Liposome-encapsulated hemoglobin attenuates cardiac dysfunction and sympathetic activity during hypohemoglobinemic shock

The use of liposome-encapsulated hemoglobin (LHb), which is a cellular Hb, has been demonstrated to be beneficial in the treatment of hypohemoglobinemic shock. As a molecule of appropriate size (220 nm) that can carry oxygen, LHb may ameliorate cardiac dysfunction during lethal hemodilation. The purpose of this study was to determine the efficacy of LHb transfusion in relieving cardiovascular dysfunction in a rat model of lethal progressive hemodilution. Over the course of 150 min, rats were subjected to blood withdrawal (0.2 mL/min) and simultaneously transfused with LHb, washed rat red blood cells, or 5% albumin. Temporal changes in cardiac function, heart-type fatty acid-binding protein levels, plasma levels of catecholamines, heart rate variability, and hypoxia-inducible factor 1α expression were measured during lethal progressive hemodilution. More than 80% of the rats transfused with either LHb or washed rat red blood cells survived for 8 days. Liposome-encapsulated hemoglobin transfusion suppressed hypoxia-inducible factor 1α expression in the heart, maintained low levels of heart-type fatty acid-binding protein, and attenuated sympathetic nerve activity as reflected by changes in heart rate variability and plasma levels of epinephrine and norepinephrine. The results indicate that LHb attenuates cardiac dysfunction and sympathetic overactivity during lethal hemorrhage.     

Neuromuscular blockade by vecuronium during induction with 5% sevoflurane or propofol

This randomized trial investigated whether 5% sevoflurane potentiated neuromuscular blockade by vecuronium. General anaesthesia was induced with 5% sevoflurane in oxygen in 16 patients or with propofol in 16 patients. After loss of consciousness, vecuronium was administered to all participants at randomly assigned doses of 25, 30, 35 or 40 μg/kg. Neuromuscular blockade was assessed by use of acceleromyography to measure responses to train-of-four stimuli in the adductor pollicis and corrugator supercilii muscles. Maximum blockade was significantly more intense in the adductor pollicis among patients in the sevoflurane group than in the propofol group, whereas there was no significant between-group difference at the corrugator supercilii muscles. In both groups, maximum blockade at the corrugator supercilii was significantly less intense than that achieved at the adductor pollicis. In the dose-response analysis, the 50% and 95% effective doses were lower for sevoflurane than for propofol in both muscles, although this did not reach statistical significance. It is concluded that induction of general anaesthesia with sevoflurane might provide improved conditions for intubation and reduce airway problems.     

Prevalence of copy-number neutral LOH in glioblastomas revealed by genomewide analysis of laser-microdissected tissues

We have employed a laser-capture microdissection technique and single-nucleotide polymorphism arrays to characterize genomic alterations associated with the development of glioblastoma multiforme (GBM). Combined analysis of loss of heterozygosity (LOH) and copy number revealed that more than half (56.3%) of the 254 identified LOH loci showed no copy-number alteration, indicating the presence of copy-number neutral LOH (cnLOH). Furthermore, we found a GBM case that showed cnLOH in 18 of the 22 autosomes. These results were confirmed by quantitative real-time PCR, microsatellite analysis, and fluorescence in situ hybridization. The high rate of cnLOH suggests that epigenetic abnormalities of many genes are involved in the development and progression of GBMs.     

Diurnal rhythms in fetal heart rate baseline and sustained fetal tachycardia in twin pregnancy

OBJECTIVE: To elucidate the synchronization of phases of diurnal rhythms in fetal heart rate (FHR) baseline between twin fetuses and the occurrence of sustained fetal tachycardia. METHODS: FHR was simultaneously recorded in twins for 24 h in 7 monochorionic diamniotic (MD) and 8 dichorionic diamniotic (DD) twin pregnancies at 35 to 38 weeks of gestation. The diurnal rhythms of the hourly mean FHR baseline were tested in each fetus, and the time of occurrence of sustained fetal tachycardia was compared between twins. The correlation coefficients and phase lags of diurnal rhythms between the hourly mean FHR baselines of twins were calculated in each case. RESULTS: There were significant diurnal rhythms in the hourly mean FHR baselines of all twin fetuses (p<0.01). The patterns of diurnal rhythms were similar for each pair of twins, with the exception of the periods of sustained fetal tachycardia. Sustained fetal tachycardia was not coincident between twins. Analysis in which the periods of sustained fetal tachycardia were excluded demonstrated a significant correlation between the hourly mean FHR baselines of twins in all cases (p<0.01). In the case of DD twins, the phase lag between twins was 0; however, phase lags were observed in 4 cases of MD twins. CONCLUSIONS: The results of this study revealed that the diurnal rhythms in the FHR baseline correlated well between twins, and that the occurrences of sustained fetal tachycardia were completely independent.     

Effect of serum depletion on centrosome overduplication and death of human pancreatic cancer cells after exposure to radiation.

The tumor microenvironment is one of the key factors affecting the cellular response to radiation; however, the influence of serum concentration on tumor radiosensitivity remains poorly understood. We recently discovered that gamma-irradiation of tumor cells causes centrosome overduplication, which may lead to lethal nuclear fragmentation through the establishment of multipolar mitotic spindles. In the present study, we investigated the effect of serum depletion on radiation-induced cell death in relation to the centrosome dynamics in human pancreatic cancer cells. Exposure of Capan-1 cells to gamma-irradiation resulted in a time-dependent increase in cells containing multiple centrosomes in association with the appearance of mitotic cell death. Treatment of irradiated cells with serum depletion drastically accelerated centrosome overduplication and the formation of multipolar spindles, resulting in increased nuclear fragmentation and cell death. Cell cycle analysis of irradiated cultures revealed that the reduced serum level increased the population of cells arrested in the G2/M phase, which might be responsible for the abnormal centrosome accumulation. These findings suggest that serum concentration can influence radiation-induced cell killing through modulating cell cycle progression and possibly centrosome overduplication.     

Lung cancer in a child with a substantial family history of cancer.

The occurrence of primary lung cancer is rare in childhood. The case of an 11-year-old boy with primary lung cancer is presented in this report. He had a substantial family history of cancer. His chief complaint was coughing with right chest pain. A chest radiograph showed a coin lesion in the right lower lung. A right lower lobectomy revealed a squamous cell carcinoma (stage IIIA at Japanese TNM classification). Systemic chemotherapy using cisplatin, vindesine, THP-adriamycin and cyclophosphamide was performed. Six months after surgery, a recurrent tumor occurred. An analysis of the familial cancer related genes (p53 gene and mismatch repair gene) showed no abnormality.     

Assessment of intratumor heterogeneity in mesenchymal uterine tumor by an <Superscript>18</Superscript>F-FDG PET/CT texture analysis

Objective

The aim of this study was to retrospectively evaluate the clinical significance of ¹⁸F-FDG PET/CT textural features for discriminating uterine sarcoma from leiomyoma.

Methods

Fifty-five patients with suspected uterine sarcoma based on ultrasound and MRI findings who underwent pretreatment ¹⁸F-FDG PET/CT were included. Fifteen patients were histopathologically proven to have uterine sarcoma, 14 patients by surgical operation and one by biopsy, and 40 patients were diagnosed with leiomyoma by surgical operation or in a follow-up for at least 2 years. A texture analysis was performed on PET/CT images from which second- and higher order textural features were extracted in addition to standardized uptake values (SUVs) and other first-order features. The accuracy of PET features for differentiating between uterine sarcoma and leiomyoma was evaluated using a receiver-operating-characteristic (ROC) analysis.

Results

The intratumor distribution of ¹⁸F-FDG was more heterogeneous in uterine sarcoma than in leiomyoma. Entropy, correlation, and uniformity calculated from normalized gray-level co-occurrence matrices and SUV standard deviation derived from histogram statistics showed greater area under the ROC curves (AUCs) than did maximum SUV for differentiating between sarcoma and leiomyoma. Entropy, as a single feature, yielded the greatest AUC of 0.974 and the optimal cut-off value of 2.85 for entropy provided 93% sensitivity, 90% specificity, and 92% accuracy. When combining conventional features with textural ones, maximum SUV (cutoff: 6.0) combined with entropy (2.85) and correlation (0.73) provided the best diagnostic performance (100% sensitivity, 94% specificity, and 95% accuracy).

Conclusions

In combination with the conventional histogram statistics and/or volumetric parameters, ¹⁸F-FDG PET/CT textural features reflecting intratumor metabolic heterogeneity are useful for differentiating between uterine sarcoma and leiomyoma.