A prominent feature of thalamocortical circuitry in sensory systems is the extensive and highly organized feedback projection from the cortex to the thalamic neurons that provide stimulus-specific input to the cortex. In lightly sedated rats, we found that focal enhancement of motor cortex activity facilitated sensory-evoked responses of topographically aligned neurons in primary somatosensory cortex, including antidromically identified corticothalamic cells; similar effects were observed in ventral posterior medial thalamus (VPm). In behaving rats, thalamic responses were normally smaller during whisking but larger when signal transmission in brainstem trigeminal nuclei was bypassed or altered. During voluntary movement, sensory activity may be globally suppressed in the brainstem, whereas signaling by cortically facilitated VPm neurons is simultaneously enhanced relative to other VPm neurons receiving no such facilitation.The somatosensory system intimately cooperates with the motor system during tactile exploration and active touch. In the whisker sensorimotor system of rats, extensive interconnections exist between sensory and motor neural subsystems 1 . During whisking, motor cortex activity is elevated 2 , but sensory-evoked responses in the lemniscal system are typically attenuated 3-7 .Motor cortex projections to deep layers of primary somatosensory cortex (S1) can potentially excite corticothalamic cells either mono-synaptically or by local circuit interactions 8,9 . S1 corticothalamic neurons are thus strategically positioned to regulate activity in thalamocortical circuits during voluntary movement 9 . Corticothalamic feedback can enhance thalamic firing and response tuning 10,11 . The circumstances in which corticothalamic neurons are engaged are not yet known. A substantial proportion of corticothalamic cells are weakly responsive or even silent in anesthetized 12,13 and awake animals 14-17 .We found that S1 corticothalamic neurons in whisker/barrel cortex responded more robustly to whisker deflections when motor cortex activity was focally enhanced. Similar effects were observed in topographically aligned thalamic neurons in the VPm. Thus, corticothalamocortical circuitry is engaged by other functionally related cortical centers. During whisking in behaving rats, VPm responses were suppressed when whisker follicles were stimulated but were enhanced when processing in brainstem nuclei was bypassed or experimentally altered.

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Ischemic bowel disease represents a broad spectrum of diseases with various clinical and radiologic manifestations, which range from localized transient ischemia to catastrophic necrosis of the gastrointestinal tract. The primary causes of insufficient blood flow to the intestine are diverse and include thromboembolism, nonocclusive causes, bowel obstruction, neoplasms, vasculitis, abdominal inflammatory conditions, trauma, chemotherapy, radiation, and corrosive injury. Computed tomography (CT) or magnetic resonance (MR) imaging can demonstrate the ischemic bowel segment and may be helpful in determining the primary cause. The CT and MR imaging findings include bowel wall thickening with or without the target sign, intramural pneumatosis, mesenteric or portal venous gas, and mesenteric arterial or venous thromboembolism. Other CT findings include engorgement of mesenteric veins and mesenteric edema, lack of bowel wall enhancement, increased enhancement of the thickened bowel wall, bowel obstruction, and infarction of other abdominal organs. However, regardless of the primary cause, the imaging findings of bowel ischemia are similar. Furthermore, the bowel changes simulate inflammatory or neoplastic conditions. Understanding the pathogenesis of various conditions leading to mesenteric ischemia helps the radiologist recognize ischemic bowel disease and avoid delayed diagnosis, unnecessary surgery, or less than optimal management.

Purpose: To evaluate the efficacy and safety of gefitinib plus simvastatin (GS) versus gefitinib alone (G) in previously treated patients with advanced non-small cell lung cancer (NSCLC).Experimental Design: Between May 2006 and September 2008, 106 patients (51% men, 75% adenocarcinoma, 50% never smoker) were randomly assigned to G alone (250 mg/d, n ¼ 54) or GS (250 and 40 mg/d, respectively, n ¼ 52). One cycle was 4 weeks of treatment. Therapy was continued until disease progression or intolerable toxicity was observed. The primary endpoint was response rate (RR). Secondary endpoints included toxicity, progression-free survival (PFS), and overall survival (OS).Results: The RR was 38.5% (95% CI, 25.3-51.7) for GS and 31.5% (95% CI, 19.1-43.9) for G. The median PFS was 3.3 months [M] (95% CI, 1.4-5.2M) for GS and 1.9M (95% CI, 1.0-2.8M) for G. The median OS was 13.6M (95% CI, 7.1-20.1M) for GS and 12.0M (95% CI, 7.8-16.2M) for G. In exploratory subgroup analysis, GS showed higher RR (40% vs. 0%, P ¼ 0.043) and longer PFS (3.6M vs.

. The ability of rats using their whiskers to perform fine tactile discrimination rivals that of humans using their fingertips. Rats must perform these discriminations rapidly and accurately while palpating the environment with their whiskers. This suggests that whisker-derived inputs produce a robust and reliable code, capable of capturing complex, high-frequency information. The first neural representation of whisker-derived stimulus information is in primary afferent neurons of the trigeminal ganglion. Here we demonstrate that there is a continuum of directiondependent response profiles in trigeminal neurons and provide the first quantitative analysis of the encoding of complex stimuli by these neurons. We show that all classes of trigeminal ganglion neurons respond with highly reproducible temporal spike patterns to transient stimuli. Such a robust coding mechanism may allow rapid perception of complex tactile features.

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Local circuitry within layer IV whisker-related barrels is preferentially sensitive to thalamic population firing synchrony, and neurons respond most vigorously to stimuli, such as high-velocity whisker deflections, that evoke it. Field potential recordings suggest that thalamic barreloid neurons having similar angular preferences fire synchronously. To examine whether angular tuning of cortical neurons might also be affected by thalamic firing synchrony, we characterized responses of layer IV units to whisker deflections that varied in angular direction and velocity. Barrel regular-spike units (RSUs) became more tuned for deflection angle with slower whisker movements. Deflection amplitude had no affect. Barrel fast-spike units (FSUs) were poorly tuned for deflection angle, and their responses remained constant with different deflection velocity. The dependence of angular tuning on deflection velocity among barrel RSUs appears to reflect the same underlying response dynamics that determine their velocity sensitivity and receptive field focus. Unexpectedly, septal RSUs and FSUs are largely similar to their barrel counterparts despite available evidence suggesting that they receive different afferent inputs and are embedded within different local circuits.

An apparent causal association between crizotinib treatment and renal cyst development emerged during clinical trials in anaplastic lymphoma kinase (ALK)-positive non–small cell lung cancer (NSCLC). Serious adverse event (SAE) reports of renal cysts from a safety database of 1375 patients from four clinical trials were reviewed. A blinded, retrospective, independent radiologic review (IRR) was performed using scans from patients on study for ≥6 months in three clinical trials; risk factors for renal cyst development were assessed. Among 17 patients with renal cysts reported as SAEs, evidence of invasion into adjacent structures was noted in seven patients, with no evidence of malignancy found. These patients generally did not require dose reductions, none required permanent crizotinib discontinuation due to this AE, and most continued treatment with clinical benefit. In the blinded IRR, among 255 crizotinib-treated patients, 22%, 3%, and 2% had preexisting simple cysts, complex cysts, or both, respectively. At the 6-month tumor assessment, 9% of all patients had acquired new cysts, and 2% of patients with preexisting cysts had developed new cysts and enlargements (>50%) of preexisting simple cysts. Asians appeared to have an increased risk of developing new cysts on treatment; Koreans in particular had 5.18 times higher odds of developing cysts than non-Asians (95% confidence interval, 1.51–17.78; P = 0.05). Crizotinib treatment appears to be associated with an increased risk of development and progression of renal cysts in patients with ALK-positive NSCLC. While close monitoring is recommended, dosing modification was not generally necessary, allowing patients to remain on crizotinib treatment.