Breakdown of calcium homeostasis in relation to tissue depolarization: comparison between gray and white matter ischemia.

In vitro studies suggest that ischemic injury of cerebral white matter is mediated by nonsynaptic cellular mechanisms, such as Ca2+ entry into axons through reversal of the Na+ -Ca2+ exchanger. The authors investigated extracellular Ca2+ concentration in relation to tissue depolarization (direct current potential) in vivo using ion-selective electrodes in cortical gray and subcortical white matter of alpha-chloralose-anesthetized cats during 120 minutes of global cerebral ischemia. On induction of ischemia, regional CBF, as measured by hydrogen clearance, ceased. The direct current potential decreased rapidly within minutes in gray matter and with little time delay in white matter. Extracellular Ca2+ concentration decreased just as quickly in gray matter. In white matter, in contrast, extracellular Ca2+ increased in the first 20 to 30 minutes, and a delayed and much slower decline, compared with gray matter, was observed thereafter, reaching a minimal level only about 60 minutes after occlusion. Our results suggest that smaller and delayed transmembrane shifts of Ca2+ are correlates of delayed ischemic membrane dysfunction in central white matter tracts, which may be explained by a lack of synaptic mechanisms.     

Frequency of common bile duct motion artifacts caused by inferior vena cava pulsation on magnetic resonance cholangiopancreatography.

PURPOSE: We assessed the frequency of common bile duct (CBD) motion artifacts caused by inferior vena cava (IVC) pulsation on magnetic resonance cholangiopancreatography (MRCP). METHODS: We retrospectively evaluated CBD motion artifacts in 4 MRCP sequences from each of 115 consecutive patients. RESULTS: We observed 37 (32.2%) ghost artifacts at the ventral and dorsal aspects of the CBD on transaxial, half-Fourier acquisition single-shot turbo spin-echo (HASTE-ax) images; no such artifacts were observed on transaxial T(2)-weighted turbo spin-echo images. In 10 patients, we observed 9 (7.8%) pseudo-defects of the CBD on 3-dimensional T(2)-weighted turbo spin-echo with navigator-triggered prospective acquisition correction technique MRCP and 6 (5.2%) pseudo-defects on single-shot rapid acquisition with relaxation enhancement MRCP. Pseudo-defects were significantly more frequent in patients with ghost artifacts than without (9 of 37 [24.3%] versus one of 78 [1.3%]; P<0.01, McNemar test). CONCLUSION: Although uncommon, pseudo-defects of the CBD caused by IVC pulsation are observed on MRCP. MRCP interpretation that includes comparison with HASTE-ax images can diminish the potential misinterpretation of such CBD motion artifact as bile duct tumor or biliary stone.     

Long-Lasting Enhancement of the Membrane-Associated Protein Kinase C Activity in the Hippocampal Kindled Rat

Abstract: We demonstrated that only membrane-associated protein kinase C (PKC) activity increased in the bilateral hippocampus (HIPP) up to 4 weeks and in the amyg-dala/pyriform cortex (AM/PC) at 4 weeks after the last kindled seizure. The enhancement of the membrane-associated PKC activity exceeds the increase in the protein concentration, which was observed in part. The overwhelming increase in the PKC activity should be of significance in the long-term maintenance of the kindling phenomenon.     

Anti-NGF therapy profoundly reduces bone cancer pain and the accompanying increase in markers of peripheral and central sensitization

Bone cancer pain can be difficult to control, as it appears to be driven simultaneously by inflammatory, neuropathic and tumorigenic mechanisms. As nerve growth factor (NGF) has been shown to modulate inflammatory and neuropathic pain states, we focused on a novel NGF sequestering antibody and demonstrated that two administrations of this therapy in a mouse model of bone cancer pain produces a profound reduction in both ongoing and movement-evoked bone cancer pain-related behaviors that was greater than that achieved with acute administration of 10 or 30 mg/kg of morphine. This therapy also reduced several neurochemical changes associated with peripheral and central sensitization in the dorsal root ganglion and spinal cord, whereas the therapy did not influence disease progression or markers of sensory or sympathetic innervation in the skin or bone. Mechanistically, the great majority of sensory fibers that innervate the bone are CGRP/TrkA expressing fibers, and if the sensitization and activation of these fibers is blocked by anti-NGF therapy there would not be another population of nociceptors, such as the non-peptidergic IB4/RET-IR nerve fibers, to take their place in signaling nociceptive events.     

Severe Cerebral Venous and Sinus Thrombosis: Clinical Course,Imaging Correlates,and Prognosis

Background

Severe cerebral venous-sinus thrombosis (CVT) is a rare disease, and its clinical course, imaging correlates, as well as long-term prognosis have not yet been investigated systematically.

Methods

Multicenter retrospective study. Inclusion criteria were CVT, Glasgow coma scale ≤9, and treatment in the intensive care unit. Primary outcome was death or dependency, assessed by a modified Rankin Score (mRS) >2 at last follow-up.

Results

114 patients were included. At last follow-up (median 2.5 years), 38 patients (33.3 %) showed no or minor residual symptoms (mRS = 0 or 1), 12 (10.5 %) had a mild (mRS = 2), 13 (11.4 %) a moderate (mRS = 3), 12 (10.5 %) a severe disability (mRS = 4 or 5), and 39 (34.2 %) had died. In bivariate analysis, predictors of poor outcome were any signs of mass effect on imaging, clinical deterioration after admission, and age. In contrast, clinical symptoms on admission and parenchymal lesions per se, such as edema, infarction, or hemorrhage were not predictive. Multivariate predictors of poor outcome were an increase in National Institutes of Health Stroke Scale ≥3 after admission [odds ratio (OR) 6.7], bilateral motor signs in the further course (OR 9.2), and midline shift (OR 5.1).

Conclusion

The outcome of severe CVT is almost equally divided between severe impairment or death and survival with no or only mild handicap. Specifically, space-occupying mass effect and associated neurologic deterioration seem to determine a poor outcome. Therefore, early detection and treatment of mass effect should be the focus of critical care.

     

Serum cytochrome c level as a prognostic indicator in patients with systemic inflammatory response syndrome

BACKGROUND: Apoptosis may play an important role in the development of systemic inflammatory response syndrome (SIRS) and progression to multiple organ dysfunction syndrome (MODS). To quantify the extent of apoptosis in these morbidities, we developed a sandwich ELISA system to measure serum cytochrome c (cyt-c) levels and we investigated the prognostic significance of cyt-c concentration in SIRS/MODS patients. METHODS: Cyt-c concentrations in patients with SIRS (n=53) with or at risk for MODS were measured and compared with those of control subjects (n=14). RESULTS: Cyt-c concentrations in SIRS/MODS patients increased (0.24-210 ng/ml), whereas those in control subjects were under detection limits (0.1 ng/ml). Cyt-c concentrations in non-survivors increased significantly compared with those in survivors both on the day of admission and on the fifth hospital day. A significant positive correlation was found between cyt-c concentration and two representative organ dysfunction scores, APACHE II and multi-organ failure (MOF) score. Cyt-c concentrations increased earlier than MOF score during the exacerbation phase and rapidly decreased during the convalescence phase in a survivor, but the level continued to be high in a non-survivor. CONCLUSIONS: Determination of serum cyt-c concentrations may be useful to assess the severity of organ dysfunction and to predict the prognosis of SIRS/MODS patients.     

The white blood cell count is an independent predictor of no-reflow and mortality following acute myocardial infarction in the coronary interventional era

BACKGROUND: In the era before the use of coronary reperfusion therapy, an elevated white blood cell (WBC) count was associated with a higher risk of adverse events following acute myocardial infarction (AMI). However, the relationship between WBC count and prognosis after AMI has not been investigated since coronary intervention was introduced. AIM: To evaluate whether a high WBC count within 48 hours of the onset of AMI predicts future adverse events in patients undergoing percutaneous coronary intervention (PCI). METHOD: We evaluated 1,016 patients who underwent PCI in the acute phase of MI using the Japanese Acute Coronary Syndrome Study (JACSS) database. RESULTS. WBC count was significantly associated with smoking, sudden onset AMI, and the no-reflow phenomenon during PCI, as were age, peak creatine kinase level, and Killip class. An elevated WBC count was significantly associated with higher risk of in-hospital mortality. Patients in the highest quartile of WBC count were about three times more likely to have a poor prognosis after AMI compared to those in the lowest quartile. CONCLUSIONS: The WBC count is of great significance for stratifying patient risk and can be used as a universal marker for predicting future adverse events following any treatment for AMI.