Incorporating DNA Sequencing into Current Prenatal Screening Practice for Down's Syndrome

PMCID: PMC3604109This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Sympathoinhibitory effect of statins in chronic heart failure

Contains fulltext : 89087.pdf (publisher's version ) (Closed access)OBJECTIVES: Increased (central) sympathetic activity is a key feature of heart failure and associated with worse prognosis. Animal studies suggest that statin therapy can reduce central sympathetic outflow. This study assessed statin effects on (central) sympathetic activity in human chronic heart failure (CHF) patients. METHODS: Sympathetic activity was measured in eight patients with CHF patients during 8 weeks after discontinuation and 4 weeks after restart of statin therapy by microneurography for direct muscle sympathetic nerve recording (MSNA) and measurement of arterial plasma norepinephrine concentrations. RESULTS: During discontinuation of statin therapy, MSNA was significantly increased (73 +/- 4 vs. 56 +/- 5 and 52 +/- 6 bursts/100 beats, p = 0.01). Burst frequency was significantly higher after statin discontinuation (42 +/- 3 burst/min without statin vs. 32 +/- 3 and 28 +/- 3 burst/min during statin therapy, p = 0.004). Mean normalized burst amplitude and total normalized MSNA were significantly higher after statin discontinuation (mean normalized burst amplitude 0.36 +/- 0.04 without statin vs. 0.29 +/- 0.04 and 0.22 +/- 0.04 during statin, p < 0.05; total normalized MSNA 15.70 +/- 2.78 without statin, vs. 9.28 +/- 1.41 and 6.56 +/- 1.83 during statin, p = 0.009). Arterial plasma norepinephrine levels and blood pressure were unaffected. INTERPRETATION: Statin therapy inhibits central sympathetic outflow in CHF patients, as measured by MSNA.1 april 201

ATBF1 and NQO1 as candidate targets for allelic loss at chromosome arm 16q in breast cancer: Absence of somatic ATBF1 mutations and no role for the C609T NQO1 polymorphism

<p>Abstract</p> <p>Background</p> <p>Loss of heterozygosity (LOH) at chromosome arm 16q is frequently observed in human breast cancer, suggesting that one or more target tumor suppressor genes (TSGs) are located there. However, detailed mapping of the smallest region of LOH has not yet resulted in the identification of a TSG at 16q. Therefore, the present study attempted to identify TSGs using an approach based on mRNA expression.</p> <p>Methods</p> <p>A cDNA microarray for the 16q region was constructed and analyzed using RNA samples from 39 breast tumors with known LOH status at 16q.</p> <p>Results</p> <p>Five genes were identified to show lower expression in tumors with LOH at 16q compared to tumors without LOH. The genes for NAD(P)H dehydrogenase quinone (<it>NQO1</it>) and AT-binding transcription factor 1 (<it>ATBF1</it>) were further investigated given their functions as potential TSGs. <it>NQO1 </it>has been implicated in carcinogenesis due to its role in quinone detoxification and in stabilization of p53. One inactive polymorphic variant of <it>NQO1 </it>encodes a product showing reduced enzymatic activity. However, we did not find preferential targeting of the active <it>NQO1 </it>allele in tumors with LOH at 16q. Immunohistochemical analysis of 354 invasive breast tumors revealed that NQO1 protein expression in a subset of breast tumors is higher than in normal epithelium, which contradicts its proposed role as a tumor suppressor gene.</p> <p><it>ATBF1 </it>has been suggested as a target for LOH at 16q in prostate cancer. We analyzed the entire coding sequence in 48 breast tumors, but did not identify somatic sequence changes. We did find several in-frame insertions and deletions, two variants of which were reported to be somatic pathogenic mutations in prostate cancer. Here, we show that these variants are also present in the germline in 2.5% of 550 breast cancer patients and 2.9% of 175 healthy controls. This indicates that the frequency of these variants is not increased in breast cancer patients. Moreover, there is no preferential LOH of the wildtype allele in breast tumors.</p> <p>Conclusion</p> <p>Two likely candidate TSGs at 16q in breast cancer, <it>NQO1 </it>and <it>ATBF1</it>, were identified here as showing reduced expression in tumors with 16q LOH, but further analysis indicated that they are not target genes of LOH. Furthermore, our results call into question the validity of the previously reported pathogenic variants of the <it>ATBF1 </it>gene.</p

How to identify potentially preventable readmissions by classifying them using a national administrative database

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Influence of an anti-tumor necrosis factor monoclonal antibody on cytokine levels in patients with sepsis

OBJECTIVESTo determine the safety, pharmacokinetics, and activity of an anti-tumor necrosis factor (TNF)-α monoclonal antibody in severe sepsis. DESIGNOpen-label, prospective, phase II multicenter trial with escalating doses of a murine monoclonal antibody (CB0006). SETTINGTwelve academic medical center intensive care units in the United States and Europe. PATIENTSEighty patients with severe sepsis or septic shock who received standard supportive care and antimicrobial therapy in addition to the anti-TNF antibody. INTERVENTIONSPatients were treated intravenously with one of four dosing regimens with CB00060.1 mg/kg, 1.0 mg/kg, 10 mg/kg or two doses of 1 mg/kg 24 hrs apart. MEASUREMENTS AND MAIN RESULTSThe murine monoclonal anti-TNF antibody was well tolerated despite the development of anti-murine antibodies in 98% of patients. No survival benefit was found for the total study population, but patients with increased circulating TN