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21.
Elizabeth Tan-Chiu Greg Yothers Edward Romond Charles E Geyer Michael Ewer Deborah Keefe Richard P Shannon Sandra M Swain Ann Brown Louis Fehrenbacher Victor G Vogel Thomas E Seay Priya Rastogi Eleftherios P Mamounas Norman Wolmark John Bryant 《Journal of clinical oncology》2005,23(31):7811-7819
PURPOSE: Trastuzumab is effective in treating human epidermal growth factor receptor 2 (HER2) -positive breast cancer, but it increases frequency of cardiac dysfunction (CD) when used with or after anthracyclines. PATIENTS AND METHODS: National Surgical Adjuvant Breast and Bowel Project trial B-31 compared doxorubicin and cyclophosphamide (AC) followed by paclitaxel with AC followed by paclitaxel plus 52 weeks of trastuzumab beginning concurrently with paclitaxel in patients with node-positive, HER2-positive breast cancer. Initiation of trastuzumab required normal post-AC left ventricular ejection fraction (LVEF) on multiple-gated acquisition scan. If symptoms suggestive of congestive heart failure (CHF) developed, source documents were blindly reviewed by an independent panel of cardiologists to determine whether criteria were met for a cardiac event (CE), which was defined as New York Heart Association class III or IV CHF or possible/probable cardiac death. Frequencies of CEs were compared between arms. RESULTS: Among patients with normal post-AC LVEF who began post-AC treatment, five of 814 control patients subsequently had confirmed CEs (four CHFs and one cardiac death) compared with 31 of 850 trastuzumab-treated patients (31 CHFs and no cardiac deaths). The difference in cumulative incidence at 3 years was 3.3% (4.1% for trastuzumab-treated patients minus 0.8% for control patients; 95% CI, 1.7% to 4.9%). Twenty-seven of the 31 patients in the trastuzumab arm have been followed for > or = 6 months after diagnosis of a CE; 26 were asymptomatic at last assessment, and 18 remained on cardiac medication. CHFs were more frequent in older patients and patients with marginal post-AC LVEF. Fourteen percent of patients discontinued trastuzumab because of asymptomatic decreases in LVEF; 4% discontinued trastuzumab because of symptomatic cardiotoxicity. CONCLUSION: Administering trastuzumab with paclitaxel after AC increases incidence of CHF and lesser CD. Potential cardiotoxicity should be carefully considered when discussing benefits and risks of this therapy. 相似文献
22.
Sachin Malik Suroor A. Khan Priya Ahuja Satish K. Arya Shikha Sahu Kapendra Sahu 《Medicinal chemistry research》2013,22(12):5633-5653
Malaria is the leading infectious disease found in humans, affecting third-world countries. Worldwide, more than two billion people are at risk of malaria, with about 500 million clinical cases of malaria each year and one million deaths. In this focused review, an effort has been made to summarize the reactions of singlet oxygen with organic substrates, their stereoselectivity, stereospecificity and utilization in generating dioxetanes and endoperoxides. The study of production and reactivity indications of this exceptional molecule has emerged as a rich and diverse area in the synthesis of antimalarials like artemisinin and its semisynthetic derivatives, structurally simple 1,2,4-trioxanes, sesquiterpene isonitriles, synthetic cyclic, and other acyclic peroxides. Artermisinin, a mainstay in antimalarial drug therapy, meets the dual challenge posed by drug-resistant parasites and rapid advancement of lethal malarial threat. The cardinal mechanism of peroxidation and ring closure in its production are induced by singlet oxygen and acid. Moreover, its complex structure restricts the complete chemical synthesis of artemisinin. Consequently, the limited availability coupled with increasing demand for artemisinin has paved the way for the preparation of synthetic alternatives of artemisinin and its derivatives. Likewise, past evidence of the structure–activity relationship indicate the importance of singlet oxygen in antimalarial drug synthesis. It is anticipated that this compendium on the chemistry of singlet oxygen will be of use to organic/medicinal chemists and pharmacologists working on antimalarial drug development. 相似文献
23.
Ashley Sharp Berit Muller-Pebody Andre Charlett Bharat Patel Rebecca Gorton Jonathan Lambourne Martina Cummins Adela Alcolea-Medina Mark Wilks Robin Smith Damien Mack Susan Hopkins Andrew Dodgson Phillipa Burns Nelun Perera Felicia Lim Gopal Rao Priya Khanna Elizabeth Johnson Andrew Borman Silke Schelenz Rebecca Guy Joanna Conneely Rohini J Manuel Colin S Brown 《Euro surveillance : bulletin européen sur les maladies transmissibles = European communicable disease bulletin》2021,26(8)
Background Candida auris is an emerging multidrug-resistant fungal pathogen associated with bloodstream, wound and other infections, especially in critically ill patients. C. auris carriage is persistent and is difficult to eradicate from the hospital environment.AimWe aimed to pilot admission screening for C. auris in intensive care units (ICUs) in England to estimate prevalence in the ICU population and to inform public health guidance.MethodsBetween May 2017 and April 2018, we screened admissions to eight adult ICUs in hospitals with no previous cases of C. auris, in three major cities. Swabs were taken from the nose, throat, axilla, groin, perineum, rectum and catheter urine, then cultured and identified using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS). Patient records were linked to routine ICU data to describe and compare the demographic and health indicators of the screened cohort with a national cohort of ICU patients admitted between 2016 and 2017.ResultsAll C. auris screens for 921 adults from 998 admissions were negative. The upper confidence limit of the pooled prevalence across all sites was 0.4%. Comparison of the screened cohort with the national cohort showed it was broadly similar to the national cohort with respect to demographics and co-morbidities.ConclusionThese findings imply that C. auris colonisation among patients admitted to ICUs in England is currently rare. We would not currently recommend widespread screening for C. auris in ICUs in England. Hospitals should continue to screen high-risk individuals based on local risk assessment. 相似文献
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25.
R. Gina Silverstein Michael Centore Andrea Pollack Gabrielle Barrieau Priya Gopalan 《Journal of psychosomatic obstetrics and gynaecology》2013,34(4):304-310
Purpose: To evaluate the feasibility and acceptability of a protocol determining the relationship between emergency team response (ETR) during childbirth and acute stress disorder (ASD) and post-traumatic stress disorder (PTSD) symptoms.Methods: In a prospective, observational, cohort design, women experiencing ETR during childbirth were approached and recruited on postpartum day-1 and followed for six weeks. Demographics, obstetric and birth characteristics, ASD scores and PTSD scores (by Impact of Events Scale, IES and PCL-civilian) were recorded. Recruitment and retention rates were recorded, and scores were compared to women who did not experience ETR.Results: Three hundred sixty-nine were approached and 249 were enrolled (67.5% recruitment rate). One hundred twenty-five completed all procedures (50.2% retention). Twenty experienced ETR (3.5% event rate), 12 enrolled (60.0% recruitment rate) and 8 completed the study (66.7% retention). The ETR group had higher PCL and IES scores (PCL: ETR median 12, non-ETR median 2, p?=?.08; IES: ETR median 22.5, non-ETR median 20, p?=?.08). ASD scores were similar between groups.Conclusions: Methodology investigating the link between ETR and postpartum psychological distress is feasible and acceptable. A relationship between ETR and PTSD symptoms appears to exist, with ETR being associated with higher PTSD scores compared to non-ETR childbirths. Methods that incorporate awareness of the unique concerns of vulnerable populations are needed. 相似文献
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29.
PB Shetty H Tang BO Tayo AC Morrison CL Hanis DC Rao JH Young ER Fox E Boerwinkle RS Cooper NJ Risch X Zhu;the Candidate Gene Association Resource 《Journal of hypertension》2012,30(10):1970-1976
OBJECTIVE:: Genetic variants in 296 genes in regions identified through admixture mapping of hypertension, BMI, and lipids were assessed for association with hypertension, blood pressure (BP), BMI, and high-density lipoprotein cholesterol (HDL-C). METHODS:: This study identified coding SNPs identified from HapMap2 data that were located in genes on chromosomes 5, 6, 8, and 21, wherein ancestry association evidence for hypertension, BMI, or HDL-C was identified in previous admixture mapping studies. Genotyping was performed in 1733 unrelated African-Americans from the National Heart, Lung and Blood Institute's Family Blood Pressure Project, and gene-based association analyses were conducted for hypertension, SBP, DBP, BMI, and HDL-C. A gene score based on the number of minor alleles of each SNP in a gene was created and used for gene-based regression analyses, adjusting for age, age, sex, local marker ancestry, and BMI, as applicable. An individual's African ancestry estimated from 2507 ancestry-informative markers was also adjusted for to eliminate any confounding due to population stratification. RESULTS:: CXADR (rs437470) on chromosome 21 was associated with SBP and DBP with or without adjusting for local ancestry (P?0.0006). F2RL1 (rs631465) on chromosome 5 was associated with BMI (P?=?0.0005). Local ancestry in these regions was associated with the respective traits as well. CONCLUSION:: This study suggests that CXADR and F2RL1 likely play important roles in BP and obesity variation, respectively; and these findings are consistent with those of other studies, so replication and functional analyses are necessary. 相似文献
30.
Patterns of occurrence of dengue and chikungunya,and spatial distribution of mosquito vector Aedes albopictus in Swabi district,Pakistan
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