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"Lassiter, William L"
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Pharmacogenetic and clinical risk factors for bevacizumab-related gastrointestinal hemorrhage in prostate cancer patients treated on CALGB 90401 (Alliance)
The objective of this study was to discover clinical and pharmacogenetic factors associated with bevacizumab-related gastrointestinal hemorrhage in Cancer and Leukemia Group B (Alliance) 90401. Patients with metastatic castration-resistant prostate cancer received docetaxel and prednisone ± bevacizumab. Patients were genotyped using Illumina HumanHap610-Quad and assessed using cause-specific risk for association between single nucleotide polymorphisms (SNPs) and gastrointestinal hemorrhage. In 1008 patients, grade 2 or higher gastrointestinal hemorrhage occurred in 9.5% and 3.8% of bevacizumab (
n
= 503) and placebo (
n
= 505) treated patients, respectively. Bevacizumab (
P
< 0.001) and age (
P
= 0.002) were associated with gastrointestinal hemorrhage. In 616 genetically estimated Europeans (
n
= 314 bevacizumab and
n
= 302 placebo treated patients), grade 2 or higher gastrointestinal hemorrhage occurred in 9.6% and 2.0% of patients, respectively. One SNP (rs1478947; HR 6.26; 95% CI 3.19–12.28;
P
= 9.40 × 10
−8
) surpassed Bonferroni-corrected significance. Grade 2 or higher gastrointestinal hemorrhage rate was 33.3% and 6.2% in bevacizumab-treated patients with the AA/AG and GG genotypes, versus 2.9% and 1.9% in the placebo arm, respectively. Prospective validation of these findings and functional analyses are needed to better understand the genetic contribution to treatment-related gastrointestinal hemorrhage.
Journal Article
Charlotte, NC
The rapid evolution of Charlotte, North Carolina, from \"regional backwater\" to globally ascendant city provides stark contrasts of then and now. Once a regional manufacturing and textile center, Charlotte stands today as one of the nation's premier banking and financial cores with interests reaching broadly into global markets. Once defined by its biracial and bicultural character, Charlotte is now an emerging immigrant gateway drawing newcomers from Latin America and across the globe. Once derided for its sleepy, nine-to-five \"uptown,\" Charlotte's center city has been wholly transformed by residential gentrification, corporate headquarters construction, and amenity-based redevelopment. And yet, despite its rapid transformation, Charlotte remains distinctively southern-globalizing, not yet global. This book brings together an interdisciplinary team of leading scholars and local experts to examine Charlotte from multiple angles. Their topics include the banking industry, gentrification, boosterism, architecture, city planning, transit, public schools, NASCAR, and the African American and Latino communities. United in the conviction that the experience of this Sunbelt city-center of the nation's fifth-largest metropolitan area-offers new insight into today's most pressing urban and suburban issues, the contributors to Charlotte, NC: The Global Evolution of a New South City ask what happens when the external forces of globalization combine with a city's internal dynamics to reshape the local structures, landscapes, and identities of a southern place.
eBook
Transient Vasopressin-Resistant Diabetes Insipidus of Pregnancy
OSMOREGULATION is markedly altered in normal human pregnancy. Osmotic thresholds for both thirst and secretion of arginine vasopressin decrease, and plasma osmolality and sodium levels are reduced by 10 mOsm per kilogram and 4 mmol per liter, respectively, as compared with levels measured before pregnancy.
1
2
3
Despite this lower osmolality, pregnant women maintain basal levels of plasma arginine vasopressin of 1 to 2 pg per milliliter — values similar to those of nongravid subjects — and concentrate their urine appropriately when they are dehydrated.
3
,
4
This is all the more intriguing since two developments during normal gestation would be expected to interfere . . .
Journal Article