tbuckley/cabot-search huggingface dataset:
Association Between Physical Activity and Risk of Bleeding in Children With Hemophilia
Authors: Carolyn R. Broderick, Robert D. Herbert, Jane Latimer, Chris Barnes, Julie A. Curtin, Erin Mathieu, Paul Monagle, Simon A. Brown
Journal: JAMA (2012)

Vigorous physical activity is thought to increase risk of bleeds in children with hemophilia, but the magnitude of the risk is unknown.To quantify the transient increase in risk of bleeds associated with physical activity in children with hemophilia.A case-crossover study nested within a prospective cohort study was conducted at 3 pediatric hemophilia centers in Australia between July 2008 and October 2010. A total of 104 children and adolescent boys aged 4 through 18 years with moderate or severe hemophilia A or B were monitored for bleeds for up to 1 year. Following each bleed, the child or parent was interviewed to ascertain exposures to physical activity preceding the bleed. Physical activity was categorized according to expected frequency and severity of collisions. The risk of bleeds associated with physical activity was estimated by contrasting exposure to physical activity in the 8 hours before the bleed with exposures in two 8-hour control windows, controlling for levels of clotting factor in the blood.Association of physical activity and factor level with risk of bleeding.The participants were observed for 4839 person-weeks during which time 436 bleeds occurred. Of these, 336 bleeds occurred more than 2 weeks after the preceding bleed and were used in the primary analysis of risk. Compared with inactivity and category 1 activities (eg, swimming), category 2 activities (eg, basketball) were associated with a transient increase in the risk of bleeding (30.6% of bleed windows vs 24.8% of first control windows; odds ratio, 2.7; 95% CI, 1.7-4.8, P < .001). Category 3 activities (eg, wrestling) were associated with a greater transient increase in risk (7.0% of bleed windows vs 3.4% of first control windows; odds ratio, 3.7; 95% CI, 2.3-7.3, P < .001). To illustrate absolute risk increase, for a child who bleeds 5 times annually and is exposed on average to category 2 activities twice weekly and to category 3 activities once weekly, exposure to these activities was associated with only 1 of the 5 annual bleeds. For every 1% increase in clotting factor level, bleeding incidence was lower by 2% (95% CI, 1%-3%; P = .004).In children and adolescents with hemophilia, vigorous physical activity was transiently associated with a moderate relative increase in risk of bleeding. Because the increased relative risk is transient, the absolute increase in risk of bleeds associated with physical activity is likely to be small.
Successful treatment of low dose cytosine arabinoside for acute myelofibrosis with immature myeloblast (AML‐MO)
Authors: Heiwa Kanamori, Juichi Tanabe, Tadashi Koike, Yoshimi Hashimoto, Michio Matsuzaki, Hitoshi Kitamura, Shigeki Motomura, Hiroshi Mohri, Takao Ohkubo
Journal: American Journal of Hematology (1994)
SHOULD CORONARY DISEASE AND HYPERTENSION BE A CAUSE FOR REJECTION IN INDUSTRY?
Authors: H. M. F. BEHNEMAN
Journal: JAMA (1941)

The answer to the highly controversial question Should coronary disease and hypertension be a cause for rejection in industry? depends to a great extent on who is asked—the injured worker, the employer, the trade union, the insurance carrier or the industrial physician. These are the people primarily involved in the solution of one of the most frequent yet most complicated problems confronting the  of industrial medicine. I use the word student because I know of no other pathologic problem in this specialty requiring more careful study in each individual case if the problem is at all concerned with industrial liability.  High in morbidity and highest in mortality, heart disease is the most expensive illness. More than a fifth of cardiac disorders occurs in persons under the age of 40, and it costs this country $250,000,000 a year in lost wages, in addition to the cost of physical and financial
Possible Interaction of Sulfinpyrazone with Coumarins
Authors: James W. Davis, Leo E. Johns
Journal: New England Journal of Medicine (1978)

To the Editor: On the basis of the observations of Seiler and Duckert1 that the addition of sulfinpyrazone to plasma displaced phenprocoumon from protein-binding sites, Koch-Weser and Sellers2 predicted that the administration of sulfinpyrazone to patients chronically treated with coumarins would potentiate anticoagulation. Our recent observations of the prothrombin time of a 53-year-old man with recurrent thromboembolism suggest that their prediction was correct. The prothrombin time had been maintained between 16 and 24 seconds for two months while he received 5 mg of warfarin each day with the exception of two days when it was omitted. One week after he . . .
Forced Diuresis A Cause of "Absent" Renal Uptake of Bone Imaging Agent
Authors: MOZAFAREDDIN K. KARIMEDDINI, RICHARD P. SPENCER
Journal: Clinical Nuclear Medicine (1987)

A 90-year-old woman was found to have elevated serum calcium values, and forced diuresis was begun in an effort to lower the serum calcium content. While putting out a volume of 6,300 ml of urine in 24 hours, a bone scan was performed. There was nonvisualization of the kidneys, without evidence of renal disease. The authors conclude that forced diuresis, with its massive fluid and electrolyte output, is a likely cause of failed visualization of the kidneys during bone imaging.
Subgaleal Hematoma Caused by Hair-Pull
Authors: Michael Scott
Journal: JAMA (1968)

<h3>To the Editor:—</h3> I read with much interest the letter by Dr. Hannibal Hamlin, (<b>204</b>:339, 1968) "Surgical Hematoma Caused by Hairpull." Although the cause for the hematoma may well have been such a maneuver, the report gave no absolute evidence that blood was present under the galea, since no aspiration was done. The etiology of hairpulling is therefore conjectural. There was no hair pulled from the scalp, and there were no additional injuries. It is not unusual for a child 3 years of age to react to questions with "silence." The child did have a head injury which could have been an etiological factor. My case of nontraumatic spontaneous subaponeurotic hematoma (<b>107</b>:348,1936) was possibly related to atypical scurvy. Although there was no proof that the etiology was vitamin C deficiency, there was no history if injury directly to the head; the family was poor, and fresh fruit, milk,
P250 Association Between PGRN and Airway Inflammation in COPD: Abstract P250 Table 1
Authors: MJ Ungurs, NJ Sinden, RA Stockley
Journal: Thorax (2012)

<h3>Background</h3> Progranulin (PGRN) is an anti-inflammatory protein, which is converted into pro-inflammatory granulin peptides (GRNs) by neutrophil elastase (NE) and proteinase-3 (PR3) (1). Neutrophilic inflammation is implicated in the pathophysiology of COPD, therefore the influence of PGRN on mechanisms of neutrophilic inflammation may be of great relevance to understanding and treating inflammation in the disease. <h3>Methods</h3> Sputum and serum samples were obtained from COPD patients with chronic bronchitis at exacerbation and in the subsequent clinically stable state. Sputum samples were graded by purulence and cultured for quantitative microbiology. PGRN was measured in sputum sol phase together with leukotriene B4 (LTB4), interleukin 8 (IL-8), myeloperoxidase (MPO), tumour necrosis factor α (TNFα), NE and PR3. PGRN and C-reactive protein (CRP) were measured in the serum. <h3>Results</h3> PGRN was lower in purulent sputum (median=38.91 ng/ml (IQR=1.55–89.71 ng/ml)) than mucoid (median=79.78 ng/ml (IQR=51.57–111.24 ng/ml)) (p=0.024, n=69). In purulent sputum PGRN correlated negatively with bacterial load and markers of inflammation (Table 1). Serum PGRN did not correlate with CRP, but was higher in stable COPD patients (median=65.71 ng/ml (IQR=0–86.46 ng/ml)) than healthy controls (median=38.55 ng/ml (IQR=36.11–44.82 ng/ml)) (p=&lt;0.001, n=20), and increased further during purulent exacerbations (median=75.43 ng/ml (IQR=64.83–85.28 ng/ml)) (p=0.010, n=25). <h3>Conclusion</h3> The concentration of PGRN in the lung is associated with the increased inflammation seen with bacterial infection and exacerbation as assessed by markers of inflammation. The conversion of PGRN to GRNs may provide a mechanism by which neutrophil proteases regulate inflammation in COPD. Elevated circulating PGRN may reflect systemic inflammation associated with COPD. Kessenbrock K, et al. J Clin Invest. 2008 Jul; 118(7):2438–47.
Measles Vaccine and Travelers
Authors: David O. Freedman
Journal: Annals of Internal Medicine (1990)

Letters and Corrections15 March 1990Measles Vaccine and TravelersDavid O. Freedman, MDDavid O. Freedman, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-76-3-112-6-475 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor:The need for adequate immunity to measles in international travelers, outlined by Hill and Pearson (1) and von Reyn and Saviteer (2), is clear cut. These authors have not adequately emphasized, however, the logistic or financial impact that the administration of a live-virus vaccine such as the measles vaccine will have on the pretravel immunization protocols used by travel clinics. Well-defined administration guidelines for the spacing of live-antigen preparations with other live-virus preparations or with immune globulin (a biological given to virtually all travelers to the developing world) will-with the addition of measles vaccine-ultimately lead to the...References1. HillPearson DR. Measles prophylaxis for international travel [Editorial]. Ann Intern Med. 1989;111:699-700. LinkGoogle Scholar2. von ReynSaviteer CS. Measles immunization for international travelers [Letter]. Ann Intern Med. 1989;111:766-7. LinkGoogle Scholar3. General recommendations on immunization. MMWR. 1989;38:205-14, 219-27. MedlineGoogle Scholar1. HillPearson DR. Measles prophylaxis for international travel [Editorial]. Ann Intern Med. 1989;11:699-700. LinkGoogle Scholar2. Measles: reassessment of current immunization policy. American Academy of Pediatrics, Committee on Infectious Diseases. American Academy of Pediatrics News. 1989;5:6. Google Scholar3. Measles prevention: recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR. 1989;38:(Suppl 9). Google Scholar4. SteffenRickenbachWilhelmHelmingerSchar RMUAM. Health problems after travel to developing countries. J Infect Dis. 1987;156:84-91. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 March 1990Volume 112, Issue 6Page: 475-476KeywordsGlobulinsImmunityMeaslesVaccines Issue Published: 15 March 1990 PDF DownloadLoading ...
Abstract 1083: The pivotal role of IKKalpha in the development of spontaneous lung squamous cell carcinomas.
Authors: Zuoxiang Xiao, Qun Jiang, Jami Willette-Brown, Feng Zhu, Sichuan Xi, Sandra Burkett, Fanching Lin, Timothy Back, Mahesh Datla, Zhonghe Sun, Romina Goldszmid, Xiaolin Wu, David Schrump, Howard Young, Georgio Trinchieri, Robert Wiltrout, Yinling Hu
Journal: Cancer Research (2013)

Abstract During the last decades lung cancer has become the leading cause of cancer deaths in the world, and the need to develop better diagnostic techniques and therapies is urgent. To advance the understanding of this disease, various genetically engineered and chemical induced mouse models have been established. However, there are no robust animal models of lung squamous cell carcinomas (SCCs), one of the major types of lung cancer. Here, we generated Ikkα-KA/KA knock-in mice (KA/KA) in which an ATP binding site of IKKα, Lys 44 was replaced by alanine. All the knock-in mice at 4 to 6 months of age developed spontaneous lethal lung SCCs associated with markedly increased leukocyte infiltration and expression of cytokines, and chemokines in the lungs. Furthermore, we identified deregulated c-myc, Nanog, Oct3/4, p53, Rb, EGFR, MAPK, Jun-B, p63, Trim29, Rhov, CDK1, and IGF1 in mouse lung SCCs, and identified reduced IKKα and IκBα and increased ROS1 in mutant lungs and SCCs, some of which were found in human lung SCCs. Lung cancers were prevented by reintroducing epithelial-cell IKKα, depleting macrophages or depleting lymphocytes. This study not only provides a novel model for studying the pathogenesis, treatment, early detection, and prevention of human lung SCCs, but also demonstrates how a single mutation in IKKα elicits malignancy through the combined epithelial-cell-autonomous and immune mechanisms. Citation Format: Zuoxiang Xiao, Qun Jiang, Jami Willette-Brown, Feng Zhu, Sichuan Xi, Sandra Burkett, Fanching Lin, Timothy Back, Mahesh Datla, Zhonghe Sun, Romina Goldszmid, Xiaolin Wu, David Schrump, Howard Young, Georgio Trinchieri, Robert Wiltrout, Yinling Hu. The pivotal role of IKKalpha in the development of spontaneous lung squamous cell carcinomas. [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 1083. doi:10.1158/1538-7445.AM2013-1083
Abstract 2283: β-catenin silencing induces both apoptotic and autophagic cell death through LKB1/AMPK signal in head and neck cancer cells
Authors: Hyo Won Chang, So Young Moon, Hyo Jung Kim, Myung Jin Lee, Mi Ra Kim, Jung Je Park, Ji Hyun Seo, Seong Who Kim, Sang Yoon Kim
Journal: Cancer Research (2012)

Abstract β-Catenin, a multifunctional protein involved in key molecule of Wnt signaling transduction, has been well known to regulate cell proliferation, differentiation, cell-cell adhesion, survival, and apoptosis as well as plays an important role in human tumorigenesis. Our previous report showed that Wnt/β-catenin pathway controls radiosensitivity of head and neck caner (HNC) cell via cyclooxygenase-2-mediated Ku expression. However, the specific molecular mechanisms of β-catenin in tumor cell survival and death are still not fully understood, so in the present study we attempted to elucidate the mechanism of cell death in HNC cell by studying how β-catenin silencing regulates cell death through KB1/AMPK signaling. We performed β-catenin knockdown in HNC cell by using small interfering RNA. Its effect on the cell viability was confirmed by observation of cell morphologic change, electron microscopy, MTT and FACS analysis. Also, we confirmed the expression of several proteins corresponding signal pathway by western blot analysis. β-catenin silencing significantly induced G1 cell-cycle arrest and also increased the expression of Bax and the active form of caspase-3, and decreased the expression of Bcl-2, demonstrating the sequential activation of apoptotic cascades following treatment with β-catenin siRNA in HNC cell. Interestingly, β-catenin silencing induced autophagy as well as apoptosis. We confirmed that the numbers of autophagic vacuoles and the expression of LC3-II increased in cells treated with β-catenin siRNA. This is probably because LKB1-dependent AMPK is activated by β-catenin silencing in HNC cell. Activated AMPK, in β-catenin silenced AMC-HN-3 cells, causes a G1 cell cycle arrest by phosphorylated p53 as well as inhibited protein synthesis by suppressing mTOR activity. Also, Treatment with LKB1 siRNA or compound C in AMC-HN-3 cells preserved cell viability against β-catenin silencing-induced cytotoxicity. Taken together, our data show that β-catenin silencing induces cell death through LKB1/AMPK signal, and as a result, apoptosis and autophagy are induced together in HNC cell, suggesting that a novel interaction between β-catenin and LKB1/AMPK signaling pathway occurs. Our study provides new insights into understanding the cellular and molecular mechanisms involving β-catenin silencing-induced cell death. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2283. doi:1538-7445.AM2012-2283
Old docs and new tricks
Authors: Louis B Jacques
Journal: BMJ (2005)

Editor—Spurgeon reports that the doctors' standards of care drop with years in practice.1 When I began clinical practice in the late 1980s I thought that one key to being a “good doc” was keeping up with the latest drugs and technologies. I was dismayed to see seasoned colleagues who were slow to change.

I then saw many new drugs get pulled from the market (rofecoxib is not the first non-steroidal anti-inflammatory drug to be withdrawn) and various medical fads come and go. Evidence based medicine appropriately shed light on the poor evidence available to support most things that physicians do.

Armed with this keener analytical approach, I came to realise that most claims of benefit are greatly exaggerated compared with absolute incremental changes and that most patients are not like trial subjects. Although an intervention might benefit a population, it is much less certain that it will benefit the patient who sits before me.

I suspect that seasoned doctors are better than their junior colleagues at some things, and worse at others. Maybe the ability to see the big picture, diagnostically and therapeutically, is enhanced by experience. Meanwhile the emphasis on the newest treatment detail might wane. Perhaps that is a reason why I have conflicting opinions about whether doctors get better with time.
The exchange between proglycogen and macroglycogen and the metabolic role of the protein-rich glycogen in rat skeletal muscle.
Authors: M Huang, C Lee, R Lin, R Chen
Journal: Journal of Clinical Investigation (1997)

The aim of this study is to determine if proglycogen and macroglycogen are kinetically related in rat skeletal muscle. Eight groups of anesthetized fasted rats (seven hepatic-occluded and one nonoccluded) were intravenously infused with [3-3H]glucose at a rate of 1.7 microCi x min(-1) for 20 min. At the end of infusion, hindlimb muscles were excised and rapidly frozen in liquid nitrogen. Proglycogen was extracted by precipitation in 10% TCA; and macroglycogen as a part of total glycogen by precipitation in 20% KOH-65% ethanol. Along with the tracer, the occluded rats were also infused with: saline (group 1); insulin at rates ranging from 5 to 50 mU x min(-1) (groups 2 to 5); and insulin at a rate of 10 mU x min(-1) plus glucose at rates of 10.2 and 20.4 micromol x min(-1), respectively (groups 6 and 7). The infusion regimens resulted in up to 30-fold difference in whole-body glucose utilization among the rats. In the rats infused with saline and insulin at a rate of 5 mU x min(-1), [3H]glucose was found to be exclusively incorporated into proglycogen. Incorporation into macroglycogen was found in the rats infused with insulin at rates > 10 mU x min(-1). Supplementary glucose infusion increased the synthesis of [3H]proglycogen (four- to sixfold), and equilibrated the two extractable forms of glycogen in the insulin-infused rats. In the saline-infused nonoccluded rats, only proglycogen was found to be labeled. In conclusion, our data indicate that in the intact and hepatic-occluded rats, proglycogen in the skeletal muscles may undergo synthesis and degradation of its own more readily than exchange between itself and depot macroglycogen.
Officials reject claims of drug industry's influence
Authors: Ray Moynihan
Journal: BMJ (2004)

Questioned repeatedly about the effect of the drug industry on doctors' prescribing, medical education, scientific research, and drug evaluation, government officials told a parliamentary inquiry last week that there was no evidence of unhealthy influence.

Four senior officials from the Department of Health and one from the Department of Trade and Industry were giving evidence at the first public hearing of the far reaching inquiry of the House of Commons Health Committee into the industry's influence on the health system.

Committee chairman David Hinchliffe, who is soon to retire, told the BMJ that a key reason for the inquiry was the …
Bedside Diagnosis of Systolic Murmurs
Authors: N J Lembo, L J Dell'Italia, M H Crawford, R A O'Rourke
Journal: New England Journal of Medicine (1988)

The diagnostic accuracy of bedside maneuvers in the evaluation of patients with systolic murmurs has not been assessed objectively. Therefore, we evaluated 50 patients with documented systolic murmurs and compared all standard bedside techniques. Murmurs originating within the right-sided chambers of the heart were best differentiated from all other murmurs by augmentation of their intensity with inspiration (100 percent sensitivity, 88 percent specificity) and diminution of their intensity with expiration (100 percent sensitivity, 88 percent specificity). The murmur of hypertrophic cardiomyopathy was distinguished from all other murmurs by an increase in intensity with the Valsalva maneuver (65 percent sensitivity, 96 percent specificity) and during squatting-to-standing action (95 percent sensitivity, 84 percent specificity), and by a decrease in intensity during standing-to-squatting action (95 percent sensitivity, 85 percent specificity), passive leg elevation (85 percent sensitivity, 91 percent specificity), and handgrip (85 percent sensitivity, 75 percent specificity). The murmurs of mitral regurgitation and ventricular septal defect had parallel responses to all maneuvers, but could be differentiated from other systolic murmurs by augmentation of their intensity with handgrip (68 percent sensitivity, 92 percent specificity) and during transient arterial occlusion (78 percent sensitivity, 100 percent specificity), and by a decrease in their intensity during the inhalation of amyl nitrite (80 percent sensitivity, 90 percent specificity). No single maneuver identified the murmur of aortic stenosis, but the diagnosis could be made by exclusion. Although no single maneuver is 100 percent accurate in diagnosing the cause of a systolic murmur, its origin can be determined accurately at the bedside by observation of the response to a combination of maneuvers.
Science Organization Sponsors Discussions About What Constitutes Health Care Reform
Authors: Charles Marwick
Journal: JAMA (1992)

WHEN IT COMES to deciding what goes into the health care package—services that would be covered by a national health insurance plan—the first thing is to put everyone in the same boat. A two-tiered system, one that provides coverage for those who can pay or are covered by insurance, and another for the poor, the unemployed, or the inadequately insured, is unacceptable. And coverage should be universal. These are conclusions from a draft document being discussed by the American College of Physicians (Philadelphia, Pa) for dealing with one aspect of health care reform—the services to which all should have access. <h3>Series of Meetings</h3> The draft was summarized by Janet Weiner, research associate at the college, during a Washington, DC, meeting on health care reform, one of a series sponsored by the American Association for the Advancement of Science. This meeting was devoted to defining the minimum standard of health care.