tbuckley/cabot-search huggingface dataset:
Dollar Cost per Positive Test for Automated Multiphasic Screening
Authors: Morris F. Collen, Robert Feldman, Abraham B. Siegelaub, Derek Crawford
Journal: New England Journal of Medicine (1970)

Abstract The costs to identify a clinically important test by an automated multiphasic screening program provide useful information in planning for a specified target population. When 44,663 multiphasic examinations performed in a 12-month period were analyzed, the most costly procedure was found to be the detection of breast cancer ($408.00 per positive mammogram), even when it was limited to women over the age of 47, and the least expensive was hearing impairment ($1.55 per positive audiogram). All other tests ranged between these extremes, usually varying with age and sex of the examinees. These unit costs are critically related to a multiphasic laboratory load of 500 patients per week. The results clearly show how the prevalence of an abnormal test depends on the specific population examined, especially as related to its age–sex composition.
Myeloproliferative Neoplasms
Authors: Ayalew Tefferi, Animesh Pardanani
Journal: JAMA Oncology (2015)

Polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) constitute the BCR-ABL1-negative myeloproliferative neoplasms and are characterized by mutually exclusive Janus kinase 2 (JAK2), calreticulin (CALR), and myeloproliferative leukemia virus oncogene (MPL) mutations; respective frequencies of these mutations are approximately 95%, 0%, and 0% in PV, 60%, 20%, and 3% in ET, and 60%, 25%, and 7% in PMF. These mutations might be accompanied by other mutations that are less specific to myeloproliferative neoplasms but are prognostically relevant, such as additional sex combs-like 1 (ASXL1). Characteristic bone marrow morphology is required for World Health Organization-compliant diagnosis, especially in distinguishing ET from prefibrotic PMF and masked PV. Survival is the longest in ET, although still inferior to that of the age- and sex-matched control population; median survivals for patients younger than 60 years are approximately 33 years for ET, 24 for PV, and 15 for PMF. Major disease complications include thrombosis and leukemic or fibrotic transformation. In PV and ET, risk factors for survival include older age, leukocytosis, and thrombosis, whereas JAK2 mutation in ET is associated with increased risk of thrombosis. In PMF, type 1 or type 1-like CALR mutations are associated with superior and ASXL1 with inferior survival. Prevention of thrombosis in PV is secured by phlebotomy (hematocrit target &lt;45%) and in both PV and ET by low-dose aspirin therapy; high-risk patients derive additional antithrombotic benefit from cytoreductive therapy with hydroxyurea as first-line and interferon-alfa and busulfan as second-line drugs of choice. Although the JAK inhibitor ruxolitinib was recently approved for use in hydroxyurea-resistant PV, its role in routine clinical practice remains debatable. In myelofibrosis, stem cell transplant is the current treatment of choice for genetically or clinically high-risk disease; for all other patients requiring treatment, participation in clinical trials may be preferred because currently available drugs, including JAK inhibitors, are palliative and not shown to be disease modifying.
Prognostic Factors in Meningococcal Disease
Authors: Michael Radetsky
Journal: JAMA (1997)

<h3>To the Editor.</h3> —We are indebted to Dr Barquet and colleagues for the recent report of their vast experience of meningococcal infections and for their efforts to create a validated bedside scoring system.<sup>1</sup>However, without further clarification it would be treacherous to interpret their data as proving that preadmission antimicrobials significantly decrease the risk of a fatal outcome. Based on the rapidity and severity of disease, the authors categorized the 624 cases of infection into fulminant, acute, and subacute subgroups. Yet they did not stratify by subgroup the relationship between preadmission antimicrobials and outcome. Although only 5% of the total number of cases of meningococcal infection were classified as "fulminant," 41% of the deaths occurred in this group (fatality rate of 44%). Contrast this to the "acute" group (71% of cases, 48% of deaths, fatality rate of 3.6%) and the "subacute" group (23% of cases, 8% of deaths, fatality
A History of Cocaine: the Mystery of Coca Java and the Kew PlantKarchS224 pp Price £29.95; US$39.95 ISBN 1-85315-547-0 (h/b) London: RSM Press, 2003
Authors: Anthony D Dayan
Journal: Journal of the Royal Society of Medicine (2003)

Strange history, intriguing curiosities, unhappy lessons for would-be controllers of the cocaine trade and satisfaction for the armchair traveller await the reader of this handsomely produced paperback. Over the years, Professor Karch has written much about cocaine, its actions and its licit and illegal usage, and this new book extends his previous writings on the ways in which cocaine has been used and abused by various European governments for their own purposes. It presents six accounts of the earliest botanical studies, planting and trade in cocaine which illustrate the ability of the species to thrive in Java (now part of Indonesia) as well as in South America, how 19th century pharmacognostic confusion muddled the start of legal international trade in the plant and its alkaloid, and the early appreciation of the source and potential medicinal value of cocaine. It is even possible to discern an early approach to ‘crack cocaine’ in comments on the use of alkaline cocaine mixtures.
THE SANATORIUM FOR INCIPIENT PULMONARY TUBERCULOSIS.ITS AIMS, METHODS AND RESULTS.
Authors: FREDERICK L. HILLS
Journal: JAMA (1905)

<h3>HOME AND SANATORIUM TREATMENT.</h3> The open-air treatment of tuberculosis is to-day an established fact. Its curative value is proven beyond cavil. It is not an experiment. It does not mean, however, that the patient is to be restored simply by a few weeks' or months' sojourn in a "lodge in some vast wilderness" or out-of-door life at a fashionable mountain resort or a tent life in his own back yard under the simple guidance of his own sweet will. It means rather a systematic regulated life under rigid discipline and routine. It means the constant watchfulness of every symptom, not by the patient himself, for this leads to introspection and consequent defeat, but by a well-trained nurse and a physician of experience. It means expense to the individual in time, in patience and in money. To the rich or the well-to-do this may
TELEMETERING TRANSMITTER MUST BE LICENSED
Authors: Ben J. Waple
Journal: JAMA (1960)

<h3>To the Editor:—</h3> An article by Dunn and Beenkem entitled "Short Distance Radio Telemetering of Physiological Information" inThe Journal, April 4, 1959, page 1618, has just been brought to the attention of the Federal Communications Commission (FCC). This article describes a miniature transmitter operating on 104 megacycles that can be attached to a living subject and which is designed to transmit physiological data. Doctors, not being radio technicians, may be assumed to be unfamiliar with the federal radio regulations. We are taking this means to describe these regulations to the American Medical Association and request that they be brought to the attention of its members. A telemetering transmitter such as is described in this article must be licensed before it may be operated legally. When used in connection with experimentation or research, the transmitter may be licensed in the Experimental Radio Service, subject to the condition that no harmful
In vivo and in vitro effects of thrombin and plasmin on human factor VIII (ahf)
Authors: Eric Chun‐Yet Lian, Roger L. Nunez, Donald R. Harkness
Journal: American Journal of Hematology (1976)

Abstract The relationship between factor VIII (AHF) procoagulant activity and factor VIII‐related antigen were examined in patients with disseminated intravascular coagulation (DIC), pulmonary embolism (PE), and coronary artery disease with or without myocardial infarction (MI). It was found that 13 of 13 patients with DIC, 17 of 17 patients with PE, and 10 of 12 patients with MI possessed a significantly elevated factor VIII‐related antigen to factor VIII activity ratio (VIII‐ratio). The VIII‐ratio returned to normal in each of 2 patients with DIC and 1 patient with PE after treatment with heparin, heparin and α‐amino‐caproic acid, and heparin and coumadin respectively. In contrast, the VIII‐ratio was slightly elevated only in 1 of 15 patients with coronary artery insufficiency without MI. In in vitro studies, after treatment of plasma with thrombin or plasmin, factor VIII activity was lost, whereas the amount of factor VIII‐related antigen remained the same or was even increased when measured by agarose quantitative immunoelectrophoresis. These observations have led us to conclude that an elevated VIII‐ratio is a very sensitive indicator of intravascular coagulation.
The most basic units of thought do more, and less, than point
Authors: Frank Keil
Journal: Behavioral and Brain Sciences (1998)

Thinking of concepts as explicit lists of features used to pick out referents neatly is indeed mistaken; but there are other alternatives than making concepts mere pointers. These alternatives are suggested by the difference between meaning X and having the concept X, problems of conceptual change, implicit conceptual schemata, the conceptual requirements of the division of cognitive labor, and how concepts figure in perception versus language.
Colorectal cancer screening: Will global warming affect the accuracy of FIT testing?
Authors: G. Rennert
Journal: Gut (2010)

Colorectal cancer screening with tests that identify occult blood in faeces are currently the cornerstone of the screening programmes in most developed countries.1 The first generation of this class of tests has been proven in several randomised controlled trials to significantly reduce mortality from colorectal cancer when performed every 1–2 years after the age of 50 years.2–5 It has further been shown to be associated with reduced incidence of colorectal cancer, presumably due to additional detection of premalignant lesions.6 However, the old school of faecal occult blood tests (FOBTs), even though proven effective, suffers from less than optimal sensitivity and leaves much to be desired in terms of improved detection qualities. Newer faecal-based tests can be divided into three groups: (1) guaiac tests of higher sensitivity, such as Hemoccult Sensa; (2) high-sensitivity immunological tests and (3) stool-based genetic tests.7 8 Of these, the genetic tests are still at relatively early stages of development and scientifically are not ready yet for prime-time use, in spite of some recent suggestions in this direction.9–11 Both newer techniques of the detection of faecal occult blood, sensitive guaiac and immunological tests, have been demonstrated in several studies to have a sensitivity rate which is at least twice higher than the old generation tests …
Variation of hepatic glucuronidation: Novel functional polymorphisms of the UDP-glucuronosyltransferase UGT1A4
Authors: Ursula Ehmer, Arndt Vogel, Jan Karl Schütte, Britta Krone, Michael P. Manns, Christian P. Strassburg
Journal: Hepatology (2004)

UDP-glucuronosyltransferases are a family of drug metabolizing enzymes contributing to hepatic drug metabolism and protection against environmental toxins. The aim of this study was to identify polymorphisms at the human UGT1A gene locus and to characterize their function and potential association with hepatocellular carcinoma (HCC). Genomic DNA from the blood of 363 subjects (128 patients with HCC, 235 blood donors) was analyzed for polymorphisms of the UGT1A3, UGT1A4, UGT1A8, UGT1A9, UGT1A10 genes using polymerase chain reaction, sequencing analysis. Recombinant variant UGT protein was analyzed by activity assays. In the UGT1A8 gene an A173G variant and a conserved G to A exchange at position 765 were detected in 25% and 15%. UGT1A9 exhibited two variants C3Y and M33T in 1% and 3%. UGT1A10 exhibited conserved nucleotide exchanges (128 G-->A and 696 C-->T) in 2% and 13%. In the UGT1A3 gene a W11R, a V47A variant, and a conserved G to A exchange at position 81 with an incidence of 65%, 58%, and 65%, respectively, were identified. UGT1A4 exhibited a P24T and an L48V variant in 8% and 9%. UGT1A SNPs were not associated with HCC. UGT1A4 P24T and L48V exhibited reduced glucuronidation activities: beta-naphthylamine 30% and 50%, and dihydrotestosterone 50% and 0%, respectively. In conclusion, the high prevalence of SNPs throughout the human UGT1A gene locus illustrates a genetic basis of interindividual variations of hepatic metabolism. Two polymorphisms of the hepatic UGT1A4 protein show a differential metabolic activity toward mutagenic amines and endogenous steroids, altering hepatic metabolism and detoxification.
A non‐immunological phospholipid‐dependent coagulation inhibitor associated with IgGλ‐type multiple myeloma
Authors: Osamu Takamiya, Shinichiro Machida, Masahiro Okuda, Junzo Nojima, Chikako Koreeda, Katuhiko Kubara
Journal: American Journal of Hematology (2003)

Abstract We investigated the rare case of a patient with IgGλ multiple myeloma for whom both prothrombin time and APTT were significantly prolonged. The IgG inhibited coagulation reactions upstream from prothrombin when coagulation was initiated by mRVVT, but not by FXa, as indicated by a chromogenic substrate for FXa. The mPT and the mAPTT showed inhibition of FXa generation in both the intrinsic and extrinsic pathways. The IgG inhibited both protein C (indicated by APTT) and FX (indicated by RVV) but not amidolysis for either activated protein C or FXa. The addition of excess phospholipid significantly shortened the prolonged RVVT of the patient. It inhibited the coagulation reactions of normal plasma and was dependent on decreasing the PS concentration in the APTT reagent. It was suggested that the IgG showed lupus anticoagulant (LA)‐like activity that inhibited phospholipid‐dependent coagulation reactions in the intrinsic, extrinsic, and common pathways. However, the IgG did not bind cardiolipin–β2GPI complex, β2GPI, or prothrombin in ELISA assays. The IgG did not bind to either PS or phospholipid complexes in the presence or absence of prothrombin, FX, or FXa. Interestingly, the IgG lost its LA like‐activity when it was degraded to F(ab′)2 and Fc fragments by pepsin. We suspected that the IgG might inhibit the interaction between coagulation factors and acid phospholipid non‐immunologically and that this process requires an intact IgG conformation, although the reaction mode is still not clear. Am. J. Hematol. 75:34–39, 2004. © 2003 Wiley‐Liss, Inc.
One step forward in engaging clinicians in IT
Authors: Mark E Lloyd, Paul A Reilly
Journal: BMJ (2006)

EDITOR—We read with sympathy the experience of setting up and maintaining a database.1 As rheumatologists in a district general hospital, we went through a similar process, but with a more positive outcome.

We initially explored standalone databases, which were costly, not guaranteed to link with our hospital systems, and requiring the expense of annual back up. One of us (MEL) sat on …
Teenage Suicide Clusters-Reply
Authors: Lucy Davidson
Journal: JAMA (1990)

<h3>In Reply.—</h3> Dr Gould raises important points in directing attention to our study's limited ability to assess the relationship between media exposure and suicide risk and to the possibility of selection bias. Her first point is that the control subjects lived longer than the suicide cases and thus they had more chances than the case subjects to be exposed to media coverage of the suicides. We recognized that earlier case subjects had fewer opportunities for media exposure than control subjects and stated that our small number of cases precluded analysis by opportunity for exposure. However, since exposure via television was reported for only 1 of the 13 case subjects, we believe that the differences are actual and cannot be solely ascribed to increasing opportunities for exposure during the series. Still, we agree with Dr Gould's point and believe that it would have been better to state that our study data
Blood transfusion risk: protecting against the unknown
Authors: J. Barbara, P. Flanagan
Journal: BMJ (1998)

News p 726 

In relation to viruses— which, classically, have posed the greatest potential risk to transfusion recipients—British blood is among the safest in the world. For HIV, the risk per unit of transfusion is about 1 in 2.5 million.1 But British blood services are now faced with the challenge of managing a potential risk from the transmissible spongiform encephalopathies, notably variant Creutzfeldt-Jakob disease. This challenge is particularly difficult given the lack of firm data on either the likely scale of variant Creutzfeldt-Jakob disease infection in Britain or the likelihood that the causative agent is present in and transmissible by donated blood. The announcement by the Department of Health, following advice from the Committee on Safety of Medicines, on 26 February of “further precautionary measures” in relation to the use of British plasma in blood products brings the challenge sharply into focus.

In March 1997 the World Health Organisation concluded that there is no proved or even probable instance of transmission of Creutzfeldt-Jakob disease by blood, blood components, or plasma derivatives, though it did identify a requirement to assess further the potential risk posed to transfusion by variant Creutzfeldt-Jakob disease.2 Lack of evidence of risk is not evidence of absence …
Kindlin-2 regulates hemostasis by controlling endothelial cell–surface expression of ADP/AMP catabolic enzymes via a clathrin-dependent mechanism
Authors: Elzbieta Pluskota, Yi Ma, Kamila M. Bledzka, Katarzyna Bialkowska, Dmitry A. Soloviev, Dorota Szpak, Eugene A. Podrez, Paul L. Fox, Stanley L. Hazen, James J. Dowling, Yan-Qing Ma, Edward F. Plow
Journal: Blood (2013)
Human Prolactin: Measurement in Plasma by In Vitro Bioassay
Authors: David L. Kleinberg, Andrew G. Frantz
Journal: Journal of Clinical Investigation (1971)

Prolactin has been measured in unextracted human plasma by a sensitive and specific in vitro bioassay. Secretory activity of breast tissue fragments from mid-pregnant mice, incubated in organ culture with human plasma, serves as the histologic end point. Sensitivity is 5 ng/ml (0.14 mU/ml) or somewhat better for ovine prolactin, and approximately 0.42 mU/ml for prolactin activity of human plasma at the dilutions used in the assay. Human growth hormone as it circulates in blood, like the material extracted from pituitary glands, is strongly lactogenic. Antisera to human growth hormone are capable of completely neutralizing the prolactin effect of large amounts (600 ng/ml) of human growth hormone added to the system. Plasma prolactin activity is less than 0.42 mU/ml in normal men and women. Of 26 patients with nonpuerperal galactorrhea, 14 had elevated prolactin activities ranging from 0.42 to 3.5 mU/ml. Growth hormone levels by radioimmunoassay were far too low, in general, to account for the observed prolactin activity. All of 14 nursing mothers, 1-30 days post partum, had elevated prolactin activity with a mean of 2.29 and a total range of 0.56-4.5 mU/ml. Growth hormone was in the low normal range in all of these subjects. Seven patients on psychoactive drugs of the phenothiazine series similarly had elevated prolactin activity with low growth hormone. Antiserum to human growth hormone, when preincubated with plasma samples from each of these three groups of subjects, produced no significant inhibition of prolactin activity. In two acromegalic patients with markedly elevated growth hormone levels, antiserum to growth hormone produced complete inhibition of prolactin activity in one and partial inhibition in the other. These studies indicate that human growth hormone and human prolactin are separate molecules, with little if any immunologic cross-reactivity, at least as demonstrated by the antisera used in this study, and that their release is governed by different physiologic mechanisms.
Abstract 3078: Isolation and in vitro culturing of human circulating tumor cells
Authors: Vladimir Bobek, Katarina Kolostova
Journal: Cancer Research (2014)

Abstract The CTC-enrichment based on the size of the cells, is addressing the problem of reduced EpCAM expression, but filtration shows relatively low sensitivity and specificity, because small CTCs may escape of the detection, whereas big leukocytes may contaminate population of CTCs Isolation by size of epithelial tumor cells is based on use of filters, which preferentially capture tumor cells bigger than 8 uM. Our filtration device (MetaCell®, Metacell s.r.o., Ostrava, Czech Republic) isolates tumor cells by size from a blood sample up to 6 ml. Moreover immunocytochemistry and FISH assays can be performed on the filter. The protocol enables to isolate viable cells, allowing further in vitro experiments. Furthermore, tumor cells can be isolated without using an antibody-based approach, suggesting that the device can be used for the isolation of a large spectrum of tumor cells, including cell of non-epithelial origin. We presented the successful isolation and cultivation of CTC/DTC of the following cancer: NSCLC, mesothelioma, oesophageal cancer, colorectal cancer, gastric cancer, pancreatic cancer, leiomyosarcoma, prostate cancer, malignant melanoma and renal cancer. Citation Format: Vladimir Bobek, Katarina Kolostova. Isolation and in vitro culturing of human circulating tumor cells. [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 3078. doi:10.1158/1538-7445.AM2014-3078
The European Commission and pharmaceutical policy
Authors: M. McKee, P. Belcher
Journal: BMJ (2014)

A victory for profits over public health?

News of the allocation by the European Commission’s president elect, Jean-Claude Juncker, of portfolios to the remaining European Commissioners has been eagerly awaited. This is an intensely political process, with the largest member states vying among themselves for the main economic roles. Would Juncker follow established precedent, giving health a low priority by allocating the portfolio to one of the countries with the smallest economies and thus, in effect, least political power in the European Union? This process had seen responsibility transfer, after European Union enlargement, from Ireland to Cyprus and then Malta. Or would he break with precedent and allocate it on the basis of merit, choosing the commissioner whose expertise and experience most closely matched the role?

This time it seemed at least possible that Juncker would choose the second course, given that the line up included a very experienced candidate, Vytenis Andriukaitis, a Lithuanian surgeon who had been active in his country’s struggle for independence and gone on to become a successful health minister. European health policy experts were delighted when Juncker chose this course; subject to approval by the European Parliament, Andriukaitis will take up his role in November 2014.

Yet very shortly afterwards …