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Search Results: 1 - 10 of 408167 matches for " Helena M Earl "
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Long-Term Neurotoxicity of Chemotherapy in Adolescents and Young Adults Treated for Bone and Soft Tissue Sarcomas
Helena M. Earl,Sean Connolly,Christos Latoufis,Karen Eagle
Sarcoma , 1998, DOI: 10.1080/13577149878055
Abstract:
American Society for Clinical Oncology 39th Annual Meeting, Chicago, Illinois, USA, 31 May to 3 June 2003: Breast cancer neoadjuvant and adjuvant chemotherapy – prognostic and predictive markers
Helena Earl
Breast Cancer Research , 2003, DOI: 10.1186/bcr647
Abstract: The American Society of Clinical Oncology (ASCO) Annual Meeting is a leading educational and scientific event for oncologists, clinical researchers, academics and other health care professionals involved in multidisciplinary cancer care. This year the congress was held in Chicago, Illinois, from May 31 to June 3. The theme for the 39th annual meeting was 'Commitment, care, compassion: honouring people with cancer'. The goal of the meeting was to promote communication among cancer related medical specialities and the exchange of ideas arising from ongoing advances in oncology. This encompassed the areas of pathophysiology, diagnosis and management, and included innovations in therapies. For the first time this year, an oral presentation session was devoted to pharmacogenomics. A wide range of translational scientific research relevant to breast cancer was covered as well as new clinical data pertinent to breast oncology management.Worldwide, many research groups are concentrating on breast cancer gene expression and molecular profiling, and this area was given significant coverage at the ASCO meeting. The first presentation in the meeting's plenary session, given by Lajos Pusztai from the MD Anderson group, dealt with the predictive nature of profiling in terms of response to chemotherapy. Their group described the use of gene expression profiling in predicting complete pathological response (pCR) to neoadjuvant chemotherapy with a paclitaxel and anthracycline combination (abstract #1 [1]). In 21 patients the overall accuracy of response prediction based on a group of five genes (three oestrogen sulphotransferases, nuclear factor 1/A, and histone acetyltransferase) was 81% and the positive predictive value for pCR was 75%, with an overall specificity of 93%, although sensitivity fell to 50%.The group from Baylor College (abstract #32 [1]) presented their work on gene expression patterns for de novo and acquired resistance to docetaxel. Twenty-four patients had paired
Cancer of the Breast – a new edition of a classic reference text
Helena Earl
Breast Cancer Research , 2004, DOI: 10.1186/bcr764
Abstract: The review of epidemiology was excellent, and presumably the next edition will include the emerging evidence from the Million Woman Study on hormone replacement therapy (HRT) and breast cancer risk. As a working clinician, I particularly enjoyed the excellent coverage of nutrition and breast disease (chapter 9), prevention (chapter 12), and exercise and weight control in prevention and rehabilitation (chapter 13). These provided a comprehensive review of evidence in the subject areas I am so often challenged on by my patients and friends, but of which I am relatively ignorant. 'What is your opinion, Doctor, of a healthy life-style to reduce the risk of breast cancer or breast cancer recurrence?' There was also a very comprehensive and up to date review of both hormone therapy and chemotherapy by authors of international repute, which I could not fault.The coverage of molecular and biological aspects of breast cancer was on the whole very good, thorough, up to date and readable, and again provides an excellent reference text. I enjoyed the chapter on the genetic basis for the emergence and progression of breast cancer (10), and the molecular biology of breast cancer (11), although the latter needs some good illustrations to improve its comprehensibility. The chapter on cellular kinetics (19) was interesting but probably too long and somewhat outdated. The chapter on growth rates (21) definitely had too few pictures, and as this is an important and interesting area of research, and pertinent to the general breast cancer researcher, it needs to be re-interpreted in a more readable style. Too many mathematical equations in a text usually lead to inattention in the reader, and this important information needs to be better presented.Where did the book disappoint? The chapter that covered prognosis (22) really needs to be separated and expanded to include information on the promise of the emerging technologies of molecular profiling, proteomics, and bio-informatics. Pregna
Blood Transfusion Requirements for Patients With Sarcomas Undergoing Combined Radio- and Chemotherapy
Karen R. Sherbourne,Helena M. Earl,Lynne Whitehead,Sarah J. Jefferies,Neil G. Burnet
Sarcoma , 2005, DOI: 10.1080/13577140500180005
Abstract: Patients with bony and soft tissue sarcomas may require intensive treatment with chemotherapy and radiotherapy, which often leads to a fall in haemoglobin levels, requiring blood transfusion. There may be advantages in predicting which patients will require transfusion, partly because anaemia and hypoxia may worsen the response of tumours to chemotherapy and radiotherapy. Between 1997 and 2003, a total of 26 patients who received intensive treatment with curative intent were identified. Transfusions were given to maintain the haemoglobin at 10g/dl or above during chemotherapy, and at 12 g/dl or above during radiotherapy. Eighteen (69%) required a transfusion, the majority as a result of both the chemotherapy and RT criteria. There were 78 transfusion episodes, and 181 units of blood given. In the 18 patients who required transfusion, the average number of units was 10.1, but seven patients required more blood than this. The most significant factor influencing blood transfusion was choice of intensive chemotherapy. Intensive chemotherapy and presenting Hb less than 11.6 g/dl identified 13 out of 18 patients who needed transfusion. Adding a drop in haemoglobin of greater than 1.7 g/dl after one cycle of chemotherapy identified 16 out of 18 patients who required transfusion. The seven patients who had heavy transfusion requirements were identified by age 32 or less, intensive chemotherapy and a presenting Hb of 12 g/dl or less. Erythropoietin might be a useful alternative to transfusion in selected patient groups, especially those with heavy transfusion requirements.
Whither high-dose chemotherapy in breast cancer?
Astrid Mayer, Helena Earl
Breast Cancer Research , 2000, DOI: 10.1186/bcr262
Abstract: Our intended pun implies that we have reached a crossroads in high-dose chemotherapy for breast cancer. Is high-dose chemotherapy going anywhere, or should we allow it to wither on the vine? The conclusion of this commentary is that, in its present form, high-dose treatment has not been found to be superior to conventional-dose treatment in either the metastatic or adjuvant setting. However, we should be careful not to 'throw the baby out with the bath water'. Rather, we should look seriously at intensifying chemotherapy with more active drugs, given in different schedules. Our judgement is that using conventional cytotoxic chemotherapy, the approach pioneered by the Memorial Sloan-Kettering Hospital, New York, USA, with 'dose-dense' chemotherapy given in a 'block schedule', is likely to produce the best results [1]. However, there is also now much to be gained from looking at biological agents in combination with conventional chemotherapy, particularly with the recent encouraging results with the use of trastuzumab (Herceptin, Genentech, San Francisco, CA, USA) [2].High-dose chemotherapy in breast cancer has been a controversial issue for some time. Several phase 2 trials showed promising results in patients with chemotherapy-responsive metastatic disease, when the data were compared with the outcome in historical control individuals [3,4]. However, most recently published randomized trials demonstrate a lack of effectiveness in both the adjuvant and metastatic settings [5,6,7,8]. The trials of Bezwoda and coworkers from South Africa [9,10,11,12] remained the only important positive evidence for high-dose chemotherapy, until the publication of the onsite review of the Bezwoda studies [13] and the investigator's admission of serious scientific misconduct. Although international commentators [14,15] have suggested that further trials of high-dose chemotherapy should be carried out, our view is that such studies will have to be innovative enough to persuade oncologica
Saliva samples are a viable alternative to blood samples as a source of DNA for high throughput genotyping
Jean E Abraham, Mel J Maranian, Inmaculada Spiteri, Roslin Russell, Susan Ingle, Craig Luccarini, Helena M Earl, Paul DP Pharoah, Alison M Dunning, Carlos Caldas
BMC Medical Genomics , 2012, DOI: 10.1186/1755-8794-5-19
Abstract: Patients were recruited from the Pharmacogenetics of Breast Cancer Chemotherapy (PGSNPS) study. Paired blood and saliva samples were collected from 79 study participants. The Oragene DNA Self-Collection kit (DNAgenotek?) was used to collect and extract DNA from saliva. DNA from EDTA blood samples (median volume 8 ml) was extracted by Gen-Probe, Livingstone, UK. DNA yields, standard measures of DNA quality, genotype call rates and genotype concordance between paired, duplicated samples were assessed.Total DNA yields were lower from saliva (mean 24 μg, range 0.2–52 μg) than from blood (mean 210 μg, range 58–577 μg) and a 2-fold difference remained after adjusting for the volume of biological material collected. Protein contamination and DNA fragmentation measures were greater in saliva DNA. 78/79 saliva samples yielded sufficient DNA for use on Illumina Beadchip arrays and using Taqman assays. Four samples were randomly selected for genotyping in duplicate on the Illumina Beadchip arrays. All samples were genotyped using Taqman assays. DNA quality, as assessed by genotype call rates and genotype concordance between matched pairs of DNA was high (>97%) for each measure in both blood and saliva-derived DNA.We conclude that DNA from saliva and blood samples is comparable when genotyping using either Taqman assays or genome-wide chip arrays. Saliva sampling has the potential to increase participant recruitment within clinical trials, as well as reducing the resources and organisation required for multicentre sample collection.
CYP2D6 gene variants: association with breast cancer specific survival in a cohort of breast cancer patients from the United Kingdom treated with adjuvant tamoxifen
Jean E Abraham, Mel J Maranian, Kristy E Driver, Radka Platte, Bolot Kalmyrzaev, Caroline Baynes, Craig Luccarini, Mitul Shah, Susan Ingle, David Greenberg, Helena M Earl, Alison M Dunning, Paul DP Pharoah, Carlos Caldas
Breast Cancer Research , 2010, DOI: 10.1186/bcr2629
Abstract: This was a population based case-cohort study. We genotyped known functional variants (n = 7; minor allele frequency (MAF) > 0.01) and single nucleotide polymorphisms (SNPs) (n = 5; MAF > 0.05) tagging all known common variants (tagSNPs), in CYP2D6 in 6640 DNA samples from patients with invasive breast cancer from SEARCH (Studies of Epidemiology and Risk factors in Cancer Heredity); 3155 cases had received tamoxifen therapy. There were 312 deaths from breast cancer, in the tamoxifen treated patients, with over 18000 years of cumulative follow-up. The association between genotype and BCSS was evaluated using Cox proportional hazards regression analysis.In tamoxifen treated patients, there was weak evidence that the poor-metaboliser variant, CYP2D6*6 (MAF = 0.01), was associated with decreased BCSS (P = 0.02; HR = 1.95; 95% CI = 1.12-3.40). No other variants, including CYP2D6*4 (MAF = 0.20), previously reported to be associated with poorer clinical outcomes, were associated with differences in BCSS, in either the tamoxifen or non-tamoxifen groups.CYP2D6*6 may affect BCSS in tamoxifen-treated patients. However, the absence of an association with survival in more frequent variants, including CYP2D6*4, questions the validity of the reported association between CYP2D6 genotype and treatment response in breast cancer. Until larger, prospective studies confirming any associations are available, routine CYP2D6 genetic testing should not be used in the clinical setting.Tamoxifen has been the standard treatment for oestrogen receptor (ER)-positive breast cancer for more than three decades. Indications for its use [1] include: metastatic disease in women (pre- and post-menopausal) and men; adjuvant therapy in pre- and post-menopausal women with breast cancer (lymph node positive and negative); preventative therapy in women at high risk of breast cancer; ductal carcinoma in situ post-resection; and for the prevention of contra-lateral breast cancer. There are proven benefits ass
Challenges for Research on Intelligence
Earl Hunt,Susanne M. Jaeggi
Journal of Intelligence , 2013, DOI: 10.3390/jintelligence1010036
Abstract: After 100 years of research, the definition of the field is still inadequate. The biggest challenge we see is moving away from a de-factor definition of intelligence in terms of test scores, but at the same time making clear what the boundaries of the field are. We then present four challenges for the field, two within a biological and two within a social context. These revolve around the issues of the malleability of intelligence and its display in everyday life, outside of a formal testing context. We conclude that developments in cognitive neuroscience and increases in the feasibility of monitoring behavior outside of the context of a testing session offer considerable hope for expansion of our both the biological and social aspects of individual differences in cognition.
Radiographic Evaluation of Children with Febrile Urinary Tract Infection: Bottom-Up, Top-Down, or None of the Above?
Michaella M. Prasad,Earl Y. Cheng
Advances in Urology , 2012, DOI: 10.1155/2012/716739
Abstract: The proper algorithm for the radiographic evaluation of children with febrile urinary tract infection (FUTI) is hotly debated. Three studies are commonly administered: renal-bladder ultrasound (RUS), voiding cystourethrogram (VCUG), and dimercapto-succinic acid (DMSA) scan. However, the order in which these tests are obtained depends on the methodology followed: bottom-up or top-down. Each strategy carries advantages and disadvantages, and some groups now advocate even less of a workup (none of the above) due to the current controversies about treatment when abnormalities are diagnosed. New technology is available and still under investigation, but it may help to clarify the interplay between vesicoureteral reflux, renal scarring, and dysfunctional elimination in the future. 1. Introduction Three studies are commonly employed in the workup of febrile urinary tract infections (FUTIs): renal-bladder ultrasound (RUS), voiding cystourethrogram (VCUG), and dimercaptosuccinic acid (DMSA) scan. This paper will discuss the rationale behind the timing of these studies (“top-down” versus “bottom-up” methodology), along with the individual advantages and limitations of each approach. The debate involves the ideal outcome of interest vesicoureteral reflux (bottom-up) or renal parenchymal involvement (top-down). The controversy on this topic has swelled to the point that certain forums are even promoting a more limited workup (none of the above) for a subset of patients. Finally, new techniques and technologies using magnetic resonance (MR) urography and voiding urosonography (VUS) are emerging. These innovative studies may impact management strategies in the future. The purpose of this paper is to assess the current literature on bottom-up and top-down approaches as well as newer modalities and to evaluate the association between vesicoureteral reflux and renal scarring as it pertains to the workup of a child with FUTI. 2. Background Urinary tract infections (UTIs) in young children are common with an overall prevalence of 7.0% among infants presenting with fever and a pooled prevalence of 7.8% among children with urinary symptoms [1]. This diagnosis often leads to a radiographic workup to look for correctable urinary tract abnormalities that may predispose the child to infection. The objective is to identify which patients are susceptible to renal damage. Ideally, medical or surgical interventions can then be employed to prevent this cohort from developing future infections or sustaining further injury (although this point is also controversial). Scarring from
Efficacious End User Measures—Part 1: Relative Class Size and End User Problem Domains
E. Earl Eiland,Lorie M. Liebrock
Advances in Artificial Intelligence , 2013, DOI: 10.1155/2013/427958
Abstract:
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