Intratumor heterogeneity is a main cause of the dismal prognosis of glioblastoma (GBM). Yet, there remains a lack of a uniform assessment of the degree of heterogeneity. With a multiscale approach, we addressed the hypothesis that intratumor heterogeneity exists on different levels comprising traditional regional analyses, but also innovative methods including computer-assisted analysis of tumor morphology combined with epigenomic data. With this aim, 157 biopsies of 37 patients with therapy-naive IDH-wildtype GBM were analyzed regarding the intratumor variance of protein expression of glial marker GFAP, microglia marker Iba1 and proliferation marker Mib1. Hematoxylin and eosin stained slides were evaluated for tumor vascularization. For the estimation of pixel intensity and nuclear profiling, automated analysis was used. Additionally, DNA methylation profiling was conducted separately for the single biopsies. Scoring systems were established to integrate several parameters into one score for the four examined modalities of heterogeneity (regional, cellular, pixel-level and epigenomic). As a result, we could show that heterogeneity was detected in all four modalities. Furthermore, for the regional, cellular and epigenomic level, we confirmed the results of earlier studies stating that a higher degree of heterogeneity is associated with poorer overall survival. To integrate all modalities into one score, we designed a predictor of longer survival, which showed a highly significant separation regarding the OS. In conclusion, multiscale intratumor heterogeneity exists in glioblastoma and its degree has an impact on overall survival. In future studies, the implementation of a broadly feasible heterogeneity index should be considered. 相似文献
Streptococcus agalactiae, known as a pathogen that causes meningitis and septicemia in neonates, emerges as an invasive organism in nonpregnant adults. This case report describes the fulminant course of a necrotizing fasciitis (NF) with streptococcal toxic shock-like syndrome (STSS) in a 76-year-old diabetic patient caused by S. agalactiae, serotype V. Chronic diseases and immunodeficiency are considered to be risk factors for the acquisition of group B streptococcal disease. Since early surgical treatment in conjunction with antimicrobial and intensive care therapy is critical for the outcome of patients with NF and/or STSS, clinicians should be aware of invasive S. agalactiae infections in adults with subcutaneous emphysema. 相似文献
Due to its low profile for extrapyramidal side-effects, quetiapine has become an alternative to clozapine in the treatment of dopamimetic psychosis in patients with Parkinson's disease (PD). We describe the case of a patient with PD who developed severe akathisia, a common complication with classical antipsychotics, with quetiapine. 相似文献
The objective of the present study was to determine the role of mast cells and histamine in leukocyte-endothelium interactions
in mesenteric venules of four rat strains: Brown Norway, Lewis, Sprague-Dawley and Wistar. Intravital microscopy showed that
the mast cell stabilizer cromoglycate (5 mg/kg i.v. just before exteriorization of the mesentery) did not affect the baseline
level and velocity of leukocyte rolling in any of the four strains. This finding is in agreement with the observation that
cromoglycate pretreatment only slightly influenced mast cell degranulation in all strains except the Brown Norway. After mast
cell stabilization, only in Sprague-Dawley did topical administration of histamine (10–4 M) result in a significant increase in the level of leukocyte rolling and a decrease in the rolling velocity compared with
the time control. Histamine induced leukocyte adhesion only in the Brown Norway strain. In conclusion, the hypothesis presented
in other studies, that degranulation of mast cells, and more specifically the release of histamine, is of major importance
for the induction of leukocyte-endothelium interactions in rat mesenteric venules is not generally applicable; the present
study shows a clear strain dependency.
Received: 18 July 1997 / Received after revision: 17 November 1997 / Accepted: 13 March 1998 相似文献
Background: Short administration of volatile anesthetics preconditions myocardium and protects the heart against the consequences of subsequent ischemia. Activation of tyrosine kinase is implicated in ischemic preconditioning. The authors investigated whether desflurane-induced preconditioning depends on activation of tyrosine kinase.
Methods: Sixty-four rabbits were instrumented for measurement of left ventricular pressure, cardiac output, and myocardial infarct size (IS). All rabbits were subjected to 30 min of occlusion of a major coronary artery and 2 h of subsequent reperfusion. Rabbits underwent a treatment period consisting of either no intervention for 35 min (control group, n = 12) or 15 min of 1 minimum alveolar concentration desflurane inhalation followed by a 10-min washout period (desflurane group, n = 12). Four additional groups received the tyrosine kinase inhibitor genistein (5 mg/kg) or lavendustin A (1.3 mg/kg) at the beginning of the treatment period with (desflurane-genistein group, n = 11; desflurane-lavendustin A group, n = 12) or without desflurane inhalation (genistein group, n = 9; lavendustin A group, n = 8).
Results: Hemodynamic values were similar in all groups during baseline (left ventricular pressure, 87 +/- 14 mmHg [mean +/- SD]; cardiac output, 198 +/- 47 ml/min), during coronary artery occlusion (left ventricular pressure, 78 +/- 12 mmHg; cardiac output, 173 +/- 39 ml/min), and after 2 h of reperfusion (left ventricular pressure, 59 +/- 17; cardiac output, 154 +/- 43 ml/min). IS in the control group was 55 +/- 10% of the area at risk. The tyrosine inhibitors had no effect on IS (genistein group, 56 +/- 13%; lavendustin A group, 49 +/- 13%; each P = 1.0 vs. control group). Desflurane preconditioning reduced IS to 40 +/- 15% (P = 0.04 vs. control group). Tyrosine kinase inhibitor administration had no effect on IS reduction (desflurane-genistein group, 44 +/- 13%; desflurane-lavendustin A group, 44 +/- 16%; each P = 1.0 vs. desflurane group). 相似文献
The interactive use of magnetic resonance imaging (MRI) techniques is increasing in operating theaters. A study was performed on 17 male company volunteers to assess the neurobehavioral effects of exposure to magnetic fields from a 1.5 Tesla MRI system. The subjects' neurobehavioral performances on a neurobehavioral test battery were compared in four 1-hr sessions with and without exposure to magnetic fields, and with and without additional movements. Adverse effects were found for hand coordination (-4%, P < 0.05; Pursuit Aiming II) and near visual contrast sensitivity (-16% and -15%, P < 0.10; Vistech 6000). The results from the remaining tests were inconclusive due to a strong learning effect. No additional effect from gradient fields was detected. The results indicate that working near a 1.5 Tesla MRI system may lead to neurobehavioral effects. Further research is recommended, especially in members of operating teams using interactive MRI systems. 相似文献
PURPOSE: Frequency potentiation is the increase in force of contraction induced by an increased heart rate (HR). This positive staircase phenomenon has been attributed to changes in Ca2+ entry and loading of intracellular Ca2+ stores. Volatile anesthetics interfere with Ca2+ homeostasis of cardiomyocytes. We hypothesized that frequency potentiation is altered by volatile anesthetics and investigated the influence of halothane (H), sevoflurane (S) and desflurane (D) on the positive staircase phenomenon in dogs in vivo. METHODS: Dogs were chronically instrumented for measurement of left ventricular (LV) pressure and cardiac output. Heart rate was increased by atrial pacing from 120 to 220 beats x min(-1) and the LV maximal rate of pressure increase (dP/dt(max)) was determined as an index of myocardial performance. Measurements were performed in conscious dogs and during anesthesia with 1.0 minimal alveolar concentrations of each of the three inhaled anesthetics. RESULTS: Increasing HR from 120 to 220 beats x min(-1) increased dP/dt(max) from 3394 +/- 786 (mean +/- SD) to 3798 +/- 810 mmHg sec(-1) in conscious dogs. All anesthetics reduced dP/dt(max) during baseline (at 120 beats x min(-1): H, 1745 +/- 340 mmHg x sec(-1); S, 1882 +/- 418; D, 1928 +/- 454, all P < 0.05 vs awake) but did not influence the frequency potentiation of dP/dt(max) (at 220 beats x min(-1): H, 1981 +/- 587 mmHg x sec(-1); S, 2187 +/- 787; D, 2307 +/- 691). The slope of the regression line correlating dP/dt(max) and HR was not different between awake and anesthetized dogs. Increasing HR did not influence cardiac output in awake or anesthetized dogs. CONCLUSION: These results indicate that volatile anesthetics do not alter the force-frequency relation in dogs in vivo. 相似文献
The application of high gradient amplitudes and switching rates for MRI and spectroscopy, resulting in short rise times for the gradient field and high changes of the magnetic flux density in the patient, is known to possibly evoke peripheral nerve stimulation (PNS) in patients. These effects have been studied on 20 volunteers under different experimental circumstances. The results of these measurements are partially in line with earlier findings reported in the literature. New information is found for the dependence of the PNS threshold level as a function of the rise time of the gradient waveform. The PNS threshold level, expressed in terms of dB/dt, is found to be proportional with t?05, where t is the switch time for the gradients. Indications are found that |B|, the modulus of the gradient vector field, is more closely related to the PNS threshold level than Bz, the imaging component of the gradient field. From the experiments, it is furthermore concluded that only for the imaging protocols characterized by the application of long bipolar repetitive gradient pulse trains, such as echo-planar imaging, PNS is expected at the reported threshold levels. For the protocols based on spin echo, turbo spin echo, inversion recovery, fast field echo, etc., characterized by shorter gradient pulse trains, the threshold levels are expected to be much higher. 相似文献