tbuckley/cabot-search huggingface dataset:
Cellular determinants for preclinical activity of a novel CD33/CD3 bispecific T-cell engager (BiTE) antibody, AMG 330, against human AML
Authors: George S. Laszlo, Chelsea J. Gudgeon, Kimberly H. Harrington, Justine Dell’Aringa, Kathryn J. Newhall, Gary D. Means, Angus M. Sinclair, Roman Kischel, Stanley R. Frankel, Roland B. Walter
Journal: Blood (2013)
Cardiac Autonomic Nervous Dysfunction in Diabetic Patients With a Mitochondrial DNA Mutation
Authors: Yukihiko Momiyama, Yoshihiko Suzuki, Masako Ohtomo, Yoshihito Atsumi, Kempei Matsuoka, Fumitaka Ohsuzu, Mitsuru Kimura
Journal: Diabetes Care (2002)

To elucidate the degree and characteristics of cardiac autonomic nervous dysfunction in diabetic patients associated with a mitochondrial DNA mutation at base pair 3243.We investigated heart rate variability using 24-h Holter monitoring in 10 diabetic patients with the mutation compared with 55 ordinary diabetic patients and 45 nondiabetic control subjects.Age and sex were similar in the three groups. Between patients with the mutation and ordinary diabetic patients, the duration of diabetes and blood glycemic levels were not different. In the time domain analysis of heart rate variability, patients with the mutation and ordinary diabetic patients had significantly smaller SDNN index and pNN50 than control subjects. Compared with ordinary diabetic patients, patients with the mutation had smaller SDNN index (P < 0.02), but rMSSD and pNN50 were not different. In the frequency domain analysis, total, low frequency (LF), and high frequency (HF) spectra were significantly smaller in patients with the mutation and ordinary diabetic patients than in control subjects. Compared with ordinary diabetic patients, patients with the mutation had smaller total and LF spectra (P < 0.02). However, HF spectra were not significantly different. Notably, the LF/HF spectra ratio was lower in patients with the mutation than in ordinary diabetic patients and control subjects (P < 0.05), but this ratio was similar in ordinary diabetic patients and control subjects.Our results suggest that diabetic patients with the mitochondrial DNA mutation have more severely impaired cardiac autonomic nervous function with sympathovagal imbalance, as compared with ordinary diabetic patients.
The Traumatic Neurosis
Authors: Marjorie C. Meehan
Journal: JAMA (1968)

Industrial injuries, automobile accidents, military experience, large disasters, and small personal mishaps all lead to claims for compensation. Psychological factors increase many of the claims. Traumatic neurosis, sometimes called "compensation neurosis," is widespread and has been the subject of numerous papers in both medical and legal literature. Many of these deal with limited aspects of the subject and reflect the biased viewpoint of either the insurance company or the plaintiff. Dr. Keiser, a psychiatrist, has attempted to cover the entire subject and to avoid bias. He has succeeded very well. Following a brief history of the problem and a short discussion of personality structure, Keiser discusses the causes of traumatic neurosis. He shows how many factors enter in and how varied are the forms the disorders can take. He discusses frankly the importance of secondary gain, the patient's desire not only for money but for sympathy, freedom from responsibility, or
Expert panel to look into blocked anaesthetic tubing incidents
Authors: C. McKenna
Journal: BMJ (2002)

An expert group will be set up to investigate 13 incidents involving blocked anaesthetic tubing, Liam Donaldson, the chief medical officer for England and Wales, has announced. One of the incidents led to the death of a 9 year old boy.

The 13 incidents occurred between 1988 and 2001 in 11 hospitals in the Essex area. In relation to the number …
Activation of ER stress and mTORC1 suppresses hepatic sortilin-1 levels in obese mice
Authors: Ding Ai, Juan M. Baez, Hongfeng Jiang, Donna M. Conlon, Antonio Hernandez-Ono, Maria Frank-Kamenetsky, Stuart Milstein, Kevin Fitzgerald, Andrew J. Murphy, Connie W. Woo, Alanna Strong, Henry N. Ginsberg, Ira Tabas, Daniel J. Rader, Alan R. Tall
Journal: Journal of Clinical Investigation (2012)

Recent GWAS have identified SNPs at a human chromosom1 locus associated with coronary artery disease risk and LDL cholesterol levels. The SNPs are also associated with altered expression of hepatic sortilin-1 (SORT1), which encodes a protein thought to be involved in apoB trafficking and degradation. Here, we investigated the regulation of Sort1 expression in mouse models of obesity. Sort1 expression was markedly repressed in both genetic (ob/ob) and high-fat diet models of obesity; restoration of hepatic sortilin-1 levels resulted in reduced triglyceride and apoB secretion. Mouse models of obesity also exhibit increased hepatic activity of mammalian target of rapamycin complex 1 (mTORC1) and ER stress, and we found that administration of the mTOR inhibitor rapamycin to ob/ob mice reduced ER stress and increased hepatic sortilin-1 levels. Conversely, genetically increased hepatic mTORC1 activity was associated with repressed Sort1 and increased apoB secretion. Treating WT mice with the ER stressor tunicamycin led to marked repression of hepatic sortilin-1 expression, while administration of the chemical chaperone PBA to ob/ob mice led to amelioration of ER stress, increased sortilin-1 expression, and reduced apoB and triglyceride secretion. Moreover, the ER stress target Atf3 acted at the SORT1 promoter region as a transcriptional repressor, whereas knockdown of Atf3 mRNA in ob/ob mice led to increased hepatic sortilin-1 levels and decreased apoB and triglyceride secretion. Thus, in mouse models of obesity, induction of mTORC1 and ER stress led to repression of hepatic Sort1 and increased VLDL secretion via Atf3. This pathway may contribute to dyslipidemia in metabolic disease.
Allocation of Resources to Manage Hypertension
Authors: William B. Stason, Milton C. Weinstein
Journal: New England Journal of Medicine (1977)

Hypertension is one of the foremost public-health problems facing this nation. Its high prevalence, the enhanced risks of mortality and morbidity from the cardiovascular and cerebrovascular diseases associated with it, and the availability of treatment that has been shown to be effective, at least in selected patients,1,2 combine to highlight its importance. The problem is compounded by the fact that many people are unaware that they have hypertension, and others, though aware, are on either no treatment or inadequate treatment.3Our purpose is to apply cost-effectiveness analysis to the management of essential hypertension, both to determine how resources can be . . .
Early mobilisation of acute whiplash injuries
Authors: K. Hashemi
Journal: BMJ (1986)

with those in the white population from the same catchment area.'Results in Asian women are much poorer than those in white women.Their complaints are also less accessible, more complex, and apparently more affected by transcultural factors than those of their husbands.Bangladeshi women here are socially, linguistically, and culturally more isolated.Also their complaints did not affect fertility as directly as their partners': they were often a manifestation of marital or family strife.Modified Masters and Johnson sex therapy can achieve a good outcome with male sexual problems in Bangladeshi patients when both partners attend.Motivation is likely to be highest when fertility is directly affected.
Mandatory reporting to the police of all sexually active under-13s
Authors: Ruth Bastable, Julian Sheather
Journal: BMJ (2005)

New protocols may undermine confidential sexual health services for young people 

C onfidential sexual health services for young people are under threat. This summer, following the Bichard Report into the killings of Jessica Chapman and Holly Wells,1 several protocols relating to the disclosure of information about sexually active young people have been issued by area child protection committees in England and Wales. At the same time the government is consulting on a new version of its statutory guidance on child protection, Working Together to Safeguard Children .2 The protocols require mandatory reporting of all sexually active young people under 13 to the police and the collection of data in relation to sexually active young people under 16. Although the protocols'legal status is unclear and the intended uses of data about under 16 year olds are uncertain, their combined effects are predictable: health professionals can no longer assume that their work with this age group will be in confidence, and young people will turn …
Mechanisms of endotoxin tolerance. The role of the spleen.
Authors: S E Greisman, E J Young, J B Workman, R M Ollodart, R B Hornick
Journal: Journal of Clinical Investigation (1975)

Splenectomy markedly impaired the production of circulating anti-endotoxin antibodies during the initial 10 days after .v. administration of a Boivin preparation of Escherichia coli endotoxin (ET) in both rabbit and man. Increase in antibodies with secondary (flocculating and bactericidal) activities were virtually abolished, whereas increases in antibodies with primary (binding) activity were significantly reduced. On the basis of these findings, splenectomized rabbit and man were employed to test the hypothesis that the early phase (less than 72 h) of pyrogenic tolerance to endotoxin is independent of anti-endotoxin antibody but that such antibody contributes significantly to the later phase (less than or equal to 72 h) of tolerance. In the splenectomized rabbit, the initial pyrogenic reponses to ET and the subsequent tolerant responses at 24 and 48 h were comparable to sham-operated controls...
Diparcol in Parkinsonism
Authors: E. Brauer
Journal: BMJ (1949)

<h3>Background</h3> The last decade has witnessed the emergence of simulation as a useful, but some times challenging teaching methodology. This is supported by a number of sources of evidence, which focus strongly upon student evaluation of the learning experience. The challenges are equally worth consideration. These include issues such as the commissioning of space and staff expertise in resourcing and creating a situation which is as close to real practice as possible. <h3>Aims</h3> To explore the use of a complex simulated scenario with third year children’s nursing students. To share the process of educational evaluation that was undertaken. To share the results of this educational intervention. <h3>Methods</h3> Children’s nursing students were exposed to a complex simulated clinical shift. The activities included: managing the clinical area; the transfer of a sick child; managing a medication error; subsequent discussion with the parents; and prioritising and organising care. The use of role-play was utilised throughout, to create a realistic experience and the simulation activity took place in two settings to enable the transfer of a child from one clinical area (the assessment unit) area to another (the ward). The simulation experience was undertaken at the end of the third year undergraduate program by three cohorts of students (n = 41). Following the experience, data were collected through a post-simulation de-briefing and a Likert style questionnaire, enabling the collection of qualitative and quantitative evaluation data concerned with the student’s experience of the simulation. <h3>Results and conclusion</h3> Overwhelmingly, the results showed that this was a positive experience for the students, demonstrating a number of perceived improvements in the application of their clinical skills. These included: development of specific management skills; enhanced confidence; development of self-awareness; and the transferability of skills to practice. Students also demonstrated strong agreement in terms of the realism of the experience.
Relationship between lung biopersistence and biological effects of man-made vitreous fibers after chronic inhalation in rats.
Authors: T W Hesterberg, W C Miiller, R Mast, E E McConnell, D M Bernstein, R Anderson
Journal: Environmental Health Perspectives (1994)

This article describes the relationship between fiber biopersistence and the chronic toxicity of different chemical compositions of man-made vitreous fibers (MMVF) in the lung. Rats were exposed in "nose-only" inhalation chambers, 6 hr/day, 5 days/week, for 24 months to aerosol concentrations of 30 mg/m3 containing comparable fiber numbers and similar dimensions of fibrous glass (FG) or refractory ceramic fiber (RCF). Interim sacrifices were performed periodically to monitor fiber number and dimensions in the lung and the progression of pulmonary alterations. At each interim sacrifice, three to six recovery animals were removed from each exposure group and held until two years to determine the biopersistence of fibers after different exposure times. Fibers were recovered from the ashed lungs, counted, and measured using optical and scanning electron microscopy (SEM). Fiber chemistry was assessed in 91-week recovery lungs using energy dispersive spectroscopy (EDS) analysis. RCF induced lung fibrosis and an elevation in lung tumors and pleural mesotheliomas. FG exposure resulted in no lung fibrosis, no statistically significant increase in the lung tumor incidence, and no mesotheliomas. After two years of continuous exposure, the number of World Health Organization fibers per milligram dry lung recovered from RCF and FG exposed lungs was comparable. EDS analysis of recovery lungs showed that most of the alkalis and alkaline earths had leached from the FG fibers over time. A slight change in RCF chemistry was observed. These findings indicate that the change in the chemical composition of fibers may be an important determinant of the chronic toxicity of MMVFs.
α-Fetoprotein Screening and the Standard of Care-Reply
Authors: Michael John Hughey
Journal: JAMA (1987)

<h3>In Reply.—</h3> The survey that was the basis of this study was performed in April 1985, a fact that was regrettably removed from the original manuscript in the editing process. I share Dr Weiss' surprise that only 15% of plans surveyed at the time were routinely offering serum α-fetoprotein screening. Our group model health maintenance organization (NorthCare Medical Group/PruCare of Illinois) reached the same conclusion as Dr Weiss—that serum α-fetoprotein screening should be routinely offered to all patients—and it has offered such screening for several years. Nonetheless, I am uncomfortable in declaring serum α-fetoprotein screening to be "the standard of care," particularly when less than two years ago only 15% of groups routinely offered this test. Neither the current editions of<i>Williams' Obstetrics</i><sup>1</sup>nor Danforth's and Scott's<i>Obstetrics and Gynecology</i><sup>2</sup>recommend that this test be done routinely. Based on my informal knowledge of medical group practices throughout the
Neutrophil-endothelial cell interactions. Modulation of neutrophil adhesiveness induced by complement fragments C5a and C5a des arg and formyl-methionyl-leucyl-phenylalanine in vitro.
Authors: M G Tonnesen, L A Smedly, P M Henson
Journal: Journal of Clinical Investigation (1984)

Neutrophil adherence to vascular endothelial cells is the initial event in the emigration of neutrophils through blood vessel walls to tissue sites of inflammation; this process is attributed to the generation of extravascular chemotactic factors. To investigate the effect of chemotactic factors on neutrophil adherence to endothelium, we developed a sensitive, reproducible in vitro microtiter adherence assay. Base-line nonstimulated adhesion of human neutrophils to cultured human umbilical vein endothelial cell monolayers was 35.2 +/- 0.9%, which is equivalent to three to four neutrophils per endothelial cell. Addition of either purified complement fragment C5a des arg, or formyl-methionyl-leucyl-phenylalanine (FMLP), in concentrations ranging from 10(-10) to 10(-6) M, increased neutrophil adherence to endothelium in a dose-dependent manner. Purified C5a and C5a des arg were essentially equal in their ability to enhance neutrophil adherence, in contrast to the previously described greater in vitro potency of C5a compared with C5a des arg in stimulating neutrophil chemotaxis and enzyme release. Nonstimulated neutrophils adhered preferentially to human endothelial cells compared with fibroblasts or smooth muscle cells, suggesting that endothelial cells may make a unique contribution to the base-line adhesive interaction. However, chemotactic factors appear to enhance neutrophil adherence to endothelium by exerting an effect primarily on the neutrophil. In the presence of chemotactic factor, neutrophils adhered equally well to different cell types or to protein-coated plastic. Pretreatment of endothelial cells with chemotactic factor for as long as 4 h failed to increase subsequent neutrophil adherence. In contrast, pretreatment of neutrophils with chemotactic factor increased adherence to endothelium. Chemotactic factor-stimulated neutrophil adherence to endothelium occurred rapidly (within 2 min), diminished upon removal of stimulus, but could be rapidly and maximally restimulated upon readdition of the original dose of chemotactic factor. Thus, adherence to endothelium stimulated by chemotactic factor would appear to be a dynamic neutrophil response capable of rapid modulation, possibly important to the ability of neutrophils to adhere to and then migrate through vessel walls to localize at sites of inflammation.
Crack Cocaine Use and Sexual Behavior Among People With AIDS
Authors: Theresa Diaz
Journal: JAMA (1993)

<h3>To the Editor.</h3> —Crack cocaine use, because of its association with risky sexual behaviors,<sup>1-3</sup>may play an important role in the acquisition and transmission of human immunodeficiency virus (HIV) infection.<sup>4,5</sup>Because of their addiction, crack users may not discontinue high-risk sexual behaviors, eg, prostitution, even if they are aware of their HIV status. To examine this possibility, we analyzed data collected from interviews of 3927 persons at least 18 years of age reported to health departments with acquired immunodeficiency syndrome (AIDS) or HIV infection between June 1, 1990, and January 31, 1993. This special surveillance project is currently being conducted by the Centers for Disease Control and Prevention in collaboration with 11 state and local health departments. We elicited detailed information on drug use and sexual activities within the past 5 years. Among men, those who used crack but did not inject drugs were more likely to have
Hospitals earn $30 000 extra from surgical patients who have complications, study finds
Authors: M. McCarthy
Journal: BMJ (2013)

Surgical complications can substantially boost US hospitals’ revenues, a new study shows.

The findings indicate that under the current US healthcare payment system a hospital’s income may suffer if it implements quality improvement measures to reduce infections and other common complications of surgery and numbers of avoidable admissions to intensive care.

In the study, published in JAMA ,1 the researchers looked at the financial effects of surgical complications on the revenues of Texas Health, a 12 hospital network that includes a mix of higher and lower …
Recurrence Rates after Treatment of Breast Cancer with Standard Radiotherapy with or without Additional Radiation
Authors: Harry Bartelink, Jean-Claude Horiot, Philip Poortmans, Henk Struikmans, Walter Van den Bogaert, Isabelle Barillot, Alain Fourquet, Jacques Borger, Jos Jager, Willem Hoogenraad, Laurence Collette, Marianne Pierart
Journal: New England Journal of Medicine (2001)

Radiotherapy prevents local recurrence of breast cancer after breast-conserving surgery. We evaluated the effect of a supplementary dose of radiation to the tumor bed on the rates of local recurrence among patients who received radiotherapy after breast-conserving surgery for early breast cancer.
P5-13-15: Proteomic Identification of Predictive Biomarkers of Resistance to Neoadjuvant Chemotherapy in Luminal Breast Cancer: A Possible Role for 14–3-3 and BID?
Authors: VC Hodgkinson, D ELFadl, V Agarwal, V Garimella, PJ Drew, MJ Lind, L Cawkwell
Journal: Cancer Research (2011)

Abstract Background: Chemotherapy resistance is a major obstacle in effective neoadjuvant treatment for oestrogen receptor (ER)-positive breast cancer. The ability to predict tumour response would allow chemotherapy administration to be directed towards only those patients who would benefit, thus maximising treatment efficiency. We aimed to identify protein biomarkers associated with chemotherapy resistance, using proteomic analysis of fresh ER-positive breast cancer samples, and then to perform pilot clinical validation experiments. Materials and Methods: Chemotherapy resistant and chemotherapy sensitive tumour samples were collected from breast cancer patients who received standard anthracycline-based neoadjuvant therapy consisting of epirubicin with cyclophosphamide followed by docetaxel. Comparative proteomics experiments were performed using invasive ductal carcinomas which demonstrated ER-positivity (luminal subtype). Protein expression was compared between chemotherapy resistant and chemotherapy sensitive tumour samples using 2-dimensional gel electrophoresis (2-DE) with MALDI-TOF/TOF mass spectrometry (MS). In addition the Panorama XPRESS Profiler725 antibody microarray, containing 725 antibodies from a wide variety of cell signalling and apoptosis pathways, was employed in the discovery phase. Differentially expressed proteins (DEPs) were submitted to Ingenuity Pathway Analysis (IPA) to identify any canonical pathway links. A pilot series of archival breast cancer samples, from patients treated with neoadjuvant anthracycline-based chemotherapy, was used for preliminary clinical validation of putative predictive biomarkers. Results: Five datasets were generated by antibody microarray analysis, revealing 41 targets. Of these, 7 DEPs were identified in at least 2 datasets and these included 14–3-3, BID and Bcl-xL. The top canonical pathway matched in IPA was “ERK5 signaling”, which involved 6 DEPs, including 14–3-3. The “PI3/AKT” pathway also involved 6 DEPs, including 14–3-3 and Bcl-xL. Three datasets were generated using 2-DE with MALDI-TOF/TOF MS, containing over 300 DEPs. These included several isoforms of 14–3-3. Differential expression of 14–3-3, BID and Bcl-xL was confirmed by immunoblotting in samples used for the discovery phase. A pilot clinical validation using immunohistochemical analysis of archival breast cancers revealed 14–3-3 tau and tBID to be significantly associated with chemotherapy resistance. Discussion: We have successfully utilised clinical tumour samples for the discovery of putative biomarkers of chemotherapy resistance using two complementary proteomic platforms. We propose a potential role for 14–3-3 tau and BID as predictive biomarkers of chemotherapy resistance in ER-positive tumours and further validation in a larger sample series is now required. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-13-15.