No abstract

Intracellular and extracellular recordings were performed in lateral thalamic nuclei (ventroanterior-ventrolateral, ventroposterolateral, centralis, lateralis, and reticularis) of cats under barbiturate anesthesia. Neurons were driven antidromically and/or synaptically by stimulating cortical projection areas and prethalamic afferent pathways. Three neuronal populations were identified on the basis of electrophysiological and anatomical criteria: thalamic relay neurons, local interneurons, and reticularis thalami neurons. At rest, two coexistent rhythms were observed in thalamic neurons. Brief episodes (1-2 s) of membrane-potential oscillations at frequencies of 8-12 Hz appeared with a periodicity of about 10 s. In relay neurons, each episode was characterized by a sequence of hyperpolarizations and burst discharges. These rhythmic episodes of hyperpolarization recurring about every 10 s could be reversed in sign by hyperpolarizing currents or by Cl injection, hence suggesting that they were mainly composed of rhythmic inhibitory postsynaptic potentials (IPSPs). This result also indicated that the slow 0.1-Hz rhythm was imposed on relay neurons by other neuronal pools. Following a complete isolation of the thalamus by cortical and high brain stem lesions, the slow 0.1-Hz rhythm was still present, and it was concluded that this rhythm was generated within the thalamus by inhibitory elements. In thalamic interneurons (identified by electrophysiological criteria) brief episodes (1-2 s) of repetitive depolarizations (8-12 Hz) and burst discharges recurred every 10 s. In the interval, the membrane potential of interneurons slowly hyperpolarized, contrasting with the rhythmic phasic hyperpolarizations observed in relay neurons. Electrophysiological properties shared by most relay neurons included a) afterspike hyperpolarizing potentials of long duration, which were blocked by injections of a Ca chelator; b) a pacemaker potential in the vicinity of the spike trigger level; and c) a low-threshold somatic Ca conductance that underlies burst discharges. As a general rule, prethalamic volleys induced faster rising and shorter lasting EPSPs than cortical volleys. Moreover prethalamic afferent-evoked responses could be associated with production of fast prepotentials, some of which appeared to result from dendritic spiking. It appears that synaptic and intrinsic membrane properties of thalamic neurons allow them to function under two modes: a relay mode and an oscillatory mode; the oscillatory mode being intrinsic to the thalamus and the relay mode being commanded and maintained by cortical and brain stem structures.

No abstract

• Thalidomide and prednisone maintenance after transplantation improves progressionfree but not overall survival.We conducted a randomized, controlled trial comparing thalidomide-prednisone as maintenance therapy with observation in 332 patients who had undergone autologous stem cell transplantation with melphalan 200 mg/m 2 . The primary end point was overall survival (OS); secondary end points were myeloma-specific progression-free survival, progression-free survival, incidence of venous thromboembolism, and health-related quality of life (HRQoL). With a median follow-up of 4.1 years, no differences in OS between thalidomide-prednisone and observation were detected (respective 4-year estimates of 68% vs 60%, respectively; hazard ratio ‫؍‬ 0.77; P ‫؍‬ .18); thalidomide-prednisone was associated with superior myeloma-specific progression-free survival and progression-free survival (for both outcomes, the 4-year estimates were 32% vs 14%; hazard ratio ‫؍‬ 0.56; P < .0001) and more frequent venous thromboembolism (7.3% vs none; P ‫؍‬ .0004). Median survival after first disease recurrence was 27.7 months with thalidomide-prednisone and 34.1 months in the observation group. Nine second malignancies were observed with thalidomide-prednisone versus 6 in the observation group. Those allocated to thalidomideprednisone reported worse HRQoL with respect to cognitive function, dyspnea, constipation, thirst, leg swelling, numbness, dry mouth, and balance problems. We conclude that maintenance therapy with thalidomide-prednisone after autologous stem cell transplantation improves the duration of disease control, but is associated with worsening of patient-reported HRQoL and no detectable OS benefit. (Blood. 2013;121(9):1517-1523)