Essential role of adenosine, adenosine A1 receptors, and ATP-sensitive K+ channels in cerebral ischemic preconditioning.

Preconditioning with sublethal ischemia protects against neuronal damage after subsequent lethal ischemic insults in hippocampal neurons. A pharmacological approach using agonists and antagonists at the adenosine A1 receptor as well as openers and blockers of ATP-sensitive K+ channels has been combined with an analysis of neuronal death and gene expression of subunits of glutamate and gamma-aminobutyric acid receptors, HSP70, c-fos, c-jun, and growth factors. It indicates that the mechanism of ischemic tolerance involves a cascade of events including liberation of adenosine, stimulation of adenosine A1 receptors, and, via these receptors, opening of sulfonylurea-sensitive ATP-sensitive K+ channels.     

Change to AXB Phenotype in Genetic A2B Following Carcinoma of the Cervix

In a woman of A₂B genotype, phenotypic change from A₂B to A_xB is documented five yean after a successful operation for carcinoma of the cervix. Serum anti-A activity developed in addition to previously noted anti-A₁. There appears to be an absolute decrease in conversion of H to A substance, occurring independently of hematologic or other malignant disease.     

Reliability and accuracy of MRI scanogram in the evaluation of limb length discrepancy

The purpose of this study was to compare MRI scanogram with traditional radiographic methods for measurement of limb length. The authors hypothesized that MRI scanogram would be as reliable and accurate as radiographic scanogram in measurement of limb length without exposing patients to ionizing radiation. Twelve cadaveric femurs were measured using AP conventional radiographic scanogram, CT scanogram, MRI scanogram, and electronic caliper. Three orthopaedists performed two separate measurements using each technique. Intraobserver and interobserver variability was assessed for each of the three radiographic techniques. Accuracy was assessed by comparison of radiographic measurements to electronic caliper measurements of femur length. The reliability of all three radiographic limb length measurement techniques was excellent (ICC > 0.99). The accuracy of plain radiographic scanogram was slightly superior to CT scanogram and MRI scanogram. The mean absolute differences for radiographic, CT, and MRI scanograms compared with the gold standard, direct caliper measurement, were 0.52 mm, 0.68 mm, and 2.90 mm, respectively. All three scanogram techniques showed excellent reliability and accuracy. Radiographic scanogram remains the gold standard for leg length measurement. MRI scanogram is slightly less accurate compared with radiographic scanogram, but it does not use ionizing radiation. MRI scanogram merits clinical study and comparison with the traditional radiographic scanogram method for measurement of limb length.     

Response repetition vs. response change modulates behavioral and electrophysiological effects of distraction

If stimulation occasionally contains distracting information, behavioral responses to task-relevant aspects of the stimulation are prolonged and more error prone. Additionally, event-related potentials (ERPs) acquired in an auditory distraction paradigm show that the distracting information elicits the components mismatch negativity (MMN), P3a and reorienting negativity (RON). Here, we assess to what extent sequential dependencies in the stimulation influence such indicators of distraction. Data of four experiments were reanalyzed for response repetition and response change trials separately. Behavioral performance on Deviants suggests markedly smaller distraction effects in change compared to repetition trials. However, the presence of MMN-P3a-RON in both response repetition and response change trials shows that sequential features in stimulation do not dissolve distraction, but might substantially contribute to the (behavioral) effects measured in distraction paradigms and should be controlled for.     

Roughness perception in sounds: behavioral and ERP evidence

The mismatch negativity (MMN) correlates of the perception of roughness, the unpleasant character of sounds caused by the perception of amplitude fluctuation in the range of 20-200 Hz, were studied on the basis of a variation in the degree of modulation (=modulation index m), which is a main parameter influencing roughness. A psychophysical study showed that perceived roughness of tones increased with modulation index for m-values from 0 up to 1.2. For larger values of m, roughness perception remained stable. In a subsequent ERP-study, infrequent amplitude modulated (AM) tones with varying modulation index were presented in the context of a series of pure tones in an ignore condition. The amplitude of the mismatch negativity correlated highly with the roughness ratings (r = -0.93) and did not increase monotonously with increasing modulation index. We conclude that perceived roughness rather than its physical correlate in sounds is reflected by the MMN and that roughness is thus preattentively encoded.     

Impact of Mucinous Histology on the Prognosis of Stage I–III Adenocarcinomas of the Appendix: a Population-Based,Propensity Score-Matched Analysis

Background

Whereas the poor prognosis of signet ring cell adenocarcinomas of the appendix is well known, the significance of mucinous histology remains unclear. The aim of this population-based study was to evaluate if mucinous histology is an independent prognostic factor in appendiceal adenocarcinomas.

Methods

Patients with stage I–III adenocarcinoma of the appendix who underwent surgery between 2004 and 2012 were identified in the Surveillance, Epidemiology, and End Results database. Overall survival (OS) and cancer-specific survival (CSS) were assessed using risk-adjusted Cox proportional hazards regression models and propensity score methods.

Results

Overall, 980 patients with appendix cancer were included, of which 449 (45.8 %) had a mucinous histology. In an unadjusted analysis, the 5-year OS and CSS in patients with a mucinous adenocarcinoma (MC) was 76.8 % (95 % confidence interval (95 %CI): 72.1–81.7 %) and 81.0 % (95 %CI: 76.6–85.6 %), respectively, compared with 70.0 % (95 %CI: 65.1–75.3 %) and 76.2 % (95 %CI: 71.5–81.2 %) in patients with non-mucinous adenocarcinoma (NMC) (P?=?0.082 and P?=?0.368). In multivariable analysis, no impact on survival was observed for OS (HR?=?1.22, 95 %CI: 0.89–1.68, P?=?0.208) and CSS (HR?=?1.21, 95 %CI: 0.84–1.74, P?=?0.296). After propensity score matching, nearly identical survival rates were observed (OS: HR?=?1.03, 95 %CI: 0.71–1.49, P?=?0.881 and CSS: HR?=?1.05, 95 %CI: 0.70–1.59, P?=?0.803).

Conclusions

The present population-based, propensity score matched analysis shows that mucinous histology does not affect survival in stage I–III appendiceal adenocarcinoma patients. Therefore, the same treatment strategies can be applied for patients with NMC and MC of the appendix.

     

Kainic acid induced seizures: changes in somatostatin, substance P and neurotensin

The neuropeptides somatostatin, neurotensin and substance P were investigated in rats during and after limbic seizures induced by systemic injection of kainic acid (10 mg/kg, i.p.). Three hours after injection of the toxin, pronounced decreases (40-50%) in somatostatin-like immunoreactivity in frontal cortex, striatum, dorsal hippocampus and amygdala/pyriform cortex were observed. Concomitantly, neurotensin-like and substance P-like immunoreactivities were also reduced in the frontal cortex and the hippocampus. These early decreases in peptide levels may result from increased release and subsequent inactivation of the peptides during acute seizures. At later time intervals, 3, 10 and 30 days after injection of kainic acid, the initially decreased peptide levels were partially normalized. However, the reduction in somatostatin-like immunoreactivity in amygdala/pyriform cortex and striatum persisted up to 30 days. Neurotensin-like immunoreactivity remained decreased in the frontal cortex. On the other hand, neurotensin- and substance P-like immunoreactivities were increased in the striatum and substantia nigra 10-30 days after injection of kainic acid. These late changes in peptide levels may suggest destruction of peptidergic neurons or adaptive changes induced by the convulsions. Pretreatment of rats with cysteamine (100 mg/kg, i.p.), an agent which decreases brain somatostatin levels, had no effect on the intensity of kainic acid induced convulsions, although a slightly earlier onset of seizures was observed. The changes in peptide levels, especially the marked decreases in somatostatin content after systemic injection of kainic acid, suggest considerable acute and chronic alterations in peptidergic systems caused by limbic convulsions.