tbuckley/cabot-search huggingface dataset:
<i>ABCB1</i> (<i>MDR 1</i>) Polymorphisms and Progression-Free Survival among Women with Ovarian Cancer following Paclitaxel/Carboplatin Chemotherapy
Authors: Sharon E. Johnatty, Jonathan Beesley, Jim Paul, Sian Fereday, Amanda B. Spurdle, Penelope M. Webb, Karen Byth, Sharon Marsh, Howard McLeod, Paul R. Harnett, Robert Brown, Anna deFazio, Georgia Chenevix-Trench
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The human ABCB1 gene encodes P-glycoprotein, which transports a broad range of anticancer drugs, including paclitaxel. Although the functional consequences of ABCB1 polymorphisms have been the subject of numerous studies, few have assessed the association with clinical outcome. Experimental Design: We assessed the association between the 2677G&amp;gt;T/A, 3435C&amp;gt;T, and 1236C&amp;gt;T ABCB1 polymorphisms and progression-free and overall survival in 309 patients from the Australian Ovarian Cancer Study treated with paclitaxel/carboplatin and subsequently tested significant observations in an independent validation set. Results: Women who carried the minor T/A alleles at the 2677G&amp;gt;T/A polymorphism were significantly less likely to relapse following treatment compared with homozygote GG carriers (PLog-rank = 0.001) in the Australian Ovarian Cancer Study cohort. Subgroup analyses showed that this effect was limited to cases with residual disease ≤1 cm (PLog-rank = 0.0004), not for those with residual disease &amp;gt;1 cm (PLog-rank = 0.3). This effect was not confirmed in an independent validation set of carboplatin/paclitaxel-treated patients (n = 278) using a higher residual disease cut point (≤2 cm). However, analysis of the unrestricted data set expanded to include docetaxel-treated patients (n = 914) did support an effect of the 2677T/A allele in patients with no macroscopic residual disease (hazard ratio, 0.70; 95% confidence interval, 0.46-1.04; Pone-sided = 0.039). Conclusion: Our findings indicate that there is an effect of the 2677G&amp;gt;T/A polymorphism on progression-free survival in ovarian cancer patients who are treated with a taxane/carboplatin, which is dependent on the extent of residual disease, with a better prognosis for patients with the 2677T/A allele and minimal residual disease.
A Randomized Phase II Study of Gefitinib Plus Simvastatin Versus Gefitinib Alone in Previously Treated Patients with Advanced Non–Small Cell Lung Cancer
Authors: Ji-Youn Han, Soo-Hyun Lee, Nam Jin Yoo, Lee Suk Hyung, Yoon Joo Moon, Tak Yun, Heung Tae Kim, Jin Soo Lee
Journal: Clinical Cancer Research (2011)

Abstract Purpose: To evaluate the efficacy and safety of gefitinib plus simvastatin (GS) versus gefitinib alone (G) in previously treated patients with advanced non–small cell lung cancer (NSCLC). Experimental Design: Between May 2006 and September 2008, 106 patients (51% men, 75% adenocarcinoma, 50% never smoker) were randomly assigned to G alone (250 mg/d, n = 54) or GS (250 and 40 mg/d, respectively, n = 52). One cycle was 4 weeks of treatment. Therapy was continued until disease progression or intolerable toxicity was observed. The primary endpoint was response rate (RR). Secondary endpoints included toxicity, progression-free survival (PFS), and overall survival (OS). Results: The RR was 38.5% (95% CI, 25.3–51.7) for GS and 31.5% (95% CI, 19.1–43.9) for G. The median PFS was 3.3 months [M] (95% CI, 1.4–5.2M) for GS and 1.9M (95% CI, 1.0–2.8M) for G. The median OS was 13.6M (95% CI, 7.1–20.1M) for GS and 12.0M (95% CI, 7.8–16.2M) for G. In exploratory subgroup analysis, GS showed higher RR (40% vs. 0%, P = 0.043) and longer PFS (3.6M vs. 1.7M, P = 0.027) compared with G alone in patients with wild-type epidermal growth factor receptor (EGFR) nonadenocarcinomas. Adverse events in both arms were generally mild and mainly consisted of skin rashes. Conclusions: Although no superiority of GS to G was demonstrated in this unselected NSCLC population, GS showed higher RR and longer PFS compared with G alone in patients with wild-type EGFR nonadenocarcinomas. Simvastatin may improve the efficacy of gefitinib in that subgroup of gefitinib-resistant NSCLC patients. Clin Cancer Res; 17(6); 1553–60. ©2011 AACR.
Serum Alanine Aminotransferase Levels Decrease Further With Carbohydrate Than Fat Restriction in Insulin-Resistant Adults
Authors: Marno Celeste Ryan, Fahim Abbasi, Cindy Lamendola, Susan Carter, Tracey Lynn McLaughlin
Journal: Diabetes Care (2007)

Although weight loss interventions have been shown to reduce steatosis in nonalcoholic fatty liver disease (NAFLD), the impact of dietary macronutrient composition is unknown. We assessed the effect on serum alanine aminotransferase (ALT) concentrations of two hypocaloric diets varying in amounts of carbohydrate and fat in obese insulin-resistant individuals, a population at high risk for NAFLD.Post hoc analysis of ALT concentrations was performed in 52 obese subjects with normal baseline values and insulin resistance, as quantified by the steady-state plasma glucose (SSPG) test, who were randomized to hypocaloric diets containing either 60% carbohydrate/25% fat or 40% carbohydrate/45% fat (15% protein) for 16 weeks. The primary end point was change in ALT, which was evaluated according to diet, weight loss, SSPG, and daylong insulin concentrations.Although both diets resulted in significant decreases in weight and SSPG, daylong insulin, and serum ALT concentrations, the 40% carbohydrate diet resulted in greater decreases in SSPG (P < 0.04), circulating insulin (P < 0.01), and ALT (9.5 +/- 9.4 vs. 4.2 +/- 8.3 units/l; P < 0.04) concentrations. ALT changes correlated with improvement in insulin sensitivity (P = 0.04) and daylong insulin (P < 0.01). Individuals with ALT concentrations above the proposed upper limits experienced significant declines in ALT, unlike those with lower ALT levels.In a population at high risk for NAFLD, a hypocaloric diet moderately lower in carbohydrate decreased serum ALT concentrations to a greater degree than a higher-carbohydrate/low-fat diet, despite equal weight loss. This may result from a relatively greater decline in daylong insulin concentrations. Further research with histological end points is needed to further explore this finding.
Increased Dose Density Is Feasible: A Pilot Study of Adjuvant Epirubicin and Cyclophosphamide followed by Paclitaxel, at 10- or 11-Day Intervals with Filgrastim Support in Women with Breast Cancer
Authors: Monica N. Fornier, Andrew D. Seidman, Diana Lake, Gabriella D'Andrea, Jacqueline Bromberg, Mark Robson, Catherine Van Poznak, Katherine S. Panageas, Marietta Atienza, Larry Norton, Clifford Hudis
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Because Cancer and Leukemia Group B 9741 trial showed a benefit for every 14-day administration of chemotherapy compared with every 21-day treatment, we hypothesized that even greater dose density would be more effective. We conducted a pilot trial to assess the feasibility of dose-dense chemotherapy consisting of a standard regime at 10- to 11-day intervals in the adjuvant/neoadjuvant setting. A 2-day window was allowed for scheduling logistics. Experimental Design: Thirty-nine women with early-stage breast carcinoma were accrued from April 2004 to October 2004. Median age was 47 years (range, 26-67 years). Patients received therapy with 100 mg/m2 epirubicin and 600 mg/m2 cyclophosphamide (EC) q 10 to 11 days for four cycles followed by 175 mg/m2 paclitaxel q 10 to 11 days for four cycles, all with filgrastim support (300 μg s.c. daily) from day 2 to 24 h before the next treatment. Results: Thirty-five (90%) patients completed all planned therapy. The median intertreatment interval was 10 days (range, 8-28 days). Cycles (80.7%) were delivered at no more than 10- to 11-day intervals. There were five dose reductions of 25% for grade 3 nonhematologic toxicity in five patients. Six (16%) patients developed febrile neutropenia defined as temperature &amp;gt;38°C with absolute neutrophil count &amp;lt;1,000/μL. All febrile neutropenia was during therapy with EC. Other grade 3 toxicities included bone pain, hand and foot syndrome, neuropathy, mucositis, nausea, and vomiting. Conclusions: Therapy with EC for four cycles followed by paclitaxel for four cycles at 10- to 11-day intervals is feasible. The ∼30% reduction in intertreatment interval compared with every 14-day treatment could increase the efficacy of adjuvant chemotherapy.
Recurrent fever after a holiday in Turkey
Authors: A. Egli, N. Khanna, T. Schmid, S. Rudin, R. Frei, A. Blaich
Journal: BMJ (2011)

In early October 2010, a 64 year old man presented to our hospital with chest pain, fever, and night sweats, which had been present since his return to Switzerland three weeks earlier. He had been on holiday in Turkey from July to mid-September. On further questioning he reported an episode of diarrhoea and sickness associated with fever shortly after returning home to Switzerland. During his stay in Turkey he had eaten fresh food, including meat and dairy products. Furthermore, he had experienced a myocardial infarction and had undergone angiography and insertion of a bare metal stent on 4 September while in Turkey. Previously he had been treated with a calcium channel blocker and an angiotensin II receptor antagonist because of high blood pressure. On admission, aspartate aminotransferase at 79 U/L (reference range 11-36), alanine aminotransferase at 86 U/L (10-37), γ glutamyltransferase at 192 U/L (11-66), alkaline phosphatase at 238 U/L (0-129), and C reactive protein (CRP) at 25.4 mg/L (0-10) were all slightly raised. Stenosis of the right coronary artery was seen on angiography and another stent was inserted. Over the next seven days he developed recurrent fevers, which were accompanied by chills and temperatures as high as 39.5°C. Ten of 13 aerobic blood cultures taken at three to 10 days after presentation grew very small Gram negative rods two and a half to three days after incubation. Bloods taken during this time showed a normal white cell count and slightly decreased haemoglobin of 130 g/L (140-180). An abdominal ultrasound showed an enlarged spleen and mild hepatosteatosis. Computed tomography of the chest and abdomen and transoesophageal echocardiography were performed to look for a source of infection, but all were uninformative.
Imatinib mesylate therapy in newly diagnosed patients with Philadelphia chromosome–positive chronic myelogenous leukemia: high incidence of early complete and major cytogenetic responses
Authors: Hagop M. Kantarjian, Jorge E. Cortes, Susan O'Brien, Francis Giles, Guillermo Garcia-Manero, Stefan Faderl, Deborah Thomas, Sima Jeha, Mary Beth Rios, Laurie Letvak, Kathy Bochinski, Ralph Arlinghaus, Moshe Talpaz
Journal: Blood (2002)
Lymphoreticular Tumors in Argentina&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;
Authors: P. Correa, G. T. O'Conor, Santiago Besuschio, Carlos Ghinelli
Journal: JNCI Journal of the National Cancer Institute (1973)

Diagnoses of lymphoreticular tumors in 5 medical centers of Buenos Aires were reviewed, and Hodgkin's disease subtypes were reclassified according to the Rye classification. Hodgkin's disease was found to be the most frequent solid lymphoma. Lymphosarcoma and reticulum cell sarcoma increased in frequency with age. Hodgkin's disease was distributed bimodally, with peaks in young adults and in the aged. All lymphomas developed more frequently in males than in females. The frequency of subtypes of Hodgkin's disease differed, probably representing urban-rural extraction of the population.
What do under 15 year old schoolboy rugby union players think about protective headgear?
Authors: C F Finch, A S McIntosh, P McCrory
Journal: British Journal of Sports Medicine (2001)

Objectives —When protective headgear is designed, the attitudes of the intended users needs to be taken into account, as well as safety performance criteria. The aim of this study was therefore to determine the attitudes of schoolboy rugby union players towards protective headgear. Methods —A survey of 140 rugby union players (82.4% response rate) from 10 randomly selected school teams in metropolitan Sydney was conducted at the end of the 1999 playing season. All players were aged 14–16 years. All teams had participated in a trial of headgear during the 1999 season in which six of the teams had been assigned to a headgear trial arm and four teams to a control arm. Players completed a self report questionnaire during a supervised session at school. The questionnaire collected information on recent head injuries, use of protective equipment, and attitudes towards headgear. Results —Some form of protective equipment was always worn by 76.1% of players: 93.6% reported using a mouthguard and 79.3% a helmet/headgear during the 1999 season. The two most important reasons for wearing headgear were related to safety concerns. Players with no recent head/neck injury were more likely to report that they felt safer when wearing headgear (p&lt;0.001) and less likely to cite a previous injury as a motivating factor for wearing headgear (p&lt;0.001) than those who had sustained a recent head/neck injury. Of the players who wore headgear during the 1999 season, 67% said that they played more confidently when they wore headgear, but 63% said that their head was hotter. Few players reported that their head was uncomfortable (15%) or that it was hard to communicate (3%) when they wore headgear. The main reasons for not wearing headgear were related to its design features: uncomfortable (61%) and it was hot (57%). Conclusions —The primary reason cited by players for wearing headgear is safety. Receiving an injury would also motivate non-wearers to wear headgear. Players report that they are more confident and able to tackle harder if they wear headgear, suggesting that a belief in its protective capabilities may influence behaviour. These attitudes need to be addressed in the design of effective headgear as well as in strategies to promote its use.
The role of informed consent in tuberculosis testing and screening
Authors: Carl H. Coleman, Michael J. Selgelid, Andreas Reis, Lee B. Reichman, Ernesto Jaramillo
Journal: European Respiratory Journal (2012)

n December 2010, the World Health Organization (WHO) endorsed the use of a new DNA-based test for tuberculosis (TB), the Gene Xpert [1].This test is expected to revolutionise the care of TB and, especially, multidrug-resistant (MDR)-TB, by providing accurate diagnoses in less than 2 h [2].As healthcare professionals begin to incorporate rapid TB testing into clinical practice, questions about the need for informed consent will inevitably arise.Yet, despite decades of debate about informed consent to HIV testing and screening [3], informed consent to TB testing and screening has received virtually no discussion in the ethical or legal literature.In this editorial, we argue that, in most situations, TB testing and screening does not require a specific informed consent process, but that patients should be notified about testing and given the opportunity to object.If an objection is raised, the burden should be on those proposing coercive testing to show that the expected public health benefits are sufficient to justify overriding the individual's choice.We conclude by identifying limited circumstances in which specific informed consent to TB testing should be required.
Sport-Related Sudden Natural Death in the City of Birmingham
Authors: R M Whittington, A Banerjee
Journal: Journal of the Royal Society of Medicine (1994)

We undertook a prospective study of all consecutive deaths reported to the Coroner for Birmingham and Solihull in a 5 year period. We identified 52 sudden deaths associated with symptoms commencing during sport participation. We studied the characteristics of these individuals. The majority had been performing at accustomed levels of activity without symptoms for several years. The extrapolation of our findings to preventive strategies remains unclear but we wish to highlight the importance of recognizing premonitory effort-related symptoms.
Lessons from Cost-Effectiveness Research for United States Public Health Policy
Authors: Scott D. Grosse, Steven M. Teutsch, Anne C. Haddix
Journal: Annual Review of Public Health (2007)

The application of cost-effectiveness analysis to health care has been the subject of previous reviews. We address the use of economic evaluation methods in public health, including case studies of population-level policies, e.g., environmental regulations, injury prevention, tobacco control, folic acid fortification, and blood product safety, and the public health promotion of clinical preventive services, e.g., newborn screening, cancer screening, and childhood immunizations. We review the methods used in cost-effectiveness analysis, the implications for cost-effectiveness findings, and the extent to which economic studies have influenced policy and program decisions. We discuss reasons for the relatively limited impact to date of economic evaluation in public health. Finally, we address the vexing question of how to decide which interventions are cost effective and worthy of funding. Policy makers have funded certain interventions with rather high cost-effectiveness ratios, notably nucleic acid testing for blood product safety. Cost-effectiveness estimates are a decision aid, not a decision rule.
Recommended Guidelines for the Treatment of Cancer Treatment-Induced Diarrhea
Authors: Al B. Benson, Jaffer A. Ajani, Robert B. Catalano, Constance Engelking, Steven M. Kornblau, James A. Martenson, Richard McCallum, Edith P. Mitchell, Thomas M. O'Dorisio, Everett E. Vokes, Scott Wadler
Journal: Journal of Clinical Oncology (2004)

To update and expand on previously published clinical practice guidelines for the treatment of cancer treatment-induced diarrhea.An expert multidisciplinary panel was convened to review the recent literature and discuss recommendations for updating the practice guidelines previously published by this group in the Journal of Clinical Oncology in 1998. MEDLINE searches were performed and the relevant literature published since 1998 was reviewed by all panel members. The treatment recommendations and algorithm were revised by panel consensus.A recent review of early toxic deaths occurring in two National Cancer Institute-sponsored cooperative group trials of irinotecan plus high-dose fluorouracil and leucovorin for advanced colorectal cancer has led to the recognition of a life-threatening gastrointestinal syndrome and highlighted the need for vigilant monitoring and aggressive therapy for this serious complication. Loperamide remains the standard therapy for uncomplicated cases. However, the revised guidelines reflect the need for recognition of the early warning signs of complicated cases of diarrhea and the need for early and aggressive management, including the addition of antibiotics. Management of radiation-induced diarrhea is similar but may not require hospitalization, and chronic low- to intermediate-grade symptoms can be managed with continued loperamide.With vigilant monitoring and aggressive therapy for cancer treatment-induced diarrhea, particularly in patients with early warning signs of severe complications, morbidity and mortality may be reduced.
Splicing Factor hnRNP A2/B1 Regulates Tumor Suppressor Gene Splicing and Is an Oncogenic Driver in Glioblastoma
Authors: Regina Golan-Gerstl, Michal Cohen, Asaf Shilo, Sung-Suk Suh, Arianna Bakàcs, Luigi Coppola, Rotem Karni
Journal: Cancer Research (2011)

Abstract The process of alternative splicing is widely misregulated in cancer, but the contribution of splicing regulators to cancer development is largely unknown. In this study, we found that the splicing factor hnRNP A2/B1 is overexpressed in glioblastomas and is correlated with poor prognosis. Conversely, patients who harbor deletions of the HNRNPA2B1 gene show better prognosis than average. Knockdown of hnRNP A2/B1 in glioblastoma cells inhibited tumor formation in mice. In contrast, overexpression of hnRNP A2/B1 in immortal cells led to malignant transformation, suggesting that HNRNPA2B1 is a putative proto-oncogene. We then identified several tumor suppressors and oncogenes that are regulated by HNRNPA2B1, among them are c-FLIP, BIN1, and WWOX, and the proto-oncogene RON. Knockdown of RON inhibited hnRNP A2/B1 mediated transformation, which implied that RON is one of the mediators of HNRNPA2B1 oncogenic activity. Together, our results indicate that HNRNPA2B1 is a novel oncogene in glioblastoma and a potential new target for glioblastoma therapy. Cancer Res; 71(13); 4464–72. ©2011 AACR.
Collagen type I 1 Sp1 polymorphism, osteoporosis, and intervertebral disc degeneration in older men and women
Authors: S M F Pluijm
Journal: Annals of the Rheumatic Diseases (2003)

To examine whether collagen type I alpha1 (COLIA1) Sp1 polymorphism is associated with osteoporosis and/or intervertebral disc degeneration in older people.COLIA1 genotype was determined in 966 men and women (>/=65 years) of the Longitudinal Aging Study Amsterdam. The guanine (G) to thymidine (T) polymorphism in the first intron of the COLIA1 gene was detected by PCR and MscI digestion. In the total sample, quantitative ultrasound (QUS) measurements, serum osteocalcin (OC), and urine deoxypyridinoline (DPD/Cr(urine)) were assessed. A follow up of fractures was done every three months. In a subsample, total body bone mineral content (n = 485) and bone mineral density (BMD) of the hip and lumbar spine (n = 512) were measured by dual energy x ray absorptiometry (DXA). Prevalent vertebral deformities and intervertebral disc degeneration were identified on radiographs (n = 517).People with the TT genotype had a higher risk of disc degeneration than those with the GG and GT genotypes (OR = 3.6; 95% CI 1.3 to 10). For men, higher levels of OC were found in those with the T allele than in those without it (GG v (GT+TT) 1.96 (0.06) nmol/l v 2.19 (0.09) nmol/l). COLIA1 polymorphism was not significantly associated with other measures of osteoporosis in either men or women.COLIA1 Sp1 polymorphism may be a genetic risk factor related to intervertebral disc degeneration in older people. Previously reported associations between the COLIAI Sp1 genotype and lower BMD or QUS values, higher levels of DPD/Cr, and an increased fracture risk in either men or women could not be confirmed.