High-grade bladder cancer: association of the apparent diffusion coefficient with metastatic disease: preliminary results

Purpose:

To assess the utility of apparent diffusion coefficient (ADC) values obtained from diffusion‐weighted imaging (DWI) in distinguishing high‐grade bladder cancer with and without metastatic disease.

Materials and Methods:

Seventeen patients with histologically confirmed high‐grade bladder cancer who underwent pelvic magnetic resonance imaging (MRI) at 1.5T including DWI using b‐values of 0, 400, and 800 sec/mm² were assessed. Histologic findings and follow‐up imaging were used to establish the reference standard in terms of metastatic disease. Two radiologists independently recorded ADC of all lesions following a training session, with their results averaged. Mann–Whitney U‐test, receiver operating characteristic (ROC) curve analysis and intraclass correlation coefficient (ICC) were used for data analysis.

Results:

Metastatic disease was characterized as present or absent in eight and nine patients, respectively. ADC was significantly lower among cases with metastatic disease than among cases without metastatic disease, both within the entire cohort (1.07 ± 0.18 × 10^?3 mm²/s vs. 1.45 ± 0.22 × 10^?3 mm²/s; P = 0.002) and within the subset of patients with muscle‐invasive tumor (1.06 ± 0.19 × 10^?3 mm²/s vs. 1.45 ± 0.23 × 10^?3 mm²/s; P = 0.017). Area under the ROC curve for identifying metastatic disease using ADC was 0.944, with optimal threshold of 1.21 × 10^?3 mm²/s, which was associated with a sensitivity of 87.5%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 90.0%. Interreader agreement for ADC was excellent (ICC = 0.91).

Conclusion:

In this preliminary study, ADC was significantly different between cases of high‐grade urothelial carcinoma of the bladder with and without metastatic disease. These results may have value in assessing the metastatic potential of patients with localized high‐grade tumors of the bladder. J. Magn. Reson. Imaging 2012;35:1478–1483. © 2012 Wiley Periodicals, Inc.

     

A Mg-dependent ecto-ATPase is increased in the infective stages of<Emphasis Type="Italic"> Trypanosoma cruzi</Emphasis>

In this work, we describe the ability of living epimastigotes of Trypanosoma cruzi to hydrolyze extracellular ATP. In these intact parasites, there was a low level of ATP hydrolysis in the absence of any divalent metal (2.42±0.31 nmol Pi/h×10⁸ cells). ATP hydrolysis was stimulated by MgCl₂, and the Mg-dependent ecto-ATPase activity was 27.15±2.91 nmol Pi/h×10⁸ cells. The addition of MgCl₂ to the extracellular medium increased the ecto-ATPase activity in a dose-dependent manner. This stimulatory activity was also observed when MgCl₂ was replaced by MnCl₂, but not by CaCl₂ or SrCl₂. The apparent K_m for Mg-ATP^2– was 0.61 mM, and free Mg²⁺ did not increase the ecto-ATPase activity. This ecto-ATPase activity was insensitive to the inhibitors of other ATPase and phosphatase activities. To confirm that this Mg-dependent ATPase was an ecto-ATPase, we used an impermeant inhibitor, DIDS (4, 4.diisothiocyanostylbene 2-2-disulfonic acid) as well as suramin, an antagonist of P₂ purinoreceptors and inhibitor of some ecto-ATPases. These two reagents inhibited the Mg²⁺-dependent ATPase activity in a dose-dependent manner. A comparison among the Mg²⁺-ecto-ATPase activities of the three forms of T. cruzi showed that the noninfective epimastigotes were less efficient at hydrolyzing ATP than the infective trypomastigote and amastigote stages.     

The time course of vasoconstriction and endothelin receptor A expression in pulmonary arterioles of mice continuously exposed to ambient urban levels of air pollution

The present study aimed to verify the time course of the effects of environmental levels of urban air pollution toxicity on lung arterioles. BALB/c mice (n=56) were continuously exposed to selective chambers equipped with (filtered, F) or without (non-filtered, NF) filter devices for particles and toxic gases for 24 h/day, over 14, 21, 30 or 45 days. After exposure, we evaluated the lumen-wall relationship (an estimator of arteriolar narrowing), endothelial nitric oxide synthase (eNOS) and endothelin type A receptor (ETAr) expression in the vascular wall and inflammatory influx of the peribronchiolar area. Concentrations of fine particulate matter (PM≤2.5 μg/m³), nitrogen dioxide (NO₂), black smoke (BS), humidity and temperature in both the environment and inside the chambers were measured daily. Filters cleared 100% of BS and 97% of PM inside the F chamber. The arteriole wall of the lungs of mice from NF chamber had an increased ETAr expression (p≤0.042) concomitant to a decrease in the lumen/wall ratio (p=0.02) on the early days of exposure, compared to controls. They also presented a progressive increment of inflammatory influx in the peribronchiolar area during the study (p=0.04) and decrement of the eNOS expression on the 45th day of exposure in both vascular layers (p≤0.03). We found that after 14 days of exposure, the ambient levels of air pollutants in Sao Paulo induced vasoconstriction that was associated with an increase in ETAr expression. These vascular results do not appear to be coupled to the progressive inflammatory influx in lung tissue, suggesting a down-regulation of vasoconstrictive mechanisms through an imbalance in the cytokines network. It is likely that these responses are protective measures that decrease tissue damage brought about by continuous exposure to air pollutants.     

Missed diagnosis in hematological patients—an autopsy study

Autopsy findings of missed diagnoses that would probably have changed management or prognosis occur in up to 29% of cases in general hospitals. Such proportions may be higher in subsets of patients with complex diseases. We reviewed 2908 consecutive autopsies performed over a period of 29 months in a large-volume hospital, analyzing 118 autopsies of patients with hematological malignancies or severe aplastic anemia. A review of macroscopic reports as well as microscopic examination of tissue samples was performed. Medical records were reviewed for clinical diagnoses. Discordances between clinical and autopsy diagnoses were classified using Goldmans criteria. Additionally, we searched for clinical parameters correlated with occurrence of class-I discrepancy using a multivariate method. Median age was 46.5 years, and 25.4% had received a hematopoietic stem-cell transplant. Overall, 11.9% (6.6–19.1%) of patients died before conclusion of the hematological diagnosis and 33% (24.6–42.3%) died with no active hematological disease. We found class-I discrepancy in 31.3% (23.1–40.5 %) of cases. The most common among these diagnoses were hematological disease, pneumonia and gastrointestinal bleeding. In a univariate analysis, being elderly (P=0.04) was positively correlated with the finding of class-I discrepancies; while, having received previous specific hematological treatment (P=0.0005) or hematopoietic stem-cell transplants (P=0.013), or being admitted to a specialized hematology unit (P=0.0006) were negatively correlated to the occurrence of such discrepancies. Multivariate analysis showed that care in a specialized hematology unit (OR 0.34, 0.12–0.93) was independently associated with lower occurrence of discrepancies. We concluded that critical diagnoses are often missed in highly complex hematological patients especially in the absence of admission to specialized hematology units.     

Effect of acute swimming exercise at different intensities but equal total load over metabolic and molecular responses in swimming rats

Journal of Muscle Research and Cell Motility - Acute metabolic and molecular response to exercise may vary according to exercise’s intensity and duration. However, there is a lack regarding...     

Utilization of the lower inflection point of the pressure-volume curve results in protective conventional ventilation comparable to high frequency oscillatory ventilation in an animal model of acute respiratory distress syndrome

INTRODUCTION: Studies comparing high frequency oscillatory and conventional ventilation in acute respiratory distress syndrome have used low values of positive end-expiratory pressure and identified a need for better recruitment and pulmonary stability with high frequency. OBJECTIVE: To compare conventional and high frequency ventilation using the lower inflection point of the pressure-volume curve as the determinant of positive end-expiratory pressure to obtain similar levels of recruitment and alveolar stability. METHODS: After lung lavage of adult rabbits and lower inflection point determination, two groups were randomized: conventional (positive end-expiratory pressure = lower inflection point; tidal volume=6 ml/kg) and high frequency ventilation (mean airway pressures= lower inflection point +4 cmH2O). Blood gas and hemodynamic data were recorded over 4 h. After sacrifice, protein analysis from lung lavage and histologic evaluation were performed. RESULTS: The oxygenation parameters, protein and histological data were similar, except for the fact that significantly more normal alveoli were observed upon protective ventilation. High frequency ventilation led to lower PaCO2 levels. DISCUSSION: Determination of the lower inflection point of the pressure-volume curve is important for setting the minimum end expiratory pressure needed to keep the airways opened. This is useful when comparing different strategies to treat severe respiratory insufficiency, optimizing conventional ventilation, improving oxygenation and reducing lung injury. CONCLUSIONS: Utilization of the lower inflection point of the pressure-volume curve in the ventilation strategies considered in this study resulted in comparable efficacy with regards to oxygenation and hemodynamics, a high PaCO2 level and a lower pH. In addition, a greater number of normal alveoli were found after protective conventional ventilation in an animal model of acute respiratory distress syndrome.