tbuckley/cabot-search huggingface dataset:
Phase II trial of docetaxel (D) and high-dose celecoxib (C) in patients (Pts) with hormone resistant prostate cancer (HRPC)
Authors: B. Kasimis, J. Cogswell, S. Hwang, V. Chang, M. Llorente, I. Boholli, S. Srinivas, E. Morales, C. Davis, M. Blumenfrucht
Journal: Journal of Clinical Oncology (2004)

4616 Background: COX-2 is an inducible enzyme, which converts arachidonic acid to prostaglandins. COX-2 is over expressed in 89.3% of our pts with prostate cancer and is an independent predictor of survival (Cogswell et al; Proc ASCO 2003, #1675). Both D and C are angiogenesis inhibitors and induce apoptosis; their combination could be synergistic. In an ongoing pilot trial we determined the effects on PSA, Overall Response(OR), toxicity, and survival. Methods: Eighteen (18) pts with HRPC progressing by rising PSA and radiographic manifestations were treated with D 30mg/m2 IV over 30min,weekly for 3 wks and C 400mg po bid daily of each 4wk cycle. All pts were assessed by PSA and radiological tests every 2 cycles. Dose modifications for hematologic, hepatic and renal toxicity were made. Detailed renal function tests were assessed by a nephrologist. The RECIST criteria and PSA decline by ≥50% were used. Sample size was determined by Simon's Optimal Two-Stage design. Results: The median age was 73.5 years(55–94), ECOG PS 1(0–1),LDH 180.5 U/L(125–899 ), Hgb 11.9g/dL (8.6–14.6), PSA 215.8 ng/dL (28.5–2675). The median number of cycles was 3(2–6).The median follow up was 6 mos (2–11+). Soft tissue metastases were present in 15 pts (83.3%) and bone metastases in 17 pts (94.4 %). Seventeen(17)pts are evaluable for response. Of these, 11 pts(64.7%) had PSA responses and the PSA normalized in 4pts (23.5%).Soft tissue responses were seen in 5(2CR's + 3PR's)pts(29.4%)and SD in 5pts(29.4%). One pt(5.9%) had an impressive bone scan response. The OR for 11pts was 64.7%. One pt withdrew due to abdominal pain, 2pts(11.7%) had grade III diarrhea and one had grade III nail changes. There was excellent renal tolerance (Yudd et al; Proc ASCO 2004 subm ). Conclusions: The combination of D and C is well tolerated. The OR rate was 64.7%. PSA decline by≥50%, PSA normalization, soft tissue, and bone scan responses were demonstrated. Further accrual and longer follow up will determine its full impact in pts with HRPC. (Supported by Aventis and Pfizer). Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Aventis
Perinatal loss and parental bereavement
Authors: S K Theut, F A Pedersen, M J Zaslow, R L Cain, B A Rabinovich, J M Morihisa
Journal: American Journal of Psychiatry (1989)

The authors studied 25 middle-class pregnant women and their husbands who had experienced perinatal losses (16 miscarriages, seven stillbirths, and two neonatal deaths) within the previous 2 years. The Perinatal Bereavement Scale was designed to determine whether parents who have experienced a late perinatal loss (stillbirth or neonatal death) display more unresolved grief during a subsequent pregnancy and during the postnatal period than parents who have experienced a miscarriage. A three-factor repeated measures analysis of variance indicated significantly greater grief for the late-loss group, for the mothers, and during the pregnancy preceding the birth of the viable child.
Characterization of an in vitro model of human melanoma invasion based on reconstructed human skin
Authors: P. Eves, C. Layton, S. Hedley, R.A. Dawson, M. Wagner, R. Morandini, G. Ghanem, S. Mac Neil
Journal: British Journal of Dermatology (2000)

The purpose of this study was to compare the invasive properties of normal human cutaneous melanocytes and of a cutaneous melanoma cell line (HBL) in a three-dimensional model of reconstructed human skin. Specifically, we asked to what extent the pigmentary and invasive behaviour of both cells is influenced by their interaction with adjacent skin cells (keratinocytes and fibroblasts) and the basement membrane (BM). In the presence of a BM, normal human melanocytes within this model remained within the basal layer of keratinocytes and did not pigment spontaneously. When the BM was removed, melanocytes were found suprabasally and pigmented extensively. No significant invasion of melanocytes into the dermis was detected in the presence or absence of the BM. HBL melanoma cells showed no significant ability to invade into the dermis in the absence of other cells, irrespective of the presence or absence of the BM. However, when added to keratinocytes and fibroblasts, HBL cells showed a capacity to invade into the dermis, both in the presence and absence of the BM. Associated with HBL invasion into the dermis, we noted significant keratinocyte entry into the dermis. On their own, keratinocytes entered the dermis in the absence of the BM but showed no significant penetration into the dermis when the BM was present. In summary, this model demonstrates clear differences between melanocytes and a melanoma cell line with respect to their invasive properties. It also allows demonstration of interactions between cells, and between cells and the BM. The study also provides evidence for a synergistic interaction between this melanoma cell line and keratinocytes in penetrating the BM.
Stimulating translational research: several European life science institutions put their heads together
Authors: Mohamed Bentires-Alj, Abinaya Rajan, Wim van Harten, Henri G.A.M. van Luenen, Stefan Kubicek, Jesper B. Andersen, Janna Saarela, Simon J. Cook, Geert Van Minnebruggen, Sergio Roman-Roman, Cornelia Maurer, Janine T Erler, Michela G. Bertero
Journal: Trends in Molecular Medicine (2015)
The Global Deterioration Scale for assessment of primary degenerative dementia
Authors: Reisberg B, Ferris Sh, de Leon Mj, Crook T
Journal: American Journal of Psychiatry (1982)

Cognitive decline associated with old age and consistent with the diagnosis of primary degenerative dementia is a unique clinical syndrome with characteristic phenomena and progression. The authors describe a Global Deterioration Scale for the assessment of primary degenerative dementia and delineation of its stages. The authors have used the Global Deterioration Scale successfully for more than 5 years and have validated it against behavioral, neuroanatomic, and neurophysiologic measures in patients with primary degenerative dementia.
Abstract 19538: Brief Exposure to Marijuana Secondhand Smoke Impairs Vascular Endothelial Function
Authors: Xiaoyin Wang, Ronak Derakhshandeh, Shilpa Narayan, Emmy Luu, Stephenie Le, Olivia M Danforth, Hilda J Rodriguez, Richard E Sievers, Suzaynn F Schick, Stanton A Glantz, Matthew L Springer
Journal: Circulation (2014)

Objectives: Despite general public awareness that tobacco secondhand smoke (SHS) is harmful, much of the public still regards marijuana SHS as benign. Because marijuana smoke and tobacco smoke are chemically and physically similar (other than nicotine and tetrahydrocannabinol (THC)), we tested this assumption by asking whether short exposure to marijuana SHS causes acute vascular endothelial dysfunction similar to that caused by tobacco SHS. Exposure to tobacco SHS impairs arterial flow-mediated dilation (FMD) in humans and rats. Methods: We used a rat model to test the effects of secondhand marijuana smoke on FMD. We exposed anesthetized rats to marijuana SHS using a modified cigarette smoking machine, and measured FMD three times: before 30-min exposure (“pre”), 10 min after end of exposure (“post10”), and 40 min after end of exposure (“post40”). FMD was measured by micro-ultrasound measurements of femoral artery diameter before and after transient (5 min) surgical ligation of the common iliac artery. C...
ClinGen — The Clinical Genome Resource
Authors: Heidi L. Rehm, Jonathan S. Berg, Lisa D. Brooks, Carlos D. Bustamante, James P. Evans, Melissa J. Landrum, David H. Ledbetter, Donna R. Maglott, Christa Lese Martin, Robert L. Nussbaum, Sharon E. Plon, Erin M. Ramos, Stephen T. Sherry, Michael S. Watson
Journal: New England Journal of Medicine (2015)

On autopsy, a patient is found to have hypertrophic cardiomyopathy. The patient’s family pursues genetic testing that shows a “likely pathogenic” variant for the condition on the basis of a study in an original research publication. Given the dominant inheritance of the condition and the risk of sudden cardiac death, other family members are tested for the genetic variant to determine their risk. Several family members test negative and are told that they are not at risk for hypertrophic cardiomyopathy and sudden cardiac death, and those who test positive are told that they need to be regularly monitored for cardiomyopathy on echocardiography. Five years later, during a routine clinic visit of one of the genotype-positive family members, the cardiologist queries a database for current knowledge on the genetic variant and discovers that the variant is now interpreted as “likely benign” by another laboratory that uses more recently derived population-frequency data. A newly available testing panel for additional genes that are implicated in hypertrophic cardiomyopathy is initiated on an affected family member, and a different variant is found that is determined to be pathogenic. Family members are retested, and one member who previously tested negative is now found to be positive for this new variant. An immediate clinical workup detects evidence of cardiomyopathy, and an intracardiac defibrillator is implanted to reduce the risk of sudden cardiac death.
Abstract 3198: The impact of aerobic exercise on oxygenation and vascularity in breast cancer models
Authors: Jennifer M. Wiggins, Jennifer A. Lee, Lori Rice, Dietmar Siemann
Journal: Cancer Research (2015)

Abstract Background: Intratumoral hypoxia (pO2 &amp;lt;10mmHg) is associated with aggressive tumor progression and poor patient outcome. It is often found in solid tumors, and can constitute a major obstacle to anticancer therapy. The primary cause of abnormal oxygen tensions in tumors is the aberrant tumor vasculature, characterized by tortuous, leaky and immature vessels. A number of intervention strategies designed to overcome tumor hypoxia have been investigated including high oxygen content breathing and the use of bioreductive prodrugs, but these have had only moderate success in the clinic. Purpose: The goal of the present investigations was to determine whether aerobic exercise could be applied as a means to improve tumor physiology and decrease tumor hypoxia in breast cancer models. Methods: The effects of single and repeated bouts of moderate intensity exercise (treadmill running) were studied in mice bearing syngeneic murine mammary carcinoma models (EMT6 and 4T1). The exercise intensities were determined by measuring the anaerobic threshold, which is reflected by the steady rise in blood lactate during an exercise bout. Mice were orthotopically injected with tumor cells and once the tumors reached a size of 250 mm3, the mice were exposed to either a single bout of exercise or daily exercise bouts performed for 5 consecutive days. Controls for each treatment consisted of sedentary mice exposed to a stationary treadmill for the equivalent amount of time. Following cessation of each exercise regime tumors were harvested, sectioned and evaluated by immunofluorescence. Vessel density (MECA-32), blood perfusion (Hoechst-33342) and hypoxia (EF5) were quantified and significance was established at p&amp;lt;0.05. Results: Preliminary data indicate that even a single exercise bout may begin to demonstrate improvements in blood vessel perfusion and tumor oxygenation. Importantly, after 5 daily bouts of exercise, there was a significant increase in the number of patent vessels and improvement in oxygenation in the tumors of exercising mice compared to those of sedentary controls. Conclusion: The results indicate that moderate aerobic exercise can improve the oxygenation status of solid tumors. These findings suggest that such a non-toxic intervention may have potential utility in overcoming hypoxia-associated treatment resistance in cancer patients and improve patient outcome. Citation Format: Jennifer M. Wiggins, Jennifer A. Lee, Lori Rice, Dietmar Siemann. The impact of aerobic exercise on oxygenation and vascularity in breast cancer models. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3198. doi:10.1158/1538-7445.AM2015-3198
Abstract 15347: Provider Type and Quality of Outpatient Cardiovascular Disease Care, Implications for the Affordable Care Act: Insights from the NCDR®PINNACLE Registry
Authors: Salim S Virani, Thomas M Maddox, Paul S Chan, Fengming Tang, Julia M Akeroyd, Samantha Risch, Anita Deswal, Biykem Bozkurt, Christie M Ballantyne, Laura A Petersen
Journal: Circulation (2014)

INTRODUCTION: Due to implementation of the Affordable Care Act (ACA), between 30-40 million Americans will be eligible to receive health care coverage. The current number of physicians may not be sufficient to accommodate this patient influx. One proposed solution is to utilize non-physicians (nurse practitioners [NPs] and physician assistants [PAs]) for chronic disease care delivery. It is not known whether the quality of care delivered by non-physicians is comparable to that delivered by physicians.

METHODS: Within the American College of Cardiology’s outpatient PINNACLE® registry, we compared the quality of coronary artery disease (CAD), heart failure (HF), and atrial fibrillation (AF) care delivered by physicians and non-physicians for outpatients with visits between January 1 and December 31, 2012. We performed hierarchical regression with further adjustment for provider gender, number of outpatient visits, and patient’s age, gender, and insurance.

RESULTS: We included 672 providers (540 physicians and 132 non-physicians [114 NPs, 18 PAs]) in 33 practices who cared for 279,770 patients. In adjusted analyses (Table), compliance with most CAD, HF, and AF measures was comparable between physicians and non-physicians, except a lower rate of beta-blocker use, antiplatelet therapy use, and cardiac rehabilitation referral among CAD patients receiving care from physicians compared with non-physicians. Results were consistent when comparing compliance with CAD, HF, and AF measures for practices with physician-only providers (n = 57) versus practices with both physicians and non-physicians (n = 33) (data not shown).

CONCLUSION: A collaborative care delivery model employing both physicians and non-physicians may deliver a comparable quality of outpatient cardiovascular care compared with a physician-only model. These results have implications for how resources are allocated for cardiovascular care delivery as more Americans access care under the ACA.

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2-Year Outcomes After Iliofemoral Self-Expanding Transcatheter Aortic Valve Replacement in Patients With Severe Aortic Stenosis Deemed Extreme Risk for Surgery
Authors: Steven J. Yakubov, David H. Adams, Daniel R. Watson, Michael J. Reardon, Neal S. Kleiman, David Heimansohn, James Hermiller, G. Chad Hughes, J. Kevin Harrison, Joseph Coselli, Jose Diez, Theodore Schreiber, Thomas G. Gleason, John Conte, G. Michael Deeb, Jian Huang, Jae Oh, Timothy Byrne, Michael Caskey, Jeffrey J. Popma
Journal: Journal of the American College of Cardiology (2015)
Using mortality reviews to shape future service planning
Authors: Sega Pathmanathan, Rebecca Dickinson, Simon Hart, Jaymin Morjaria
Journal: European Respiratory Journal (2013)

Introduction:  Clinical governance is an important part of service evaluation and future planning. To facilitate reflection and learning from inpatient care, we commenced a monthly meeting to discuss all deaths occurring on the respiratory unit.  Methods:  All deaths, between November 2010 to 2012 in the unit (60 inpatient including 6 high dependency beds), were reviewed in a monthly departmental meeting. In addition to cause of death, co-morbidities were collated for each patient.  Results:  There were 4560 admissions in the unit with 325 deaths (7.1% of all admissions). 123 deaths were related to COPD, 86 related to pneumonia, 61 to cancer and cardiac conditions contributed to 90 deaths. 253 cases (of which 210 were primarily respiratory) were reviewed and data included in the analysis. The most common cause of death (1a on death certificate) was pneumonia (76 deaths; 23.3% of all deaths). Of the respiratory deaths, COPD contributed 50 (19.8%), lung cancer 29 (11.5%) and fifty-five (22%) were caused by other primary respiratory conditions (e.g., pulmonary fibrosis, pulmonary embolism). Of note, cardiac conditions were the most frequent co-morbidity in respiratory deaths (74).  Conclusion:  Inpatient mortality meetings allow the members of the respiratory department to discuss challenging cases and learn from their outcomes with the aim of improving service provision. In total, smoking-related lung diseases contributed to 161 deaths (64%). The Hull and East Riding area has a higher smoking rate than the average in the UK (32% vs 22%). To combat this we have introduced an on-site smoking cessation service in the chest clinic and on all hospital wards with the aim of improving patient education, overall health, and reducing mortality.
Comparison of secular trends in pneumococcal serotypes causing invasive disease in Denver, Colorado (1971–2004) and serotype coverage by marketed pneumococcal vaccines
Authors: D. Akduman, J.M. Ehret, F.N. Judson
Journal: Clinical Microbiology and Infection (2006)

Invasive pneumococcal isolates from three hospitals in Denver, CO, USA were serotyped between 1971 and 2004. Serotype 14 was most common (13.2%), and other prevalent serotypes (3, 4, 6, 9 and 19) together accounted for 44.1% of the isolates. All prevalent serotypes and 91.3% of the total isolates were covered by pneumococcal polysaccharide vaccine, while 79.1% of prevalent serotypes and 56.7% of total isolates were covered by pneumococcal conjugate vaccine. Serotypes 6, 9 and 14 were more common in the final decade than in the first decade studied (37.3% vs. 20.2%), whereas serotypes 3 and 23 were more common in the first decade (18.5% vs. 11.0%).
ReEBOV Antigen Rapid Test kit for point-of-care and laboratory-based testing for Ebola virus disease: a field validation study
Authors: Mara Jana Broadhurst, John Daniel Kelly, Ann Miller, Amanda Semper, Daniel Bailey, Elisabetta Groppelli, Andrew Simpson, Tim Brooks, Susan Hula, Wilfred Nyoni, Alhaji B Sankoh, Santigi Kanu, Alhaji Jalloh, Quy Ton, Nicholas Sarchet, Peter George, Mark D Perkins, Betsy Wonderly, Megan Murray, Nira R Pollock
Journal: The Lancet (2015)
Cartilage T1ρ and T2 Relaxation Times in Patients With Mild‐to‐Moderate Radiographic Hip Osteoarthritis
Authors: Cory Wyatt, Deepak Kumar, Karupppasamy Subburaj, Sonia Lee, Lorenzo Nardo, Divya Narayanan, Drew Lansdown, Thomas Vail, Thomas M. Link, Richard B. Souza, Sharmila Majumdar
Journal: Arthritis & Rheumatology (2015)

Objective To analyze region‐specific T1ρ and T2 relaxation times of the hip joint cartilage in relation to presence or absence of radiographic hip osteoarthritis (OA) and presence or absence of magnetic resonance imaging (MRI)–detected cartilage defects. Methods Weight‐bearing radiographs and 3T MRI studies of the hip were obtained from 84 volunteers. Based on Kellgren/Lawrence (K/L) scoring of the radiographs, 54 subjects were classified as healthy controls (K/L grade ≤1) and 30 were classified as having mild or moderate radiographic hip OA (K/L grades 2 or 3, respectively). Two‐dimensional fat‐suppressed fast spin‐echo MRI sequences were used for semiquantitative clinical scoring of cartilage defects, and a T1ρ/T2 sequence was used to quantitatively assess the cartilage matrix. The femoral and acetabular cartilage was then segmented into 8 regions and the mean T1ρ/T2 values were calculated. Differences in T1ρ and T2 relaxation times were compared between subjects with and those without radiographic hip OA, and those with and those without femoral or acetabular cartilage defects. Results Higher T1ρ and T2 relaxation times in the anterior superior and central regions of the acetabular cartilage were seen in individuals with radiographic hip OA and those with acetabular cartilage defects compared to their respective controls ( P &lt; 0.05). In the femoral cartilage, the differences in T1ρ and T2 were not significant for any of the comparisons. Significant differences in the T1ρ and T2 values (each P &lt; 0.05) were found in more subregions of the cartilage and across the whole cartilage when subjects were stratified based on the presence of MRI‐detected cartilage defects than when they were stratified based on the presence of radiographic hip OA. Conclusion T1ρ and T2 relaxation parameters are sensitive to the presence of cartilage degeneration. Both parameters may therefore support MRI evidence of cartilage defects of the hip.
Submucosal haemorrhage or ruptured nodule in a multinodular goitre?
Authors: B G Issa, M F Scanlon, R Walsh
Journal: BMJ (1997)

Introducing the postoperative care team Effective postoperative care remains surgeons' roleEditor-I am concerned that the suggestions made by David R Goldhill might be taken too seriously rather than remain a point for discussion. 1 Goldhill is right in his assertion that patients can fare badly in their postoperative course because of lack of attention by their attendants and lack of understanding of common postoperative complications.I believe, however, that he has missed the opportunity to lay the blame at the correct door.Surely it is the surgeons' role to carry out preoperative assessment, surgery, and effective postoperative care.If they choose to emphasise their importance in the operating theatre, delegating their other responsibilities to their trainees, the nurse practitioners, and the anaesthetists, why should we encourage this path?Undoubtedly, anaesthetists are fast becoming the new generalists, with an increasing role outside the operating theatre.These new skills and responsibilities include pain control, intensive care, and transoesophageal echocardiography, to name but a few.Some of my professional colleagues may relish even more diversification and abhor my comments.Goldhill implies that anaesthetists and postoperative care nurses will lead the postoperative care team; indeed, this is already happening in North America, where they have been sent to run preoperative assessment clinics by surgeons based in the operating room.If the surgical ward round in your hospital has become a quick look through the laboratory results and a glance at the chest radiograph before a rush to the changing rooms then I suggest that waiting for the confidential inquiry into perioperative deaths to point out the obvious is not the solution.