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Objectives: To determine the diagnostic yield of testing multiple blocks for HER2 in cases of multifocal breast carcinoma. Methods: We identified 246 consecutive cases of multifocal invasive breast carcinoma in which HER2 was tested on more than 1 tumor focus. We performed an audit of all cases with respect to tumor size, grade, and histologic type. Results: HER2 status was concordant between multiple foci in 230 (93.5%) of 246 cases, with the largest focus having the most positive HER2 result in 242 (98.4%) of 246 cases. We did not find a single case in which a smaller focus demonstrated a more positive HER2 status unless this focus was either higher grade or different histologically. Conclusions: Our findings support the evaluation of HER2 on the largest focus, with additional testing on smaller foci having a different histologic type or higher grade. [ABSTRACT FROM AUTHOR]

Men with high sperm DNA damage have a reduced fertility potential. Correlation of specific clinical factors to the degree of sperm DNA damage remains unclear. This retrospective study evaluated the frequency and severity of sperm DNA damage in men with different aetiologies of male factor infertility. Patients with mate factor infertility (n = 288) underwent flow cytometry-based sperm DNA damage assessment and results were correlated with the major aetiologies of male infertility: varicocele, bacteriospermia and idiopathic infertility. Sperm DNA damage was significantly correlated to the patient's age, sperm motility, normal morphology and vitality (P < 0.001). High sperm DNA damage (≥30%) was most frequently found in the group with bacteriospermia (48%), compared with 30% of the men with varicoceles and 22% of the men with idiopathic infertility (P < 0.02). White some tendency was observed for a correlation of increasing sperm DNA damage in patients with grade III and bilateral varicoceles, this difference did not reach statistical significance. The data support the importance of proper physical and laboratory investigations of the fertility status in men to correctly diagnose and treat mate infertility. [ABSTRACT FROM AUTHOR]

Focuses on the reassessment of inflammation of airways in chronic bronchitis in Canada. Association of chronic bronchitis with mucus hypersection; Condition for the terminology justification of chronic bronchitis; Consideration of chronic bronchitis as the causative factor of chronic productive cough.

A letter to the editor is presented in response to the article "Electronic health records and clinical decision support systems: Impact on national ambulatory care quality," by Max Romano and Randall Stafford in the January 24, 2011 issue, as well as a response by the authors to the letter.

Objective: To compare DNA damage in ejaculated and testicular spermatozoa in patients with previously unsuccessful oral antioxidant treatment.Design: Prospective clinical study.Setting: University-affiliated teaching hospital.Patient(s): Twelve men with persistently high sperm DNA damage.Intervention(s): Evaluation of DNA damage of ejaculated and testicular spermatozoa by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) assay.Main Outcome Measure(s): The DNA damage of ejaculated spermatozoa compared with that of testicular spermatozoa, both samples collected on the day of intracytoplasmic sperm injection.Result(s): Ejaculated spermatozoa showed a threefold higher DNA damage when compared with testicular samples (39.7% +/- 14.8 vs. 13.3% +/- 7.3).Conclusion(s): Our results indicated that in patients with previously unsuccessful oral antioxidant treatment the retrieved testicular spermatozoa had a lower degree of DNA damage compared with ejaculated sperm collected on the same day. [ABSTRACT FROM AUTHOR]

Assessment of sperm DNA damage has been suggested as a negative predictor of fertility potential. Multiple pathological factors acting at both the intra-testicular and post-testicular levels may contribute to sperm DNA damage. The relative contribution of each of these factors in an individual with high DNA damage (>30%) is unclear. The management of patients with elevated DNA damage is also challenging. The purpose of our retrospective study was to evaluate the clinical course of patients with sperm DNA damage over 30% and to assess the effect of non-specific (oral antioxidant) and cause-specific treatments on the quality of their sperm DNA. Results of our retrospective study suggest that the evaluated group with high DNA damage was diagnostically heterogeneous and comprised patients with varicoceles, bacteriospermia and idiopathic infertility. A three month course of antioxidant therapy reduced sperm DNA damage in only 30/61 (49%) patients with significant improvement between the initial and post-treatment DNA Fragmentation Index (DFI) results (46.8%±14.1 vs. 36.7%±16.6, p < .001). The positive effect of antioxidants could be age-dependent, as patients older that 40 years of age showed no improvement after such treatment. The cause-specific treatments showed superior results compared to antioxidants alone. Improvement was observed in 7/9 (78%) of patients after surgical varicocele repair between the initial and post-treatment DFI results (44.7%±12.8 vs. 28.4%±9.5, p < .03). The majority of the patients 13/14 (93%) with bacteriospermia had improvement in sperm DFI results after antibiotic treatment (50.4%±19.1 vs. 38.6%±18.7, p < .001). [ABSTRACT FROM AUTHOR]

The purpose of this study was to analyze the relationship of male age and DNA integrity in men presenting for investigation of infertility. We found that men 45 years and older had significantly greater DNA fragmentation than younger men. [Copyright &y& Elsevier]

[Display omitted] [ABSTRACT FROM AUTHOR]

Objectives: Human epidermal growth factor receptor 2 (HER2; ERBB2 gene) is of prognostic and predictive significance in breast carcinoma. Both fluorescence in situ hybridization (FISH) and dual-color in situ hybridization (DISH) methods are available. DISH and FISH are highly concordant in validation studies, but differences may be more prevalent in the equivocal range. Our goal was to compare FISH and DISH on a cohort enriched for equivocal cases, with respect to HER2 determination.Methods: The cohort was enriched for equivocal (2+) cases. DISH and FISH were evaluated using standard protocols and the results compared with respect to HER2 status, HER2 copy number, and HER2/chromosome 17 (Chr17) ratio.Results: In total, 109 cases were identified. The agreement rate of DISH with FISH was 74%. The mean ± SD HER2/Chr17 ratio by DISH was 1.63 ± 0.08 vs 1.59 ± 0.26 by FISH (P = .45). The mean ± SD HER2 copy number by DISH was 4.56 ± 0.45 vs 4.75 ± 1.08 by FISH (P = .004). Individual signals were more easily resolved using FISH in cases with higher copy numbers.Conclusions: In our cohort enriched for equivocal cases, the numerical values of HER2 copy number were significantly lower using DISH, resulting in discordances. Although DISH is a valid method, variations with FISH may be expected in high-equivocal cases and in quality assurance activities. [ABSTRACT FROM AUTHOR]

Background Since 2003, the Seventh Report of the Joint National Committee (JNC-7) has been the predominant guideline for blood pressure management. A 2014 expert panel recommended increasing the blood pressure targets for patients age 60 years and older, as well as those with diabetes or chronic kidney disease. Objectives The purpose of this study was to examine the effect of the 2014 expert panel blood pressure management recommendations on patients managed in U.S. ambulatory cardiovascular practices. Methods Using the National Cardiovascular Data Registry PINNACLE Registry, we assessed the proportion of patients who met the 2003 and 2014 panel recommendations, highlighting the populations of patients for whom the blood pressure goals changed. Results Of 1,185,253 patients in the study cohort, 706,859 (59.6%) achieved the 2003 JNC-7 goals. Using the 2014 recommendations, 880,378 (74.3%) patients were at goal. Among the 173,519 (14.6%) for whom goal achievement changed, 40,323 (23.2%) had a prior stroke or transient ischemic attack, and 112,174 (64.6%) had coronary artery disease. In addition, the average Framingham risk score in this group was 8.5 ± 3.2%, and the 10-year ASCVD risk score was 28.0 ± 19.5%. Conclusions Among U.S. ambulatory cardiology patients with hypertension, nearly 1 in 7 who did not meet JNC-7 recommendations would now meet the 2014 treatment goals. If the new recommendations are implemented in clinical practice, blood pressure target achievement and cardiovascular events will need careful monitoring, because many patients for whom the target blood pressure is now more permissive are at high cardiovascular risk. [ABSTRACT FROM AUTHOR]

Background In a significant update, the 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol guidelines recommend fixed-dose statin therapy for those at risk and do not recommend nonstatin therapies or treatment to target low-density lipoprotein cholesterol (LDL-C) levels, limiting the need for repeated LDL-C testing. Objectives The goal of this study was to examine the impact of the 2013 ACC/AHA cholesterol guidelines on current U.S. cardiovascular practice. Methods Using the NCDR PINNACLE (National Cardiovascular Data Registry Practice Innovation and Clinical Excellence) registry data from 2008 to 2012, we assessed current practice patterns as a function of the 2013 cholesterol guidelines. Lipid-lowering therapies and LDL-C testing patterns by patient risk group (atherosclerotic cardiovascular disease [ASCVD], diabetes, LDL-C ≥190 mg/dl, or an estimated 10-year ASCVD risk ≥7.5%) were described. Results Among a cohort of 1,174,545 patients, 1,129,205 (96.1%) were statin-eligible (91.2% ASCVD, 6.6% diabetes, 0.3% off-treatment LDL-C ≥190 mg/dl, 1.9% estimated 10-year ASCVD risk ≥7.5%). There were 377,311 patients (32.4%) not receiving statin therapy and 259,143 (22.6%) receiving nonstatin therapies. During the study period, 20.8% of patients had 2 or more LDL-C assessments, and 7.0% had more than 4. Conclusions In U.S. cardiovascular practices, 32.4% of statin-eligible patients, as defined by the 2013 ACC/AHA cholesterol guidelines, were not currently receiving statins. In addition, 22.6% were receiving nonstatin lipid-lowering therapies and 20.8% had repeated LDL-C testing. Achieving concordance with the new cholesterol guidelines in patients treated in U.S. cardiovascular practices would result in significant increases in statin use, as well as significant reductions in nonstatin therapies and laboratory testing. [ABSTRACT FROM AUTHOR]

Testicular spermatozoa are utilized to achieve pregnancy in couples with severe male factor infertility. Several studies suggest that aneuploidy rates in spermatozoa are elevated at the testicular level in infertile patients compared to ejaculates of normal controls. However, essential data regarding aneuploidy rates between ejaculated and testicular spermatozoa in the same individuals is lacking. The purpose of our study was to compare aneuploidy rates at the testicular and post-testicular level from the same patients with persistently high sperm DNA damage. Ejaculates and testicular biopsies were obtained from eight patients with persistently high DNA damage (>30%). Both ejaculated and testicular samples were analyzed for sperm DNA damage and sperm aneuploidy for chromosomes 13, 18, 21, X, and Y. In addition, semen samples from ten normozoospermic men presenting for fertility evaluation served as a control group. A strong correlation between the alteration of spermatogenesis and chromatin deterioration was observed in our study. In the same individuals, testicular samples showed a significantly lower DNA damage compared to ejaculated spermatozoa (14.9% ± 5.0 vs. 40.6% ± 14.8, P < 0.05), but significantly higher aneuploidy rates for the five analyzed chromosomes (12.41% ± 3.7 vs. 5.77% ± 1.2, P < 0.05). While testicular spermatozoa appear favourable for ICSI in terms of lower DNA damage, this potential advantage could be offset by the higher aneuploidy rates in testicular spermatozoa. [ABSTRACT FROM AUTHOR]

Objective: To determine the utility and cost of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) screening in infertile males. Design: Cohort study. Setting: Canadian tertiary-level male infertility clinic and university-affiliated laboratories. Patient(s): 5,588 male infertility patients. Intervention(s): CT and NG testing on 8,972 urine and semen samples. Main Outcome Measure(s): Prevalence of CT and NG infection in infertile males versus general male population in Canada over 8 years (2003–2010) and the reagent cost to detect one case of CT or NG. Result(s): In infertile males, the prevalence rate for CT and NG was 0.304% and 0.0537%, which was statistically significantly lower (3.4- and 8.1-fold lower, respectively) than the age-adjusted general population prevalence. With the reagents costing $86.20 per patient tested, the reagent cost alone to diagnose one case of CT or NG was $38,669. Conclusion(s): The prevalence of CT and NG in this study are among the lowest reported in the male infertility literature. These findings question the utility of CT/NG screening in this low-risk population and emphasize that decisions about the utility of screening must be based on the prevalence rates of the disease in the studied population. [ABSTRACT FROM AUTHOR]

Telomeres play a fundamental role in the organization of the sperm nucleus resulting in the looped chromosome configuration and non-random positioning of chromosomes. Telomeres localize in the nuclear periphery and interact dynamically by forming dimers and tetramers. The purpose of this study was to evaluate the relationship of telomere interactions to DNA damage, a factor known to adversely influence male fertility. Telomeres were localized by fluorescence in situ hybridization (FISH) using human chromosome pan-telomeric probe in ten samples with low and ten samples with high sperm DNA damage. The samples with a low DNA fragmentation index (DFI) had a mean number of telomere signals of 21.7±1.9 compared to a mean of 26.5±3.4 signals in the samples with a high DFI ( p<.005). The percentage of cells with a typical telomere distribution of ≤23 telomere-telomere dimers was observed in 70.8%±15.6 samples with a low DFI compared to 44.2%±22.4 in samples with a high DFI ( p<.05). These results suggest that sperm DNA damage is associated with disruption of the normal telomere-telomere interactions leading to possible loss of the looped chromosome configuration. Improperly packed and organized sperm chromatin might have a high probability of disrupting the extremely structured sequence of sperm chromosome deposition, activation, and processing by the oocyte at the time of fertilization. These results might provide additional information on the nature of sperm DNA damage and the role of such damage on fertilization and development of the zygote. [ABSTRACT FROM AUTHOR]

Objectives: To analyze the relationship between DNA damage and standard semen parameters (SSP) in patients who present for fertility evaluation. Evaluation of male fertility includes assessment of the SSP and increasingly sperm DNA damage. However, the relationship between DNA damage and SSP remains controversial. Methods: Following Institutional Research Ethics Board approval, semen samples from 2586 unselected nonazoospermic patients were subjected to computer-assisted semen analysis and flow cytometry-based sperm DNA damage assessment expressed as the DNA fragmentation index. Results: Sperm DNA damage was significantly negatively correlated to sperm SSP (concentration, motility, and normal morphology) and positively correlated to patient''s age. DNA damage increased in association with the number of abnormalities in SSP. Patients with oligoasthenoteratozoospermia had significantly higher DNA damage and more frequent DNA damage over 30% compared with normozoospermic patients and patients with abnormalities in 1 or 2 SSP. Conclusions: Our results indicate that DNA damage is significantly correlated to SSP as well as age. In addition, the degree of DNA damage increases with the number of abnormal parameters in a sample and is most severe in patients with oligoasthenoteratozoospermia. Complex and possibly age-related mechanisms of DNA damage in human spermatozoa may be responsible for the strong relationship between SSP and DNA fragmentation index. [Copyright &y& Elsevier]

The purpose of our study was to analyze the relationship of leukocytospermia to sperm DNA damage as assessed by the DNA integrity assay. Results indicate that leukocytospermia has a significant negative effect on the standard semen parameters of concentration, motility, and morphology but at most a very weak effect on DNA integrity as measured by the DNA fragmentation assay. [Copyright &y& Elsevier]

: ObjectivesThis study was designed to document the association of endocardial fibroelastosis (EFE) and maternal autoantibodies.: BackgroundNeonatal lupus erythematosus is associated with the transplacental passage of maternal anti-Ro and anti-La antibodies, leading to complete atrioventricular block (CAVB). In some cases, CAVB is associated with EFE. Isolated EFE may be independently related to maternal anti-Ro and anti-La antibodies.: MethodsWe identified three cases (one fetus and two infants, all female) of isolated EFE in infants born to autoantibody-positive mothers in the absence of CAVB. Demographics, echocardiograms, and pathology were reviewed. Immunohistochemical analyses for immunoglobulin (Ig)G, IgM, IgA, T-cell, B-cell, and terminal deoxynucleoleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) (test for cell apoptosis) staining were performed on multiple sections of the heart in each case and compared with negative controls.: ResultsTwo cases died and one received a cardiac transplant. All three cases had histologically confirmed EFE. All cases demonstrated significant diffuse IgG infiltration. To a lesser extent, myocardial tissue was also positive for IgM, CD43, and Granzyme B. None of the specimens were TUNEL positive.: ConclusionsThese are the first reported cases of isolated EFE associated with maternal anti-Ro and anti-La antibodies in the absence of CAVB. The diffuse deposition of IgG and the presence of a T-cell infiltrate throughout the myocardium suggest that the transplacental passage of maternal autoantibodies induces an immune reaction within the myocardium, leading to isolated EFE. Autoantibody-mediated EFE may be an etiologic factor in cases of fetal and neonatal “idiopathic” dilated cardiomyopathy. [Copyright &y& Elsevier]

Our study aimed to compare the frequency of epididymal protein P34H deficiency in a population of men undergoing routine infertility evaluation with that in men with proven fertility. Our results suggest that a significant proportion of men investigated for male infertility may be epididymal protein P34H deficient. [Copyright &y& Elsevier]

Introduction: Human spermatozoa have unique, well-organized nuclear architecture different from somatic cells. Improperly packaged sperm chromatin will have a high probability of disrupting the particularly structured sequence of fertilization. The evaluation of nuclear organization in spermatozoa is challenging due to the extreme compactness of chromatin and the absolute necessity for induced nuclear decondensation (ND), which itself alters native sperm architecture. The purpose of our study was to identify sperm ND protocol that results in minimal disturbance of sperm architecture. Materials and Methods: Three widely used ND protocols for fluorescence in situ hybridization (FISH) were evaluated in this study: protocol 1 was combined denaturation and decondensation with 0.5N NaOH; in protocol 2, decondensation was achieved with 10mM dithiothreitol (DTT) and lithium diiodosalicylate (LIS); in protocol 3, 2.5mM DTT and heparin was used for ND. Protocols 2 and 3 were followed by denaturation with formamide at 75°C. The effect of denaturation and hybridization on spontaneous ND was also evaluated. Samples were counterstained with DAPI. Images were acquired using unbiased sampling and digital image morphometry analysis by Visiopharm Integrator System. Results were compared to neat samples using SPSS 16.0 statistical computer software. Results: Comparison of ND protocols is provided in the table. Mild decondensation was defined as 1.5 3 fold increase in nuclear area. Spontaneous ND occurred in an unexpectedly large proportion of spermatozoa during denaturation (74%) and hybridization (39%). Conclusions: Combined denaturation and decondensation with 0.5N NaOH demonstrated superior results providing uniform mild ND with over 80% of nucleus suitable for FISH sperm architecture assessment. The influence of spontaneous ND should be considered in any FISH preparation protocols. [ABSTRACT FROM AUTHOR]