Nonrandom distribution of oncogene amplifications in bilateral breast carcinomas: Possible role of host factors and survival bias

Amplification of HER2, C-MYC and CCND1 oncogenes is a hallmark of breast cancer (BC); however, its involvement in the bilateral form of this disease has not been investigated yet. In this study, 50 bilateral BC (biBC) pairs (100 tumors) and 72 control unilateral BC were examined using real-time PCR analysis of microdissected archival tissues. In biBC, the frequency of >3-fold oncogene amplification was 6/100 (6%) for HER2, 6/100 (6%) for C-MYC and 7/100 (7%) for CCND1. Altogether, 18/100 (18%) biBC tumors had increased gene dosage of at least one oncogene. Tumors forming synchronous biBC pairs had amplification in 11/46 cases (24%). In 3 of 8 patients with amplification-positive carcinomas, the amplification was detected in both neoplasms: 2 biBC had concordant activation of the same oncogene (HER2 and CCND1, respectively), and in the remaining case distinct oncogenes were affected (HER2 and C-MYC). In contrast, amplifications in metachronous biBC were strongly discordant: none of 27 first carcinomas carried this abnormality, while the frequency of amplification in second tumors (7/27; 26%) was similar to the one observed in unilateral BC (20/72; 28%). The trend toward concordance of oncogene amplification status in synchronous but not in metachronous biBC pairs can be explained by the nearly identical natural history of the disease in simultaneously arising tumors. The skewed pattern of amplifications in metachronous biBC might be attributed to their association with adverse BC prognosis; it appears that only patients with amplification-negative first BC have sufficient chances to survive until the development of the contralateral carcinoma.     

Comprehensive Human Virus Screening Using High-Throughput Sequencing with a User-Friendly Representation of Bioinformatics Analysis: a Pilot Study

High-throughput sequencing (HTS) provides the means to analyze clinical specimens in unprecedented molecular detail. While this technology has been successfully applied to virus discovery and other related areas of research, HTS methodology has yet to be exploited for use in a clinical setting for routine diagnostics. Here, a bioinformatics pipeline (ezVIR) was designed to process HTS data from any of the standard platforms and to evaluate the entire spectrum of known human viruses at once, providing results that are easy to interpret and customizable. The pipeline works by identifying the most likely viruses present in the specimen given the sequencing data. Additionally, ezVIR can generate optional reports for strain typing, can create genome coverage histograms, and can perform cross-contamination analysis for specimens prepared in series. In this pilot study, the pipeline was challenged using HTS data from 20 clinical specimens representative of those most often collected and analyzed in daily practice. The specimens (5 cerebrospinal fluid, 7 bronchoalveolar lavage fluid, 5 plasma, 2 serum, and 1 nasopharyngeal aspirate) were originally found to be positive for a diverse range of DNA or RNA viruses by routine molecular diagnostics. The ezVIR pipeline correctly identified 14 of 14 specimens containing viruses with genomes of <40,000 bp, and 4 of 6 specimens positive for large-genome viruses. Although further validation is needed to evaluate sensitivity and to define detection cutoffs, results obtained in this pilot study indicate that the overall detection success rate, coupled with the ease of interpreting the analysis reports, makes it worth considering using HTS for clinical diagnostics.     

Immigrant Caregivers: The Double Burden Experience of Immigrants Caring for a Family Member With Severe Mental Illness

Community Mental Health Journal - The aim of this study is to examine the factors that shape the burden experience among immigrants caring for a family member with severe mental illness. In-depth...     

Half-dose gadobenate dimeglumine versus standard-dose gadodiamide in dynamic magnetic resonance imaging of non-cirrhotic livers: a retrospective intra-individual crossover comparison

Purpose

The purpose of this study was to compare enhancement characteristics of half-dose gadobenate dimeglumine (0.05 mmol kg^?1) with standard-dose gadodiamide (0.10 mmol kg^?1), in the assessment of hepatic vessels and lesions, using retrospective intra-individual crossover comparison methodology.

Methods

Ethics committee approval was obtained. From 2004 to 2012, 21 patients underwent MRI examination with both standard-dose gadodiamide and half-dose gadobenate dimeglumine, using the same liver MRI protocol at 1.5 T. Eighteen patients whose scans showed no artifacts were selected. Quality of liver lesion [12 hemangiomas, 7 focal nodular hyperplasias (FNHs)] and liver vessel enhancement, and the global diagnostic quality of studies were ranked on a scale of 1–4 by two independent radiologists. Contrast-to-noise ratio (CNR) and % enhancement of liver vessels and lesions were calculated based on region of interest, signal intensity, and noise standard deviation measurements performed at 0, 20 s, 1, 3, and 5 min post-contrast injection. Qualitative and quantitative results were compared using the paired Wilcoxon signed rank and Student’s t-tests, respectively.

Results

No qualitative differences were noted in enhancement of liver vessels, hemangiomas, and FNHs. There was no statistically significant difference between the global diagnostic qualities of scans performed with the two contrast agents. Quantitatively, liver vessels and hemangiomas did not demonstrate statistically significant differences in contrast enhancement. At 20 s, FNHs achieved higher CNR (P = 0.02) with gadodiamide.

Conclusion

Half-dose gadobenate dimeglumine results in similar contrast enhancement compared to standard-dose gadodiamide in assessment of liver vessels, hemangiomas, and FNHs, and is a reasonable alternative to standard doses of extracellular agents in dynamic liver MRI.     

Morphologic characteristics of chernobyl-related childhood papillary thyroid carcinomas are independent of radiation exposure but vary with iodine intake

BACKGROUND: The Chernobyl accident caused an unprecedented increase in papillary thyroid carcinoma (PTC) incidence with a surprisingly short latency and unusual morphology. We have investigated whether unexpected features of the PTC incidence after Chernobyl were radiation specific or influenced by iodine deficiency. METHODS: PTCs from children from Belarus, Ukraine, and the Russian Federation exposed to fallout from Chernobyl were compared with PTCs from children not exposed to radiation from the same countries, from England and Wales (E&W) and from Japan. The degree and type of differentiation, fibrosis, and invasion were quantified. RESULTS: There were no significant differences between PTCs from radiation-exposed children from Belarus, Ukraine, and the Russian Federation and PTCs from children from the same countries who were not exposed to radiation. Childhood PTCs from Japan were much more highly differentiated (p < 0.001), showed more papillary differentiation (p < 0.001) and were less invasive (p < 0.01) than "Chernobyl" tumors, while tumors from E&W generally showed intermediate levels of degree and type of differentiation and invasion. There was a marked difference between the sex ratios of children with PTCs who were radiation exposed and those who were not exposed (F:M exposed vs. unexposed 1.5:1 vs. 4.2:1; chi(2) = 7.90, p < or = 0.01005). CONCLUSIONS: The aggressiveness and morphological features of Chernobyl childhood PTCs are not associated with radiation exposure. The differences found between tumors from the Chernobyl area, E&W, and Japan could be influenced by many factors. We speculate that dietary iodine levels may have wide implications in radiation-induced thyroid carcinogenesis, and that iodine deficiency could increase incidence, reduce latency, and influence tumor morphology and aggressiveness.     

Renal fractional flow reserve: a hemodynamic evaluation of moderate renal artery stenoses.

The objective of this study was to perform a hemodynamic evaluation of moderate (50-90%) renal artery stenosis (RAS) under conditions of rest and maximum hyperemia. Identifying patients with RAS who have hemodynamically significant stenoses and are most likely to benefit from revascularization is clinically important. Current methods used to evaluate RAS, including angiography, have limitations. Physiologic evaluation of RAS may have a role in identifying patients with hemodynamically significant stenosis. Patients with suspected renovascular hypertension due to aorto-ostial RAS were included in the study. Hyperemia was induced by administration of intrarenal papavarine. Translesional pressure gradients were measured and renal fractional flow reserve (FFR) was calculated using a 0.014' pressure guidewire. Thirteen patients and 14 arteries with moderately severe (50-90%) RAS were studied. The mean translesional pressure gradient rose from a baseline of 6.3 +/- 3.9 to 17.5 +/- 10.8 mm Hg with maximal hyperemia. The renal FFR ranged from 0.58 to 0.95. There was a poor correlation between angiographic stenosis measurement and the renal FFR (r = -0.18; P = 0.54) and the hyperemic translesional mean pressure gradient (r = 0.22; P = 0.44). There was an excellent correlation between renal FFR and the resting mean translesional pressure gradient (r = -0.76; P = 0.0016) and the hyperemic mean translesional pressure gradient (r = -0.94; P < 0.0001). Selective renal arterial papavarine administration induces maximum hyperemia, permitting the calculation of renal FFR in renal arteries with aorto-ostial stenoses. The renal FFR correlates well with other hemodynamic parameters of lesion severity, but poorly with angiographic measures of lesion severity.     

Nondisclosure of HIV Infection to Sex Partners and Alcohol’s Role: A Russian Experience

Nondisclosure of one’s HIV infection to sexual partners obviates safer sex negotiations and thus jeopardizes HIV transmission prevention. The role of alcohol use in the disclosure decision process is largely unexplored. This study assessed the association between alcohol use and recent nondisclosure of HIV serostatus to sex partners by HIV-infected risky drinkers in St. Petersburg, Russia. Approximately half (317/605; 52.4 %) reported not having disclosed their HIV serostatus to all partners since awareness of infection. Using three separate GEE logistic regression models, we found no significant association between alcohol dependence, risky alcohol use (past 30 days), or alcohol use at time of sex (past 30 days) with recent (past 3 months) nondisclosure (AOR [95 % CI] 0.81 [0.55, 1.20], 1.31 [0.79, 2.17], 0.75 [0.54, 1.05], respectively). Alcohol use at time of sex was associated with decreased odds of recent nondisclosure among seroconcordant partners and among casual partners. Factors associated with nondisclosure were relationship with a casual partner, a serodiscordant partner, multiple sex partners, awareness of HIV diagnosis less than 1 year, and a lifetime history of sexually transmitted disease. Nondisclosure of HIV status to sex partners is common among HIV-infected Russians, however alcohol does not appear to be a predictor of recent disclosure.     

Plasma Parathyroid Hormone Is Independently Related to Nocturnal Blood Pressure in Hypertensive Patients: The Styrian Hypertension Study

High parathyroid hormone (PTH) has been linked with high blood pressure (BP), but the relationship with 24‐hour ambulatory blood pressure monitoring is largely unknown. The authors therefore analyzed cross‐sectional data of 292 hypertensive patients participating in the Styrian Hypertension Study (mean age, 61±11 years; 53% women). Median plasma PTH (interquartile range) determined after an overnight fast was 49 pg/mL (39–61), mean daytime BP was 131/80±12/9 mm Hg, and mean nocturnal BP was 115/67±14/9 mm Hg. In multivariate regression analyses adjusted for BP and PTH‐modifying parameters, PTH was significantly related to nocturnal systolic and diastolic BP (adjusted β‐coefficient 0.140 [P=.03] and 0.175 [P<.01], respectively). PTH was not correlated with daytime BP readings. These data suggest a direct interrelationship between PTH and nocturnal BP regulation. Whether lowering high PTH concentrations reduces the burden of high nocturnal BP remains to be shown in future studies.