tbuckley/cabot-search huggingface dataset:
Abstract C7: Targeting the androgen receptor with novel combination therapeutic strategies in metastatic/castrate-resistant prostate cancer
Authors: Leigh Ellis, Swathi Ramakrishnan, Shengyu Ku, Roberto Pili
Journal: Cancer Research (2012)

Abstract While recent advances have resulted in the FDA approval of novel therapies for metastatic/castrate resistant prostate cancer, responses are not often durable and novel therapeutic interventions are still required. Recent work within our laboratory has resulted in the development of a novel orthotopic syngeneic transplant mouse model of prostate cancer. Further, treatment with a HDAC and mTORC1 inhibitor in combination resulted in greater anti-tumor and increased overall survival in tumor bearing animals. HDAC/mTORC1 combination therapy also resulted in decreased androgen receptor (AR) transcriptional activity without loss of AR protein expression. Current investigations are underway to delineate molecular mechanisms underlying sustained AR expression. Through this understanding, novel therapeutic interventions which will augment combined HDAC/mTORC1 inhibitor therapy are under investigation. Citation Format: Leigh Ellis, Swathi Ramakrishnan, Shengyu Ku, Roberto Pili. Targeting the androgen receptor with novel combination therapeutic strategies in metastatic/castrate-resistant prostate cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr C7.
Prognostic Significance of Thrombocytopenia During Hirudin and Heparin Therapy in Acute Coronary Syndrome Without ST Elevation
Authors: John W. Eikelboom, Sonia S. Anand, Shamir R. Mehta, Jeffrey I. Weitz, Cheelong Yi, Salim Yusuf
Journal: Circulation (2001)

Background —The development of thrombocytopenia in acute coronary syndromes (ACS) appears to be associated with adverse clinical outcomes. Unfractionated heparin is a recognized cause of thrombocytopenia, but the incidence, predictors, and prognostic significance of thrombocytopenia during hirudin therapy in ACS have not been reported. Methods and Results —Patients with ACS without ST elevation were randomized in a double-blind manner to receive a 72-hour intravenous infusion of unfractionated heparin or hirudin. Platelet counts were measured at baseline and within 24 hours of completion of study drug. The overall incidence of thrombocytopenia (&lt;100×10 9 /L) was 1% and was similar in unfractionated heparin– and hirudin-treated patients ( P =0.42). Thrombocytopenia during study drug infusion was an independent predictor of 7-day outcomes, including death (OR, 6.7; 95% CI, 1.9 to 25); the composite of death, myocardial infarction, and recurrent ischemia (OR, 2.0; 95% CI, 1.0 to 1.5); revascularization (OR, 4.0; 95% CI, 2.2 to 7.1); and major bleeding (OR, 8.3; 95% CI, 3.4 to 17.7). Among patients who developed thrombocytopenia, hirudin (OR, 5.4; 95% CI, 2.6 to 11.3) but not unfractionated heparin (OR, 2.0; 95% CI, 0.3 to 14.4) therapy was associated with a significantly increased risk of major bleeding. Conclusions —Early-onset thrombocytopenia in patients with ACS without ST elevation is strongly associated with adverse clinical outcomes, including death, ischemic events, and bleeding. The excess of major bleeding in hirudin-treated patients who develop thrombocytopenia suggests that thrombocytopenia may contribute to the increased risk of bleeding observed with hirudin.
THE DENTAL NURSE.CHAIRMAN'S ADDRESS BEFORE THE SECTION ON STOMATOLOGY AT THE FIFTY-FOURTH ANNUAL SESSION OF THE AMERICAN MEDICAL ASSOCIATION AT NEW ORLEANS, MAY 5-8, 1903.
Authors: M. L. RHEIN
Journal: JAMA (1903)

th i -tuture of neurologic medicine as worked out along hurrf • 6S W^* he °f vast importance to the welfare of "i-i things come to him who waits," he who would utlk*e them must act.lSIDLIOGltAl'IIY.1.Broca:
Stability of peripheral hematological parameters after chronic acetylcholinesterase inhibition in man
Authors: Pamela L. Moriearty, Cindy L. Womack, Barrett W. Dick, Jerry A. Colliver, Randall S. Robbs, Robert E. W. Becker
Journal: American Journal of Hematology (1991)

Abstract Acetylcholinesterase (AChE; EC 3.1.1.7) is present in both primitive and mature erythroid cells, and a role has been suggested for the enzyme in regulation of differentiation in the human erythron. AChE is also a major enzyme in the central nervous system; alteration of its activity has been proposed as a therapeutic strategy in Alzheimer disease. We recently treated 18 Alzheimer disease patients with metrifonate, a long‐acting AChE inhibitor, over periods up to 7 months, with resulting erythrocyte AChE inhibition as high as 82 per cent of baseline values. Despite chronic reduction of enzyme activity, no significant alterations were noted in erythrocyte, leukocyte or platelet characteristics or numbers that would suggest a deleterious effect of AChE inhibition on normal differentiation. Thus, any modification of developmental pathways appears to be compensated by other regulatory mechanisms in the intact organism.
Rating Long-Term Care Facilities on Pressure Ulcers
Authors: Dan R. Berlowitz
Journal: Annals of Internal Medicine (1996)

Letters15 September 1996Rating Long-Term Care Facilities on Pressure UlcersDan R. Berlowitz, MD, MPH, Gary H. Brandeis, MD, and Mark A. Moskowitz, MDDan R. Berlowitz, MD, MPHCenter for Health Quality, Outcomes, and Economic Research, Bedford, MA 01730, Gary H. Brandeis, MDCenter for Health Quality, Outcomes, and Economic Research, Bedford, MA 01730, and Mark A. Moskowitz, MDCenter for Health Quality, Outcomes, and Economic Research, Bedford, MA 01730Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-125-6-199609150-00033 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We agree with Dr. Finucane that the association among nutrient intake, measures of nutritional status, and the development of pressure ulcers is complex. Unfortunately, our database did not contain information on these variables. Such information would have been useful, both to better define this clinical condition and to understand differences in patient mix that may affect a facility's rate of pressure ulcer development. Further studies are needed in this area. Author, Article, and Disclosure InformationAffiliations: Center for Health Quality, Outcomes, and Economic Research, Bedford, MA 01730 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byCytokine Production and Monocyte HLA-DR Expression as Predictors of Outcome for Patients with Community-Acquired Severe InfectionsTrophic Effect of Human Pericardial Fluid on Adult Cardiac Myocytes 15 September 1996Volume 125, Issue 6Page: 520KeywordsDatabasesLong-term careNutrientsNutritionPressure ulcers Issue Published: 15 September 1996 Copyright & PermissionsCopyright © 1996 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Pulmonary Disease Reviews
Authors: Harry B. Greenberg
Journal: JAMA (1981)

Knowing the oxygen tensions in the pulmonary arteries of patients with failing respiration helps the physician to treat such patients, according to Drs Wilson and Bone. Their chapter in<i>Pulmonary Disease Reviews</i>includes abstracts of articles that rely heavily on data from Swan-Ganz flow-directed pulmonary artery catheters and other monitoring devices. In the other chapters, 30 contributors comment on abstracts of articles they selected from the late-1977 to mid1979 literature. Their subjects range from oxygen transfer to lung cancer and the treatment of tuberculosis. Stead and Dutt discuss new concepts of antituberculosis chemotherapy. Several of their abstracted articles emphasize the excellent results of short-course therapy with isoniazid and rifampin. Earlier reports exaggerated the synergistic toxicity of these drugs. Bates presents papers about other pulmonary infections. He considers the possibility of Legionnaires' disease in every case of undiagnosed pneumonia and cites disturbing reports of multiple-drug-resistant pneumococci. He wonders whether physicians should
Simultaneous two level oesophageal pH monitoring in healthy controls and patients with oesophagitis: comparison between two positions.
Authors: P Singh, R H Taylor, D G Colin-Jones
Journal: Gut (1994)

For oesophageal pH monitoring, the pH probe is usually positioned 5 cm above the lower oesophageal sphincter (LOS). This is by convention, and has not been compared with other positions in its ability to discriminate between physiological and abnormal acid reflux. Using simultaneous two level 24 hour pH monitoring (5 and 10 cm above manometrically determined LOS) in 31 controls and 51 patients with reflux oesophagitis, the significance of the precise position of the probe in the oesophagus was examined. Secondly, this study compared the discrimination between the two groups achieved at the two levels. Patients had greater acid exposure than controls at both levels. In controls, acid exposure was greater at distal than at the proximal level except the supine acid exposure, which was similar at both levels. In patients, acid exposure was greater at the distal level for all variables (median % of total time pH &lt; 4 = 11.7 v 7.6; p = 0.001). There was excellent correlation between the two levels for all variables in controls (r = 0.883, 0.935, 0.813, and p &lt; 0.001 for percentage of time pH &lt; 4 for total, supine, and upright times) as well as in patients (r = 0.848, 0.848, 0.779, and p &lt; 0.001). On discriminant and receiver operating characteristic analysis, pH threshold 4 seemed as good as or better than other pH thresholds in discriminating between controls and patients. The percentage of total time pH below 4 seemed to discriminate as well or better than other variables at both levels. The distal level (5 cm above LOS) provided slightly better discrimination than proximal level (10 cm) (percentage of subjects correctly classified=81.7 v 75.6). The critical factor for the reliability of the test is not the precise position of the pH probe relative to the LOS, but that the same position is consistently used in patients and controls.
“Due Process” in Hospital Peer Review
Authors: John D. Blum
Journal: New England Journal of Medicine (1976)

The movement toward institutional peer review is an outgrowth of both the hospital's responsibility to protect patients and the development of private and governmental medical-review programs. While hospitals are experiencing continuing pressures to conduct medical review, they are also being confronted by staff members who are aware of the fact that institutional review committees must adopt procedures that uphold the due-process rights of those on review. The hospital is thus faced with a potential dilemma, caught between a duty to protect the patient and the duty to uphold the rights of the private physician. Generally, this dual responsibility of the . . .
Ventricular Visualization on Brain Scan with Intracranial Hemorrhage in Disseminated Phycomycosis
Authors: EDWIN C. GLASS, ROBERT C. STADALNIK, CHARLES A. BARNETT
Journal: Clinical Nuclear Medicine (1978)

Infections with fungi of the class Phycomycetes result in distinctive tissue changes characterized by growth of hyphae in and around blood vessels, causing necrosis and hemorrhagic infarction of tissue. A brain scan on a patient with a phycomycotic intracranial aneurysm demonstrated ventricular visualization at a time when there was clinical and autopsy evidence of rupture of the aneurysm.
Effects of Valve Surgery on Left Ventricular Contractile Function in Patients With Long-term Mitral Regurgitation
Authors: Mark R. Starling
Journal: Circulation (1995)

Patients with long-term mitral regurgitation were studied both before and 1 year after successful valve surgery to test the hypothesis that impaired left ventricular contractile function improves after surgery for long-term mitral regurgitation in humans.Fifteen patients with long-term mitral regurgitation were studied. Micromanometer left ventricular pressures and radionuclide angiograms for left ventricular volumes were acquired over a range of loading conditions both before and 1 year after successful valve surgery for long-term mitral regurgitation. To assess both left ventriculoarterial coupling to evaluate the interaction of the left ventricle with the arterial system with the use of the left ventricular contractile index, Ees, and effective arterial elastance, Ea. Left ventricular pump efficiency was expressed as the ratio of forward left ventricular stroke work to the corresponding pressure-volume area. All patients had successful mitral valve surgery as manifest by no or only trivial residual mitral regurgitation on physical examination and Doppler echocardiography. The average radionuclide regurgitant index of 1.28 +/- 0.56 was also less than the preoperative value of 2.70 +/- 0.80 (P < .0001). The mean left ventricular end-diastolic volume index decreased from 137 +/- 37 to 90 +/- 31 mL/m2 (P < .001), and the average left ventricular end-systolic volume index also decreased (59 +/- 29 to 45 +/- 27 mL/m2, P < .01), although individual variation was observed. The average left ventricular ejection fraction fell from 0.58 +/- 0.12 to 0.53 +/- 0.16, which was not significant. In contrast, Ees increased from a mean value of 0.95 +/- 0.66 mm Hg/mL during the preoperative study to 2.62 +/- 2.16 mm Hg/mL at the 1-year postsurgical study (P < .01). This improvement in left ventricular contractility was observed in patients with long-term mitral regurgitation, who before surgery had preserved left ventricular ejection fraction (P < .001), less left ventricular dilation at end diastole (P < .01) and end systole (P < .001), and less impaired left ventricular contractility. Because effective arterial elastance was unchanged, left ventriculoarterial coupling also improved from an average of 0.47 +/- 0.39 to 1.81 +/- 1.63 (P < .01). Consequently, left ventricular pump efficiency improved from a mean preoperative value of 0.23 +/- 0.10 to 0.55 +/- 0.22 at the 1-year postsurgical study (P < .0001).The results indicate that left ventricular contractile impairment is reversible in many patients with long-term mitral regurgitation. In fact, these data indicate that mitral valve surgery can be recommended to preserve left ventricular contractility in patients with long-term mitral regurgitation, particularly in those patients who before surgery have normal left ventricular ejection fractions and less left ventricular dilation and contractile impairment.
Small peptide inhibitors of the CXCR4 chemokine receptor (CD184) antagonize the activation, migration, and antiapoptotic responses of CXCL12 in chronic lymphocytic leukemia B cells
Authors: Meike Burger, Tanja Hartmann, Myriam Krome, Justyna Rawluk, Hirokazu Tamamura, Nobutaka Fujii, Thomas J. Kipps, Jan A. Burger
Journal: Blood (2005)
Noxythiolln-resistant organisms in a district general hospital.
Authors: B Chattopadhyay
Journal: BMJ (1977)

Twelve strains of Pseudomonas aeruginosa, three strains of Klebsiella aerogenes, and two strains of Escherichia coli were found to be resistant to noxythiolin. Some of the pseudomonads were isolated from patients in the same ward, not all of whom were on noxythiolin treatment. The strains from these patients were indistinguishable from each other on phage typing, which suggested cross-contamination. No Gram-positive organism was found to be resistant to noxythiolin. Noxythiolin should not be used before a disc diffusion sensitivity test has been performed to determine whether the organisms are sensitive to it. This is particularly important when pseudomonads are the offending organisms.
Novel c-CBL and CBL-b ubiquitin ligase mutations in human acute myeloid leukemia
Authors: Michael A. Caligiuri, Roger Briesewitz, Jianhua Yu, Lisheng Wang, Min Wei, Kristy J. Arnoczky, Trent B. Marburger, Jing Wen, Danilo Perrotti, Clara D. Bloomfield, Susan P. Whitman
Journal: Blood (2007)
Late MRD response determines relapse risk overall and in subsets of childhood T-cell ALL: results of the AIEOP-BFM-ALL 2000 study
Authors: Martin Schrappe, Maria Grazia Valsecchi, Claus R. Bartram, André Schrauder, Renate Panzer-Grümayer, Anja Möricke, Rosanna Parasole, Martin Zimmermann, Michael Dworzak, Barbara Buldini, Alfred Reiter, Giuseppe Basso, Thomas Klingebiel, Chiara Messina, Richard Ratei, Giovanni Cazzaniga, Rolf Koehler, Franco Locatelli, Beat W. Schäfer, Maurizio Aricò, Karl Welte, Jacques J.M. van Dongen, Helmut Gadner, Andrea Biondi, Valentino Conter
Journal: Blood (2011)
NF-κB–inducing kinase plays an essential T cell–intrinsic role in graft-versus-host disease and lethal autoimmunity in mice
Authors: Susan E. Murray, Fanny Polesso, Alexander M. Rowe, Soumen Basak, Yoshinobu Koguchi, Katelynne Gardner Toren, Alexander Hoffmann, David C. Parker
Journal: Journal of Clinical Investigation (2011)

NF-κB–inducing kinase (NIK) is an essential upstream kinase in noncanonical NF-κB signaling. NIK-dependent NF-κB activation downstream of several TNF receptor family members mediates lymphoid organ development and B cell homeostasis. Peripheral T cell populations are normal in the absence of NIK, but the role of NIK during in vivo T cell responses to antigen has been obscured by other developmental defects in NIK-deficient mice. Here, we have identified a T cell–intrinsic requirement for NIK in graft-versus-host disease (GVHD), wherein NIK-deficient mouse T cells transferred into MHC class II mismatched recipients failed to cause GVHD. Although NIK was not necessary for antigen receptor signaling, it was absolutely required for costimulation through the TNF receptor family member OX40 (also known as CD134). When we conditionally overexpressed NIK in T cells, mice suffered rapid and fatal autoimmunity characterized by hyperactive effector T cells and poorly suppressive Foxp3(+) Tregs. Together, these data illuminate a critical T cell–intrinsic role for NIK during immune responses and suggest that its tight regulation is critical for avoiding autoimmunity.
A little bit of measles does you good
Authors: F. Shann
Journal: BMJ (1999)

Measles still kills 800 000 children in developing countries every year,1 although immunisation has substantially reduced the number of deaths. Immunisation lowers mortality primarily by reducing the incidence of measles, but it may also lower mortality by increasing the age at which children are infected and by reducing the severity of infection in immunised children and their contacts.2 Morever, the vaccine itself may reduce mortality from conditions other than measles.

Epidemiological research has shown two important characteristics of measles: the severity of clinical illness is largely determined by the infecting dose, and, surprisingly, mild infection and standard doses of Schwarz vaccine substantially reduce mortality from conditions other than measles.3 Children infected with a large dose of measles virus have a shorter incubation period, more severe disease, and a higher mortality. Children who are infected outside the home (primary cases) have milder disease than secondary cases (who are …
Hypernatremia and Intracranial Hemorrhage in Neonates
Authors: Michael A. Simmons, Eugene W. Adcock, Harry Bard, Frederick C. Battaglia
Journal: New England Journal of Medicine (1974)

Records of all newborn admissions over a two-year period were reviewed for the occurrence of hypernatremia and intracranial hemorrhage. When restrictive criteria for the use of sodium bicarbonate were instituted, the incidence of hypernatremia fell from 8.8 to 0.6 per cent. In addition, the frequency of intracranial hemorrhage declined over the same period (13.4 to 2.6 per cent). Hypernatremia was associated with a high mortality risk (71 per cent in the combined years). Eleven of 24 patients with hypernatremia died of intracranial hemorrhage. Intracranial hemorrhage was associated with hypernatremia or excessive sodium administration in 25 of 32 cases (81 per cent). These data suggest that excessive sodium bicarbonate administration to newborns, with or without hypernatremia, may place the infant at higher risk of intracranial hemorrhage. Thus, the newborn's sodium intake from all sources should be carefully controlled, and intakes of more than 8 mg per kilogram of body weight per 24 hours should be regarded as excessive. (N Engl J Med 291:6–10, 1974)
Myocarditis and Cardiomyopathy
Authors: Thomas N. James
Journal: New England Journal of Medicine (1983)

For most physicians "myocarditis" means not only inflammation but also infection of the myocardium. Whether that meaning is correct or not, it is what the term suggests to most of us. Thus, when "myocarditis" is used to describe the heart in pheochromocytoma1 or in Friedreich's ataxia,2 there is an element of unintended deception at least for the former and probably for the latter, given that an infectious source is not known to be present in either disease. When we think of infections of the myocardium, viruses quickly spring to mind, but proof that they are to blame remains disappointingly elusive. . . .
Excision and Skin Grafting of Thermal Burns
Authors: Dennis P. Orgill
Journal: New England Journal of Medicine (2009)

A 45-year-old man presents with extensive burns after a house fire. Excision and grafting are recommended for management of his burns. Depending on the depth and extent of the burn, early excision and grafting promote wound healing, reduce the risk of infection, and shorten hospitalization but increase the need for blood transfusion, as compared with conservative management.
IMPROVING PERIOPERATIVE CARDIAC RISK ASSESSMENT AND BETA-BLOCKER USE FOR NON-CARDIAC SURGERY (INCREASE): THE INCREASE QUALITY IMPROVEMENT PROJECT
Authors: Anitha Rajamanickam, Ali Usmani, Eric Hixson, Prabhakaran Anbazhagan, Anuradha Ramaswamy, Mike Pecic, Amir Jaffer, Brian Harte
Journal: Journal of the American College of Cardiology (2010)
Ethical and Technical Aspects of Genetic Intervention
Authors: Bernard D. Davis
Journal: New England Journal of Medicine (1971)

The dramatic recent advances in molecular and cellular genetics have led to the widespread belief that we will soon be able to cure hereditary diseases by genetic manipulation, and that the same technics could then be used to control human behavior. Though these assumptions are unlikely to be true, for reasons discussed below, concern over the possible political abuse of such powers has clearly contributed to (and been fed by) the current wave of anti-scientism. Indeed, fear of genetic manipulation seems to have generated especially strong anxiety. Thus, a recent report of the highly responsible Friends Service Committee,1 on moral . . .
THE LYMPHATIC PATHWAY FROM THE NOSE AND PHARYNX
Authors: Joseph M. Yoffey, Eugene R. Sullivan
Journal: The Journal of Experimental Medicine (1939)

Vaccinia virus dropped into the nose of a susceptible animal does not appear in cervical lymph in less than 12 hours. After 12 hours, and thereafter continuously for 7 days, a stream of virus is entering the blood through the cervical lymph ducts. Virus passes through the lymph nodes. Virus is fixed by the lymphocytes, and the significance of this is discussed.
Christina Bernard (nee Russell)
Authors: G. Russell, R. S Gordon
Journal: BMJ (2001)

Obstetrician and gynaecologist who worked with Fleming on the role of penicillin in treating venereal diseaseDuring the second world war Jack Suchet was initially retained at St Mary's, where he was not only registrar in the department of obstetrics but also became assistant and then director of the department of venereology.He became adviser in venereology to the war office and because of this appointment he worked closely with Sir Alexander Fleming on the role of penicillin in the revolutionary