Accuracy of sonographically guided 14-gauge core-needle biopsy: results of 715 consecutive breast biopsies with at least two-year follow-up of benign lesions

PURPOSE: The objective of this study was to examine the diagnostic accuracy of sonographically guided 14-gauge core-needle biopsy (CNB). METHODS: Sonographically guided 14-gauge CNBs of 715 breast lesions were performed in 652 patients. Histopathologic results were correlated with imaging findings, and repeat biopsy was recommended in the cases of discordance between the radiologic and pathologic results. Long-term follow-up was used for patients with CNB findings of a benign lesion. RESULTS: Sonographically guided CNB revealed malignancy in 311 lesions (43%). Thirty-one lesions with CNB findings indicating benign conditions underwent additional image-guided or excisional biopsy because of indeterminate pathologic features, disagreement between radiologic and pathologic results, surgeon preference, or patient request. Within these 31 cases, 9 malignancies were diagnosed. The duration of follow-up for the remaining 373 benign lesions varied from 27 to 60 months. In 3 of these 373 cases, carcinoma was diagnosed at the site of CNB. The false-negative rate of 14-gauge sonographically guided CNB was 3.7%, and the sensitivity of sonographically guided CNB for the diagnosis of breast cancer was 96.3%. CONCLUSIONS: Sonographically guided 14-gauge CNB is a safe and accurate method for evaluating breast lesions that require tissue sampling. Radiologic-pathologic correlation and follow-up of benign lesions are essential for a successful breast biopsy program.     

Establishing a murine pancreatic cancer CaSm model: up-regulation of CaSm is required for the transformed phenotype of murine pancreatic adenocarcinoma.

We have recently shown that the cancer-associated Sm-like protein (CaSm) is overexpressed in human pancreatic adenocarcinoma (PC). However, the role of CaSm in the process of neoplastic transformation remains unclear. To define further the role of CaSm in PC transformation, we have established a murine model based on the murine pancreatic cancer cell lines Panc02 and Panc03. CaSm is overexpressed in the aggressive Panc02 cells and expressed at much lower levels in the more indolent Panc03 cells. Up-regulation of CaSm in Panc03 cells increased in vitro proliferation and anchorage-independent growth and promoted subcutaneous tumor establishment and growth in syngeneic mice. Conversely, adenoviral down-regulation of CaSm in Panc02 led to significant inhibition of cellular proliferation and anchorage-independent growth in vitro and complete abolition of tumor growth and metastasis in vivo. Up-regulation of CaSm in NIH3T3 resulted in loss of contact inhibition and increased soft agar colony formation in vitro. The requirement for CaSm overexpression for neoplastic transformation confirms the concept that CaSm is a critical oncogene and potential target for molecular intervention. Furthermore, establishment of the murine clinically relevant model of pancreatic metastases provides a framework for the generation of preclinical data to support the development of novel molecular therapies targeting CaSm.     

Virtual time-to-contact of postural stability boundaries as a function of support surface compliance

This study investigated the hypothesis that virtual time-to-contact, which specifies the time to reach the functional stability boundary, is a variable controlled in the maintenance of upright posture. Three different levels of support surface compliance were used on a force platform (no foam, 5 cm of foam, and 15 cm of foam). The participant's task was to stand still under each surface support condition both with and without vision. The stability boundary was determined for each set of conditions where the participant was required to lean as far as possible in all directions of the horizontal plane without losing stability. The results showed that the no vision conditions had a significantly larger center of pressure displacement than the vision conditions. No vision and increasing support surface compliance also increased the velocity of the center of pressure trajectory. The distribution of the radial displacement of the center of pressure showed relatively equal frequency over spatial location with no central tendency. The virtual time-to-contact with the stability boundary decreased as platform surface support became more compliant. Furthermore, the distribution of virtual time over the effective scaling range was a power law with a larger exponent in the more unstable no vision and increasing surface foam conditions. The findings provide additional evidence for the hypothesis that virtual time-to-contact with stability boundaries is a postural control variable that is regulated rather than the preservation of minimal motion around the center of the stability region as proposed in pendulum models of posture.     

Effect of Chinese medicines Chan Su and Lu-Shen-Wan on serum digoxin measurement by Digoxin III, a new digoxin immunoassay

Chan Su and Lu-Shen-Wan are Chinese medicines that crossreact with digoxin immunoassays. Recently, Abbott Laboratories released a new digoxin immunoassay, Digoxin III. We studied potential interference of Chan Su and Lu-Shen-Wan with the Digoxin III assay by comparing results obtained by using Digoxin II and fluorescence polarization immunoassay, also manufactured by Abbott Laboratories. Aliquots of a drug-free serum pool were supplemented with aqueous extract of Chan Su or Lu-Shen-Wan and apparent digoxin concentrations were measured using all three digoxin assays. Significant crossreactivity of Chan Su and Lu-Shen-Wan was observed with the new Digoxin III assay. Moreover, when mice were fed with Chan Su or Lu-Shen-Wan, significant apparent digoxin concentrations were also observed in the sera of mice using the Digoxin III assay indicating that such interferences are also present in vivo. When serum pools prepared from patients receiving digoxin were further supplemented with Chan Su or Lu-Shen-Wan extract, falsely elevated digoxin values were observed with both Digoxin III and fluorescence polarization immunoassay, but digoxin values were falsely lowered using the Digoxin II assay. For example, when one aliquot of Digoxin Serum Pool 1 containing 0.94 ng/mL of digoxin was supplemented with 5.0 microg/mL of Chan Su extract, the digoxin concentration was falsely elevated to 6.60 ng/mL as measured by the Digoxin III assay and 6.99 as measured by the fluorescence polarization immunoassay assay. In contrast, the observed digoxin value was falsely lowered to 0.72 ng/mL using the Digoxin II assay. Interference of Chan Su and Lu-Shen-Wan in the Digoxin III assay cannot be eliminated by monitoring free digoxin concentrations. Digibind neutralizes digoxin-like immunoreactive components of Chan Su and such effect can be monitored by measuring apparent free digoxin concentrations using the Digoxin III assay. We conclude the both Chan Su and Lu-Shen-Wan significantly interfere with serum digoxin measurements by the new Digoxin III assay.     

Aging and time-to-postural stability following a visual perturbation

BACKGROUND AND AIMS: Postural stability is essential to the performance of most daily activities and is necessary to lead an independent lifestyle. Most functional assessments of balance have only evaluated spatial properties of posture, however, assessments should also evaluate balance in the temporal domain. Both domains provide crucial information to an individual's postural stability. The following study examines time to regain stability and the magnitude of postural motion following a virtual perturbation. METHODS: To examine the temporal limitations imposed by age (n=45), 3 adult age groups were tested, young (18-19 yr), young old (60-69 yr), and old adults (70-79 yr). Participants were placed into a virtual room appearing as if the visual surround moved in a discrete antero-posterior motion. A force platform was used to assess postural motion across 4 visual perturbation conditions, 9 and 18 cm and 0.3 and 0.6 Hz. RESULTS: Young adults exhibited significantly less postural motion than both of the older age groups and required the least amount of time to regain postural stability following the discrete visual perturbation, while the old adults required the greatest amount of time. CONCLUSIONS: These findings indicate that even small visual perturbations induce strong temporal limitations which are magnified by advancing age. Furthermore, the postural saturation (reduction in postural motion) that is typically found in young adults with increasing movement magnitude was not found in either of the older adult groups. Older adults are at a higher risk of losing balance during this period of time to reacquire postural stability which appears to be unaffected by elevated visual motion.     

Common Topological Features in Band Structure of RNiSb and RSb Compounds for R = Tb,Dy, Ho

The electronic and band structures of ternary RNiSb and binary RSb compounds for R = Tb, Dy, Ho, have been investigated using an ab initio method accounting for strong electron correlations in the 4f shell of the rare-earth metals. These ternary compounds are found to be semiconductors with the indirect gap of 0.21, 0.21, and 0.26 eV for Tb, Dy, and Ho(NiSb), respectively. In contrast, in all binary RSb compounds, bands near the Fermi energy at the Г and X points are shifted relatively to RNiSb and form hole and electron pockets, so the energy gap is closed in RSb. The band structure typical for semimetals is formed in all RSb compounds for R = Tb, Dy, Ho. For the first time, we identify similar features near the Fermi level in the considered binary semimetals, namely, the presence of the hole and electron pockets in the vicinity of the Г and X points, the nonsymmetric electron pocket along Γ–X–W direction and hole pockets along the L–Γ–X direction, which were previously found experimentally in the other compound of this series GdSb. The magnetic moment of all considered compounds is fully determined by magnetic moments of the rare earth elements, the calculated effective magnetic moments of these ions have values close to the experimental values for all ternary compounds.     

Whole-genome haplotyping by dilution,amplification, and sequencing

Standard whole-genome genotyping technologies are unable to determine haplotypes. Here we describe a method for rapid and cost-effective long-range haplotyping. Genomic DNA is diluted and distributed into multiple aliquots such that each aliquot receives a fraction of a haploid copy. The DNA template in each aliquot is amplified by multiple displacement amplification, converted into barcoded sequencing libraries using Nextera technology, and sequenced in multiplexed pools. To assess the performance of our method, we combined two male genomic DNA samples at equal ratios, resulting in a sample with diploid X chromosomes with known haplotypes. Pools of the multiplexed sequencing libraries were subjected to targeted pull-down of a 1-Mb contiguous region of the X-chromosome Duchenne muscular dystrophy gene. We were able to phase the Duchenne muscular dystrophy region into two contiguous haplotype blocks with a mean length of 494 kb. The haplotypes showed 99% agreement with the consensus base calls made by sequencing the individual DNAs. We subsequently used the strategy to haplotype two human genomes. Standard genomic sequencing to identify all heterozygous SNPs in the sample was combined with dilution-amplification–based sequencing data to resolve the phase of identified heterozygous SNPs. Using this procedure, we were able to phase >95% of the heterozygous SNPs from the diploid sequence data. The N50 for a Yoruba male DNA was 702 kb whereas the N50 for a European female DNA was 358 kb. Therefore, the strategy described here is suitable for haplotyping of a set of targeted regions as well as of the entire genome.     

Sternal Fracture Should Prompt the Evaluation of the Entire Spine in Trauma Patients

Abstract Background and Purpose: Sternal fracture has traditionally been considered an indicator of a severe mechanism of trauma, which warrants careful evaluation of the patient for accompanying injuries. The purpose of this study is to determine the incidence, distribution and mechanisms of spinal fractures associated with fractures of the sternum. Material and Methods: Trauma registry data, medical records and X-rays of all patients admitted to the Trauma Unit at Hillel-Yaffe Medical Center, Hadera, Israel, with a diagnosis of sternal fracture during a 6-year period, between January 1, 1997 and December 31, 2002, were reviewed retrospectively. Results: 147 patients with sternal fracture were eligible for analysis. The combination of spinal fracture in association with sternal fracture was found in 19 patients (13%), ten males (52.7%) and nine females (47.3%). Mean age was 49 years and mean Injury Severity Score (ISS) 18.6. Motor vehicle accidents were the most common cause of these fractures. An unusually high proportion of cervical spine fractures (36.8%) was noted. Three of the 19 patients (15.5%) with sternal and spinal fractures also suffered from cardiac contusion, confirmed by an elevation of the MB fraction of creatine phosphokinase, ECG changes, and regional hypokinetic areas on echocardiography. Conclusion: Recent studies indicate that the incidence of sternal fracture has risen while its association with accompanying serious injuries has lessened. This is most likely due to the increased use of seat belts in motor vehicle accidents. In both theory and practice spinal fracture is an associated injury in cases of sternal fracture, and usually involves the thoracic level. The authors describe an almost equal distribution of the level of spinal injury, with an unusually high proportion of cervical involvement. They also found a high incidence of myocardial contusion among patients with combined sternal and spinal fractures. Therefore, X-ray evaluation of the entire spine in patients suffering from a fractured sternum, and closer cardiac monitoring of patients with both sternal and spinal fractures are recommended.     

Bystander effect contributes to the antitumor efficacy of CaSm antisense gene therapy in a preclinical model of advanced pancreatic cancer.

Pancreatic adenocarcinoma (PC) is an aggressive malignancy resistant to standard treatment modalities. Previously, we have reported that cancer-associated Sm-like protein (CaSm) contributes to the neoplastic transformation of PC. In this study, we utilized a recently established preclinical model of PC to determine if molecular targeting of CaSm can serve as the basis for a novel PC therapy. In a subcutaneous tumor model, intratumoral administration of an adenoviral vector encoding CaSm antisense RNA (Ad-alphaCaSm) significantly inhibited Panc02 tumor growth. Furthermore, in a metastatic tumor model, systemic administration of Ad-alphaCaSm resulted in a significant decrease in the number of hepatic metastases and increased survival time. We assessed the efficiency of in vivo delivery and observed significant levels of vector transduction in tissues containing PC, as well as a bystander effect that was amplifying the efficacy of CaSm gene therapy. This bystander effect was also active in vitro and was shown to be at least partially independent of host-related mechanisms. We conclude that CaSm antisense gene therapy is an effective novel therapy for PC and that the antitumor efficacy is dependent on both direct and bystander mechanisms.