tbuckley/cabot-search huggingface dataset:
Cyr61 (CCN1) is a novel target for Zometa (zoledronic acid) in breast cancer bone metastasis.
Authors: I Espinoza, H Liu, M Dimri, R Lupu
Journal: Cancer Research (2009)

Abstract Abstract #3074 Background: Cyr61, currently known as CCN1, is a pro-angiogenic factor highly expressed in triple negative breast carcinomas. CCN1 binds, among others, to αvβ3 integrin receptor, which is concomitantly expressed with CCN1 in triple negative carcinomas. It has clinically established that a greater part of the tumor initially diagnose as triple negative eventually metastasize to the bone. Women with advanced breast cancer often develop bone metastases. Currently, many patients receive bisphosphonate treatment as a support treatment to maintain bone density. Zometa (Zoledronic acid=ZOL), a third generation amino-bisphosphonate, inhibits bone resorption and it might prevent development of new osteolytic lesions; lesions induced by tumor metastases. Provided that: 1) ZOL has a direct anti-tumor activity on breast cancer cells in vitro, 2) CCN1:αvβ3 is an autocrine loop shown to be involved in breast cancer cells which metastasize to the bone, 3) ZOL inhibits αvβ3 expression in the cell surface of endothelial cells, and CCN1 induces the expression of αvβ3 expression.&amp;#x2028; Material and Methods: Using MTT assay we analyzed the effect of ZOL in the viability of cells overexpressing CCN1:αvβ3. The study whether the effect of ZOL was at the transcriptional level of CCN1 a Luciferase reporter assay was performed. To study whether FOXO3a binding site on CCN1 promoter was an important site for ZOL effect on CCN1 we used a CCN1-promoter containing a deletion in the FOXO3a binding site and we performed the Luciferase reporter assay. We also analyze the effect of ZOL in the anchorage-independent growth by soft agar assay and in the branching and morphogenesis in 3D Matrigel culture.&amp;#x2028; Results: We found that: a) ZOL regulates the expression of CCN1 expression in triple negative breast cancer cell lines; b) the IC50 for Zometa for CCN1:αvβ3 expressing cells is lower (about 12μM) than the IC50 for cells that express low to undetectable levels of CCN1:αvβ3 cells; c) ZOL specifically inhibited CCN1 at a protein and transcription expression levels in a concentration-dependent manner; d) FOXO3a is the site by which ZOL induces transcriptional activation of CCN1; e) ZOL induced specific inhibition of anchorage independent growth of CCN1:αvβ3 cells in a dose dependent manner, and f) ZOL induces Mesenchimal-Epithelial Transition (MET) of CCN1:αvβ3 expressing cells and inhibited the generation of branching and morphogenesis in 3D in Matrigel culture of CCN1:αvβ3 expressing cells.&amp;#x2028; Discusion: Collectively, these data demonstrated for first time a specific effect of ZOL on a pro-angiogenic factor involved in triple negative carcinomas; providing a new model for the development of a therapeutic strategy for ZOL. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3074.
Boarded to Death — Why Maintenance of Certification Is Bad for Doctors and Patients
Authors: Paul S. Teirstein
Journal: New England Journal of Medicine (2015)

Interview with Dr. Steven Weinberger on the pros and cons of the new Maintenance of Certification standards. (11:27)Download In January 2014, the American Board of Internal Medicine changed its certification policies for physicians, adding ongoing maintenance of certification requirements that many physicians see as expensive busywork that distracts them from patient care.
An Unusual Case of Brucellosis
Authors: Samuel E. Halpern
Journal: JAMA (1968)

A patient with brucellosis was a unique example of host-parasite relationship. Initially, the patient had peripheral bleeding, thrombocytopenia, and blood cultures positive for Brucella abortus without signs of any systemic infection. Prednisone alone produced a return of the platelet count to normal in a period of 17 days. As an outpatient, symptoms and spinal fluid findings of meningitis developed, with sterile cerebrospinal fluid (CSF) cultures. Blood cultures for Brucella abortus were positive, but the thrombocytopenia did not recur. The meningitis responded to appropriate antibiotic treatment. The literature has reported thrombocytopenia as a manifestation of brucellosis.
752 EFFECT OF TIPS ON SOLUBLE CD163 IN PATIENTS WITH LIVER CIRRHOSIS
Authors: P. Holland-Fischer, T.D. Sandahl, H. Grønbæk, H. Vilstrup, S. Moestrup, O. Riggio, L. Ridola, N.K. Aagaard, H. Møller
Journal: Journal of Hepatology (2009)
Influence of documented history of coronary artery disease on outcomes in patients admitted for worsening heart failure with reduced ejection fraction in the EVEREST trial
Authors: Robert J. Mentz, Bradley D. Allen, Mary J. Kwasny, Marvin A. Konstam, James E. Udelson, Andrew P. Ambrosy, Angela J. Fought, Muthiah Vaduganathan, Christopher M. O'Connor, Faiez Zannad, Aldo P. Maggioni, Karl Swedberg, Robert O. Bonow, Mihai Gheorghiade
Journal: European Journal of Heart Failure (2012)
Accidental poisoning in children.
Authors: R. Wigglesworth, B. T. Williams
Journal: BMJ (1968)

MMICBRSJOURNALor absence of dentures has much effect, except when the level is still very high.This may seem surprising, but a little consideration of the mechanism involved shows that it can be expected.The alcohol concentration of even a weak drink such as beer is several hundred times as high as that of the tissue fluids of even a very drunk man, so it is not surprising that traces in the mouth, pharynx, tonsils, and probably even the sinuses lead to very high breath readings immediately after drink- ing.This high figure falls exponentially so that the time taken to fall to a negligible level is not much affected by the nature of the drink, and is in fact 15 to 30 minutes.Two mechanisms are involved in this fall, evaporation into the breath and diffusion through the mucous membranes.If alcohol is trapped under a dental plate it can still be absorbed, and if it cannot escape into the breath it cannot affect the breath alcohol level, so that dentures make very little difference.Alcohol on the surface of the dentures them- selves will quickly evaporate, as they are nonabsorbent.Similarly, washing the mouth with water will not remove alcohol from the mucous membranes of the mouth much faster than the breath does, and will not affect the pharynx and sinuses at all.If the breath contains alcohol, mouth washing may give a spuriously low reading by cooling the breath,' so from a legal point of view it is a practice to be deprecated.-Iam, etc.,
Abstract 4715: Genetic susceptibility to radiation-associated colon and rectum cancers among atomic-bomb survivors with special reference to the <i>CD14</i> gene
Authors: Tomonori Hayashi, Yukari Morishita, Hiroko Nagamura, Mayumi Maki, Yoichiro Kusunoki, Kengo Yoshida, Kazue Imai, John B. Cologne, Kei Nakachi
Journal: Cancer Research (2010)

Abstract Past epidemiology studies reported that atomic-bomb (A-bomb) radiation exposure enhanced risk of colon cancer, but not rectum cancer, among the survivors. The reason for this different sensitivity to radiation remains to be elucidated. Colorectal cancer is a multi-factorial disease, the onset of which is attributed to both environmental and genetic factors, with animal experiments showing that intestinal bacterial toxins accelerate carcinogenesis. It was recently reported that single nucleotide polymorphisms (SNPs) identified in the promoter region of CD14, encoding a receptor for the lipopolysaccharide component of the outer membrane of Gram-negative bacteria, regulate CD14 gene expression and thereby affect susceptibility to inflammatory diseases such as atopic dermatitis, coronary artery disease, and hepatic diseases. This study investigated relationship between a novel CD14 gene polymorphism and the development of radiation-associated colon and rectum cancers among an A-bomb survivor cohort, in terms of a case-cohort study. On the basis of this T/G polymorphism, we determined CD14 genotypes with 210 colorectal cancer cases and with a subcohort of 2,160 individuals who were randomly selected from the cohort. Our results showed that the individuals exposed to A-bomb radiation (≥5 mGy) were at an increased risk of colon cancer, but not rectum cancer, with relative risk (RR) of 1.19/Gy (95%CI: 1.04-1.36). When we divided the study subjects into three groups for radiation dose and into two groups for CD14 genotypes, significantly high risk of colon cancer was found with RR of 2.40 (95%CI: 1.37-4.23) for the combined category of CD14-T/T homozygote and the highest dose (≥0.7Gy), compared with the baseline category (CD14-T/G or G/G and no dose). These results suggest that CD14-related inflammatory response might be involved in the development of radiation-associated colon cancer, not rectum cancer, among A-bomb survivors, and that the CD14 genotyping might be involved in individual risk of colon cancer together with radiation dose. To find a functional significance of this polymorphism, we are currently working on ELISA-based assay to measure serum levels of soluble CD14 among healthy individuals in relation to the CD14 genotyping. 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 4715.
LIGATION OF THE PULMONARY VEIN.AN EXPERIMENTAL OPERATIVE PROCEDURE IN THE TREATMENT OF PULMONARY TUBERCULOSIS.
Authors: GROESBECK WALSH
Journal: JAMA (1907)

In the autunm of 1900 and the early winter of 1901 I began a series of animal experiments with the idea of establishing the ligation of the pulmonary vein for the relief of pulmonary tuberculosis as a regular surgical procedure. The experiments were performed in the anatomic laboratory of the Northwestern University Medical School with the cooperation of Dr. Edward Clark Streeter of Chicago. A dozen or more dogs were used and the mortality rate was 100 per cent. Th s would seem to preclude absolutely the right of this operation to exist, and yet I believe the failure was due to causes which might have been obviated had the anatomic difficulties of the operation been more clearly understood at the time. The operation suggested itself when I first heard in a medical clinic of the great infrequency with which pulmonary tuberculosis and mitral insufficiency are associated. The idea of
Mutations in the 180–kD bullous pemphigoid antigen (BPAG2), a hemidesmosomal transmembrane collagen (COL17A1), in generalized atrophic benign epidermolysis bullosa
Authors: John A. McGrath, Biljana Gatalica, Angela M. Christiano, Kehua si, Katsushi Owaribe, James R. McMillan, Robin A.J. Eady, Jouni Uitto
Journal: Nature Genetics (1995)
Was it a heart attack?
Authors: C. J McKenna
Journal: BMJ (2002)

The World Health Organization's classic definition of acute myocardial infarction requires that at least two of the following three criteria are met: a history of typical symptoms of ischaemic chest discomfort; evolutionary electrocardiographic tracings involving the development of Q waves; and an increase in the creatinine kinase level greater than twice the upper reference limit.1 While this definition is clear cut, many patients who have had myocardial infarction will be excluded. Recent developments in the detection of small quantities of myocardial necrosis using serum cardiac troponin levels have prompted a new definition of myocardial infarction. This may well lead to an increase in the number of patients diagnosed and improved patient outcomes, but it may also confuse clinicians, epidemiologists, and most importantly patients themselves.

Acute coronary syndromes without accompanying elevation of the ST segment on the presenting standard 12 lead electrocardiogram cover a range from unstable angina to non-ST elevation or non-Q myocardial infarction. Patients in the latter category can go on to fulfil the WHO definition of myocardial infarction by developing Q waves on serial electrocardiographic tracings during their index admission. Specific patterns …
Abstract 672: Histone deacetylase inhibition has potential to suppresse growth of androgen dependent and independent prostate cancer <i>in vitro</i> and <i>in vivo</i>.
Authors: Shinya Sato, Shugo Suzuki, Aya Naiki-Ito, Yoriko Yamashita, Makoto Asamoto, Tomoyuki Shirai, Satoru Takahashi
Journal: Cancer Research (2013)

Abstract Histone acetylation plays an important role in chromatin remodeling and gene expression. Histone deacetylase (HDAC) inhibitors regulate gene expressions through the induction of histone acetylation and have been reported to suppress growth of several malignancies including lymphoma. In this study, we examined the effects of one example on androgen dependent and independent prostate cancer growth in vivo and in vitro. In in vitro study, androgen dependent and independent prostate cancer cell lines (LNCaP and VCaP) were used. The HDAC inhibitor, OBP-801 (Generously donated by Dr. Urata, Oncolys Biopharma), significantly suppressed cell proliferation with induction of G2/M arrest, and decreased expression of cdc2, androgen receptor (AR) and PSA protein in both cell lines. OBP-801 also significantly induced apoptosis with activation of caspase 3 in LNCaP. Next, we performed two in vivo experiments. First, we transplanted an androgen independent rat prostate cancer (PLS-P) into the femurs and backs of male F344 rats, and OBP-801 was administered intravenously at doses of 0, 2.5 and 5mg/kg every other day for 2 weeks. OBP-801 significantly reduced the volume of the transplanted tumor, while inducing cleaved caspase 3 protein expression. OBP-801 also suppressed bone destruction and induction of osteoclasts in xenografts transplanted to femurs. Second, we prepared male Transgenic Rat for Adenocarcinoma of Prostate (TRAP) rats which spontaneously develop androgen dependent rat prostate cancers, and OBP-801 was given intravenously at doses of 0, 0.5 and 2mg/kg once a week for 8 weeks. As a result, body weight loss was observed in treated groups, and numbers of carcinoma acini in the lateral and ventral prostates were significantly decreased compared with the control group values. In conclusion, the obtained data suggests that OBP-801 may be a candidate therapeutic or preventing agent for androgen dependent and independent prostate cancer, although side effects such as body weight loss may occur. Elucidation of mechanisms of HDAC underlying these effects is needed. Citation Format: Shinya Sato, Shugo Suzuki, Aya Naiki-Ito, Yoriko Yamashita, Makoto Asamoto, Tomoyuki Shirai, Satoru Takahashi. Histone deacetylase inhibition has potential to suppresse growth of androgen dependent and independent prostate cancer in vitro and in vivo. [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 672. doi:10.1158/1538-7445.AM2013-672
Altered myocardial perfusion in patients with angina pectoris or silent ischemia during exercise as assessed by quantitative thallium-201 single-photon emission computed tomography.
Authors: J J Mahmarian, C M Pratt, M K Cocanougher, M S Verani
Journal: Circulation (1990)

The extent of abnormally perfused myocardium was compared in patients with and without chest pain during treadmill exercise from a large, relatively low-risk consecutive patient population (n = 356) referred for quantitative thallium-201 single-photon emission computed tomography (SPECT). All patients had concurrent coronary angiography. Patients were excluded if they had prior coronary angioplasty or bypass surgery. Tomographic images were assessed visually and from computer-generated polar maps. Chest pain during exercise was as frequent in patients with normal coronary arteries (12%) as in those with significant (greater than 50% stenosis) coronary artery disease (CAD) (14%). In the 219 patients with significant CAD, silent ischemia was fivefold more common than symptomatic ischemia (83% versus 17%, p = 0.0001). However, there were no differences in the extent, severity, or distribution of coronary stenoses in patients with silent or symptomatic ischemia. Our major observation was that the extent of quantified SPECT perfusion defects was nearly identical in patients with (20.9 +/- 15.9%) and without (20.5 +/- 15.6%) exertional chest pain. The sensitivity for detecting the presence of CAD was significantly improved with quantitative SPECT compared with stress electrocardiography (87% versus 65%, p = 0.0001). Although scintigraphic and electrocardiographic evidence of exercise-induced ischemia were comparable in patients with chest pain (67% versus 73%, respectively; p = NS), SPECT was superior to stress electrocardiography for detecting silent myocardial ischemia (52% versus 35%, respectively; p = 0.01). The majority of patients in this study with CAD who developed ischemia during exercise testing were asymptomatic, although they exhibited an angiographic profile and extent of abnormally perfused myocardium similar to those of patients with symptomatic ischemia. The prognostic significance of quantified perfusion defects detected by SPECT remains to be assessed.
China proposes strict antitobacco controls
Authors: S. Dai, L. Xu
Journal: BMJ (2015)

China’s government has published draft regulations for banning smoking in public places, which, if implemented, would become the strictest antismoking law in Chinese history.

The Cigarette Control Regulations in Public Areas, drafted by China’s health authority, the National Health and Family Planning Commission, would ban smoking in various indoor and outdoor public places, including sports venues and bus and train waiting areas. The regulations also propose that messages and graphic images illustrating the harms of tobacco should cover at least half the packaging of tobacco products, slightly less than the 65% recommended by the World Health Organization but still more than …
The Clinical Recognition of Congenital Heart Disease
Authors: David H. Spodick
Journal: JAMA (1971)

Diagnostic approaches to many congenital abnormalities deal with complexities which may daunt all but those in daily contact with this rewarding branch of cardiology. This has been due to the possible permutations and combinations involving dislocated, absent, or flawed chambers, vessels, and valves, not to mention shunts in one or both directions. Recently, increasingly sophisticated diagnostic procedures superficially appear to have narrowed the clinician's scope. Actually, the converse is true, as demonstrated by this complete book, which, on every well-written page, justifies the words "clinical recognition" of the title. Chapters progress logically from anatomy through clinical manifestations. By emphasizing deductive reasoning and minimizing rote learning, Dr. Perloff reveals a sentient physician, rather than a diagnosis machine. This approach maximizes the usefulness of clinical data and their correlation with ordinary x-ray films and electrocardiograms, as well as with pathologic physiology. Relatively pure forms of each disorder are stressed, and the composite
THE REPAIR OF CYSTOCELEBY UTILIZATION OF THE ANATOMICALLY FIXED POINTS IN THE ANTERIOR VAGINAL WALL.
Authors: E. REYNOLDS
Journal: JAMA (1903)

A year ago I read before the American Gynecological Association a paper on this same subject, setting forth what I believed to be somewhat new and important points in the repair of cystocele. My object in this present paper is to restate the facts and conclusions then brought forward, with the developments which have been obtained in another year of work, and supported by the ultimate results of the cases then reported. We hear nothing nowadays of new methods of operation in the repair of the lacerated cervix, and for several years have heard nothing of new methods in the repair of the perineum. These operations are satisfactory. The anatomic principles on which they were founded are well worked out, and there is little more to say about them, hence the silence. The third great plastic—the operation for the repair of cystocele—stands on very different ground. New operations are still proposed almost as frequently as in the
Effect of intra-aortic balloon counterpulsation on the motion and perfusion of acutely ischemic myocardium. An experimental echocardiographic study.
Authors: R E Kerber, M L Marcus, J Ehrhardt, F M Abboud
Journal: Circulation (1976)

The effect of intra-aortic balloon counterpulsation (IABC) on the motion and perfusion of ischemic left ventricular posterior myocardium was studied in 30 open-chest dogs, using ultrasound to register motion and 7-10 mu radioactive microspheres to determine perfusion. Circumflex coronary artery ligation produced acute aneurysmal bulging during isovolumetric contraction and diminished ischemic wall velocity during systolic ejection. Myocardial perfusion was determined in five dogs; perfusion of the area supplied by the ligated coronary artery fell from a control value of 72.9 +/- 13.8 (SE) to 30.0 +/- 2.3 cc/100 g/min (P less than 0.05) at 5 minutes after coronary occlusion. IABC was then administered for one hour, with a fall in aortic systolic pressure (112 +/- 6 to 105 +/- 7 mm Hg, P less than 0.05) and rise in peak aortic diastolic pressure (94 +/- 6 to 102 +/- 7 mm Hg, P less than 0.05). Despite this the ischemic area showed no change in perfusion (measured at the same time): 30.0 +/- 2.3 to 28.0 +/- 2.4 cc/100 g/min. Little change in wall motion occurred: aneurysmal bulging decreased modestly (4.5 +/- 0.3 to 3.6 +/- 0.3 mm, P less than 0.05), but ischemic wall velocity did not increase. After cessation of counterpulsation and one hour of coronary reperfusion aneurysmal bulging disappeared and wall velocity improved. The addition of norepinephrine (eight dogs) or nitroprusside (seven dogs) to intraaortic balloon counterpulsation did not cause a significant further improvement in the response of the dyskinesis during the period of ischemia. We conclude that IABC has little effect on ischemic dyskinesis, probably due to its failure to improve perfusion of the acutely ischemic myocardium.
No blame should be apportioned in corporate failure
Authors: D. Hall
Journal: BMJ (2001)

EDITOR—Hey and Chalmers express concern about the Griffiths report and the prolonged suspension of two paediatricians at North Staffordshire Hospital.1 I share their concerns.

The Griffiths inquiry faced several difficulties.

Firstly, few researchers, however meticulous, can instantly produce all the relevant data and records from projects completed some years earlier.

Secondly, the resources and range of expertise needed to conduct such a …
Oncoplastic surgery is promising
Authors: R. M Rainsbury, F. MacNeill
Journal: BMJ (2009)

Improving cosmetic outcome is secondary to achieving thorough tumour excision,1 but new techniques in oncoplastic surgery are making both goals possible.

The oncological superiority of quadrantectomy over lumpectomy has been confirmed by level 1 evidence,2 but cosmetic deformity after quadrantectomy is common and distressing. For this reason, …