tbuckley/cabot-search huggingface dataset:
OSSIFICATION IN A CHALAZION
Authors: WALTER SCOTT FRANKLIN
Journal: JAMA (1924)

<h3>History.</h3> —J. M., a man, aged 38, reported to the clinic, April 26, 1922, complaining of poor vision and inflamed eyes. He had had chronic inflammation of both lids for the last fifteen to eighteen years. The condition had improved at times only to become aggravated on slight irritation, as by wind or dust. Within the present year, the lids seemed worse and the eyes watered a great deal. For the last seventeen years the patient had noticed a swelling or lump in the right lower lid. This began as a stye, which did not come to a head, but gradually increased in size over a period of several months. Since that time it had not changed materially. It was not painful or tender but, as it had become large with a tendency to make the lid heavy, the patient requested that it be removed. The vision of the right
Dietary intake and plasma lipid levels: Authors' reply
Authors: M. Thorogood, L. Roe, K. McPherson, J. Mann
Journal: BMJ (1990)

Correlationis between plasma lipid concentrations and dietarn fat intake in diabetic patients Patients with type I diabetes (n= 13) Patients with type II diabetes (n= 37) r Value p Value r Value p V'alue I'lasma cholesterol Fat as %i energy 0-
Suppression of peripheral blood natural killer cell activity by excess thyroid hormone.
Authors: M Papic, J Stein-Streilein, M Zakarija, J M McKenzie, J Guffee, M A Fletcher
Journal: Journal of Clinical Investigation (1987)

Natural killer (NK) cells were assessed in patients with hyperthyroxinemia due to Graves' disease or treatment with thyroxine (T4). Cytolytic activity was measured with 51Cr-labeled K562 tumor cells and NK enumeration was by flow cytometry using NKH-1 monoclonal antibody to identify the relevant surface marker. Activity was uniformly decreased in association with hyperthyroxinemia, regardless of the underlying pathology; however, there was no reduction in the number of NKH-1+ cells. NK activity was enhanced by addition of interleukin 2 (IL-2) in both control and patients' cells although the value in the latter instance failed to reach the basal control level. Production of IL-2 by lymphocytes from hyperthyroxinemic subjects, in response to phytohemagglutinin, was also reduced. Since NK cells are thought to act as a defense against viral infections and some malignancies and may play a role in autoregulation of the immune system, this effect of T4 may have significant biological implications.
Secondary care beyond Tomlinson: an opportunity to be seized or squandered?
Authors: F. Moss, M. McNicol
Journal: BMJ (1992)

The Tomlinson report's emphasis on primary care and its essentially quantitative analysis of hospital care in London leaves little space for a picture of how secondary care for Londoners should look. In this article Fiona Moss and Martin McNicol argue that most outpatient work does not need to be done in hospitals. With proper organisation and better premises a genuinely specialist consultative service can be provided in primary health care centres, with benefit to patients and communication between primary and secondary care doctors. Hospitals would then house those outpatient services that needed major investigative facilities and much reduced inpatient capacity. It may no longer be necessary for each acute unit to offer a full range of services. Such a pattern of secondary care will have implications for the organisation of accident and emergency services and for postgraduate training. Above all Moss and McNicol argue that Tomlinson's recommendations demand that general practitioners and specialists should re-examine the services hospitals provide and agree on the best settings for different sorts of health care and the most appropriate skills to provide it.
Abstract LB-309: Non-covalent wild-type-sparing inhibitors of EGFR T790M .
Authors: Ho-June Lee, Gabriele Schaefer, Tim Heffron, Shiva Malek, Mark Merchant, Robert L. Yauch, Valentina Pirazzoli, Katerina Politi, Jeff Settleman
Journal: Cancer Research (2013)

Abstract Non-small cell lung cancers (NSCLC) with activating EGFR mutations respond well to the selective EGFR kinase inhibitors, gefitinib and erlotinib. Despite initial responses, most patients relapse within one year due to acquired resistance. Approximately half of these cases are associated with a secondary EGFR kinase domain mutation, T790M–the “gatekeeper” mutation. Irreversible EGFR kinase inhibitors have demonstrated pre-clinical efficacy toward EGFR T790M and have been undergoing clinical evaluation. However, the current irreversible inhibitors have yet to yield clinical activity in this setting, possibly due to dose-limiting toxicities. In a cancer cell line screening effort, we identified the PKC inhibitor, Go6976, a staurosporine derivative, as an inhibitor of EGFR mutant-driven NSCLC cells. Further analysis revealed that Go6976 potently suppresses both autophosphorylation and ligand-induced phosphorylation of EGFR mutants including T790M. Among some structurally-related bis-indole-based compounds currently undergoing clinical testing, PKC412, a FLT3 kinase inhibitor, demonstrated -100 fold greater potency against EGFR T790M than Go6976. Interestingly, while irreversible inhibitors are less potent against EGFR T790M than either EGFR WT or EGFR activating mutants, the bis-indole-based compounds show substantially greater potency against EGFR T790M, effectively sparing WT EGFR. Our findings suggest that this class of reversible inhibitors may be more effective and better tolerated than irreversible inhibitors to overcome EGFR T790M-mediated acquired drug resistance in NSCLC. Citation Format: Ho-June Lee, Gabriele Schaefer, Tim Heffron, Shiva Malek, Mark Merchant, Robert L. Yauch, Valentina Pirazzoli, Katerina Politi, Jeff Settleman. Non-covalent wild-type-sparing inhibitors of EGFR T790M . [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-309. doi:10.1158/1538-7445.AM2013-LB-309
Salicylate Therapy in Rheumatoid Arthritis
Authors: Kenneth Fremont-Smith
Journal: JAMA (1965)

Salicylates are relatively safe and inexpensive analgesic agents, and it is for analgesia that they are usually given to patients with rheumatoid arthritis. However, it has been demonstrated in the laboratory that these same drugs exert an anti-inflammatory effect in certain types of experimental inflammation.<sup>1</sup>The antirheumatic action of salicylate therapy in rheumatic fever has been accepted for many years.<sup>2</sup>Some rheumatologists have concluded from clinical experience that salicylates may also exert a therapeutically significant anti-inflammatory effect in rheumatoid arthritis,<sup>3</sup>but there is little published evidence to support or deny this postulate. The answer to this question is of obvious importance for the clinical management of patients with rheumatoid arthritis. It also has significance for the planning of clinical trials designed to evaluate the efficacy of other drugs in the treatment of rheumatoid arthritis; for one of the established criteria frequently used to assess activity of this
Differentiation and Recruitment of IL-22–Producing Helper T Cells Stimulated by Pleural Mesothelial Cells in Tuberculous Pleurisy
Authors: Zhi-Jian Ye, Qiong Zhou, Ming-Li Yuan, Rong-Hui Du, Wei-Bing Yang, Xian-Zhi Xiong, Bo Huang, Huan-Zhong Shi
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Rationale: IL-22–producing helper T cells (Th22 cells) have been reported to be involved in tuberculosis infection. However, differentiation and immune regulation of Th22 cells in tuberculous pleural effusion (TPE) remain unknown.Objectives: To elucidate the mechanism by which Th22 cells differentiate and recruit into the pleural space.Methods: The distribution and phenotypic features of Th22 cells in both TPE and blood were determined. The impacts of proinflammatory cytokines and antigen presentation by pleural mesothelial cells (PMCs) on Th22-cell differentiation were explored. The chemoattractant activity of chemokines produced by PMCs for Th22 cells was observed.Measurements and Main Results: Th22 cells were significantly higher in TPE than in blood. IL-1β, IL-6, and/or tumor necrosis factor-α promoted Th22-cell differentiation from CD4+ T cells. It was found that PMCs expressed CCL20, CCL22, and CCL27, and that TPE and PMC supernatants were chemotactic for Th22 cells. This activity was partly blocked by anti-CCL20, anti-CCL22, and anti-CCL27 antibodies. IL-22 and IL-17 significantly improved PMC wound healing. Moreover, PMCs were able to stimulate CD4+ T-cell proliferation and Th22-cell differentiation by presenting tuberculosis-specific antigen.Conclusions: The overrepresentation of Th22 cells in TPE may be due to pleural cytokines and to PMC-produced chemokines. Our data suggest a collaborative loop between PMCs and Th22 cells in TPE. In particular, PMCs were able to function as antigen-presenting cells to stimulate CD4+ T-cell proliferation and Th22-cell differentiation.
Prognostic and proliferative evaluation of ameloblastoma based on radiographic boundary
Authors: Yi Li, Bo Han, Long-Jiang Li
Journal: International Journal of Oral Science (2012)

Ameloblastoma is a benign odontogenic tumor with an aggressive biological behavior, and the surgical treatment frequently results in failure for the postoperative recurrence. The aim of this article was to investigate whether the proliferative ability and prognosis of ameloblastoma could be evaluated by the radiographic boundary. The ameloblastoma cases treated by the conservative therapy in our hospital between 1981 and 2001 were divided into three groups based on the nature of the radiographic borders of the lesions. The biologic behavior was evaluated by Ki-67 antibody immunohistochemically. Comparisons of prognosis and Ki-67 expression were carried out by statistic methods. There were 24 cases of well-defined edge with sclerosis (group I), 41 cases of well-defined edge without sclerosis (group II) and 32 cases of ill-defined edge (group III). The recurrent rates were 29.2% in group I, 43.9% in group II and 62.5% in group III (P<0.05). The cells in group III expressed the highest Ki-67 level (P<0.05). The radiographic boundary could be used as one of indicators in evaluating the proliferative ability of ameloblastoma and the patient's prognosis, which was consistent with Ki-67 expression.
Circulating Fibroblast Growth Factors as Metabolic Regulators—A Critical Appraisal
Authors: Bo Angelin, Tobias E. Larsson, Mats Rudling
Journal: Cell Metabolism (2012)

The circulating FGFs are a new group of proteins believed to function as classic hormones. With emphasis on human metabolism, we critically review current data, and propose that—although a number of questions remain—circulating FGF23 is pivotal in the control of phosphate and vitamin D metabolism, and may have additional systemic effects, particularly in chronic kidney disease; that FGF19 signaling is important for the regulation of bile acid metabolism, whereas its physiological role in promoting glucose and lipid metabolism is less well understood; and that the physiological role of circulating FGF21 in metabolic homeostasis warrants further investigation. The circulating FGFs are a new group of proteins believed to function as classic hormones. With emphasis on human metabolism, we critically review current data, and propose that—although a number of questions remain—circulating FGF23 is pivotal in the control of phosphate and vitamin D metabolism, and may have additional systemic effects, particularly in chronic kidney disease; that FGF19 signaling is important for the regulation of bile acid metabolism, whereas its physiological role in promoting glucose and lipid metabolism is less well understood; and that the physiological role of circulating FGF21 in metabolic homeostasis warrants further investigation.
Minimal Intervention — Nurse-Midwives in the United States
Authors: Mona T. Lydon-Rochelle
Journal: New England Journal of Medicine (2004)

I first observed childbirth in 1973 during a rotation at the Boston Lying-In Hospital, where I witnessed many women in labor screaming in a scopolamine stupor. What I remember most vividly were not the physicians and nurses, competent though they may have been, but the British-trained nurse-midwives who practiced as labor nurses. Their competence, confidence, and compassion had a calming effect on everyone in the room (including this terrified student-nurse). The experience was so gripping, in fact, that I left the hallowed halls of New England Deaconess Hospital for the hollows of Kentucky to enter the Frontier Nursing Service School . . .
A controlled trial on treatment of patients with HCV infection and abnormal liver function tests with or without liver biopsy
Authors: A. Andriulli, M. Persico, A. Iacobellis, G. Maio, D. Di Salvo, A. Spadaccini, D. Bacca, G. Leandro, F. Ventrella, A. Mangia
Journal: Journal of Hepatology (2003)
Unfunded Research? I Am Shocked, Shocked!
Authors: Walter Olson
Journal: JAMA (1993)

<h3>To the Editor.</h3> —We read with great interest the article by Stein et al<sup>1</sup>on funding of medical research. Their data show that 7% of the surveyed published work was not directly funded; all other aspects of their discussion are speculative, and many of their conclusions are rooted in unsupported assumptions. Most troubling is their assumption that unfunded research is more likely to be unethical. In fact, scientific misconduct is most frequently reported in well-funded groups. While we concede that some investigators may attempt to take advantage of patients or third-party payment systems, we do not believe that availability of funding is the determinant of this behavior. It is certainly clear that the study design of Stein et al does not address this issue adequately.
Preventable diabetes complications are still occurring in hospitals, audit finds
Authors: J. Wise
Journal: BMJ (2013)

More than 60 hospital inpatients with diabetes had diabetic ketoacidosis, a life threatening but entirely preventable complication, in just one week in England and Wales, a national audit report shows.1

The National Diabetes Inpatient Audit also documented 232 cases of severe hypoglycaemia requiring injectable treatment. The audit report, commissioned by the Healthcare Quality Improvement Partnership, said that these findings were “shocking” as these life threatening harms were preventable.

The audit, carried out by the NHS Health and Social Care Information Centre working with the charity Diabetes UK, collected data over five days in September 2012 from 13 410 patients with diabetes in 136 trusts in England and six local health boards in Wales. Most of the patients were admitted to hospital for reasons other than their diabetes; just 8.2% in England and 9.6% in Wales were admitted specifically for diabetes. …
762-6 Cerebral Oxygenation During Paediatric Cardiac Surgery: Identification of Vulnerable Periods by Near Infrared Spectroscopy
Authors: Piers E.F. Daubeney, Sally Pilkington, David Smith, Robert K. Lamb, James L. Monro, Steven A. Livesey, Victor T. Tsang, Steven A. Webber
Journal: Journal of the American College of Cardiology (1995)
Multiculturalism and the NHS--the experience of a not so foreign "foreign doctor"
Authors: A. Low
Journal: BMJ (2010)

The uncertainty in life expectancy plays a critical role in individual financial planning. Its impact is magnified during the retirement years (the wealth distribution stage of the life cycle), as new sources of income typically are not available to retired persons. Utilizing a multi-stage stochastic program, the authors model and solve the optimal asset allocation problem of a retired couple with uncertain life expectancy in the presence of a term life insurance policy. In the base case, they find optimal policies assuming no longevity risk (i.e., lifetime scenarios are uncertain although life expectancy is fixed on the retirement date). Next, they introduce longevity risk in the scenario generation stage through either a shift in the expected lifetimes or an unexpected cut in periodic retirement income. The authors find that the optimal asset allocation policy depends on the presence and the type of these risks, as well as the relative price of insurance and the size of any cut in pension benefits. <b>TOPICS:</b>Retirement, quantitative methods, portfolio construction
Investigations on Tuberculin
Authors: A. T. Doig, G. Gemmill, G. G. Kayne, F. V. Linggood, H. J. Parish, J. S. Westwater
Journal: BMJ (1938)

The value of the Mantoux test as a clinical aid seems to be-doubted in some quarters, apparently on the assump- tion that there is almost complete tuberculinization of the population.This may still be true of crowded urban districts, but recent epidemiological surveys have shown that in many communities a large percentage of people reach adolescence without having been infected, and, more- over, that this percentage is becoming greater as the incidence of tuberculous disease is decreasing.There can be little doubt, therefore, that with time the Mantoux test will be found more and more useful in clinical work.Since the Mantoux test is a quantitative one, the material used in its performance should be stable, and constant in composition and potency; further, the exact amount of the active principle injected should be known..Only if these conditions are fulfilled will it be possible to compare repeated tests at intervals on the same patient, and to correlate or pool the observations of different workers investigating large groups.Until a few years ago Koch's old tuberculin was always used; but it was increasingly realized that this crude material did not fulfil the conditions laid down above.Old tuberculin is usually prepared by the growth of the tubercle bacillus on a veal-infusion-peptone medium con- taining a comparatively large amount of glycerol.The mature culture is steamed and the filtrate evaporated to one- tenth of its original volume.Thus it is a complex mixture, containing, besides the active principle, much non-specific material, such as peptones, salts, glycerol, and bacillary meta- bolic products.Long (1934) has stated that its potency is due to about 1 per cent. of its total substance.It has been found that batches of old tuberculin prepared not only from different strains, but even from the same strain and in the same type of culture medium, may vary in potency.Moreover, no accurate method of standardization has been
Methotrexate and Psoriasis
Authors: Joseph Glasser
Journal: JAMA (1969)

<h3>To the Editor:—</h3> Your editorial, "Methotrexate and Psoriasis" (<b>209</b>: 1898, 1969), is timely. As one who has been occupied with my own therapy in the treatment of psoriasis for the past 14 years, I have had the opportunity of seeing a number of methotrexate-treated failures, and the complications resulting from this hazardous modality. To my knowledge, these cases were never reported in the literature or to the Food and Drug Administration. The use of methotrexate in the treatment of psoriasis has become more widespread. It is safe to assume that every serious side effect encountered in its use is not always reported by physicians. I currently have a patient under my care who revealed that he went into respiratory failure and then coma, when he had a cocktail while receiving treatment with methotrexate. This complication was never reported. Since psoriasiform lesions make their reappearance after methotrexate therapy is terminated, and
Abstract 3178: Rack1 protects N-terminal phosphorylated c-Jun from Fbw7-mediated degradation
Authors: Jinhui Zhang, Feng Zhu, Xiang Li, Yanming Xu, Cong Peng, Shengqing Li, Yong-Yeon Cho, Ke Yao, Tatyana A. Zykova, Ann M. Bode, Zigang Dong
Journal: Cancer Research (2014)

Abstract The c-Jun transcription factor is a highly unstable oncoprotein. Several ubiquitin ligases mediate c-Jun degradation. However, c-Jun can be stabilized once it is phosphorylated at the N-terminus by c-Jun N-terminal kinases (JNKs) or other protein kinases. This phosphorylation decreases c-Jun ubiquitination and degradation. The underlying mechanism for this phenomenon is still unknown. We show that receptor for activated C-kinase 1 (Rack1) can bind with c-Jun and ubiquitin ligase Fbw7 to form a complex. When c-Jun is phosphorylated at the N-terminus, c-Jun is released from the complex and cannot be ubiquitinated by Fbw7, which leads to increased stabilization and accumulation of c-Jun. These results reveal that Rack1 plays a very important role in tumorigenesis by maintaining the stability of c-Jun that has been phosphorylated at its N- terminus by JNKs or other kinases. Citation Format: Jinhui Zhang, Feng Zhu, Xiang Li, Yanming Xu, Cong Peng, Shengqing Li, Yong-Yeon Cho, Ke Yao, Tatyana A. Zykova, Ann M. Bode, Zigang Dong. Rack1 protects N-terminal phosphorylated c-Jun from Fbw7-mediated degradation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3178. doi:10.1158/1538-7445.AM2014-3178
Differential regulation of lymphokine production by distinct subunits of the T cell interleukin 2 receptor.
Authors: S Burdach, N Zessack, D Dilloo, M Shatsky, D Thompson, L Levitt
Journal: Journal of Clinical Investigation (1991)

Most biologic responses to IL-2 have been attributed to interaction of IL-2 with a high affinity receptor which consists of a heterodimer composed of two distinct IL-2-binding proteins (IL-2R alpha/IL-2R beta). However, both low affinity IL-2R alpha (55 kD) and intermediate affinity IL-2R beta (70-75 kD) also appear to be expressed independently on the cell surface. We investigated the receptor-specific regulatory effects of IL-2 on cytokine production in unstimulated and activated T cells. T cells were activated by stimulation of the antigen receptor complex with anti-CD3 mAb. IL-2 (10(2) U/ml, 1 nM) stimulation of resting cells resulted in a fivefold increase in GM-CSF release but in only minimal IFN-gamma release. IL-2 markedly augmented mRNA expression of GM-CSF but not IFN-gamma in unstimulated T cells. IL-2R beta mAb but not IL-2R alpha mAb decreased IL-2-induced GM-CSF release and mRNA expression from unstimulated T cells. IL-2 concentrations required for GM-CSF release from resting cells suggested ligand binding to an intermediate affinity receptor. GM-CSF and IFN-gamma release from activated T cells increased four- to fivefold in response to 1 nM IL-2 and IL-2 augmented both GM-CSF and IFN-gamma mRNA. IL-2R beta mAb but not IL-2R alpha mAb reduced GM-CSF release and mRNA expression in activated T cells stimulated with 1 nM IL-2. IL-2R alpha blockade markedly decreased IL-2-induced IFN-gamma release and mRNA expression from activated cells, while IL-2R beta blockade had little effect on IFN-gamma production in activated cells. IL-2R alpha blockade altered the affinity of the receptor mediating activated cell GM-CSF release from a high affinity to an intermediate affinity state. These studies indicate an independent role for IL-2R beta in mediating GM-CSF production from T cells. They also suggest that unstimulated and activated T cells, which express distinct IL-2 receptor moieties, mediate release of separate lymphokines and that different subunits of the IL-2 receptor may play an important role in the regulation of cytokine production.