tbuckley/cabot-search huggingface dataset:
Policies and Practices Related to the Role of Board Certification and Recertification of Pediatricians in Hospital Privileging
Authors: Gary L. Freed
Journal: JAMA (2006)

Privileging involves the granting of permission to perform specific professional activities under the jurisdiction of a governing body's (hospital) authority. In 1951, the Joint Commission on the Accreditation of Hospitals (later renamed the Joint Commission on Accreditation of Healthcare Organizations) was formed to codify the process of hospital assessment. In the early part of the 20th century, a parallel process was being undertaken by the medical specialties to evaluate and recognize competence among physicians through the creation of specialty boards.To describe the use of board certification in hospital privileging policies for general pediatricians and pediatric subspecialists and to identify any variation among types of hospitals.A telephone survey between January 1 and June 30, 2005, of privileging personnel among a random, weighted sample of 200 nonspecialty hospitals stratified by teaching status, children's vs general hospitals, freestanding children's hospital vs part of hospital system, and urban vs rural location.Proportion of hospitals that require board certification at initial privileging or at some point to maintain privileges and recertification to maintain privileges.Of 200 hospitals, 7 hospitals were ineligible because they did not have at least 1 pediatrician on staff. One hundred fifty-nine hospitals completed the telephone interview, resulting in an overall response rate of 82%. A total of 124 (78%) of 159 hospitals did not require general pediatricians to be board certified at initial privileging; however, 111 (70%) did require pediatricians to become board certified at some point during their tenure. Of these 124 hospitals, 52 (42%) did not report a time frame in which certification must be achieved. Forty-nine (43%) of 113 hospitals required pediatric subspecialists to achieve subspecialty certification within a specific time frame.These results raise issues regarding the manner in which board certification is used or not used by hospitals in their efforts to ensure the practice of high-quality care within their institutions. The premise for recertification is the need to assure the public of continued competence of physicians over the course of their professional careers. Increased attention by the public and regulatory agencies regarding patient safety and quality of care will likely have an impact on hospital privileging processes.
Targeting PI3K/mTOR Overcomes Resistance to HER2-Targeted Therapy Independent of Feedback Activation of AKT
Authors: Neil A. O'Brien, Karen McDonald, Luo Tong, Erika von Euw, Ondrej Kalous, Dylan Conklin, Sara A. Hurvitz, Emmanuelle di Tomaso, Christian Schnell, Ronald Linnartz, Richard S. Finn, Samit Hirawat, Dennis J. Slamon
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Altered PI3K/mTOR signaling is implicated in the pathogenesis of a number of breast cancers, including those resistant to hormonal and HER2-targeted therapies. Experimental Design: The activity of four classes of PI3K/mTOR inhibitory molecules, including a pan-PI3K inhibitor (NVP-BKM120), a p110α isoform–specific PI3K inhibitor (NVP-BYL719), an mTORC1-specific inhibitor (NVP-RAD001), and a dual PI3K/mTORC1/2 inhibitor (NVP-BEZ235), was evaluated both in vitro and in vivo against a panel of 48 human breast cell lines. Results: Each agent showed significant antiproliferative activity in vitro, particularly in luminal estrogen receptor–positive and/or HER2+ cell lines harboring PI3K mutations. In addition, monotherapy with each of the four inhibitors led to significant inhibition of in vivo growth in HER2+ breast cancer models. The PI3K/mTOR pathway inhibitors were also effective in overcoming both de novo and acquired trastuzumab resistance in vitro and in vivo. Furthermore, combined targeting of HER2 and PI3K/mTOR leads to increased apoptosis in vitro and induction of tumor regression in trastuzumab-resistant xenograft models. Finally, as previously shown, targeting mTORC1 alone with RAD001 leads to consistent feedback activation of AKT both in vitro and in vivo, whereas the dual mTOR1–2/PI3K inhibitor BEZ235 eliminates this feedback loop. However, despite these important signaling differences, both molecules are equally effective in inhibiting tumor cell proliferation both in vitro and in vivo. Conclusion: These preclinical data support the findings of the BOLERO 3 trial that shows that targeting of the PI3K/mTOR pathway in combination with trastuzumab is beneficial in trastuzumab-resistant breast cancer. Clin Cancer Res; 20(13); 3507–20. ©2014 AACR.
Abstract 2833: The protein ps20 increases tumourigenic potential in prostate cancer epithelial cells
Authors: Oliver Hickman, Annapurna Vyakarnam, Richard A.G. Smith, Angus G. Dalgleish, Prokar Dasgupta, Christine Galustian
Journal: Cancer Research (2012)

Abstract Introduction The protein ps20 encoded by the WFDC1 gene contains a highly conserved whey 4-disulphide core (WFDC) domain and is a member of a protein family that regulates inflammation. Ps20/WFDC1 is expressed by prostate cancer stromal cells but its expression by cancerous prostate epithelium is associated with tumour progression in patients. The aim of this study was to determine how WFDC1expression by prostate cancer cells alters their tumourigenic properties. Methods The cell-lines LNCAP and PC3 were transfected with WFDC1 vector or empty vector (EV) and their growth, adhesive and migratory characteristics were investigated by MTT proliferation, transwell migration and ICAM-1 adhesion assays. Results PC3 and LNCAP cells transfected with WFDC1 increased in numbers by 3148 +/−151% and 523+/−311% after 48 hours respectively compared to EV transfected cell lines (p &amp;lt;0.01 by unpaired T test). WFDC1-transfected cells became smaller and tightly clustered with greater cell-cell contact (See Figure 1). WFDC1 transfected cell migration through 8µM transwells was increased by 73% in PC3s and 57% in LNCaP compared to EV cells (p&amp;lt;0.05 by paired t-test). ICAM-1 expression increased by 67% in WFDC1-LNCAP and by 50% in WFDC1-PC3s compared to EV-cells (p&amp;lt;0.05 by paired t-test). VEGF (vascular endothelial growth factor) was also strongly detectable in the WFDC1-PC3 and LNCaP cells by western-blot whereas none was detectable in EV cells. Conclusions WFDC1 transfection of prostate cancer epithelial cells increases proliferation, migration and ICAM-1 expression, and also induces VEGF, which is a potent angiogenic growth factor. WFDC-1/ps20 may therefore be a critical target for prostate cancer therapeutics. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2833. doi:1538-7445.AM2012-2833
New Options for the Prevention of Influenza
Authors: Nancy J. Cox, James M. Hughes
Journal: New England Journal of Medicine (1999)

Influenza is a highly contagious acute respiratory disease of global importance. It is also a model of emerging and reemerging infectious diseases,1 for two reasons. First, annual epidemics of influenza are caused by viruses that have evolved sufficiently to reinfect persons who were infected by related strains that circulated previously. Second, influenza pandemics can occur unpredictably as a result of the emergence of new subtypes of influenza A viruses harbored in birds.We are faced with the near certainty that another pandemic will occur sometime in the future. This prediction is based on observations from past centuries and our current . . .
Will Bush's insurance scheme help the uninsured?
Authors: Jeanne Lenzer
Journal: BMJ (2004)

After the election of George W Bush as US president last week, healthcare specialists are debating the effect his healthcare policies may have on the US population.

The lynchpin of the president's health reform plan is the creation of health savings accounts. The accounts, according to President Bush, will help the uninsured and give consumers more control over their healthcare dollar.

The plan, part of the Medicare reform bill passed by Congress in December 2003, establishes a tax-free account that can be used to pay for medical expenses.

The account must be coupled with a high deductible insurance plan, under which the insured person will have to pay the first part of any large claim themselves. The plans are …
Abstract LB-216: Acquired lapatinib resistance in HER2-positive breast cancer cells is associated with up-regulation of mutant PI3K and/or secondary PI3K mutation.
Authors: Samuel Brady, Jian Zhang, Dihua Yu
Journal: Cancer Research (2013)

Abstract Resistance to the HER2 kinase inhibitor lapatinib is a major challenge in the treatment of HER2-positive breast cancer. To model acquired lapatinib resistance we generated two drug-resistant cell lines by extended exposure to lapatinib. Both HER2-amplified parental cell lines (BT474 and UACC893) possesssed PI3K p110α activating mutations, and were lapatinib-sensitive. Both lapatinib-resistant (LapR) cell lines possessed 2- to 3-fold increased levels of the PI3K p110α subunit and increased levels of phosphorylated Akt during lapatinib treatment. p110α increase occurred through gene amplification in the BT474 LapR cells and post-transcriptional protein increase in the UACC893 LapR cells. One of the two cell lines (BT474 LapR) also acquired a hotspot strong activating mutation (E542K) in p110α, whereas the parental cells possessed only a weak activating mutation (K111N). Mutant PI3K (E542K or H1047R) was sufficient to promote lapatinib resistance. Moreover, knockdown of p110α, but not p110β, sensitized both LapR cell lines to lapatinib. PI3K inhibitors were also effective in overcoming drug resistance. To our knowledge, this is the first suggestion of this dose-dependent effect of mutant p110α in lapatinib resistance and the first identified instance of post-transcriptional up-regulation of mutant p110α in lapatinib resistance. These findings may explain why some HER2-positive, PI3K p110α-mutant breast cancers are lapatinib-sensitive while others are lapatinib-resistant (increased level of p110α). Our findings also reinforce those of others indicating that HER2-positive breast cancer patients with mutant PI3K should be co-treated with HER2-targeting and PI3K-targeting therapies in order to prevent or overcome drug resistance. Citation Format: Samuel Brady, Jian Zhang, Dihua Yu. Acquired lapatinib resistance in HER2-positive breast cancer cells is associated with up-regulation of mutant PI3K and/or secondary PI3K mutation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-216. doi:10.1158/1538-7445.AM2013-LB-216
Welfare Reform and the Obstetrical Care of Immigrants and Their Newborns
Authors: Howard Minkoff, Tamar Bauer, Theodore Joyce
Journal: New England Journal of Medicine (1997)

On August 22, 1996, President Bill Clinton signed the Personal Responsibility and Work Opportunity Reconciliation Act. Although it does not affect the ability of low-income citizens to obtain Medicaid health coverage, the act does prohibit such coverage for some immigrants. Because illnesses in the perinatal period can affect two generations, the prohibitions may have unique consequences for pregnant women and their newborns, such as the denial of zidovudine treatment during pregnancy1 and of immunization during infancy.Before welfare reform, people who had immigrated into this country legally were generally eligible for Medicaid and other federal benefits. Undocumented immigrants were eligible . . .
Clinician Mindfulness and Patient Safety
Authors: Erica M. S. Sibinga, Albert W. Wu
Journal: JAMA (2010)

PATIENT SAFETY HAS BEEN A TOPIC OF CONSIDERABLE interest over the last decade, with evidence showing that medical errors are responsible for substantial morbidity and mortality. There has been significant progress in understanding, identifying, and addressing errors at a system level; however, the performance of individual clinicians remains a crucial and largely unaddressed element of patient safety. Individual performance is important in diagnostic errors, but these errors are difficult to measure and have received little systematic study. Diagnostic errors often stem from cognitive biases, also referred to as “cognitive dispositions to respond” (CDRs). Because CDRs are integral to human cognition, they are challenging to overcome. Croskerry has delineated more than 30 CDRs and has proposed “debiasing strategies” to prevent errors due to CDRs. Prominent among these strategies is metacognition, or an individual’s knowledge of his or her own thinking process. Notably, there is significant overlap between metacognition and mindfulness, nonjudgmental awareness of the present moment. Increased mindfulness leads to greater awareness and understanding of a person’s experiences, including thoughts, emotions, and bodily sensations. Because education can increase mindfulness, mindfulness instruction for clinicians holds promise as a debiasing strategy for reducing diagnostic and other medical errors.
B-cell clonality and infection with Helicobacter pylori: implications for development of gastric lymphoma.
Authors: D Sorrentino, G F Ferraccioli, S DeVita, C Avellini, C A Beltrami, A Labombarda, V Bernardis, F De Biase, A Trevisi, B Pivetta, M Boiocchi, E Bartoli
Journal: Gut (1996)

BACKGROUND: Although Helicobacter pylori has been implicated in the pathogenesis of gastric mucosa associated lymphoid tissue (MALT) and MALT lymphoma, it is not known how it may trigger these lesions and whether there is an identifiable pre-neoplastic stage. AIMS: To investigate the relation between MALT, H pylori infection, and B-cell clonality (a potential marker of pre-neoplastic lesions). PATIENTS: 141 subjects with simple dyspepsia. METHODS: Gastric biopsy specimens from all patients were examined for MALT and H pylori. Of these, 25 consecutive MALT positive specimens were scored for features of MALT lymphoma and VDJ clonality studied by polymerase chain reaction. RESULTS: Overall, prevalence was 62% for H pylori and 46% for MALT. VDJ clonality was frequent in the sub-group studied (nine of 25), mostly associated with lymphoid follicles (eight of nine or 89%), and with a high scoring for MALT lymphoma. VDJ clonality was equally frequent in patients with and without H pylori (seven of 20 and two of five or 35% and 40% respectively). CONCLUSIONS: B-cell clonality is unexpectedly common in subjects with simple dyspepsia and MALT raising clinical management questions. These findings also suggest that the cascade MALT formation--B-cell clonality--MALT lymphoma may not be uniquely associated with H pylori infection.
Gaseous oxide toxicity evaluated with cell monolayers on collagen-coated, gas-permeable teflon membranes.
Authors: M G Gabridge, M F Gladd
Journal: Environmental Health Perspectives (1984)

A system was developed to evaluate the cytotoxic potential of gaseous oxides in vitro. Target cells were MRC-5 human lung fibroblasts cultivated as monolayers on gas-permeable , FEP-Teflon membranes. Membranes were secured in Chamber/Dishes with a 25 mm diameter well. To promote attachment of fibroblasts to the membranes, the latter were incubated in collagen ( Vitrogen ) solutions for 10 min prior to plating the cells. The collagen pretreatment was significantly more effective than poly-L-lysine, fetal calf serum, polybrene and bovine serum albumin. Several types (mouse and calf) of acid-soluble and alcohol-soluble collagen fractions were evaluated, and all of them promoted cell attachment with equivalent efficiency. Cells on membranes were exposed to gases in a Plexiglass chamber with a gas flow of 2L/min. Sulfur dioxide caused a marked loss in cell viability (as indicated by ATP content of the monolayer) after 30 min exposure to 0.01% and 0.005%. A level of 0.001% did not affect viability, and none of the levels tested caused a sloughing of the monolayer after 90 min. Nitrogen dioxide induced a more modest drop in cell viability after 30 min exposure to 0.1%, while 0.005% and 0.05% were nontoxic. No cell sloughing occurred with NO2 exposures, and exposures to CO2 at levels of 20% for 90 min were nontoxic. This system, with cell culture monolayers on gas-permeable Teflon membranes, is simple and convenient. As such, it has potential application to cytotoxicity evaluations with numerous gases.
Religion and Psychiatry
Authors: Paul W. Pruyser
Journal: JAMA (1966)

In a vague way, relations between religion and psychiatry are as old as civilization, but that observation is as troublesome as it is edifying. For instance, the fact that ancient temple healings of the mentally deranged in Egypt, Greece, and Rome are on record says little more, after some reflection, than that ritual played an important role in ancient medicine, as it did indeed in all walks of life. The 12th-century report of a Jewish traveler who visited Dar-el-Maristan, an asylum for the insane in Bagdad kept up by the caliphate, is intriguing as an instance of religion's concern for the mentally ill, but loses some of its charm when one hears that the patients were chained to the walls in manacles. Upon hearing that, in the 14th century, some European monasteries opened their doors to the care of lunatics, one will rejoice, until one discovers that the regimen for
Absence of Secondary Malignant Neoplasms in Children With High-Risk Acute Lymphoblastic Leukemia Treated With Dexrazoxane
Authors: Elly V. Barry, Lynda M. Vrooman, Suzanne E. Dahlberg, Donna S. Neuberg, Barbara L. Asselin, Uma H. Athale, Luis A. Clavell, Eric C. Larsen, Albert Moghrabi, Yvan Samson, Marshall A. Schorin, Harvey J. Cohen, Steven E. Lipshultz, Stephen E. Sallan, Lewis B. Silverman
Journal: Journal of Clinical Oncology (2008)

Dexrazoxane is a drug used to prevent anthracycline-induced cardiotoxicity. A recent report found an association between the use of dexrazoxane and the risk of developing secondary malignant neoplasms (SMNs) in children with Hodgkin's disease. We report the absence of an association of SMNs in children with acute lymphoblastic leukemia (ALL) treated on Dana-Farber Cancer Institute ALL Consortium Protocol 95-01.Two hundred five children with high-risk (HR) ALL were randomly assigned to receive doxorubicin alone (n = 100) or doxorubicin with dexrazoxane (n = 105) during the induction and intensification phases of multiagent chemotherapy. We compared incidence of SMNs in these two groups.With a median follow-up of 6.2 years, no differences in the incidence of SMNs were noted between the group that received dexrazoxane and the group that did not (P = .66). One SMN (a melanoma located outside of the cranial radiation field) occurred in a patient who was randomly assigned to doxorubicin alone. No SMNs were observed in patients randomly assigned to receive dexrazoxane.Dexrazoxane was not associated with an increased risk of SMNs in children treated for HR ALL. Given the potential importance of dexrazoxane as a cardioprotectant, we recommend that dexrazoxane continue to be used and studied in doxorubicin-containing pediatric regimens.
RNAi profiling of primary human AML cells identifies ROCK1 as a therapeutic target and nominates fasudil as an antileukemic drug
Authors: Martin Wermke, Aylin Camgoz, Maciej Paszkowski-Rogacz, Sebastian Thieme, Malte von Bonin, Andreas Dahl, Uwe Platzbecker, Mirko Theis, Gerhard Ehninger, Sebastian Brenner, Martin Bornhäuser, Frank Buchholz
Journal: Blood (2015)
Intravascular Platelet Aggregation in the Heart Induced by Stress
Authors: JACOB I. HAFT, KAZEM FANI
Journal: Circulation (1973)

Sixteen rats, stressed by immersion in ice-cold water for 25-45 min, were found to have platelet aggregates in myocardial small vessels on electron microscopic study. None of six similar nonstressed control rats had platelets in myocardial vessels. It is concluded that stress, probably via catecholamine secretion that enhances platelet stickiness, can induce intravascular platelet aggregation. It is possible that this mechanism plays a part in the relationship between stress and acute clinical myocardial infarction.
Reduced synchrony of Ca2+ release with loss of T-tubules—a comparison to Ca2+ release in human failing cardiomyocytes
Authors: William E Louch, Virginie Bito, Frank R Heinzel, Regina Macianskiene, Johan Vanhaecke, Willem Flameng, Kanigula Mubagwa, Karin R Sipido
Journal: Cardiovascular Research (2004)

During cardiac excitation-contraction coupling, Ca2+ release from the sarcoplasmic reticulum (SR) occurs at the junctional complex with the T-tubules, containing the L-type Ca2+ channels. A partial loss of T-tubules has been described in myocytes from failing canine and human hearts. We examined how graded reduction of T-tubule density would affect the synchrony of Ca2+ release.Adult pig ventricular myocytes were isolated and cultured for 24 and 72 h. T-tubules, visualized with di-8-ANEPPS, and [Ca2+]i transients (Fluo-3) were recorded during confocal line scan imaging.Cultured cardiomyocytes exhibited a progressive reduction in T-tubule density. [Ca2+]i transients showed small areas of delayed Ca2+ release which gradually increased in number and size with loss of T-tubules. Local [Ca2+]i transients in the delayed regions were reduced. Due to these changes, loss of T-tubules resulted in an overall slowing of the rise of [Ca2+] along the entire line scan and transient magnitude tended to be reduced, but there was no change in SR Ca2+ content. Human myocytes isolated from failing hearts had a T-tubule density comparable to that of freshly isolated pig myocytes. The size, but not the number, of delayed release areas tended to be larger. The overall rate of rise of [Ca2+]i was significantly faster than in pig myocytes with low T-tubule density.Loss of T-tubules reduces the synchrony of SR Ca2+ release. This could contribute to reduced efficiency of excitation-contraction coupling in heart failure, though dyssynchrony in human failing cells appears to be modest.
Computers beat doctors in interpreting ECGs
Authors: D. Josefson
Journal: BMJ (1997)

A computer program has been shown to be better than experienced cardiologists in diagnosing heart attacks from electrocardiograms (ECGs).

Dr Lars Edenhardt and Dr Bo Heden from the department of clinical physiology at University Hospital in Lund, Sweden, used a computer programmed with neural networks, a form of artificial intelligence which mimics human learning ( Circulation 1997;96:1798-802). The computer was “taught” to recognise electrocardiographic …
Cervical collars in rheumatoid atlanto-axial subluxation: a radiographic comparison.
Authors: B Althoff, I F Goldie
Journal: Annals of the Rheumatic Diseases (1980)

Atlanto-axial subluxation occurs with a frequency varying from 6% to 45% in rheumatoid arthritis. Most patients are treated conservatively with a cervical collar. The effectiveness of different cervical collars in inhibiting anterior atlanto-axial subluxation was tested in 11 patients with classical rheumatoid arthritis. None of the collars had any major influence in inhibiting anterior subluxation of the atlas in maximal flexion. Furthermore, the harder collars with a stable cervical stand forced the atlas to subluxate anteriorly in some of the patients.