tbuckley/cabot-search huggingface dataset:
Mechanism of Intravenous Immune Globulin Therapy in Antibody-Mediated Autoimmune Diseases
Authors: Z Yu, V A Lennon
Journal: New England Journal of Medicine (1999)

For more than two decades, the intravenous administration of high doses of IgG pooled from the plasma of healthy donors (immune globulin therapy, also known as “IVIg”) has benefited patients with a variety of autoimmune disorders. Although its mechanism of action is not known, immune globulin is accepted as an effective and convenient alternative to plasmapheresis for treating diseases that are thought to be mediated by pathogenic autoantibodies or immune complexes.1 It is used increasingly to treat neurologic diseases such as inflammatory demyelinating neuropathies, multifocal motor neuropathy, inflammatory myopathies, myasthenia gravis, and the Lambert–Eaton syndrome. The efficacy of immune globulin . . .
A–Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance—Part 22
Authors: H Geyer, H Braun, L M Burke, S J Stear, L M Castell
Journal: British Journal of Sports Medicine (2011)

Practitioners who work with elite athletes know that the pressure and considerable rewards involved with success provide a high level of motivation to look for any safe and legal strategy that might enhance performance, even by small margins. Dietary supplements operate in this space, whether they promise a large performance boost or just create the fear that an athlete cannot afford to miss out on what everyone else is using. It is often tempting to overlook the lack of evidence to support the claims made about a supplement on the basis that the stakes are higher for elite athletes; therefore the cost:benefit ratio favours experimentation in the absence of clear proof. Over the past decade, however, we have become aware that the cost of getting it wrong has also escalated for elite athletes. A new hazard related to supplement use has emerged: inadvertent ingestion of substances that are banned under the antidoping codes in place in elite sport, but present in supplement products. In some cases, the level of the presence, or contamination, of banned substances in supplements presents a health hazard for all consumers. In some cases, the concentration may be too small to achieve any health or performance effect but large enough to record an infringement for athletes who submit to doping tests. Newspapers, the internet and Courts of Arbitration in Sport now bear stories of dedicated athletes whose careers have been or are being jeopardised because of the ingestion of a banned substance via a dietary supplement. This problem was first brought to scientific recognition by Hans Geyer and his colleagues from the Centre for Preventive Doping Research in Cologne. The following article provides an update of a recent review by this team.1



In the past years, an increasing number of dietary supplements containing undeclared doping …
Orofacial injuries and the use of mouthguards by the 1984 Great Britain Rugby League touring team.
Authors: P J Chapman
Journal: British Journal of Sports Medicine (1985)

Mouthguards are considered by most authorities to be an essential part of equipment for players in any body-contact sports, especially the combative type e.g. Rugby Union, Rugby League, American Football (gridiron), boxing, etc. (Turner, 1977). The qualities provided by the mouthguard are dental protection, especially of the upper anterior teeth, soft tissue protection around the mouth, a reduction in the risk of fracture of the mandible, and a reduction in the concussion force from a blow to the mandible (Clegg, 1969; Upson, 1982; Davies et al, 1977). Of the 28 players interviewed, only 7 (25%) wore mouthguards, the commonest reason for not using a mouthguard being difficulty with breathing, a finding in common with other similar surveys (Davies et al, 1977). In view of the fact that 17 (60.7%) had sustained oral injuries - dental and jaw injuries, intra-oral and circumoral lacerations, in the past, it was a surprising response to find that only 2 (7.2%) stated that mouthguards should be compulsory when playing Rugby League football.
Abstract P6-12-11: Celecoxib inhibits the growth of IBC tumors by suppressing the regulation of cancer stem-like cells by nodal
Authors: ME Reyes, D Zhang, B Eckhardt, H Masuda, DA Pirman, JM Reuben, W Woodward, P Yang, GN Hortobagyi, X Wang, NT Ueno
Journal: Cancer Research (2013)

Abstract Background: Inflammatory breast cancer (IBC) is an aggressive type of breast cancer with no known molecular targets for treatment. Although erythema is commonly associated with IBC, the molecular mechanism of inflammation in the pathogenesis of IBC remains unknown. We have previously shown that EGFR is an emerging target in IBC (Zhang D. et al Clin Can Res 2009). As crosstalk between EGFR and COX-2 plays an important role in the inflammatory response in several cancers, including breast cancer, we hypothesized that COX-2 promotes the tumorigenesis and metastasis of IBC cells. Methods: Using clinically derived IBC and non-IBC tumor samples, a Spearman's Rank correlation coefficient analysis was performed to analyze the expression levels of COX-2 and EGFR in IBC and non-IBC. The levels of COX-2 metabolites, prostaglandins (PGs) PGE2 and PGF2α, were measured in IBC and non-IBC cell lines by HPLC/MS method. Cell migration and invasion assays were performed using SUM149 and KPL-4 IBC cell lines treated with PGs or the COX-2 inhibitor, celecoxib. We evaluated the epithelial to mesenchymal transition (EMT)-like phenotype in 3D culture of SUM149 cells treated with celecoxib, and the stem-like population by mammosphere formation, and CD44+/CD24− and aldefluor+ population by FACS. We treated preclinical IBC xenograft mice with celecoxib and measured tumor growth, PGs levels, and the expression of EMT protein markers. Nodal, a stem cell regulator and potential biomarker for breast cancer progression, was evaluated in IBC cells following treatment with celecoxib and recombinant Nodal or transfection with Nodal cDNA. Results: EGFR and COX-2 expression levels positively correlated within IBC, but not non-IBC tumors. Elevated levels of PGE2 and PGF2α were identified in multiple IBC cell lines suggesting that COX activity is elevated within IBC compared to non-IBC cells. PGs altered EMT protein markers and promoted cell migration and invasion, while Celecoxib inhibited EMT and migration and invasion in SUM149 and KPL-4 cells. Celecoxib treatment inhibited tumor growth in mice, and downregulated the expression of EMT protein markers, including Nodal. Celecoxib decreased the stem-like CD44+/CD24−, and aldefluor+ population and the formation of mammospheres. Exogenous Nodal mitigated the effects of celecoxib on cell migration and invasion and the stem-like population in SUM149 cells. Conclusion: We conclude that activation of the COX-2 inflammatory signaling pathway is critical in the development and progression of IBC. This study provides a novel insight into how inflammation may regulate cancer stem cells via Nodal, and will guide future research into the development of stem cell targeted therapies for IBC. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-12-11.
The road to embryologically based dose-response models.
Authors: R J Kavlock, R W Setzer
Journal: Environmental Health Perspectives (1996)

The goal of researchers working in the area of developmental toxicology is to prevent adverse reproductive outcomes (early pregnancy loss, birth defects, reduced birth weight, and altered functional development) in humans due to exposures to environmental contaminants, therapeutic drugs, and other factors. To best achieve that goal, it is important that relevant information be gathered and assimilated in the risk assessment process. One of the major challenges of improved risk assessment is to better use all pertinent biological and mechanistic information. This may be done qualitatively (e.g., demonstrating that the experimental model is not appropriate for extrapolation purposes); semiquantitatively (using information to reduce the degree of uncertainty present under default extrapolation procedures), or quantitatively (formally describing the relationships between exposure and adverse outcome in mathematical forms, including components that directly reflect individual steps in the overall progression of toxicity). In this paper we review the recent advances in the risk assessment process for developmental toxicants and hypothesize on future directions that may revolutionize our thinking in this area. The road to these changes sometimes appears to be a well-mapped course on a relatively smooth surface; at other times the path is bumpy and obscure, while at still other times it is only a wish in the eye of the engineer to cross an uncharted and rugged environment.
The Carrier Potential of Liposomes in Biology and Medicine
Authors: Gregory Gregoriadis
Journal: New England Journal of Medicine (1976)

Absence of specificity in pharmacologically active agents is an obstacle to their effective use in biologic research and medicine. It follows that any approach enabling an agent to reach its target selectively and in a controlled fashion would contribute to the elimination of problems inherent in conventional methods. One such approach has been the development of a nontoxic and biodegradable carrier capable of containing a variety of substances of biologic interest that the carrier could, upon contact with a living entity, direct to the site of action and, subsequently, allow to perform their task. Ideally, there . . .
Liquid or Freeze-dried B.C.G. Vaccine
Authors: C. L. Miller, B. J. Kinsley
Journal: BMJ (1961)

In 1957, freeze-dried B.C.G. vaccine, prepared in Britain by Glaxo Laboratories Ltd., and liquid B.C.G. vaccine, prepared in Denmark by the State Serum Institute, were compared for their ability to induce tuberculin sensitivity and to produce local vaccination lesions (Medical Research Council, 1958Council, , 1960).The trials were made in six areas in Middlesex among 13-and 14-year-old schoolchildren, who were divided according to month of birth into two groups of similar size.One group was vaccinated with the Danish liquid vaccine; the 15 batches used, each within days of issue, were drawn from the normal supply of 1-ml.ampoules received each week from Copenhagen for distribution to local health authorities.The number of viable organisms ranged from 9 to 19 million per ml. in the various batches.The other group was vaccinated with the British dried vaccine; the four batches used, each between 5 and 10 months after preparation, were also issued in 1-ml.ampoules and contained between 2 and 6 million viable organisms per ml.The liquid and dried vaccines were both stored in a refrigerator before use.The tuberculin sensitivity produced by the batches of dried vaccine used, although slightly less than with the liquid, was regarded as satisfactory (more than 88% of those tested were positive to 3 tuberculin units (T.U.) and the remainder to 100 T.U.) both at three months-that is, between one and four months-and at one year-that is, between 9 and 13 months-after vaccination.The local vaccination lesions produced by the dried vaccine were slightly smaller than those produced by the liquid vaccine; no complications were recorded with either vaccine. Present InvestigationTo investigate the persistence of tuberculin sensitivity four years after vaccination, further tuberculin tests were made in three of the areas during February and March, 1961, on some of the children, then aged 17 and 18 years, who had already been tested both at three months and at one year after vaccination.About 50% of those eligible and invited for examination in each group completed this further test.
Effect of measuring ambulatory blood pressure on sleep and on blood pressure during sleep
Authors: R J O Davies, N E Jenkins, J R Stradling
Journal: BMJ (1994)

<h3>Abstract</h3> <b>Objective</b>: To assess whether recording of ambulatory blood pressure at night causes arousal from sleep and a change in the continuous blood pressure recorded simultaneously. <b>Design</b>: Repeated measurement of blood pressure with two ambulatory blood pressure machines (Oxford Medical ABP and A&amp;D TM2420) during continuous measurement of beat to beat blood pressure and continuous electroencephalography. <b>Setting</b>: Sleep reseach laboratory. Subjects--Six normal subjects. <b>Main outcome measures</b>: The duration of electroencephalographic arousal and the beat to beat changes in blood pressure produced by the measurement of ambulatory blood pressure; the size of any changes that this arousal and change in blood pressure produced in the blood pressure recorded by the ambulatory machine. <b>Results</b>: Both ambulatory blood pressure machines caused arousal from sleep: the mean duration of arousal was 16 seconds (95% range 0-202) with the ABP and 8 seconds (0-73) with the TM2420. Both also caused a rise in beat to beat blood pressure. During non-rapid eye movement sleep, this rise led to the ABP machine overestimating the true systolic blood pressure during sleep by a mean of 10 (SD 14.8) mm Hg and the TM2420 by a mean of 6.3 (8.2) mm Hg. On average, diastolic pressure was not changed, but measurements in individual subjects changed by up to 23 mm Hg. These changes varied in size among subjects and stages of sleep and were seen after measurements that did not cause any electroencephalographic arousal. <b>Conclusions</b>: Ambulatory blood pressure machines cause appreciable arousal from sleep and therefore alter the blood pressure that they are trying to record. This effect should be taken into account when recordings of blood pressure at night are interpreted in clinical work and epidemiological research.
Post-adolescent acne and marital break-up
Authors: C.I. Harrington
Journal: British Journal of Dermatology (1997)

Journal Article Post‐adolescent acne and marital break‐up Get access C.I. Harrington C.I. Harrington Department of Dermatology, Royal Hallamshire Hospital, Sheffield S10 2JF, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 137, Issue 3, 1 September 1997, Pages 478–479, https://doi.org/10.1111/j.1365-2133.1997.tb03771.x Published: 01 September 1997
Purine metabolism in myeloid precursor cells during maturation. Studies with the HL-60 cell line.
Authors: D L Lucas, H K Webster, D G Wright
Journal: Journal of Clinical Investigation (1983)

In studies with the human promyelocytic leukemia cell line HL-60, we defined changes in intermediary purine metabolism that appear to contribute to the regulation of terminal maturation in myeloid cells. When HL-60 cells were exposed to compounds that induce maturation, consistent alterations in purine metabolism were found to occur within 24 h of culture. Perturbation of guanosine nucleotide synthesis and decreases of up to 50% in intracellular guanylate pool sizes were associated with the induced maturation of these cells in response to diverse inducing agents. While immature HL-60 cells were observed to synthesize purine nucleotides by both de novo and salvage pathways, the activity of both pathways decreased in cells induced to mature, although the relative contribution of purine salvage increased. Moreover, incorporation of the salvage pathway precursor, [14C]hypoxanthine from the intermediate, inosine monophosphate (IMP), into guanylates was reduced by approximately 65% in induced HL-60 cells, reflecting decreased activity of both hypoxanthine phosphoribosyltransferase and IMP dehydrogenase. When various inhibitors of IMP dehydrogenase (mycophenolic acid, 3-deazaguanosine, and 2-beta-D-ribofuranosylthiazole-4-carboxamide) were evaluated for their effects upon HL-60 cells, each agent was found to induce the cells to mature morphologically and functionally. Like other inducers, these agents decreased HL-60 cell proliferation and caused the cells to acquire an ability to phagocytose opsonized yeast and reduce nitroblue tetrazolium. Each agent reduced intracellular guanosine nucleotide pool sizes and induced HL-60 cell maturation at micromolar concentrations. These observations suggest that the size of intracellular guanosine nucleotide pools, the biosynthesis of guanosine nucleotides, and the activity of IMP dehydrogenase may be central to the regulation of terminal maturation in myeloid cells.
WHO investigates possible human to human transmission of avian flu
Authors: Jane Parry
Journal: BMJ (2004)

The World Health Organization expressed concern this week that the first case of human to human transmission of H5N1 avian influenza may have occurred. Officials are investigating the case of two sisters in Vietnam who died of the disease and who may have contracted it from their brother.

Bob Dietz, WHO's spokesman in Vietnam, said: “There was a considerable delay between the infection of the man and his two sisters, and this anomaly has put a question mark over how they were infected.” One of the two sisters is not known to have been in contact with infected poultry, but was in contact with their brother shortly before being taken ill. He …
EFFECT OF TRACER RED BLOOD CELL BINDING ON THE MYOCARDIAL BLOOD FLOW OBTAINED WITH C-11 MTP
Authors: C Seki, Z Szabo, M Arai, R F Dannals, H T Ravert, A F DiPaula, L C Becker, H N Wagner
Journal: Clinical Nuclear Medicine (1993)

Seki, C; Szabo, Z; Arai, M; Dannals, R F; Ravert, H T; DiPaula, A F Jr; Becker, L C; Wagner, H N Jr. Author Information
HLA‐C and guttate psoriasis
Authors: E. Mallon, M. Bunce, H. Savoie, A. Rowe, R. Newson, F. Gotch, C.B. Bunker
Journal: British Journal of Dermatology (2000)

Psoriasis is a heterogeneous disease in its clinical expression. Both genetic and environmental factors are thought to contribute to the pathogenesis of the inflammatory and hyperproliferative components of the typical skin lesions. Predisposing genetic influences include associations with human leucocyte antigens (HLA) of which that with HLA-Cw6 is the strongest. Guttate psoriasis is a specific clinical manifestation of psoriasis frequently associated with group A beta-haemolytic streptococcal throat infection.We set out to determine whether further clinical subdivision of psoriasis is associated with tighter correlation with HLA-C alleles.We determined the HLA-C locus genotype of 29 caucasian patients with guttate psoriasis presenting consecutively with guttate psoriasis associated with a history of a sore throat and/or an antistreptolysin O titre > 200 IU mL-1. Polymerase chain reaction typing using sequence-specific primers was used to detect all known HLA-C alleles. These data were compared with a control population of 604 random caucasian cadaver donors.All patients (100%) with guttate psoriasis carried the Cw*0602 allele compared with 20% of the control population (odds ratio = infinity; 95% confidence limits 25.00-infinity; Pcorrected < 0.0000002).This result is consistent with HLA-Cw*0602 playing a part directly in the pathogenesis of guttate psoriasis.
Wim van den Brink and colleagues reply to Des Spence and Alain Braillon
Authors: W. van den Brink, K. Mann, A. Gual, H.-J. Aubin
Journal: BMJ (2014)

Two opinions about nalmefene, a new drug for treating alcohol dependence, were recently published in the BMJ : Des Spence refers to nalmefene as bad medicine and Alain Braillon accuses the European Medicines Agency (EMA) of having performed a junk evaluation of it.1 2 We challenge their arguments.

Spence incorrectly mentions that nalmefene was added to “extensive counselling,” whereas patients in the study in fact received only short sessions (10-15 minutes) of support to enhance compliance and motivation from their doctors, which is very close to standard clinical management. He then talks about the “dark art of subgroup analysis” but fails to mention that the results from the total group analyses were all very similar to those of the subgroup analyses.3 4 5 Indeed, the subgroup analysis was clearly marked as secondary analyses performed to …
GP-led service helped seven in 10 patients avoid long term sickness absence
Authors: Z. Kmietowicz
Journal: BMJ (2013)

Just under seven out of 10 patients in Leicestershire who were potentially heading for long term sickness absence have been helped to stay in work after being referred by their general practitioner to the county’s fit for work service.

Rob Hampton, a portfolio GP who runs the service, told the BMJ that 94% of general practices in Leicestershire had referred patients who had been off work for four weeks to the service, with 63% referring five patients or more.

The service was one of six pilot schemes funded by the Department for Work and Pensions, but the only one that was GP led.

Hampton told the BMJ , “The idea was …
Infarction-Associated Pericarditis
Authors: Fred M. Krainin, Athan P. Flessas, David H. Spodick
Journal: New England Journal of Medicine (1984)

To examine how often pericarditis is associated with myocardial infarction and how often it is diagnosable by electrocardiographic changes, we determined the frequency of diagnostic (Stage I) ST-segment changes in 423 consecutive patients admitted to the coronary-care unit. Careful auscultation and electrocardiography were performed at least once daily in all patients and at least twice daily in those presenting with new chest pain of any description or a pericardial rub. Thirty-one patients had pericardial rubs, usually detected within the first four days after admission. Only 1 of the 31 had diagnostic electrocardiographic changes. The 31 patients with pericarditis differed significantly from the 392 patients without pericarditis in several respects: male predominance; Killip Classes II, III, and IV; and Q-wave infarcts. However, differences in the location of the infarct and in mortality were not statistically significant. We conclude that during acute infarction-associated pericarditis the pericardial rub is the most frequent clinical sign, and ST-segment changes diagnostic of pericarditis are rare. Our findings are consistent with the confinement of pericardial involvement to the infarct zone.