tbuckley/cabot-search huggingface dataset:
Operable Breast Carcinoma Associated With Refractory Anemia
Authors: Allen R. Soble
Journal: JAMA (1976)

A WOMAN with undiagnosable anemia was cured when a localized breast cancer, necrotic and surrounded by an inflammatory reaction was removed by radical mastectomy. <h3>Report of a Case</h3> A 47-year-old woman was referred for diagnosis of fatigue and anemia of approximately one year's duration. She had been treated with cyanocobalamin injections and oral iron therapy, without hematological response. Except for cholecystectomy and surgery for anal fistula, her health had been good. There was no history of drug ingestion, except for the hematinics, or toxic exposure. Family history was negative for hematolotic disease, and there was no history or evidence of gastrointestinal bleeding or menorrhagia. Results of physical examination were normal except for the findings of pallor and a firm 4-cm mass in the upper outer quadrant of the right breast. Results of laboratory studies included a red blood cell (RBC) count of 4.22 million/cu mm, a hemoglobin level of 8.7
Screening for meticillin resistant Staphylococcus aureus (MRSA): who, when, and how?
Authors: J. E. Coia, A. T. Leanord, J. Reilly
Journal: BMJ (2014)

#### Summary points

Meticillin resistant Staphylococcus aureus (MRSA) remains one of the foremost nosocomial pathogens. The changing epidemiology and microbiology of MRSA worldwide provides an important context for decision making with regard to infection prevention and control. MRSA can be categorised as hospital associated, community onset, community associated, or livestock associated. This article concentrates on hospital associated MRSA, although both community associated and livestock associated MRSA are important emergent threats. 

Patients colonised or infected with MRSA provide a reservoir within hospitals. Transmission occurs directly from patient to patient, indirectly via the hands of hospital staff after contact with a patient who is colonised or infected, or after handling contaminated materials,1 or by direct patient contact with the contaminated environment. 

Infection prevention and control measures minimise risk of transmission to prevent healthcare associated infection. Although there is broad agreement on the control measures required for patients colonised or infected with MRSA, there is considerable controversy over the optimal strategy and extent of screening that should be undertaken.

#### Methods

We undertook a literature review using search terms from a previous systematic review of MRSA screening2 and updated to June 2013. We searched Medline and the Cochrane Library …
Resolution of bronchial inflammation is related to bacterial eradication following treatment of exacerbations of chronic bronchitis
Authors: A J White
Journal: Thorax (2003)

<b>Background:</b> Recent studies of the role of bacteria in chronic bronchitis have shown that bacterial colonisation is associated with enhanced inflammation and that purulent acute exacerbations of chronic bronchitis (AECB) are associated with bacteria and characterised by increased inflammation. Changes in bronchial inflammation in response to the success or failure of bacterial eradication following AECB were therefore studied. <b>Methods:</b> Bacterial quantitative culture and sputum markers of inflammation (myeloperoxidase (MPO), neutrophil elastase, leukotriene B4 (LTB4), sol:serum albumin ratio, and secretory leukoprotease inhibitor) were measured in patients presenting with culture positive purulent AECB and repeated 10 days and 2 months later. 41 patients provided sputum sufficient for both bacteriology and assessment of inflammation at baseline and day 10, and 46 provided sufficient sample for bacteriology, 40 of which could also be analysed for inflammation at 2 months (when clinically stable). <b>Results:</b> At day 10, 17 of the 41 patient samples had a positive bacterial culture. In the stable state, 18 of the 46 samples had a positive culture, but with a significantly lower bacterial load than at presentation. Although there was no difference between the groups at presentation, the concentration of MPO was lower (p&lt;0.05) in those in whom bacteria were eradicated by day 10 than in those with persisting bacteria. The LTB4 concentration was similarly lower (p&lt;0.001) in those in whom bacteria were eradicated than in those with persistent bacteria. In the stable clinical state the concentrations of both MPO and LTB4 were lower in those in whom bacteria were eradicated than in patients with persisting bacteria. <b>Conclusion:</b> Resolution of bronchial inflammation following AECB is related to bacterial eradication. Those in whom bacteria continue to be cultured in their sputum have partial resolution of inflammation which may reflect continued stimulation by the reduced bacterial load.
We need to separate "old" and "age"
Authors: F. Godlee
Journal: BMJ (2013)

Gloomy predictions about the social and economic impact of an ageing population are part of our accepted world view. They are used to pour cold water on aspirations for universal healthcare and to justify raising the statutory retirement age. But have we got the predictions wrong? Is the future rosier than we have been led to believe?

Jeroen Spijker and John MacInnes think so. In their Analysis this week (doi:10.1136/bmj.f6598) they say that doomsday warnings of an ever growing elderly dependent population, with fewer and fewer people for them to depend on, are based on a flawed measure. The “old age dependency ratio” uses the statutory retirement age as a cut-off. It then divides adults into those above this age (dependent) and those below …
Mesenchymal stem cells induce mature dendritic cells into a novel Jagged-2–dependent regulatory dendritic cell population
Authors: Bin Zhang, Rui Liu, Dan Shi, Xingxia Liu, Yuan Chen, Xiaowei Dou, Xishan Zhu, Chunhua Lu, Wei Liang, Lianming Liao, Martin Zenke, Robert C. H. Zhao
Journal: Blood (2008)
Plasma Renin Activity and Ischemic Heart Disease
Authors: T.W. Meade, J.A. Cooper, W.S. Peart
Journal: New England Journal of Medicine (1993)

An earlier prospective study reported an association between high levels of plasma renin activity (as measured by the renin-sodium profile) and the incidence of myocardial infarction in patients with hypertension. We have investigated the relation between plasma renin activity and ischemic heart disease in the Northwick Park Heart Study.The study included 803 white men 40 to 64 years of age selected from industrial workers in London. Plasma renin activity and established risk factors for ischemic heart disease were measured at entry, which was between 1972 and 1978. Ascertainment of the primary clinical end points of fatal or nonfatal myocardial infarction and sudden death from coronary causes was carried out until the end of 1991.In an analysis of the 86 first coronary events, we found an independent relation between higher systolic blood pressure and coronary end points (relative risk per 1 SD increase in blood pressure, 1.47; 95 percent confidence interval, 1.16 to 1.85; P < 0.001), but no relation between plasma renin activity and coronary end points (relative risk per 1 SD increase in the level of plasma renin activity, 1.04; 95 percent confidence interval, 0.84 to 1.30). In the 242 men who had hypertension of a degree similar to that of the subjects in the earlier prospective study of the renin profile, and in whom 44 of the 86 coronary events occurred, the relative risk of those in the highest as compared with the lowest third for plasma renin activity was 1.26 (95 percent confidence interval, 0.63 to 2.56).Our results suggest that there is no association between plasma renin activity and myocardial infarction or sudden death from coronary causes, at least in normotensive men.
Defucosylated Chimeric Anti-CC Chemokine Receptor 4 IgG1 with Enhanced Antibody-Dependent Cellular Cytotoxicity Shows Potent Therapeutic Activity to T-Cell Leukemia and Lymphoma
Authors: Rinpei Niwa, Emi Shoji-Hosaka, Mikiko Sakurada, Toyohide Shinkawa, Kazuhisa Uchida, Kazuyasu Nakamura, Kouji Matsushima, Ryuzo Ueda, Nobuo Hanai, Kenya Shitara
Journal: Cancer Research (2004)

Human IgG1 antibodies with low fucose contents in their asparagine-linked oligosaccharides have been shown recently to exhibit potent antibody-dependent cellular cytotoxicity (ADCC) in vitro. To additionally investigate the efficacy of the human IgG1 with enhanced ADCC, we generated the defucosylated chimeric anti-CC chemokine receptor 4 (CCR4) IgG1 antibody KM2760. KM2760 exhibited much higher ADCC using human peripheral blood mononuclear cells (PBMCs) as effector cells compared with the highly fucosylated, but otherwise identical IgG1, KM3060. In addition, KM2760 also exhibited potent ADCC in the presence of lower concentrations of human PBMCs than KM3060. Because CCR4 is a selective marker of T-cell leukemia/lymphoma, the effectiveness of KM2760 for T-cell malignancy was evaluated in several mouse models. First, to compare the antitumor activity of KM2760 and KM3060, we constructed a human PBMC-engrafted mouse model to determine ADCC efficacy with human effector cells. In this model, KM2760 showed significantly higher antitumor efficacy than KM3060, indicating that KM2760 retains its high potency in vivo. Second, KM2760 suppressed tumor growth in both syngeneic and xenograft mouse models in which human PBMCs were not engrafted. Although murine effector cells exhibited marginal ADCC mediated by KM2760 and KM3060, KM2760 unexpectedly showed higher efficacy than KM3060 in a syngeneic mouse model, suggesting that KM2760 functions in murine effector system in vivo via an unknown mechanism that differs from that in human. These results indicate that defucosylated antibodies with enhanced ADCC as well as potent antitumor activity in vivo are promising candidates for the novel antibody-based therapy.
European Medicines Evaluation Agency is ahead of national licensing authorities
Authors: F. Sauer
Journal: BMJ (1998)

EDITOR —The European Medicines Evaluation Agency was set up in 1995, and, as the constantly updated status reports on our internet website http://www.eudra.org/emea.html show, it has now carried out evaluations of 100 medicinal products for human and veterinary use. As Abbasi and Herxheimer pointed out in their editorial, the creation of the agency reformed the way in which health professionals and patients can obtain information about the medicines they prescribe and use.1

The key reform introduced with the creation of the agency is the European …
Abstract 4502: Synthesis and evaluation of curcumin-like compounds as inhibitors of the JAK/STAT pathway in cancer
Authors: Dalia Abdelhamid, Mike Corcoran, Jonathan P. Etter, Sheng Hu, Bulbul Pandit, Chenglong Li, Pui-Kai Li, James R. Fuchs
Journal: Cancer Research (2010)

Abstract Curcumin is an attractive lead compound for drug discovery and development. It displays a range of remarkable and diverse biological activities due to its interaction with numerous biological targets including the receptor tyrosine kinase Janus Kinase 2 (JAK2) which transduces cytokine and growth factor mediated signals by activating signal transducer and activator of transcription 3 (STAT3). The significant role of JAK-STAT pathway activation in the development, progression, and survival of cancer has been widely recognized since the 1980s. Based on our interest in developing more potent curcumin analogs which act as inhibitors of the JAK-STAT pathway we synthesized a series of monoketone curcumin analogs that bear a strong structural resemblance to AG490 and WP1066; known synthetic small molecule inhibitors of JAK2. A thorough investigation of the SAR of these compounds was pursued to elucidate which parts of the molecules are essential for the anti-proliferative activity. Thus hybrid molecules containing structural motifs found in all three classes of compounds were synthesized and screened using breast, prostate and colon cancer cell lines. Enzyme-linked immunosorbent assay (ELISA) measuring the relative amount of STAT3 phosphorylation was utilized to determine whether the anti-proliferative activity of these compounds was directly related to inhibition of the JAK-STAT pathway, and therefore whether these three classes of compounds exhibit similar cytotoxic mechanisms of action. Our results showed that although the monoketone curcumin analogs displayed potent cytotoxicity; they failed to inhibit STAT3 phosphorylation. The WP1066 analogs also showed potent cytotoxicity correlating directly to STAT3 inhibition. The pyridine and the halogen at the C3 position of the pyridine ring are essential for activity and appear to have a synergistic effect. Longer aliphatic chains at the benzylic position enhanced the cytotoxic activity and aromatic substitution usually led to a decrease in activity. Different structural modifications of the AG490 analogs by protection of the catechol moiety and/or changing the relative position of the substituents did not result in remarkable change in cytotoxic activity. We concluded that although the monoketone curcumin analogs bear remarkable structural resemblance to WP1066 and AG490, they do not inhibit the JAK-STAT pathway and may have a different anti-proliferative mechanism of action. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4502.
Miracles in Medicine and Problems in Pedagogy
Authors: Sherman M. Mellinkoff
Journal: JAMA (1966)

The story of Naaman, "captain of the Host of the King of Syria," is of timeless significance in medicine. Considered to be a leper, Naaman was believed doomed. His wife, at the urging of her maid, who had been taken captive in Israel by the Syrians, persuaded Naaman to ask Elisha, a prophet in Samaria, to "recover him of his leprosy." "... So Naaman came with his horses and chariot and stood at the door of the house of Elisha." But Elisha did not come out to see him and lay his hand on the sore places and call on the Lord for a cure. Instead he sent a messenger to tell Naaman, "Go and wash in the Jordan seven times, and thy flesh shall come again to thee, and thou shalt be clean." "Naaman turned and went away in a rage. And his servants came near and spake unto him....
Primary Hospital for a Presidential Visit
Authors: Herman Edgar Carr
Journal: JAMA (1977)

HOW DOES an 82-bed community hospital respond to the official White House designation of "primary hospital" for emergency services during a presidential visit? The Clinton Hospital was faced with this dilemma when President Carter decided to visit Clinton, an industrialized but relatively isolated town of 13,900 population located in north central Massachusetts. His visit was part of a campaign promise to keep in touch with the people. His advisors chose Clinton as a typical American town. The President accepted invitations to participate in its town meeting held March 16, 1977, and to remain overnight in the home of a private citizen. During his participation at the town meeting, President Carter was greeted by 15,000 people outside and 850 people inside the town hall. This was reported recently in a supplement entitled<i>The Visit</i>in the<i>Clinton Daily Item Press</i>, April 21, 1977. In the absence of formal guidelines, our hospital's
War Neurosis: A Year in a Neuropathic Hospital--II
Authors: J. A. Hadfield
Journal: BMJ (1942)

weeks after the second dose of A.P.T.The fact, however, that the Schick-positive rate a year after inoculation was rather higher in schools which had not been previously Schick-tested than in those which had suggests that -a larger second dose of A.P.T. might have given an even more favourable result.
Ocular Manifestations of Hypoxia-Inducible Factor-2α Paraganglioma-Somatostatinoma-Polycythemia Syndrome
Authors: Karel Pacak, Emily Y. Chew, Alberto S. Pappo, Chunzhang Yang, Felipe R. Lorenzo, Matthew W. Wilson, Mary Beth Aronow, James A. Young, Vera Popovic, Zhengping Zhuang
Journal: Ophthalmology (2014)
Adventure With a Safety Cap
Authors: Arthur Clateman
Journal: JAMA (1977)

To the Editor. —  I have written the following letter to the Department of Health, Education, and Welfare and would like to share it with my colleagues:  I am a very sick, disabled, retired physician who is cognizant of your various overpaternalistic and ridiculous safety requirements that actually become harassment and hazardous to one's survival.  Today I purchased a bottle of heart pills. With present federal regulations, that bottle was impossible to be opened by a 61-year-old physician weakened by severe heart disease. The effort required to open that ridiculous bottle almost caused me to go into heart failure. Eventually, I had to use a screw-driver to force it open, since I live alone and have no one to help me.  Please get this government back to some semblance of sanity and reasonableness. There are no small children in my environment who could possibly get at that medicine.  Between the
Extensive Gastric Varices Demonstrated by Technetium-99m Red Blood Cell Scintigraphy
Authors: WEI-JEN SHIH, PEGGY A. DOMSTAD, FAN-GKUM LOH, CALIXTO PULMANO
Journal: Clinical Nuclear Medicine (1987)

An alcohol abuse patient complicated by chronic pancreatitis had splenic vein thrombosis leading to gastric varices and underwent abdominal Tc-99m red blood cell scintigraphy. First pass study, sequential images up to 1 hour, and a 2.5 hour image showed abnormal radioactivity in the left side of the abdomen and midabdomen. In 24 hour images, the high level of activity in the left side persisted; in addition, there was accumulation of radioactivity in the cecum, ascending, transverse colon, the splenic fluxure, and descending colon. A splenectomy was performed and during the surgical procedure, a large dilated vein in the greater omentum was noted. It is reemphasized that delayed imaging up to 24 hours is important when the results of earlier images are equivocal or negative.
Abstract 2931: Synergy between secreted factors promotes a hyper-secretory phenotype which may fuel ovarian cancer progression.
Authors: Albert R. Davalos, Nicholas Schaum, Judith Campisi
Journal: Cancer Research (2013)

Abstract The challenge in ovarian cancer research is twofold: 1) identification of early biomarkers of the disease and 2) uncovering targetable molecules to treat malignancy while minimizing toxicity. Mutations in the BRCA1/BRCA2 gene locus account for approximately 15% of patients with ovarian cancer, but several other risk factors are known, including increasing age and obesity. We recently uncovered that a nuclear protein (HMGB1) becomes secreted when cells undergo cellular senescence and we detect increased levels in plasma from elderly compared to young individuals. Significantly, we detect abundant extranuclear HMGB1 staining in tissue from patients with serous ovarian carcinoma, suggesting the presence of senescence cells in the tumor. We find elevated levels of circulating HMGB1 in patients diagnosed with serous carcinoma. Tissue microarray data analysis correlates with reduced survival in ovarian cancer patients staining with higher levels of HMGB1. Like aging, obesity is a risk factor for ovarian cancer but how remains poorly understood. We found that plasma from mice on high fat diets contained higher levels of HMGB1 compared to mice on normal diets. To extend this observation, we found that culturing ovarian cancer derived cells with saturated fatty acids promoted significantly increased secretion of HMGB1, IL-6 and MMP-3. Moreover, senescent cells which exhibit a secretory phenotype became “hyper-secretory” when cultured with saturated fatty acids. Recent data revealed that the redox state of HMGB1 establishes the protein's function. Secreted HMGB1 synergizes with other secreted factors to stimulate secretion of inflammatory molecules. Indeed we found cells cultured with fatty acid released cf DNA (cell free DNA) which can complex with secreted HMGB1 to promote cytokine secretion. Immunocytochemsitry revealed that tissue from serous ovarian cancer patients exhibited strong FABP-4 expression, a marker for adipoctyes but also shown to be secreted in obese individuals. Taken together these results lead to the possibility that multiple cells types synergize to create a permissive microenvironment to foster ovarian cancer development and progression. Citation Format: Albert R. Davalos, Nicholas Schaum, Judith Campisi. Synergy between secreted factors promotes a hyper-secretory phenotype which may fuel ovarian cancer progression. [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 2931. doi:10.1158/1538-7445.AM2013-2931
Hypoxic preconditioning preserves antioxidant reserve in the working rat heart
Authors: D. T Engelman, M. Watanabe, R. M Engelman, J. A Rousou, E. Kisin, V. E Kagan, N. Maulik, D. K Das
Journal: Cardiovascular Research (1995)

The aim was to examine whether intracellular antioxidants play a role in myocardial preservation following hypoxic preconditioning.Isolated working rat hearts were subjected to 30 min ischaemia and 30 min reperfusion. Control hearts were compared to hearts preconditioned with 10 min hypoxia. Left ventricular function and lactate dehydrogenase (LDH) release were measured in each group. Ascorbate dependent (ADAR) and thiol dependent (TDAR) components of the endogenous myocardial antioxidant reserve were assessed using electron spin resonance spectroscopy.a Hypoxic preconditioning had no effect on left ventricular function after 10 min reoxygenation. During reperfusion, the hypoxically preconditioned hearts had a significantly increased survival rate, aortic flow, developed pressure, and dP/dtmax, and a reduced lactate dehydrogenase release, compared to non-preconditioned controls (P < 0.05). Preconditioned hearts also had significantly higher preservation of baseline ADAR (79%) and TDAR (96%) compared with control hearts, (70%) and (77%), respectively (P < 0.05).Hypoxic preconditioning enhances functional recovery and reduces cell necrosis following global ischaemia in the working rat heart. This phenomenon may, in part, be mediated through enhanced ascorbate and thiol components of the antioxidant reserve.
Margaret McCartney: Jeremy Hunt should follow his own advice on emergency care
Authors: M. McCartney
Journal: BMJ (2015)

Jeremy Hunt recently told the House of Commons, “I took my own children to an A&E department at the weekend precisely because I did not want to wait until later on to take them to see a GP.

“People do not always know whether the care that they need is urgent or whether it is an emergency, and making GPs available at the weekends will relieve a lot of pressure in A&E departments.”1

Here is the news, health secretary: GPs already work out of hours. Some work on the weekend, early mornings, and evenings of the “extended hours” contract.2 And some work when surgeries are closed, usually in cooperatives.

Fifteen years ago I worked in a general …
Attack Ferrets?-Reply
Authors: Brian A. Lauer
Journal: JAMA (1989)

In Reply. —  We have two comments regarding Ms Childs' letter.  First, household pets and children are routinely in contact with each other. It is impossible to supervise their interactions constantly. The aspect of ferret behavior of most concern is the unpredictability and unprovoked nature of many of the reported attacks. We are not aware of horses biting infants asleep in their cribs. There is no question that injuries to children from other animals are much more common; many of these could be anticipated and prevented by proper supervision. Many of the reported severe ferret injuries, however, could be prevented only by keeping the animal caged whenever there was an infant in the home.  Second, until an effective vaccine is available, we support the current recommendations regarding rabies control in ferrets.