tbuckley/cabot-search huggingface dataset:
Ductal Carcinoma in Situ: State of the Science and Roadmap to Advance the Field
Authors: Henry M. Kuerer, Constance T. Albarracin, Wei T. Yang, Robert D. Cardiff, Abenaa M. Brewster, W. Fraser Symmans, Nola M. Hylton, Lavinia P. Middleton, Savitri Krishnamurthy, George H. Perkins, Gildy Babiera, Mary E. Edgerton, Brian J. Czerniecki, Banu K. Arun, Gabriel N. Hortobagyi
Journal: Journal of Clinical Oncology (2008)

Ductal carcinoma in situ (DCIS) is the fourth leading cancer for women in the United States. Understanding of the biology and clinical behavior of DCIS is imperfect. This article highlights the current knowledge base and the scientific roadmap needed to advance the field.This article is based on work done by and consultations obtained from leading experts in the field over a 6-month period that culminated in a full-day symposium designed to systematically review the most pertinent MEDLINE published reports and develop a roadmap to elucidate the molecular steps of carcinogenesis, reduce the extent or prevent the need for therapies, eliminate recurrences, and reduce morbidity.Expression profiling of pure DCIS will help elucidate the molecular characteristics that distinguish high-risk lesions from clinically irrelevant lesions. The development of new methods of extracting RNA from processed tissues may provide opportunities for research. Mammography often underestimates the pathologic extent of DCIS; other imaging methods need to be investigated for detection and monitoring of disease stability or progression. Novel biologic agents are being delivered in neoadjuvant clinical trials, and alternative methods for breast irradiation are being studied. Future trials of treatment versus no treatment for biologically selected cases of DCIS should be developed.There is a critical need for a concerted international effort among patients with DCIS, clinicians, and basic scientists to conduct the research necessary to improve fundamental understanding of the biology and clinical behavior of DCIS and prevent development of invasive breast cancer.
Fluticasone propionate in children with moderate asthma.
Authors: M O Hoekstra, M H Grol, K Bouman, T Stijnen, G H Köeter, H F Kauffman, J Gerritsen
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Inhaled corticosteroids are considered to be effective and safe to treat children with asthma. These drugs, often used as maintenance treatment, can, however, influence the HPA-axis, which might be reflected by the serum and urine cortisol concentration. The aim of the present study was to investigate the efficacy and safety of fluticasone propionate (FP) 100 microg administered twice a day via a Diskhaler for 3 mo. FP was tested in a double-blind randomized placebo-controlled parallel trial in a group of 34 children with moderate asthma who did not use inhaled steroids for at least 4 wk prior to the study. At home, symptoms and peak flow recordings (PEFR) were noted in a diary. At each visit lung function was measured, and serum and urinary cortisol were determined. During treatment, wheezing decreased and PEFR values increased in the FP group. FEV1 and PC20-histamine increased and the reversibility decreased in the FP group. All changes were significant, with the exception of the change in nocturnal PEFR. Four weeks after cessation of FP all parameters returned to pretreatment values. Serum cortisol did not change significantly in either treatment group. The decrease in urinary cortisol in the FP group was significant only if it was compared with the increase in urinary cortisol in the placebo group. We conclude that FP 100 microg given twice a day is effective in children with moderate stable asthma. Suppression of the HPA-axis by FP 100 microg given twice daily, although not likely, cannot be ruled out by this study since the absence of a significant decrease in urinary cortisol in the FP group could be due to an insufficient number of patients. Additional studies are required to solve this problem.
Hyperexpression of the granzyme B inhibitor PI-9 in human renal allografts: A potential mechanism for stable renal function in patients with subclinical rejection
Authors: Ajda T. Rowshani, Sandrine Florquin, Frederike Bemelman, J. Alain Kummer, C. Erik Hack, Ineke J.M. Ten Berge
Journal: Kidney International (2004)
Antiretroviral Therapy for Prevention of Tuberculosis in Adults with HIV: A Systematic Review and Meta-Analysis
Authors: Amitabh B. Suthar, Stephen D. Lawn, Julia del Amo, Haileyesus Getahun, Christopher Dye, Delphine Sculier, Timothy R. Sterling, Richard E. Chaisson, Brian G. Williams, Anthony D. Harries, Reuben M. Granich
Journal: PLoS Medicine (2012)

In a systematic review and meta-analysis, Amitabh Suthar and colleagues investigate the association between antiretroviral therapy and the reduction in the incidence of tuberculosis in adults with HIV infection.
Senescent Fibroblasts in Melanoma Initiation and Progression: An Integrated Theoretical, Experimental, and Clinical Approach
Authors: Eunjung Kim, Vito Rebecca, Inna V. Fedorenko, Jane L. Messina, Rahel Mathew, Silvya S. Maria-Engler, David Basanta, Keiran S.M. Smalley, Alexander R.A. Anderson
Journal: Cancer Research (2013)

We present an integrated study to understand the key role of senescent fibroblasts in driving melanoma progression. Based on the hybrid cellular automata paradigm, we developed an in silico model of normal skin. The model focuses on key cellular and microenvironmental variables that regulate interactions among keratinocytes, melanocytes, and fibroblasts, key components of the skin. The model recapitulates normal skin structure and is robust enough to withstand physical as well as biochemical perturbations. Furthermore, the model predicted the important role of the skin microenvironment in melanoma initiation and progression. Our in vitro experiments showed that dermal fibroblasts, which are an important source of growth factors in the skin, adopt a secretory phenotype that facilitates cancer cell growth and invasion when they become senescent. Our coculture experiments showed that the senescent fibroblasts promoted the growth of nontumorigenic melanoma cells and enhanced the invasion of advanced melanoma cells. Motivated by these experimental results, we incorporated senescent fibroblasts into our model and showed that senescent fibroblasts transform the skin microenvironment and subsequently change the skin architecture by enhancing the growth and invasion of normal melanocytes. The interaction between senescent fibroblasts and the early-stage melanoma cells leads to melanoma initiation and progression. Of microenvironmental factors that senescent fibroblasts produce, proteases are shown to be one of the key contributing factors that promoted melanoma development from our simulations. Although not a direct validation, we also observed increased proteolytic activity in stromal fields adjacent to melanoma lesions in human histology. This leads us to the conclusion that senescent fibroblasts may create a prooncogenic skin microenvironment that cooperates with mutant melanocytes to drive melanoma initiation and progression and should therefore be considered as a potential future therapeutic target. Interestingly, our simulations to test the effects of a stroma-targeting therapy that negates the influence of proteolytic activity showed that the treatment could be effective in delaying melanoma initiation and progression.
Protein phosphatase 1 modulation of neostriatal AMPA channels: regulation by DARPP–32 and spinophilin
Authors: Zhen Yan, Linda Hsieh–Wilson, Jian Feng, Kazuhito Tomizawa, Patrick B. Allen, Allen A. Fienberg, Angus C. Nairn, Paul Greengard
Journal: Nature Neuroscience (1999)
Coronary Thrombosis and Its Response to Treatment
Authors: A. R. Gilchrist
Journal: BMJ (1952)

CORONARY THROMBOSISfor acute coronary insufficiency.The patient already handicapped by angina pectoris is always suspect.Any unusual, unexpected, or unprovoked attack of his pain may well prove to be an actual occlusion, if not premonitory of a major disaster in the immediate future.To establish the diagnosis of infarc- tion a search should be made for signs of tissue destruc- tion, and among these the practitioner, when other
Differential Mortality and Transplantation Rates among Asians and Pacific Islanders with ESRD
Authors: Yoshio N. Hall, Jared G. Sugihara, Alan S. Go, Glenn M. Chertow
Journal: Journal of the American Society of Nephrology (2005)

Few studies in patients with ESRD have examined outcomes in Asian or Pacific Islander subgroups compared with white individuals. The objective of this study was to assess ethnic disparities in mortality and kidney transplantation among a multiethnic cohort of incident dialysis patients. A total of 24,963 patients who initiated dialysis within the TransPacific Renal Network (Network 17) between April 1, 1995, and September 30, 2001, were studied to ascertain death and kidney transplantation through September 30, 2002. Overall, 12,902 deaths and 2258 kidney transplantations were observed during 59,075 person-years of follow-up. Mortality on dialysis among Asians and Pacific Islanders (except Chamorros) was lower than that of white individuals after controlling for differences in sociodemographic characteristics, comorbid conditions, and other risk factors for death (adjusted hazard ratio [95% confidence interval] versus white individuals: Japanese 0.64 [0.57 to 0.72], Chinese 0.64 [0.52 to 0.78], Filipino 0.64 [0.57 to 0.72], Native Hawaiian 0.84 [0.72 to 0.96], Samoan 0.62 [0.48 to 0.82], and Chamorro 0.96 [0.84 to 1.20]). In contrast, Asians and Pacific Islanders were much less likely to undergo kidney transplantation (adjusted rate ratio [95% confidence interval] versus white individuals: Japanese 0.34 [0.24 to 0.46], Chinese 0.54 [0.30 to 0.88], Filipino 0.32 [0.26 to 0.47], Native Hawaiian 0.17 [0.10 to 0.30], Samoan 0.17 [0.07 to 0.38], and Chamorro 0.04 [0.01 to 0.14]). Despite wide variations in primary cause of ESRD, clinical characteristics, and body size at dialysis initiation, Asians and Pacific Islanders experience better survival but substantially lower transplantation rates compared with white individuals. Strategies that are aimed at improving access to transplantation in Asian and Pacific Islander communities may further enhance survival among Asians and Pacific Islanders with ESRD.
Serum and pancreatic juice carcinoembryonic antigen in pancreatic and biliary disease.
Authors: D L Carr-Locke
Journal: Gut (1980)

Serum and pancreatic juice carcinoembryonic antigen (CEA) concentrations were studied in a group of 144 patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) with a variety of benign and malignant pancreatic and biliary diseases. Serum CEA was found to be a poor diagnostic and discriminating marker for pancreatic disorders and was raised in obstructive jaundice from various causes correlating with serum alkaline phosphatase. A pancreatic juice CEA concentration of greater than 106 mcg/l was associated with pancreatic disease but did not distinguish benign from malignant lesions. Criteria derived from pancreatic juice volumes and bicarbonate responses provided additional diagnostic differentiation of normal from pancreatic disease but not cancer from pancreatitis. Pancreatic juice CEA may have a limited application where imaging techniques have failed or are not available and additional study of pancreatic juice biochemistry is required before adequate diagnostic criteria can be established.
Bisphosphonates in bone cement inhibit PMMA particle induced bone resorption
Authors: A. Sabokbar, Y. Fujikawa, D. W Murray, N. A Athanasou
Journal: Annals of the Rheumatic Diseases (1998)

<h3>OBJECTIVE</h3> Wear particle induced bone resorption is thought to be one of the mechanisms that contribute to implant loosening. It has previously been shown that macrophages, in response to polymethylmethacrylate (PMMA) particles, differentiate into bone resorbing osteoclasts, and that this process is inhibited by a bisphosphonate, etidronate (EHDP). The aim of this study was to determine whether incorporating EHDP in bone cement could reduce PMMA associated bone resorption. <h3>METHODS</h3> Two concentrations of EHDP were mixed with PMMA monomer before polymerisation. Particles of PMMA (1–10 μm) were generated then added to mouse monocytes cocultured with UMR106 rat osteoblast-like cells and the extent of osteoclast differentiation was determined by assessing the extent of tartrate resistant acid phosphatase (TRAP) staining and measuring the amount of lacunar bone resorption. <h3>RESULTS</h3> The addition of PMMA to monocyte-UMR106 cocultures resulted in a marked increase in the number of TRAP positive osteoclast-like cells and a significant increase in the number of lacunar resorption pits compared with control cultures to which no particles had been added. After the addition of particles of PMMA + 20 mg EHDP, significantly fewer lacunar pits (p=0.00006) and fewer TRAP positive cells were noted compared with cocultures containing PMMA particles alone. <h3>CONCLUSIONS</h3> These results indicate that by mixing a bisphosphonate with bone cement, it is possible to inhibit PMMA particle induced bone resorption. This bisphosphonate inhibition of PMMA biomaterial wear particle containing macrophage-osteoclast differentiation and bone resorption may provide a possible therapeutic strategy to prevent or to control the osteolysis of aseptic loosening.
Diagnosis of Celiac Disease in Adults Based on Serology Test Results, Without Small-Bowel Biopsy
Authors: Jamile' Wakim–Fleming, Mangesh R. Pagadala, Martin S. Lemyre, Rocio Lopez, Arthi Kumaravel, William D. Carey, Nizar N. Zein
Journal: Clinical Gastroenterology and Hepatology (2013)
Neutrophil Count in African Americans: Lowering the Target Cutoff to Initiate or Resume Chemotherapy?
Authors: Matthew M. Hsieh, John F. Tisdale, Griffin P. Rodgers, Neal S. Young, Edward L. Trimble, Richard F. Little
Journal: Journal of Clinical Oncology (2010)

Inclusion and exclusion criteria for participation in clinical trials are meant to select patients who are appropriate for the disease under study and to protect clinical research subjectparticipants from undue risk related to the research. The selection criteria should not arbitrarily exclude subjects. In 1994, the National Institutes of Health (NIH) published guidelines on the inclusion of women and minorities in clinical trials. The guidelines were intended to ensure that women and members of minorities are included in all human subject research and specified that concerns for cost could not be viewed as an acceptable reason for excluding these groups. It is thus incumbent on researchers to ensure that undue barriers are not placed on groups of individuals that would cause their underrepresentation in publicly funded clinical research. Toward meeting these goals, the guidelines called for the initiation of programs and support for outreach efforts to recruit underrepresented groups into clinical studies. Although these efforts have led to the increased participation in some instances of previously excluded groups onto clinical trials, there may be circumstances where eligibility criteria can exclude participation of certain groups disproportionately. 1-4 Rigid requirement for minimal WBC numbers may be one such criterion deserving of further consideration in this regard. Benign ethnic neutropenia (BEN) is a condition used to describe individuals ofAfricandescentwithneutrophilcountslessthan1.510 9 cells/Lin theabsenceofothercauses 5 andconstitutesonesuchgroupforwhom minimalWBCnumbersmayarbitrarilyexcludefromparticipationin clinical trials. The risk of febrile neutropenia is determined by the durationanddepthofneutropenia,withtheriskgreatestwhenthe neutrophils are below 0.5 10 9 cells/L. 6-8 There are currently insufficientdatatoindicatethatindividualswithBENwouldfacea higher risk of febrile neutropenia greater than those without BEN. Therefore, BEN may unduly exclude clinical trials participation in a greater proportion of individuals from certain ethnic groups compared with others. It follows that exclusion of individuals with BENmaybeatoddswithNIHguidelinesaimedtowardenhancing
Role of CT in assessing pleural malignancy prior to thoracoscopy: Table 1
Authors: R J Hallifax, M Haris, J P Corcoran, S Leyakathalikhan, E Brown, D Srikantharaja, A Manuel, F V Gleeson, M Munavvar, N M Rahman
Journal: Thorax (2014)

The definitive diagnosis of pleural malignancy depends upon histological confirmation by pleural biopsy. CT is reported to have a high sensitivity and specificity for the diagnosis of malignant pleural disease, and is part of the routine diagnostic workup of these patients. The aim of this study was to assess the sensitivity and specificity of CT in detecting pleural malignancy prior to definitive histology obtained via thoracoscopy in a large cohort of patients with suspected malignant pleural disease. Retrospective review of thoracoscopies between January 2008 and January 2013 at two UK tertiary referral centres: Oxford and Preston. The histological results were compared with the CT reported diagnosis before the procedure. CT scan reports were assessed by independent respiratory physicians as to whether the radiologist concluded evidence of malignant pleural disease or benign features only. 211 (57%) of 370 patients included in the analysis had malignant disease: CT scans were reported as 'malignant' in 144, giving a sensitivity of 68% (95% CI 62% to 75%). Of the 159 patients with benign disease, 124 had CT scans reported as benign: specificity 78% (72% to 84%). The positive predictive value of a malignant CT report was 80% (75% to 86%), with a negative predictive value of 65% (58% to 72%). A significant proportion of patients being investigated for malignant disease will have malignancy despite a negative CT report. The use of CT alone in determining which patients should have invasive pleural biopsies should be re-evaluated, and further studies to define the diagnostic pathway are now required.
The case for knowledge translation: shortening the journey from evidence to effect
Authors: D. Davis
Journal: BMJ (2003)

A large gulf remains between what we know and what we practise.Eisenberg and Garzon point to widespread variation in the use of aspirin, calcium antagonists, blockers, and anti-ischaemic drugs in the United States, Europe, and Canada despite good evidence on their best use. 1 Such variation is common not only internationally but within countries. 2Large gaps also exist between best evidence and practice in the implementation of guidelines.Failure to follow best evidence highlights issues of underuse, overuse, and misuse of drugs 3 and has led to widespread interest in the safety of patients. 4ot surprisingly, many attempts have been made to reduce the gap between evidence and practice.These have included educational strategies to alter practitioners' behaviour 5 and organisational and administrative interventions.We explore three constructs: continuing medical education (CME), continuing professional development (CPD), and (the newest of the three) knowledge translation (box).Knowledge translation both subsumes and broadens the concepts of CME and CPD and has the potential to improve understanding of, and overcome the barriers to, implementing evidence based practice. Concepts of CME and CPDContinuing medical education CME refers to education after certification and licensure.It is arguably the most complex, and clearly the longest, phase of medical education.Most physicians think of continuing medical education in terms of the traditional medical conference, with rows of tables, pitchers of ice water, green table cloths, and a lecturer at the front of the room. 7Many accreditation systems in the United States, United Kingdom, and Canada value attendance at such activities.This reinforces the teacher driven nature of continuing medical education, which gives little attention to the concept of professional development. Continuing professional developmentCPD embodies both professional learning and personal growth.It incorporates much of the theory and practice of adult learning, 8 self directed learning, 9 reflective practice, 10 and other models.It also offers the possibility of embracing topics beyond those included in traditional medical education-for example, bioethics, business management, and communication skills-topics rarely included in continuing medical education programmes. 11Although the focus on subjective, learner centred curriculums is laudable, it means that continuing professional development can contribute only marginally to improving public health.
Survival after myocardial infarction in the rat. Role of tissue angiotensin-converting enzyme inhibition.
Authors: K C Wollert, R Studer, B von Bülow, H Drexler
Journal: Circulation (1994)

Chronic treatment with high doses of angiotensin-converting enzyme (ACE) inhibitors prolongs survival after myocardial infarction. Since the plasma renin-angiotensin system (RAS) is not consistently activated in the chronic phase after myocardial infarction, the beneficial effects of ACE inhibition have been attributed, in part, to inhibition of an activated tissue RAS. However, a relation between tissue ACE inhibition and long-term efficacy (ie, concerning left ventricular [LV] hypertrophy and survival) has not been established. The present study was designed to evaluate the impact of low-dose ACE inhibition (predominant inhibition of plasma ACE) and high-dose ACE inhibition associated with substantial tissue ACE inhibition) on reversal of LV hypertrophy and 1-year mortality after myocardial infarction in the rat.Infarcted rats were randomized to placebo, low-dose lisinopril, or high-dose lisinopril (each, n = 80) and compared with sham-operated animals (n = 40). In a separate group of animals, tissue ACE activity was determined after 6 weeks of therapy, demonstrating that both regimens were effective with regard to both plasma and pulmonary ACE inhibition; however, only high-dose lisinopril inhibited renal ACE. Neither dose affected LV ACE activity and ACE mRNA levels as determined by competitive polymerase chain reaction, whereas LV ANF mRNA levels were significantly reduced by high-dose lisinopril. High-dose lisinopril reduced arterial blood pressure and normalized right ventricular and LV weight and resulted in a substantial reduction of 1-year mortality, whereas the low dose did not (1 year mortality: placebo, 56.3%; low dose, 53.3%; high dose, 22.9%, P < .0001 versus low dose and versus placebo).Hemodynamically effective ACE inhibition is required for reduction of LV hypertrophy and long-term mortality after myocardial infarction in the rat. Sustained inhibition of renal ACE during long-term therapy may contribute to the beneficial effect of high-dose lisinopril. Low-dose lisinopril, although exerting sustained inhibition of the plasma ACE, does not improve survival after myocardial infarction.