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91.
Gerber JM Smith BD Ngwang B Zhang H Vala MS Morsberger L Galkin S Collector MI Perkins B Levis MJ Griffin CA Sharkis SJ Borowitz MJ Karp JE Jones RJ 《Blood》2012,119(15):3571-3577
Relapse of acute myeloid leukemia (AML) is thought to reflect the failure of current therapies to adequately target leukemia stem cells (LSCs), the rare, resistant cells presumed responsible for maintenance of the leukemia and typically enriched in the CD34(+)CD38(-) cell population. Despite the considerable research on LSCs over the past 2 decades, the clinical significance of these cells remains uncertain. However, if clinically relevant, it is expected that LSCs would be enriched in minimal residual disease and predictive of relapse. CD34(+) subpopulations from AML patients were analyzed by flow cytometry throughout treatment. Sorted cell populations were analyzed by fluorescence in situ hybridization for leukemia-specific cytogenetic abnormalities (when present) and by transplantation into immunodeficient mice to determine self-renewal capacity. Intermediate (int) levels of aldehyde dehydrogenase (ALDH) activity reliably distinguished leukemic CD34(+)CD38(-) cells capable of engrafting immunodeficient mice from residual normal hematopoietic stem cells that exhibited relatively higher ALDH activity. Minimal residual disease detected during complete remission was enriched for the CD34(+)CD38(-)ALDH(int) leukemic cells, and the presence of these cells after therapy highly correlated with subsequent clinical relapse. ALDH activity appears to distinguish normal from leukemic CD34(+)CD38(-) cells and identifies those AML cells associated with relapse. 相似文献
92.
We here investigate the occurrence of fluoride intake-associated alterations in patients with hematologic disease on triazol antifungal medication. Clinical, laboratory, and radiology data of overall 43 patients with hematologic malignancies taking voriconazole (n = 20), posaconazole (n = 8), and itraconazole (n = 4), and a hematologic patient control group (n = 11) are described. Bone pain and radiologic evidence of periostitis were exclusively observed in patients receiving long-term voriconazole. Cessation of treatment led to clinical improvement in all cases. In line with clinical evidence, fluoride serum concentration was elevated in patients receiving voriconazole (median, 156.5 μg/L; interquartile range, 96.8 μg/L; normal < 30 μg/L) but not in the other treatment groups (P < .001 for all comparisons vs voriconazole). We conclude that serum fluoride levels were elevated on average 5-fold above normal levels in hematologic patients receiving voriconazole. Clinically relevant skeletal disease was associated with renal insufficiency and above 10-fold elevated fluoride levels, and was reversible on termination of voriconazole treatment. 相似文献
93.
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95.
Léonie Egli Virgile Lecoultre Fanny Theytaz Vanessa Campos Leanne Hodson Philippe Schneiter Bettina Mittendorfer Bruce W. Patterson Barbara A. Fielding Philipp A. Gerber Vittorio Giusti Kaspar Berneis Luc Tappy 《Diabetes》2013,62(7):2259-2265
Excess fructose intake causes hypertriglyceridemia and hepatic insulin resistance in sedentary humans. Since exercise improves insulin sensitivity in insulin-resistant patients, we hypothesized that it would also prevent fructose-induced hypertriglyceridemia. This study was therefore designed to evaluate the effects of exercise on circulating lipids in healthy subjects fed a weight-maintenance, high-fructose diet. Eight healthy males were studied on three occasions after 4 days of 1) a diet low in fructose and no exercise (C), 2) a diet with 30% fructose and no exercise (HFr), or 3) a diet with 30% fructose and moderate aerobic exercise (HFrEx). On all three occasions, a 9-h oral [13C]-labeled fructose loading test was performed on the fifth day to measure [13C]palmitate in triglyceride-rich lipoprotein (TRL)-triglycerides (TG). Compared with C, HFr significantly increased fasting glucose, total TG, TRL-TG concentrations, and apolipoprotein (apo)B48 concentrations as well as postfructose glucose, total TG, TRL-TG, and [13C]palmitate in TRL-TG. HFrEx completely normalized fasting and postfructose TG, TRL-TG, and [13C]palmitate concentration in TRL-TG and apoB48 concentrations. In addition, it increased lipid oxidation and plasma nonesterified fatty acid concentrations compared with HFr. These data indicate that exercise prevents the dyslipidemia induced by high fructose intake independently of energy balance.It is currently suspected that overconsumption of fructose, in the form of either sugar or high-fructose corn syrup, may promote obesity and favor the development of metabolic diseases such as type 2 diabetes and dyslipidemia (1,2). This is supported by a large number of studies in rodents, which demonstrate that a high-sucrose diet causes obesity, diabetes, dyslipidemia, and hepatic steatosis (3) and that this effect is mainly due to the fructose component of sucrose (4,5). Consistent with this hypothesis, epidemiological studies have shown that high intakes of sugar, fructose, or sweetened beverages are associated with the development of obesity (6,7), diabetes (8), hypertriglyceridemia (9), an increase in small dense atherogenic LDL particles (10), high blood pressure (11), albuminuria (12), and nonalcoholic fatty liver diseases (13). Several short-term studies have further documented that hypercaloric, high-fructose diets can cause increases in a number of cardiometabolic risk factors in humans, such as fasting and postprandial hypertriglyceridemia (14–18), ectopic lipid deposition in liver cells (19,20), impaired postprandial glucose homeostasis (18), and hepatic insulin resistance (21,22). Some of these effects may be related, at least in part, to the fact that fructose can be converted into fatty acids, which has been demonstrated after both acute (23) and chronic (18) fructose feeding. Exercise is very efficient at reducing the metabolic dysfunctions associated with obesity (24,25), and although many of these effects appear to be related to enhanced energy expenditure and improved energy balance (26,27), there is growing evidence that such improvements are independent of the changes in energy balance or body composition (28,29). Exercise has also been shown to prevent the accumulation of triglyceride-rich lipoprotein (TRL)-triglycerides (TG) and improve the plasma atherogenic lipid profile in healthy subjects fed a high-carbohydrate diet (30). The purpose of this study was to investigate whether exercise would similarly prevent fructose-induced metabolic effects. 相似文献
96.
Thomas JA Gerber L Moreira DM Hamilton RJ Bañez LL Castro-Santamaria R Andriole GL Isaacs WB Xu J Freedland SJ 《Journal of internal medicine》2012,272(1):85-92
Abstract. Thomas J‐A II, Gerber L, Moreira DM, Hamilton RJ, Bañez LL, Castro‐Santamaria R, Andriole GL, Isaacs WB, Xu J, Freedland SJ (Durham VA Medical Center, Durham, NC, USA; Duke University School of Medicine, Durham, NC, USA; The Author Smith Institute for Urology, New Hyde Park, NY, USA; Memorial Sloan‐Kettering Cancer Center, New York, NY, USA; GlaxoSmithKline, Research Triangle Park, NC, USA; Washington University School of Medicine, St. Louis, MO, USA; Johns Hopkins Hospital, Baltimore, MD, USA; Wake Forest University, Winston‐Salem, NC, USA; and Duke University School of Medicine, Durham, NC, USA). Prostate cancer risk in men with prostate and breast cancer family history: results from the REDUCE study (R1). J Intern Med 2012; 272 : 85–92. Background. To what degree the associations between PCa risk and family history of prostate cancer (PCa) and/or breast cancer (BCa) are attributable to screening biases is unclear. We examined these questions within the REDUCE study, where biopsies were largely independent of prostate specific antigen (PSA) minimizing screening biases. Methods. Data were from REDUCE, which tested dutasteride 0.5 mg daily for PCa risk reduction in men with PSA 2.5–10.0 ng mL?1 and a negative prestudy biopsy. Among men undergoing at least one on‐study biopsy with complete data (n = 6415; 78.1%), the association between family history and PCa risk was tested using multivariate logistic regression adjusting for clinicodemographic characteristics. Results. A family history of PCa alone was associated with increased PCa diagnosis (OR: 1.47, 95%CI: 1.22–1.77). In North America, PCa family history was not related to PCa diagnosis (OR: 1.02, 95%CI: 0.73–1.44), whereas outside North America, PCa family history was significantly related to diagnosis (OR: 1.72, 95%CI: 1.38–2.15) (P‐interaction = 0.01). A family history of both PCa and BCa (OR: 2.54, 95%CI: 1.72–3.75) but not BCa alone (OR: 1.04, 95%CI: 0.84–1.29) was associated with increased PCa risk versus no family history and irrespective of geographical region. Conclusions. In REDUCE, PCa family history was significantly related to PCa diagnosis, although only for men outside North America. The presence of both PCa and BCa family history significantly increased risk versus PCa family history alone, irrespective of geographical region. Ultimately, our observations may support the need for changes in how we address family history in terms of both risk of PCa diagnosis and general risk stratification. 相似文献
97.
Douglas PS Carr JJ Cerqueira MD Cummings JE Gerber TC Mukherjee D Taylor AJ 《Journal of nuclear cardiology》2012,19(3):534-550
Technological advances and increased utilization of medical testing and procedures have prompted greater attention to ensuring the patient safety of radiation use in the practice of adult cardiovascular medicine. In response, representatives from cardiovascular imaging societies, private payers, government and nongovernmental agencies, industry, medical physicists, and patient representatives met to develop goals and strategies toward this end; this report provides an overview of the discussions. This expert "think tank" reached consensus on several broad directions including: the need for broad collaboration across a large number of diverse stakeholders; clarification of the relationship between medical radiation and stochastic events; required education of ordering and providing physicians, and creation of a culture of safety; development of infrastructure to support robust dose assessment and longitudinal tracking; continued close attention to patient selection by balancing the benefit of cardiovascular testing and procedures against carefully minimized radiation exposures; collation, dissemination, and implementation of best practices; and robust education, not only across the healthcare community but also to patients, the public, and media. Finally, because patient radiation safety in cardiovascular imaging is complex, any proposed actions need to be carefully vetted (and monitored) for possible unintended consequences. 相似文献
98.
99.
Joseph C. Klink Lionel L. Bañez Leah Gerber Amy Lark Robin T. Vollmer Stephen J. Freedland 《World journal of urology》2013,31(6):1497-1503
Purpose
Inflammation may play a role in the development and progression of many cancers, including prostate cancer. We sought to test whether histological inflammation within prostate cancer was associated with more aggressive disease.Methods
The slides of prostatectomy specimens were reviewed by a board-certified pathologist on 287 men from a Veterans Affairs Medical Center treated with radical prostatectomy from 1992 to 2004. The area with the greatest tumor burden was scored in a blinded manner for the degree of inflammation: absent, mild, or marked. We used logistic and Cox proportional hazards regression analysis to examine whether categorically coded inflammation score was associated with adverse pathology and biochemical progression, respectively.Results
No inflammation was found in 49 men (17 %), while 153 (53 %) and 85 (30 %) had mild and marked inflammation. During a median follow-up of 77 months, biochemical recurrence occurred among 126 (44 %) men. On multivariate analysis, more inflammation was associated with greater risk of positive margins, capsular penetration, and seminal vesicle invasion (all p < 0.05). Marked inflammation was associated with increased PSA recurrence risk when adjusting for preoperative features only (HR 2.08, 95 % CI 1.02–4.24), but not after adjusting for pathologic features.Conclusions
Inflammation within prostate cancer was associated with more advanced disease, although it is unclear whether aggressive disease caused increased inflammation or inflammation caused aggressive disease. 相似文献100.
Michael Untch Bernd Gerber Nadia Harbeck Christian Jackisch Norbert Marschner Volker M?bus Gunter von Minckwitz Sibylle Loibl Matthias W. Beckmann Jens-Uwe Blohmer Serban-Dan Costa Thomas Decker Ingo Diel Thomas Dimpfl Wolfgang Eiermann Tanja Fehm Klaus Friese Fritz J?nicke Wolfgang Janni Walter Jonat Marion Kiechle Uwe K?hler Hans-Joachim Lück Nicolai Maass Kurt Possinger Achim Rody Anton Scharl Andreas Schneeweiss Christoph Thomssen Diethelm Wallwiener Anja Welt 《Breast care (Basel, Switzerland)》2013,8(3):221-229