary melanomas and metastases lacked v10. CD44v RNA patterns were closely similar in cultured melanocytes and all melanoma cell lines. Melanocytes expressed high levels of CD44s but no CD44v, whereas all melanoma cell lines expressed CD44v at the surface. Interestingly, expression of v5 was strongly increased in the highly metastatic cell lines. Our results suggest a role for CD44 variant domains, particularly v5 and v10, in human melanocytic tumor progression. © 1995 Wiley-Liss, Inc.     

Genetic heterogeneity of the ichthyosis,hypogonadism, mental retardation,and epilepsy syndrome

Major diagnostic criteria for the Rud syndrome are ichthyosis, hypogonadism, mental retardation, and epilepsy. Two unrelated patients are presented and compared with 28 reported cases. Genetical heterogeneity of the Rud syndrome is suggested by differences in clinical features, histological and endocrinological findings, steroid sulfatase activity, and modes of inheritance.     

Comparison of contractile responses to donitriptan and sumatriptan in the human middle meningeal and coronary arteries

Donitriptan is a potent, high efficacy agonist at 5-HT(1B/1D) receptors. We investigated the contractile effects of donitriptan and sumatriptan on human isolated blood vessels of relevance to therapeutic efficacy in migraine (middle meningeal artery) and coronary adverse events (coronary artery). Furthermore, using the concentration-response curves in the middle meningeal artery, we predicted the plasma concentration needed for the therapeutic effect of donitriptan. Both donitriptan and sumatriptan contracted the middle meningeal artery with similar apparent efficacy (E(max): 103+/-8% and 110+/-12%, respectively), but the potency of donitriptan (pEC(50): 9.07+/-0.14) was significantly higher than that of sumatriptan (pEC(50): 7.41+/-0.08). In the coronary artery, the contraction to donitriptan was biphasic with a significantly higher maximal response (E(max): 29+/-6%) than sumatriptan (E(max): 14+/-2%; pEC(50): 5.71+/-0.16), yielding two distinct pEC(50) values (8.25+/-0.16 and 5.60+/-0.24). Incubation with the 5-HT(2) receptor antagonist ketanserin (10 microM) eliminated the low affinity component of the concentration-response curve of donitriptan and the resultant E(max) and pEC(50) were 9+/-2% and 7.33+/-0.21, respectively. Ketanserin was without effect on the sumatriptan-induced contraction. Based on the middle meningeal artery contraction, concentrations (C(max)) of donitriptan that may be expected to have a therapeutic efficacy equivalent to that of 50 and 100 mg sumatriptan are predicted to be around 2.5 and 4.3 nM, respectively. Such concentrations are likely to induce only a small coronary artery contraction of 2.9+/-1.5% and 3.8+/-2.0%, respectively; these are not different from those by C(max) concentrations of sumatriptan (1.7+/-0.4% or 2.2+/-0.4%). The present results suggest that, like sumatriptan, donitriptan exhibits cranioselectivity and would be effective in aborting migraine attacks with a similar coronary side-effect profile as sumatriptan.