tbuckley/cabot-search huggingface dataset:
FHSA medical advisers: friends or foes?
Authors: T. Walley, J. Bligh
Journal: BMJ (1992)

antibodies as well as differences in the design of the studies, contribution to improving the outcome of life threatening the patient population, and the definition of shock.infections.The importance of resolving these uncertainties is high-CJ HINDS lighted by the financial implications of the universal introduc-Director of Intensive Care, tion of monoclonal antibodies against endotoxin for treating St Bartholomew's Hospital, suspected Gram negative sepsis and septic shock.Not only is London ECIA 7BE HA-lA expensive but vast numbers of patients would fulfil even the strictest criteria for its administration: in the United I Ledingham lMcA, McArdle CS.Prospective study of the treatment of septic shock.Lancet Kingdom there are perhaps 25 000 cases of Gram negative 2 Espevik T, Brockhaus M, Loetscher H, Nonstad U, Shalaby R. Characterization of binding and septicaemia each year. 22 Here expenditure on HA-lA could biological effects ofmonoclonal antibodiesagainst a human tumor necrosis factor receptor.JExp exceed £100m a year22; in the United States the annual cost 3 Hinshaw LB, Tekamp-Olson P, Chang ACK, Lee PA, Taylor FB Jr, Murray CK, et al.Survival of could approach$1 16b.23These figures have caused consider-primates in LD,, septic shock following therapy with antibody to tumor necrosis factor (TNFo).could approach $1-6b.2These figures have caused consider- Circ Shock 1990;30:279-92.able alarm, although they are likely to be overestimates and 4
Observations on the Late Effects of Internally Deposited Mixtures of Mesothorium and Radium in Twelve Dial Painters
Authors: W. H. Baker, J. B. Bulkley, R. A. Dudley, R. D. Evans, H. B. McCluskey, J. D. Reeves, R. H. Ryder, L. P. Salter, M. M. Shanahan
Journal: New England Journal of Medicine (1961)

CASE-history data are presented on 12 women who have carried in their skeletons for many years toxicologically interesting burdens of the radioisotopes Ra226 (radium, or Ra) and Ra228 (mesothorium, or MsTh). This is one of a series of reports from these laboratories on a continuing study of Ra and MsTh toxicity to human beings. The most recent previous publication of data obtained in this project, aside from annual progress reports, appeared in 1952.1 The effects of long continued skeletal irradiation in human beings have thus far been observed in significant detail only in persons occupationally or medically exposed to Ra . . .
Methadone and l-Methadyl Acetate
Authors: Jerome H. Jaffe
Journal: JAMA (1971)

Ten volunteer patients participating in a methadone hydrochloride maintenance program were assigned randomly to experimental (five patients) or control (five patients) groups. These patients had been in treatment for several months and had been stabilized (had no change of dose for at least three weeks) with methadone prior to inclusion in the study. Patients in the experimental group were given l-methadyl acetate (l-α acetylmethadol) on weekends and methadone on weekdays. Patients in the control group were given methadone each day. Clinic attendance, requests for change in medication, and scores on an opiate-withdrawal test instrument did not reveal differences between groups. Clinical observers blind to the experiment were unable to discriminate experimental and control patients. No untoward reactions were observed in either group. These preliminary observations suggest that l-methadyl acetate can be interchanged repeatedly with methadone without difficulty.
Antitissue antibodies in monozygotic twins with systemic lupus erythematosus.
Authors: E.J Jokinson, E.O Jänkälä
Journal: Annals of the Rheumatic Diseases (1970)

Zike, and Julian, 1961; Leonhardt, 1964), and even monozygotic twins with this disease have been re- ported by several workers (Davis and Gutridge, 1951; Wagenhals and Burgeson, 1958; Blumenfeld, Kaplan, Mills, and Clark, 1963; Joseph and Zara- fonetis, 1965; Lieberman, Heuser, Hanson, Kornreich, Donnell, and Landing, 1968).These observations have been considered to indicate that genetically determined factors may have an important role in the aetiology of SLE.The following is a report of a pair of monozygotic twins both of whom had SLE with a very similar clinical picture and who, in addition, had a very similar antitissue antibody pattern. Case reportsCase 1, a 33-year-old housewife, mother of three children, was sent to hospital for pyrexia, arthralgia, and loss of weight.She had a childhood history of frequently recurring tonsillitis.When 6 years of age she had had scarlet fever, with accompanying carditis, from which she made a good recovery.Arthralgia, especially in the fingers, wrists, elbow joints, and ankles had continued for nearly 10 years.The persistent rash on the patient's
The 'Power' of Sound Statistics
Authors: Theodore Colton
Journal: JAMA (1990)

During the dozen years or so that I have served as a biostatistical consultant to the editors of<i>JAMA</i>, the most frequent comment I have made in my reviews is the simple, straightforward question, "Can the authors provide any rationale or statistical power considerations underlying their choice of sample size?" From this experience, I infer that lack of adequate justification for sample size is a major statistical limitation that pertains to many of the manuscripts submitted to<i>JAMA</i>. I greet with great enthusiasm any attempt to disseminate more widely the message of proper statistical planning of a research endeavor, particularly in regard to choice of study size. Hence, I am delighted to see the article by Arkin and Wachtel entitled "How Many Patients Are Necessary to Assess Test Performance?" appear in this issue ofThe Journal.<sup>1</sup> The article breaks no new statistical ground. Essentially, the authors apply standard textbook
Abstract 3073: Detection and isolation of circulating tumor cells in ovarian cancer: Principles and methods
Authors: Shin-Wha Lee, Ha-Young Lee, Jin-Young Mo, Byung Chul Kim, Eun Hye Kim, Yong-Man Kim
Journal: Cancer Research (2014)

Abstract Objective: The quantitative and qualitative analysis of circulating tumor cells (CTCs) aids in diagnosis of disease, prognosis, disease recurrence, and therapeutic response in several cancers. However, detection and isolation of CTCs from the blood circulation is a difficult task because of their scarcity and the lack of reliable markers to identify these cells. Especially, in epithelial ovarian cancer, there is a little reported data for CTCs and their CTCs has been defined to the EpCAM+ cells, even though EpCAM+ cells are just a few in ovarian cancer. The aim of this study is to investigate the effective principles and methods to detect and isolate CTCs through novel markers in ovarian cancer. Methods: CTC analysis was performed in the spiking test to find cancer cells in the human serum mixed with WBCs. Four cell lines including OVCAR3, SKOV3, SNU8 and SNU251 were used and primary cancer cells from 4 patients were analyzed. Cancer cells were isolated on the basis of cell size by filtration through CytoGen capture device, followed by identification according to validated immunocytochemistry based on the expression of DAPI, CD45, EpCAM, CK, CA-125 and HE4. Results: We obtained cancer cells more than 90% based on the cell size by filtration. Immunocytochemistry confirmed the epithelial origin through the expression of CK and EpCAM in cancer cell lines. The rate of expression was 35-99 % for CK and 1-99 % for EpCAM. A small number of cancer cell lines expressed CD45 that is the marker of WBC. The expression of CA-125 and HE4 showed their ovarian origin. The rate of expression was 7-98 % for CA-125 and 40-99 % for HE4 in cancer cell lines. Primary cancer cells were detected most effectively as the method of combination with 4 markers, including DAPI, CD45, EpCAM and HE4. Conclusion: Our findings provide the first evidence for effective methods to detect and isolate CTCs in ovarian cancer. Combination of DAPI, CD45, EpCAM and HE4 could be a useful marker to support CTCs research in epithelial ovarian cancer. Citation Format: Shin-Wha Lee, Ha-Young Lee, Jin-Young Mo, Byung Chul Kim, Eun Hye Kim, Yong-Man Kim. Detection and isolation of circulating tumor cells in ovarian cancer: Principles and methods. [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 3073. doi:10.1158/1538-7445.AM2014-3073
P143 A Retrospective Study of Echocardiography and Follow-Up After Acute Pulmonary Embolism – Are We Missing Chronic Thromboembolic Pulmonary Hypertension?
Authors: D Slim, CN McBrien, LM O’Sullivan, SD Message, A Raghuram
Journal: Thorax (2012)

<h3>Introduction</h3> Pulmonary Hypertension (PH) is defined as raised Pulmonary Arterial Systolic Pressure ≥25mmHg at rest on Right Heart Catheterisation.<sup>1</sup> Chronic Thromoboembolic Pulmonary Hypertension (CTEPH) is a recognised complication of pulmonary embolism (PE),with a reported annual cumulative incidence of 3.1%.<sup>2</sup> Patients with evidence of PH or Right Ventricular Dysfunction (RVD) during admission should be referred for echocardiography usually 3–6 months after discharge to establish PH resolution.<sup>1</sup> <h3>Objective</h3> To identify patients at risk of CTEPH, evaluate their follow-up plans and establish the proportion with evidence of acute RVD/PH who are investigated for persistent PH. <h3>Methods</h3> Retrospective analysis of all diagnoses of PE on Computed Tomography Pulmonary Angiography (CTPA) in 2010 in a single Trust. Patients were stratified according to size and location of PE, and any reported radiological evidence of RVD. Echocardiography reports were reviewed for evidence of PH. <h3>Results</h3> 19.3%(329/1702) of CTPA scans revealed PE: Massive (28.6%); Submassive (28.0%); Peripheral (44.4%). Only 17.6%(58/329) had inpatient echocardiography, with 55.1%(32/58) suggesting PH (PASP≥ 36 mmHg). 78.1%(25/32) of these patients survived to 6 months and follow-up echocardiography was performed within 6 months for 40%(10/25) of this subset. Overall, 80.9% (266/329) of patients with confirmed PE survived past 6 months. Follow-up echocardiogram was performed within 6 months on 20.3% (54/266) of survivors; PH was demonstrated in 18.5%(10/54). RV strain was reported in 15.2% (50/329) of CTPA scans. Follow-up echocardiogram was performed within 6 months on 19.5% (8/41) of those alive at 6 months. 84.2%(154/183)of individuals diagnosed with a massive or submassive PE survived to 6 months. Respiratory or cardiology follow-up was planned for 23% (36/154). <h3>Conclusions</h3> Our findings suggest follow-up after acute PE is suboptimal, potentially missing early PH due to a low number of early echocardiograms. The relatively high percentage of PH on echocardiography compared to reported rates is likely due to selection bias. The results suggest there may be a missed cohort at risk of developing PH, i.e. those with RV strain on CTPA or high thrombus load, being denied early or more aggressive interventions such as pulmonary endarterectomy. <h3>References</h3> Galié et al. <i>EurRespirJ</i> 2009; 34:1219–63. Pengo et al. <i>NEJM</i> 2004; <b>350</b>:2257–64.
THE ETIOLOGY AND RECENT TREATMENT OF HAY FEVER.
Authors: H. HOLBROOK CURTIS
Journal: JAMA (1907)

The factors which enter into the causation of hay fever, or better, hyperesthetic rhinitis, a name proposed by Sajous, are: First, a nervous element; second, a pathologic change in the nasal mucous membrane; third, an exciting constitutional dyscrasia, as a lithemic or uric acid diathesis; and fourth, some adventitious irritation, as dust, pollens or animal emanations. 1. Hyperesthetic rhinitis may occur from an adynamic state of the nervous system irrespective of other causes, or may result from a combination of external irritation and a predisposing neurotic factor. The first class is illustrated by the cases of spontaneous attacks accompanied by sneezing and lachrymation, occurring at any time of day and irrespective of the season. Cases of this character demand a careful investigation as to the cause of nervous trouble, and as treatment, toning up of the general system by baths, exercise, diet, etc., I can not help mentioning a tablet
SA-4-1BBL and Monophosphoryl Lipid A Constitute an Efficacious Combination Adjuvant for Cancer Vaccines
Authors: Abhishek K. Srivastava, Gunes Dinc, Rajesh K. Sharma, Esma S. Yolcu, Hong Zhao, Haval Shirwan
Journal: Cancer Research (2014)

Abstract Vaccines based on tumor-associated antigens (TAA) have limited therapeutic efficacy due to their weak immunogenic nature and the various immune evasion mechanisms active in advanced tumors. In an effort to overcome these limitations, we evaluated a combination of the T-cell costimulatory molecule SA-4-1BBL with the TLR4 agonist monophosphoryl lipid A (MPL) as a novel vaccine adjuvant system. In the TC-1 mouse allograft model of human papilloma virus (HPV)-induced cancer, a single administration of this combination adjuvant with HPV E7 protein caused tumor rejection in all tumor-bearing mice. On its own, SA-4-1BBL outperformed MPL in this setting. Against established tumors, two vaccinations were sufficient to elicit rejection in the majority of mice. In the metastatic model of Lewis lung carcinoma, vaccination of the TAA survivin with SA-4-1BBL/MPL yielded superior efficacy against pulmonary metastases. Therapeutic efficacy of SA-4-1BBL/MPL was achieved in the absence of detectable toxicity, correlating with enhanced dendritic cell activation, CD8+ T-cell function, and an increased intratumoral ratio of CD8+ T effector cells to CD4+FoxP3+ T regulatory cells. Unexpectedly, use of MPL on its own was associated with unfavorable intratumoral ratios of these T-cell populations, resulting in suboptimal efficacy. The efficacy of MPL monotherapy was restored by depletion of T regulatory cells, whereas eliminating CD8+ T cells abolished the efficacy of its combination with SA-4-1BBL. Mechanistic investigations showed that IFNγ played a critical role in supporting the therapeutic effect of SA-4-1BBL/MPL. Taken together, our results offer a preclinical proof of concept for the use of a powerful new adjuvant system for TAA-based cancer vaccines. Cancer Res; 74(22); 6441–51. ©2014 AACR.
Human mononuclear cell factors mediate cartilage matrix degradation through chondrocyte activation.
Authors: H E Jasin, J T Dingle
Journal: Journal of Clinical Investigation (1981)

Human blood mononuclear cells (BMC) in short-term culture secrete one or more factors that induce degradation of matrix proteoglycan and collagen in cartilage explants in organ culture. Induction of matrix degradation took place both in nasal septum and articular cartilage explants in the presence of the mononuclear cell supernates. Cartilage degradation in this system was absolutely dependent on the presence of live chondrocytes. Matrix depletion did not occur in dead cartilage explants cultured with active supernates. Supernates obtained from unstimulated BMC showed variable cartilage matrix degrading activity (MDA). BMC stimulated with phytohemagglutinin (PHA) showed increased MDA, which in one dilution experiment was found to be five times higher than that in the unstimulated control supernate. Concanavalin A and pokeweed mitogen were also shown to stimulate release of MDA. Time experiments showed that most of the degrading activity was released by the mononuclear cells during the first day of culture. The cellular origin of MDA was investigated with the aid of partially purified BMC subpopulations. Removal of adherent cells resulted in a decrease of MDA release. Purified T lymphocytes failed to show enhanced MDA release in spite of their ability to mount a virtually intact proliferative response to PHA. Purified adherent cells also failed to show enhanced PHA-dependent MDA release. Nevertheless, restoration of PHA-dependent MDA release took place in reconstituted cell populations containing both T lymphocytes and monocytes. These experiments suggest that MDA may be released by adherent mononuclear cells, presumably monocytes, and that the PHA-dependent increase in MDA release may be mediated by T lymphocytes. Partial characterization of MDA by gel chromatography showed one active fraction corresponding to an apparent molecular weight ranging from 12,000 to 20,000. The fraction was also shown to degrade cartilage matrix only in the presence of live chondrocytes. These results demonstrate that factors released by human BMC mediate degradation of matrix proteoglycan and collagen in intact cartilage explants through chondrocyte activation. This pathogenic mechanism may play a role in in vivo cartilage destruction in chronic inflammatory joint diseases.
Asthma: Is It Due to an Abnormal Airway Smooth Muscle Cell?
Authors: Peter Borger, Michael Tamm, Judith L. Black, Michael Roth
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Asthma is an airway disease highly prevalent in westernized countries and of unknown etiology. Often, asthma is associated with atopy, but not all atopic individuals have asthma. Some patients with asthma outgrow symptoms, whereas many others acquire asthma later in life. Still other patients suffer from asthma their entire life. How can we explain these different patterns? It may be that asthma should be regarded as the clinical manifestation of a group of diseases with similar pathology due to a common factor. In this Pulmonary Perspective, we propose that an aberrant phenotype of airway smooth muscle (ASM) cells could be sufficient to explain the pathology of asthma. We will argue an abnormal ASM cell is a prerequisite to the development of asthma. Our postulate is that inadequate levels of C/EBPalpha, a protein that is pivotal for the suppression of both inflammation and proliferation responses, confer on ASM cells an activated phenotype that is more susceptible to mitogenic and contractile stimuli.
Monographs on Neoplastic Disease at Various Sites. Vol. IV: Tumors of the Esophagus
Authors: Joseph E. Macmanus
Journal: JAMA (1962)

The authors have brought together from widely scattered sources a large amount of material bearing on esophageal tumors in this large monograph which is their contribution toward a series of monographs on neoplastic disease being published by a large group of British medical scientists. The monograph on esophageal tumors examines the mortality from this disease in 18 separate countries with a wide discussion of the factors predisposing to the development of neoplastic disease in this organ. The pathology and natural history of the tumors are well covered. While the diagnosis and treatment chapters contain little new they do gather, in concentrated form, the material that has been available in the last few years in the important surgical literature with the particular imprint of the authors apparent in their discussion. Of particular value in the monograph is the analysis of treatment of esophageal tumors because of the large area from which
The Common Bond: The University of Texas System Cancer Center Code of Ethics
Authors: Michael A. Grodin
Journal: JAMA (1987)

"Oaths, codes, declarations and statements of principles that discuss moral issues that practitioners engaging illness should consider are among the most significant documents in the literature of health care." So states Stanley Reiser in one of the early chapters of a text focused on the creation and implementation of a code of ethics at the University of Texas (UT) Systems Cancer Center. For two years, between 1984 and 1986, the M. D. Anderson Hospital and Tumor Institute grappled with selfevaluation and introspection within its staff and between its patients and community in the compilation of a unique document. One culmination of this ongoing endeavor was a conference/critique of the proposed code, and<i>The Common Bond</i>is an edited anthology summarizing the substance and procedure of this undertaking. The UT Cancer Center is an institution dedicated to patient care, teaching, research, and education. This complex interplay of goals and interests presents
Fascinating science, compelling cause
Authors: V. K. Viswanathan
Journal: Gut Microbes (2010)

The gut is a unique niche, favored by over 400 species of mostly benign and friendly microorganisms, and, under certain circumstances, by injectisome-wielding, toxin-producing miscreants. Judging by the crowd of up to a 100 trillion, it is a popular hangout, though one wouldn’t think so at first look. I mean, honestly, who would want to hang out in such a crowded place, jostled around by passing food and fecal material, getting stuck in mucus, attacked by antimicrobial compounds and infiltrating neutrophils, sampled by dendritic cells, and the absolute ignominy of all, being flushed out unceremoniously ever so often? And yet, many do, and what they favor is the warmth of the place, the free availability of food and water, and given some adjustments, even the ability to settle down and make a colony, a biofilm one could call home, sometimes just for a few generations.
Minimal Effective Dosage of Cromolyn
Authors: Stanley Hoyt Block
Journal: JAMA (1974)

<h3>To the Editor.—</h3> Numerous studies have shown that cromolyn sodium is an effective antiasthmatic medicine when used prophylactically on a regular basis. Cromolyn inhibits the degranulation of sensitized mast cells that occurs after exposure to specific antigens, and inhibits the release of histamine and SRS-A. The manufacturers of cromolyn, and investigators, advise a starting dose of 20 mg (one capsule) four times a day by inhalation, for children 5 years old and over.<sup>1</sup>The manufacturers' brochures state that "the dose for adults and children 5 and over is the contents of one Aarane capsule inhaled four times daily at regular intervals...." Dykes<sup>2</sup>specifies the minimum dosage that is found effective. For this reason, the following case illustrates an important point. <h3>Report of a Case.—</h3> A 5-year-old white boy gave a three-year history of asthma, and had been wheezing almost daily for two years. His wheezing increased with exercise.
Pathophysiology of Vascular Calcification in Chronic Kidney Disease
Authors: Sharon M. Moe, Neal X. Chen
Journal: Circulation Research (2004)

Patients with chronic kidney disease (CKD) on dialysis have 2- to 5-fold more coronary artery calcification than age-matched individuals with angiographically proven coronary artery disease. In addition to increased traditional risk factors, CKD patients also have a number of nontraditional cardiovascular risk factors that may play a prominent role in the pathogenesis of arterial calcification, including duration of dialysis and disorders of mineral metabolism. In histological specimens from the inferior epigastric artery of dialysis patients, we have found expression of the osteoblast differentiation factor core binding factor α-1 (Cbfa1) and several bone-associated proteins (osteopontin, bone sialoprotein, alkaline phosphatase, type I collagen) in both the intima and medial layers when calcification was present. In cultured vascular smooth muscle cells, the addition of pooled serum from dialysis patients (versus normal healthy controls) accelerated mineralization and increased expression of Cbfa1, osteopontin, and alkaline phosphatase to a similar magnitude as does β-glycerophosphate alone. However, a lack of inhibitors of calcification may also be important. Dialysis patients with low levels of serum fetuin-A, a circulating inhibitor of mineralization, have increased coronary artery calcification and fetuin-A can inhibit mineralization of vascular smooth muscle cells in vitro. These data support that elevated levels of phosphorus and/or other potential uremic toxins may play an important role by transforming vascular smooth muscle cells into osteoblast-like cells, which can produce a matrix of bone collagen and noncollagenous proteins. This nidus can then mineralize if the balance of pro-mineralizing factors outweighs inhibitory factors.