Clinical presentations and outcomes of systemic lupus erythematosus patients with infection admitted to the intensive care unit.

OBJECTIVE: The objective of this article is to investigate clinical presentations and outcomes of systemic lupus erythematosus (SLE) patients with infection admitted to the intensive care unit (ICU). METHODS: SLE patients with infection, SLE patients with noninfectious causes, and non-SLE patients with infection were identified from the Cooper University Hospital Project IMPACT database between 2002 and 2010. We examined demographic data, APACHE II scores, physiologic data, laboratory data, length of stay in the ICU and hospital, and mortality of the three groups. RESULTS: Twenty-five SLE patients with infection, 45 SLE patients with noninfectious causes, and 1466 non-SLE patients with infection were included in the study. SLE patients with infection had higher APACHE II scores, higher maximum temperature, higher minimum and maximum heart rate (HR), lower minimum and maximum systolic blood pressure (SBP), and longer ICU length of stay in comparison to SLE patients with noninfectious causes. There were no statistical differences in white blood cell (WBC) count. SLE patients with infection had a higher mortality compared to SLE patients with noninfectious causes. There was no difference in mortality between SLE patients with infection and non-SLE patients with infection. CONCLUSION: SLE patients with infection in the ICU had a higher mortality and a higher APACHE II score compared to SLE patients with noninfectious causes in the ICU. Their physiologic signs including temperature, HR, and SBP were more reflective of infection than their WBC count.

Ultrasonographic elastography of thyroid nodules: is adding strain ratio to colour mapping better?

AIM: To determine the diagnostic performance of colour mapping and strain ratio for characterizing malignant thyroid nodules on ultrasonographic (US) elastography. MATERIALS AND METHODS: The study was approved by the institutional review board and written informed consent was obtained. One hundred and thirty-one patients with 142 thyroid nodules >0.5 cm were prospectively enrolled between July 2010 and January 2011. Seven radiologists performed US elastography (iU22 Vision 2010; Philips, Seattle, WA, USA) using colour mapping and strain ratio for thyroid nodules blinded to the cytopathological results. Diagnostic performances of colour mapping alone, strain ratio alone, colour mapping and strain ratio, and colour mapping or strain ratio were compared using receiver operating characteristic (ROC) curve analysis. RESULTS: Of the 142 nodules, 69 (48.6%) were benign and 73 (51.4%) were malignant. Colour mapping of elastography showed a more frequent blue colour in malignant nodules than in benign nodules (65.8% versus 24.6%, p < 0.0001). A higher ratio than 1.21 as the best cut-off value was found in 65.8% of malignant nodules and 46.4% of benign nodules (p = 0.030). Area under the ROC curve (AUC) of colour mapping alone was significantly greater than that of colour mapping or strain ratio (AUC = 0.706 versus AUC = 0.63, p = 0.0195) and similar to that of colour mapping and strain ratio (AUC = 0.673, p = 0.1364). CONCLUSION: US elastography is helpful to predict malignant thyroid nodules. However, adding strain ratio to colour mapping does not improve performance compared to colour mapping alone.

Automated volumetric breast density estimation: a comparison with visual assessment.

AIM: To compare automated volumetric breast density (VBD) measurement with visual assessment according to Breast Imaging Reporting and Data System (BI-RADS), and to determine the factors influencing the agreement between them. MATERIALS AND METHODS: One hundred and ninety-three consecutive screening mammograms reported as negative were included in the study. Three radiologists assigned qualitative BI-RADS density categories to the mammograms. An automated volumetric breast-density method was used to measure VBD (% breast density) and density grade (VDG). Each case was classified into an agreement or disagreement group according to the comparison between visual assessment and VDG. The correlation between visual assessment and VDG was obtained. Various physical factors were compared between the two groups. RESULTS: Agreement between visual assessment by the radiologists and VDG was good (ICC value = 0.757). VBD showed a highly significant positive correlation with visual assessment (Spearman's ρ = 0.754, p < 0.001). VBD and the x-ray tube target was significantly different between the agreement group and the disagreement groups (p = 0.02 and 0.04, respectively). CONCLUSION: Automated VBD is a reliable objective method to measure breast density. The agreement between VDG and visual assessment by radiologist might be influenced by physical factors.

Clinical relevance of TNM staging system according to breast cancer subtypes.

BACKGROUND: There has been reported that the association between nodal spread and tumor size was disrupted in triple-negative breast cancer (TNBC) and it showed characteristically early relapse. The TNM (tumor-node-metastasis) staging system might not be equally effective as a prognostic indicator for all subtypes. The aim of our study was to evaluate the usefulness of the staging according to subtypes. PATIENTS AND METHODS: We conducted a retrospective analysis of invasive breast cancer patients who received curative surgery at Samsung Medical Center from 2000 to 2004. Relapse-free survivals (RFS) by stage were analyzed. RESULTS: Thousand eight hundred and seventy-nine patients who were available clinicopathologic data were included. These patients were divided into three subtypes: hormone receptor (HR)+, human epidermal growth factor receptor 2+, and triple negative groups. As the stage became more advanced, the slope of each stage of the RFS curves of patients with HR+ and HER2+ steadily increased. In contrast, RFS curves intermingled and showed overlap from stage 1 to 3A in TNBC patients. There was only wide separation of RFS curves between stage 1-3A and 3B-3C in TNBC. CONCLUSIONS: The current TNM staging system might not be enough for encompassing the tumor biology and for predicting outcomes to make therapeutic decisions for all BCs, especially for TNBC patients.

Sexually dimorphic gene expression in the chick brain before gonadal differentiation.

Biological bases for sexual differences in the brain exist in a wide range of vertebrate species, including chickens. Recently, the dogma of hormonal dependence for the sexual differentiation of the brain has been challenged. We examined whether sexually dimorphic gene expression in the brain precedes gonadal differentiation. Using the Affymetrix GeneChip Chicken Genome Array, we identified 42 female- and 167 male-enhanced genes that were differentially expressed in sex-specific brains from stage 29 chicken embryos. To confirm the efficacy of the microarray, and to investigate the stage-specific expression patterns of the identified genes, we used quantitative real-time PCR analysis. Our real-time PCR results for the differentially expressed genes agreed well with our microarray results. Thus, we postulate that these genes have potential roles in the sexual differentiation of neural function and development in chickens.

Evaluation of ER and Ki-67 proliferation index as prognostic factors for survival following neoadjuvant chemotherapy with doxorubicin/docetaxel for locally advanced breast cancer.

BACKGROUND: The aim of the study was to identify reliable predictive biological markers for treatment outcome following neoadjuvant adriamycin/docetaxel (AT) chemotherapy in locally advanced breast cancer patients. MATERIALS AND METHODS: This study was a phase II study on AT neoadjuvant chemotherapy in locally advanced breast cancer patients. Patients received 50 mg/m(2) of doxorubicin intravenously (IV) over 15 min followed by docetaxel 75 mg/m(2) infused over 1 h, repeated every 3 weeks for three cycles. Surgery was performed within 3-4 weeks following the last cycle of chemotherapy. We analyzed the pre-treatment and post-treatment expression levels of ER, PgR, HER-2, Ki-67 proliferation index, and p53 and examined the correlation between the markers and clinical parameters with treatment response, overall survival and relapse-free survival following neoadjuvant treatment. RESULTS: From July 2001 to September 2004, 61 patients were enrolled. The meaningful parameters adversely influencing survival were post-treatment ER(-) status (P = 0.013) and post-treatment Ki-67 index above 1.0% (P = 0.013). At the multivariate level, the post-treatment Ki-67 proliferation index < or = 1.0 was the only meaningful prognostic factor for better survival (P = 0.033). Notably, tumors with Ki-67 index < or = 1.0 were more likely to express ER with statistical significance (P = 0.002). Tumors with ER(+) and Ki-67 index < or = 1.0 showed the highest survival rate, followed by ER(+) and Ki-67 index > 1.0%, ER(-) and Ki-67 < or = 1.0%, and ER(-) and Ki-67 > 1.0% with the worst survival (P = 0.033). CONCLUSION: Collectively, post-treatment ER status and Ki-67 proliferation index were prognostic of overall survival following neoadjuvant AT chemotherapy.

Identification and characterization of the peroxiredoxin gene family in chickens.

Peroxiredoxin (PRX) is a crucial antioxidant protein that protects against endogenously produced peroxides in prokaryotes to eukaryotes. To date, 6 different isoforms have been identified in mammals. In this study, we describe the first members of the PRX protein family to be characterized in Chicken. Through bioinformatics analysis, we observed that at least 4 different classes of PRX protein have been evolutionarily conserved in chickens. Furthermore, in vitro functional assays of the candidate chicken PRX proteins demonstrated that they had levels of antioxidant activity similar to those of the mammalian enzymes. The expression patterns of the PRX transcript in several chicken tissues were not tissue specific, suggesting that they might play an essential role as a housekeeping gene in all tissues to protect against oxidative damage. In conclusion, the sequences of the putative members of this functional gene family in chickens could be effectively retrieved in silico through bioinformatics analysis, and the functionality of their gene products evaluated by in vitro comparative assay.

Thoracic manifestation of Churg-Strauss syndrome: radiologic and clinical findings.

STUDY OBJECTIVES: To describe the radiologic and clinical findings of Churg-Strauss syndrome (CSS) and its thoracic manifestations. DESIGN: We used retrospective analysis to review and characterize the radiographic, thin-section CT, and clinical findings of CSS. PATIENTS: The study involved nine patients with CSS. The patients included four men and five women, whose ages ranged from 18 to 60 years (median, 35 years). Thin-section CT scans and chest radiographs were retrospectively analyzed by three radiologists in consensus. Clinical data were obtained by chart review. Histologic samples were available in eight patients. RESULTS: All patients had a history of asthma averaging 28 months (range, 4 to 72 months) prior to the initial symptom of vasculitis and marked peripheral blood eosinophilia (mean peak count, 8,726/microL; range, 3,000 to 32,000/microL; mean differential count, 41%; range, 19 to 67%). All patients had systemic vasculitis involving the lung and two to four extrapulmonary organs, most commonly the nervous system (n = 8) and skin (n = 7). Chest radiographs showed bilateral nonsegmental consolidation (n = 5), reticulonodular opacities (n = 3), bronchial wall thickening (n = 3), and multiple nodules (n = 1). The most common thin-section CT findings included bilateral ground-glass opacity (n = 9); airspace consolidation (n = 5), predominantly subpleural and surrounded by the ground-glass opacity; centrilobular nodules mostly within the ground-glass opacity (n = 8); bronchial wall thickening (n = 7); and increased vessel caliber (n = 5). Other findings were hyperinflation (n = 4), larger nodules (n = 4), interlobular septal thickening (n = 2), hilar or mediastinal lymph node enlargement (n = 4), pleural effusion (n = 2), and pericardial effusion (n = 2). CONCLUSIONS: In CSS, thoracic organs are invariably involved with additional diverse manifestations. The possibility of CSS should be raised in patients with a history of asthma and hypereosinophilia who present with thin-section CT findings of bilateral subpleural consolidation with lobular distribution, centrilobular nodules (especially within the ground-glass opacity) or multiple nodules, especially in association with bronchial wall thickening.

Distribution and characterization of neurosteroid sulfatase from the bovine brain.

We investigated the regional and subcellular distribution of neurosteroid sulfatase (NSS) in the bovine brain and its enzymatic properties by using dehydroepiandrosterone sulfate (DHEA-S) as a substrate. Bovine NSS was highly concentrated in the region of the midbrain and in the hypothalamus. The enzyme was found to be a microsomal enzyme. The optimal temperature of the enzyme was 50 degrees C, which was slightly lower than that of other steroid sulfatases. The optimal pH of bovine NSS was 7.4 with a second optimum at pH 4.0. The second optimal pH of 4.0 was the most characteristic property of bovine NSS. Employing DHEA-S as the substrate, apparent Km and Vmax values were 113 +/- 21 microM and 4.1 +/- 0.4 nmol/mg protein/h, respectively, whereas Km and Vmax values were found to be 1.6 +/- 0.2 M and 1.9 +/- 0.3 micromol/mg protein/h with p-nitrophenyl sulfate (NP-S) as the substrate. NSS has thus been shown to have a higher affinity for the steroid sulfate than the phenolic compound. When DHEA-S was used as the substrate, pregnenolone sulfate (Preg-S) was a competitive inhibitor with an apparent Ki value of 46 microM, and NP-S was a non-competitive inhibitor (apparent Ki=12 mM).

The length of the polyoxyethylene chain in the Triton X detergents modulates the apparent activation of neurosteroid sulfatase in bovine brain.

The effect of the Triton X series on the solubilization and enzyme activity of neurosteroid sulfatase (NSS) in the bovine midbrain was investigated. Triton X-100 and X165 stimulated NSS activity in the bovine midbrain, while Triton X-305 did not. This apparent activation was attributed to the action of the detergents, and not to the latency of the enzyme or the removal of some inhibitory substance from the microsomes. The maximum stimulation was obtained when the length of the polyoxyethylene chain of the detergent was 16.

Subunits of neurosteroid sulfatase from bovine brain.

We have purified the neurosteroid sulfatase (NSS) from Triton X-100 solubilized microsomes of bovine brain about 100-fold. The purified enzyme is composed of two catalytic units (MW: 57 kDa) and two regulatory units (MW: 38 kDa), making it an alpha(2)beta(2) heterotetramer, whose apparent molecular weight was 180 kDa by gel filtration in the presence of Triton X-100.

Intracranial hemorrhage in premature infants: sonographic-pathologic correlation.

Spontaneous intracranial hemorrhage is the most common central nervous system abnormality in premature infants. In this report the cranial sonographic and pathologic findings of 25 autopsied premature infants are correlated. The presence and size of subependymal, intraventricular, and intraparenchymal hemorrhage were well documented by sonography. Cerebellar, choroid plexus, and cortical hemorrhage, though less frequent, were also recognized. There was good correlation as to the presence and degree of hydrocephalus. Prominent subarachnoid spaces on sonography correlated poorly with subarachnoid hemorrhage at autopsy and may be a normal variant in the premature infant. Anoxic brain damage was not diagnosed early by sonography unless associated with hemorrhage, but diffuse brain atrophy with hydrocephalus exvacuo was detected by sonography.

Reversal sign on CT: effect of anoxic/ischemic cerebral injury in children.

A retrospective study was performed to determine the clinical and pathologic features, etiology, and outcome of children with the reversal sign. The reversal sign, a striking CT finding, probably represents a diffuse, anoxic/ischemic cerebral injury. CT features of the reversal sign are diffusely decreased density of cerebral cortical gray and white matter with a decreased or lost gray/white matter interface, or reversal of the gray/white matter densities and relatively increased density of the thalami, brainstem, and cerebellum. Twenty children with the reversal sign were retrospectively analyzed. We divided the patients into three groups: (1) acute reversal, (2) intermediate group, and (3) chronic reversal. There were nine cases of trauma (seven of child abuse); nine hypoxia/anoxia incidents (birth asphyxia, drowning, status epilepticus); one bacterial meningitis; and one degenerative encephalitis. All acute- and intermediate-group patients had respiratory problems requiring ventilator support and intensive care. In five of seven patients who died, autopsy findings were consistent with anoxic/ischemic encephalopathy. Surviving patients have profound neurologic deficits with severe developmental delay. The CT reversal sign carries a poor prognosis and indicates irreversible brain damage.

Spatial distribution of mammalian cells grown on macroporous microcarriers with improved attachment kinetics.

Vero and HepG2 cells were cultivated on macroporous gelatin microcarriers prepared by the calcium carbonate inclusion method. Cell attachment to these microcarriers was slow. For HepG2 cells the subsequent growth was poor. Modification of the microcarriers by incorporation of (diethylamino)ethyl-HCl improved HepG2 attachment and subsequent growth. Optical sectioning with confocal microscopy allowed visualization of the distribution of cells within microcarriers. In most microcarriers, cells were found to preferentially populate regions close to the external surface and some cavities in the interior. Despite the incomplete occupancy of the interior of the microcarriers, high cell concentrations were achieved.

Foreign body granulomas of the breast presenting as bilateral spiculated masses.

In Asia, mammography following the injection of foreign materials into the breasts for cosmetic augmentation is frequently seen and diagnosis based on the typical radiologic findings is straightforward. We report the unusual radiologic findings in two patients with foreign body granulomas caused by injected foreign materials and discovered incidentally during screening work up. The mammographic findings were bilateral, hyperdense, spiculated masses, with occasional microcalcification, and at sonography, markedly hypoechoic, spiculated solid masses, located near the pectoralis muscle and partly extending into it, were observed. These radiologic findings mimicked malignancy.

Functional MR imaging of working memory in the human brain.

OBJECTIVE: In order to investigate the functional brain anatomy associated with verbal and visual working memory, functional magnetic resonance imaging was performed. MATERIALS AND METHODS: In ten normal right handed subjects, functional MR images were obtained using a 1.5-T MR scanner and the EPI BOLD technique. An item recognition task was used for stimulation, and during the activation period of the verbal working memory task, consonant letters were used. During the activation period of the visual working memory task, symbols or diagrams were employed instead of letters. For the post-processing of images, the SPM program was used, with the threshold of significance set at p <.001. We assessed activated brain areas during the two stimulation tasks and compared the activated regions between the two tasks. RESULTS: The prefrontal cortex and secondary visual cortex were activated bilaterally by both verbal and visual working memory tasks, and the patterns of activated signals were similar in both tasks. The superior parietal cortex was also activated by both tasks, with lateralization to the left in the verbal task, and bilaterally without lateralization in the visual task. The inferior frontal cortex, inferior parietal cortex and temporal gyrus were activated exclusively by the verbal working memory task, predominantly in the left hemisphere. CONCLUSION: The prefrontal cortex is activated by two stimulation tasks, and this is related to the function of the central executive. The language areas activated by the verbal working memory task may be a function of the phonological loop. Bilateral prefrontal and superior parietal cortices activated by the visual working memory task may be related to the visual maintenance of objects, representing visual working memory.

Airway reactivity to bronchoconstrictor and bronchodilator: assessment using thin-section and volumetric three-dimensional CT.

OBJECTIVE: To determine the extent to which thin-section and volumetric threedimensional CT can depict airway reactivity to bronchostimulator, and to assess the effect of different airway sizes on the degree of reactivity. MATERIALS AND METHODS: In eight dogs, thin-section CT scans were obtained before and after the administration of methacholine and ventolin. Cross-sectional areas of bronchi at multiple levels, as shown by axial CT, proximal airway volume as revealed by three-dimensional imaging, and peak airway pressure were measured. The significance of airway change induced by methacholine and ventolin, expressed by percentage changes in cross-sectional area, proximal airway volume, and peak airway pressure was statistically evaluated, as was correlation between the degree of airway reactivity and the area of airways. RESULTS: Cross-sectional areas of the bronchi decreased significantly after the administration of methacholine, and scans obtained after a delay of 5 minutes showed that normalization was insufficient. Ventolin induced a significant increase in cross-sectional areas and an increase in proximal airway volume, while the effect of methacholine on the latter was the opposite. Peak airway pressure increased after the administration of methacholine, and after a 5-minute delay its level was near that of the control state. Ventolin, however, induced no significant decrease. The degree of airway reactivity did not correlate with airway size. CONCLUSION: Thin-section and volumetric spiral CT with three-dimensional reconstruction can demonstrate airway reactivity to bronchostimulator. The degree of reactivity did not correlate with airway size.

Mitochondrial DNA polymorphism in Jindo dogs.

Mitochondrial DNA (mtDNA) polymorphism was studied in 21 Jindo dogs inhabiting Jin Island off the Korean peninsula. The polymorphism was analyzed with 10 restriction endonucleases that recognize six base pairs. The sizes of the mtDNA fragments produced by digestion using each endonucleases were separated by agarose gel electrophoresis, and the polymorphisms were detected with Japanese mongrel dog mtDNA as a probe. The mtDNA polymorphism in Jindo dogs was observed with four restriction endonucleases, Apa I, EcoR V, Hinc II, and Sty I. However, no polymorphism was detected with BamH I, Bgl II, EcoR I, Hind III, Pst I, or Xba I. The observed restriction endonuclease morphs were classified into 4 types of distinct cleavage patterns. The average number of nucleotide substitutions per nucleotide site in Jindodogs was estimated to be 0.0086. By UPG phylogenetic analysis, the 4 mtDNA types showed only one cluster. This suggests that Jindo dogs have not diverged from the other cluster up to the present and the species is considerably pure.

Very-low-birth-weight, preterm infants with or without intracranial hemorrhage. Neurologic, cognitive and cranial MRI correlations at 4-8-year follow-up.

Fourteen very-low-birth-weight (VLBW) preterm infants with and without intracranial hemorrhage (ICH) were prospectively followed from birth to 4 to 8 years for the purpose of determining neurologic and cognitive sequelae associated with ICH severity and to correlate outcomes with brain morphology as determined by Magnetic Resonance Imaging (MRI). Intracranial hemorrhage was documented by cranial ultrasonography performed in early life. Follow-up assessments included neurologic and psychometric examinations and cranial MRI scans. Of six children with no ICH, five had normal results on all three follow-up measures. Three children with Grade I-II ICH had mild to moderate neurologic and cognitive sequelae with focal white matter MRI abnormalities. Five children with Grade III-IV ICH had severe neurologic, cognitive, and MRI deficits, including MRI regional and diffuse white matter abnormalities and/or cortical atrophy. Focal and diffuse neurologic deficits correlated with the extent of MRI morphologic abnormalities. Results of this study indicate that ICH severity correlated with outcomes in children at follow-up; the more severe the ICH, the more adverse the neurologic, cognitive, and MRI results. MRI white matter abnormalities were present in all children with any degree ICH, while ventriculomegaly was seen only in severe ICH (Grade III-IV ICH). Neurologic deficits correlated with MRI structural abnormalities.