tbuckley/cabot-search huggingface dataset:
Abstract 1428: Bone marrow adipocyte-derived CXCL1 and CXCL2 in prostate tumor progression in bone.
Authors: Aimalie L. Hardaway, Mackenzie M. Herroon, Erandi N. Rajagurubandara, Izabela Podgorski
Journal: Cancer Research (2013)

Abstract Prostate cancer (PCa) is the second most common cause of death from cancer in men. Bone is a primary site for tumor metastasis and obese and overweight men have a three-fold higher risk of progression to metastatic disease compared to normal-weight men receiving the same treatment. Recent epidemiological evidence suggests that obesity is an independent prognostic contributor to the development of distant metastases and death from PCa. Obesity leads to adipocyte accumulation within the bone marrow, which stimulates infiltration of inflammatory cells, particularly macrophages, and promotes inflammation. Many of the inflammatory cytokines released by both adipocytes and macrophages are involved in increased tumor growth, neovascularization, and cell survival. CXCL1 and CXCL2 are two such chemokines that have been implicated in prostate, breast, and ovarian tumorigenesis. Therefore, we hypothesized that obesity-induced bone marrow adiposity and inflammation would alter prostate tumor behavior in the bone via CXCL1- and CXCL2-dependent mechanisms. Histological evaluations confirmed that mice fed high fat diet (HFD) had increased adipocyte accumulation within the bone. PC3-DsRed cells intratibially injected into HFD mice progressed strikingly faster and grew much larger than those injected into mice on normal (LFD) diet. RT PCR analyses revealed an induction of several inflammatory genes, including CXCL1 and CXCL2, in the marrow of obese mice, and these levels were further increased in tumor-bearing tibiae of HFD hosts. In vitro short-term exposure of tumor cells to media conditioned by primary bone marrow derived adipocytes (Adipo CM) led to increased growth and invasiveness. This effect was further potentiated by chronic exposure to Adipo CM. CXCL1 and CXCL2 expression and secretion increased in co-culture of tumor cells with bone marrow macrophages in the presence of adipocyte-derived factors. Studies are currently underway to determine the role of obesity-induced marrow CXCL1 and CXCL2 in osteoclastogenesis and bone resorption. We are also investigating additional inflammatory mediators that sustain the upregulation of CXC1 and CXCL2 in the tumor microenvironment. Collectively, the results of our studies demonstrate that adipocyte-induced upregulation of CXCL1 and CXCL2 may play a critical role in promoting prostate tumor aggressiveness and survival in the bone metastatic niche. Citation Format: Aimalie L. Hardaway, Mackenzie M. Herroon, Erandi N. Rajagurubandara, Izabela Podgorski. Bone marrow adipocyte-derived CXCL1 and CXCL2 in prostate tumor progression in bone. [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 1428. doi:10.1158/1538-7445.AM2013-1428
Type E Botulism
Authors: Ernest A. Ager, Claude E. Dolman
Journal: JAMA (1964)

SIX IMMUNOLOGIC TYPES of<i>Clostridium botulinum</i>have been identified, designated as types A through F. Almost all human botulism has resulted from ingestion of toxin produced by types A, B, and E. Types A and B botulism have been associated mainly with the consumption of inadequately processed vegetables and meats. The less common type E botulism, however, is generally associated with fish and marine mammal products. This communication reports an outbreak of confirmed type E botulism related to a primitive foodstuff in a remote area of the Olympic Peninsula of Washington. <h3>Report of Cases</h3> At noon on May 25, 1961, a 22-year-old American Indian man ( patient 1) with abdominal pain, vertigo, diplopia, visual blurring, vomiting, and beginning dehydration was seen by a physician. Onset of the illness had been at approximately 6 am. Although acutely and severely ill, the patient refused hospitalization and returned to his home. At 3 PM
Ethnic variation in epidemiology and rehabilitation of hip fracture
Authors: S J Calder, G H Anderson, W M Harper, P J Gregg
Journal: BMJ (1994)

Acyclovir and post-herpetic neuralgia and ocular involvement J I McGill, J E White Herpes zoster infection is a common clinical problem in elderly people.Three of the consequences of such infection are acute rash, post-herpetic neuralgia, and, for those with trigeminal infection, ocular complications.Post-herpetic neuralgia is a severe, prolonged, debilitating complication with no known effective treatment.Acyclovir treats acute rash,14 but its role in preventing post-herpetic neuralgia and ocular compli- cations remains controversial.These complications can be severe and sight threatening and can require prolonged treatment.Topical acyclovir has been shown to be beneficial when given prophylactically and in established cases.5We examined whether high oral doses of acyclovir (800 mg five times a day for seven days) have a beneficial effect on post-herpetic neuralgia and reduce ocular involvement in the long term.*P=0 009, Fisher's exact test.
European Union criticised for health policies towards developing countries
Authors: R. Watson
Journal: BMJ (2009)

The European Union has been accused this week of applying double standards, by trying to reduce the price of generic drugs within its own borders while preventing developing countries from enjoying the same benefits.

The criticism is contained in a report published by Oxfam and Health Action International Europe on 20 October. The two organisations maintain that the EU is insisting on tough new intellectual property rights for the benefit of drug companies in the bilateral free trade agreements that it is negotiating with developing countries.

This, they say, will lead to higher prices for drugs. Citing an accord between the EU …
THE SIGNIFICANCE OF PRESENT ENTRANCE REQUIREMENTS
Authors: WILBURT C. DAVISON
Journal: JAMA (1931)

ABSTRACT There are only two main reasons for entrance requirements: (a) to provide the student with adequate preparation, both scientific and cultural, in order to enable him to profit best from his medical instruction, and (b) to provide the medical schools with students of adequate intelligence and to keep out those who are intellectually weak and likely to fail. The present entrance requirements date from a financial catastrophe in 1888 and are due to two persons, Miss Mary E. Garrett and Dr. William H. Welch. Because of the suspension of dividends by the Baltimore and Ohio Railroad in 1888 and the loss of endowment revenue, the Johns Hopkins University could not start its school of medicine. However, in 1893, Miss Mary E. Garrett made the opening possible by contributing $300,000 on the understanding that only those who were already graduates in arts or who had an equivalent training should be received
Abstract B52: A novel quantitative proteomics approach to identify proteins that elicit antibody responses in vaccinated pancreatic cancer patients.
Authors: Darshil T. Jhaveri, Min-Sik Kim, Lanqing Huang, Rajni Sharma, Robert A. Anders, Akhilesh Pandey, Elizabeth M. Jaffee
Journal: Cancer Research (2013)

Abstract Pancreatic cancer is the fourth leading cause of cancer deaths in the US. Less than 4% of patients have an overall survival of more than 5 years. Our lab has developed an allogeneic, granulocyte-macrophage colony-stimulating factor (GM-CSF) secreting pancreatic cancer vaccine that has recently completed phase II clinical trials. The application of proteomic approaches has gained ground in the identification of new cancer biomarkers, which are beneficial for both early detection and determination of new targets for development of biologically relevant therapies. We have developed a novel Serum Antibodies based SILAC-Immunoprecipitation (SASI) approach. The SASI approach utilizes immunoprecipitation by serum antibodies, which is coupled to the quantitative stable isotope labeling by amino acids in cell culture (SILAC) to identify proteins that elicit an increased antibody response post-vaccination. Using mass spectrometric analysis, the SASI approach comprehensively identified &amp;gt;40 proteins that elicited at least a 2-fold increase in antibody response post-vaccination, from each of the three patients' sera used. The list of identified proteins includes membrane proteins such as MHC class I complex, transferrin receptor (TFRC) and CD9, secreted proteins such as mesencephalic astrocyte-derived neurotrophic factor (MANF), as well as several cytoplasmic proteins such as regulatory subunit 12A of protein phosphatase 1 (PPP1R12A), galectin 3 and regulatory subunit 8 of the 26S proteasome (PSMC5). Most significantly, the antibody responses detected against these proteins in patients with &amp;gt;3 years disease-free survival suggests an anti-tumor potential of targeting these proteins. We further analyzed PSMC5, TFRC and PPP1R12A for tissue expression in normal, pre-malignant and pancreatic tumor specimens and found these proteins to increase in expression with tumor development. In addition, these proteins were shown to be pancreatic cancer associated antigens that are recognized by post-vaccination antibodies in the sera of patients that received the vaccine and have demonstrated a favorable disease free survival. Overall, our data demonstrates that the novel SASI approach can enable identification of candidate proteins as possible new biomarkers for screening, and as new targets for therapeutic intervention. Citation Format: Darshil T. Jhaveri, Min-Sik Kim, Lanqing Huang, Rajni Sharma, Robert A. Anders, Akhilesh Pandey, Elizabeth M. Jaffee. A novel quantitative proteomics approach to identify proteins that elicit antibody responses in vaccinated pancreatic cancer patients. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B52.
Coexisting granular cell myoblastoma and squamous carcinoma of the bronchus.
Authors: S S Hurwitz, A A Conlan, M C Gritzman, L H Krut
Journal: Thorax (1982)

Granular cell myoblastoma is a rare tumour of uncertain _ origin.The tongue, subcutaneous tissue, and breast are the sites most frequently affected, but almost every body .
Inhibition of nitric oxide synthesis in ischemia/reperfusion of the rat liver is followed by impairment of hepatic microvascular blood flow
Authors: Thomas A. Koeppel, Jochen C. Thies, Peter Schemmer, Michael Trauner, Martha-Maria Gebhard, Gerd Otto, Stefan Post
Journal: Journal of Hepatology (1997)

Recent studies provide evidence that nitric oxide (NO) has beneficial effects in hepatic ischemia/reperfusion injury. The purpose of this study was to evaluate whether nitric oxide is involved in the regulation of hepatic microvascular perfusion after warm hepatic ischemia. Therefore, we performed a study using in vivo fluorescence microscopy.Clamping of the left liver lobe was performed in male Wistar rats for the duration of 70 min. One experimental group (n=8) received L-NAME (Nw-nitro-L-arginine methyl ester hydrochloride), an NO-synthase inhibitor, 1 min prior to reperfusion. A second experimental group (n=8) received L-arginine (NO-substrate) continuously infused throughout the observation period. Controls (n=8) received equivalent volumes of an isotonic solution and underwent the same procedures. Hepatic microvascular blood flow and leukocyte-endothelial cell interaction was studied between 20 and 90 min after reperfusion using in vivo fluorescence microscopy.Inhibition of NO-synthesis during reperfusion by application of L-NAME caused a marked decrease in sinusoidal blood flow velocity. Furthermore, we noted an increase of non-perfused sinusoids in this group. Treatment with L-arginine improved functional perfusion of hepatic acini and reduced significantly the number of adherent leukocytes in sinusoids and venules compared to control animals.Our results provide further evidence that NO maintains postischemic hepatic microvascular perfusion and that inhibition of NO synthesis has detrimental effects on hepatic microhemodynamics during reperfusion.
Clinical advantage of endoscopic submucosal dissection over endoscopic mucosal resection for early mesopharyngeal and hypopharyngeal cancers
Authors: T. Iizuka, D. Kikuchi, S. Hoteya, M. Nakamura, S. Yamashita, T. Mitani, H. Takeda, N. Yahagi
Journal: Endoscopy (2011)

<b>Background and study aims:</b> In previous series, endoscopic mucosal resection (EMR) has been used for the treatment of early-stage mesopharyngeal and hypopharyngeal cancers to preserve patients' quality of life. Endoscopic submucosal dissection (ESD) offers potential advantages in comparison to EMR. So the aim of this retrospective study was to assess the utility of ESD compared with EMR for early-stage cancers of the meso- and hypopharynx. <b>Patients and methods:</b> We studied 56 patients with 69 lesions who underwent either EMR or ESD between April 2001 and December 2008. EMR was performed until January 2007, and ESD was performed from February 2007 onward. We evaluated the en bloc resection rate, R0 resection rate, and treatment-related complications as short-term outcomes. Local recurrence, lymph node metastasis, and disease-related deaths were compared to evaluate long-term outcomes. <b>Results:</b> The en bloc and R0 resection rates were respectively 98 % and 79 % in the ESD group and 37 % and 26 % in the EMR group. There were no cases of treatment-related complications in the EMR group, but postoperative subcutaneous emphysema was observed in two patients in the ESD group. In the EMR group, one patient developed a local recurrence and one developed metastasis to the cervical lymph node and died of primary cancer. <b>Conclusions:</b> ESD is a useful method of treatment for early mesopharyngeal and hypopharyngeal cancers and may be superior to EMR.
Trial participants need to be more representative of patients
Authors: Bob Roehr
Journal: BMJ (2008)

A new report is calling for changes in the conduct of clinical trials in the United States to reduce disparities of age, sex, race, and comorbidity.The goal is to give a more representative picture of the benefits and risks of a treatment across the entire population but particularly among those who bear the greatest burden of the morbidity.The eliminating disparities in clinical trials (EDICT) initiative was conducted over two years by the Baylor College of Medicine in Houston and the Intercultural Cancer Council.It is part of an ongoing four year project to reduce barriers to participation in trials.The report of the initiative was released on 1 April in Washington, DC.The report describes itself as a "nationwide call to action . . .that removes the barriers to clinical trial participation and advances education and information sharing [as] a critical step to improving the health status of all Americans."Recommendations include harmonising the Food and Drug Administration's regulations on trial design and conduct with those of the National Institutes of Health requiring diversity; increasing collaboration between government and industry in trials; and fostering community involvement in all phases of trial design and implementation.It calls on journals to require researchers to include an analysis of how their trial participants match the population that bears the greatest burden of that condition.It also seeks better education of institutional review boards on their ethical responsibilities and of the general public about the trials process.Calls for better education of review boards and the public are likely to draw little opposition.But other recommendations are likely to require an increase in the size of a trial to provide sufficient numbers for subgroup analysis according to sex, race, age, and comorbidity.This will increase the cost of trials and could delay the introduction of new drugs to the marketplace.Information on EDICT is available at www.bcm.edu/edict. Trial participants need to represent patients betterUK NEWS Wakefield tells GMC he was motivated by concern for autistic children, p 738 World NEWS Australian drug firms give details of sums spent courting doctors, p 742 bmj.com reducing inequalities in health will need a long timeframe, MPs are told
Asylum seekers in Britain
Authors: P Hall
Journal: BMJ (1994)

EDITOR, - In her news article Claudia Court states that 700 people are seeking asylum in Britain1; this is a considerable underestimate. The Home Office's latest figures show that 45 800 people were waiting for their applications to be processed at the end of 1993 (personal communication). To achieve the coveted status of refugee applicants have to demonstrate a well founded fear of persecution, usually because of religious or political beliefs; only 3% succeeded in 1992. The number …
Role of salivary protease activity in adherence of gram-negative bacilli to mammalian buccal epithelial cells in vivo.
Authors: D E Woods, D C Straus, W G Johanson, J A Bass
Journal: Journal of Clinical Investigation (1981)

Serious illness is accompanied by markedly increased susceptibility to colonization of the respiratory tract by gram-negative bacilli and an increase in the number of such organisms which adhere to regional epithelial cells during incubation in vitro. Trypsinization of cells from normal subjects causes a similar increase in bacillary adherence. We studied bacillary adherence to buccal cells in vitro, protease activity of upper respiratory secretions with a fibrin plate technique, and the amount of fibronectin on the surface of buccal cells with a direct radioimmunobinding assay. Among 10 patients seriously ill with acute respiratory failure bacillary adherence to buccal cells and protease activity in secretions were increased compared with controls and cell-surface fibronectin was decreased; all patients were colonized in vivo with gram-negative bacilli. These changes were persistent and 80% of the patients died. Serial determinations were made in eight patients undergoing coronary artery bypass surgery. Following surgery, protease activity and bacillary adherence increased and cell-surface fibronectin decreased; 38% of coronary artery bypass patients became colonized. In these uncomplicated patients the changes observed were transient, largely returning to normal by the third postoperative day. Increased protease activity of secretions and alterations in epithelial cell surfaces as reflected by loss of buccal cell-surface fibronectin occur swiftly after major illness and appear to underlie enhanced cell adherence of bacilli and colonization of the upper respiratory tract. These findings suggest new approaches to the prevention of nosocomial pneumonia.
BRAF inhibitors reverse the unique molecular signature and phenotype of hairy cell leukemia and exert potent antileukemic activity
Authors: Valentina Pettirossi, Alessia Santi, Elisa Imperi, Guido Russo, Alessandra Pucciarini, Barbara Bigerna, Gianluca Schiavoni, Elisabetta Fortini, Ariele Spanhol-Rosseto, Paolo Sportoletti, Roberta Mannucci, Maria Paola Martelli, Ludger Klein-Hitpass, Brunangelo Falini, Enrico Tiacci
Journal: Blood (2014)
Prevalence and risk factors for abdominal bloating and visible distention: a population-based study
Authors: X Jiang, G R Locke, R S Choung, A R Zinsmeister, C D Schleck, N J Talley
Journal: Gut (2008)

<h3>Background:</h3> Abdominal bloating and visible distention are common yet poorly understood symptoms. Epidemiological data distinguishing visible distention from bloating are not available. We aimed to evaluate the prevalence and potential risk factors for abdominal bloating and visible distention separately in a representative US population, and their association with other functional gastrointestinal disorders (FGIDs). <h3>Methods:</h3> The validated Talley Bowel Disease Questionnaire was mailed to a cohort selected at random from the population of Olmsted County, Minnesota. The complete medical records of responders were abstracted; 2259 subjects (53% females; mean age 62 years) provided bloating and distention data. <h3>Results:</h3> The age and sex-adjusted (US White 2000) overall prevalence per 100 for bloating was 19.0 [95% confidence interval (CI), 16.9 to 21.2] vs 8.9 (95% CI, 7.2 to 10.6) for visible distention. Significantly increased odds for bloating alone and separately for distention (vs neither) were detected in females, and in those with higher overall Somatic Symptom Checklist (SSC) scores and higher scores of each individual SSC item. Further, females [odds ratio (OR), 1.5; 95% CI, 1.0 to 2.1], higher SSC score (OR, 1.4; 95% CI, 1.1 to 1.8), constipation-predominant irritable bowel syndrome (OR, 2.3; 95% CI, 1.3 to 4.1), dyspepsia (OR, 1.9; 95% CI, 1.1 to 3.2), and gastro-intestinal symptom complex overlap (OR, 1.7; 95% CI, 1.1 to 2.7) significantly increased odds for distention over bloating alone. <h3>Conclusions:</h3> Bloating and distention are common and have similar risk factors; somatisation probably plays a role.
2012 ACCF/AHA Focused Update Incorporated Into the ACCF/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction
Authors: Jeffrey L. Anderson, Cynthia D. Adams, Elliott M. Antman, Charles R. Bridges, Robert M. Califf, Donald E. Casey, William E. Chavey, Francis M. Fesmire, Judith S. Hochman, Thomas N. Levin, A. Michael Lincoff, Eric D. Peterson, Pierre Theroux, Nanette K. Wenger, R. Scott Wright, William A. Zoghbi, Thomas E. Arend, William J. Oetgen, Charlene May, Lisa Bradfield, Sue Keller, Ezaldeen Ramadhan, Gordon F. Tomaselli, Nancy Brown, Rose Marie Robertson, Gayle R. Whitman, Judy L. Bezanson, Jody Hundley
Journal: Circulation (2013)
Severe myocardial ischaemia induced by intravenous adrenaline.
Authors: A Horak, R Raine, L H Opie, E A Lloyd
Journal: BMJ (1983)

Normalisation of eosinophil counts in sputum of asthmatic patients reduces eosinophilic exacerbations. However, the effect of this strategy on airway remodelling remains to be determined. We compared bronchial inflammation and collagen deposition after 2 yrs of treatment guided by either sputum eosinophils (sputum strategy, SS) or by clinical criteria (clinical strategy, CS). As a pilot study, 20 mild asthmatic patients were randomly assigned to CS or SS strategies. Bronchial biopsies were obtained when minimum treatment needed to maintain control was identified and this was continued for 2 yrs. Biopsies were immunostained for inflammatory cells, mucin 5A (MUC5A) and collagen. The mean dose of inhaled corticosteroids at the start and end of the study was similar in both SS and CS groups. Forced expiratory volume in 1 s increased in both groups at the study end. In SS, mucosal lymphocyte and eosinophil counts, but not neutrophils, were reduced at the end of the study. In CS, only activated eosinophil and neutrophil counts decreased. MUC5A staining decreased in SS but not CS. No change in collagen deposition underneath the basement membrane was observed in either strategy. Treatment strategies that normalise sputum eosinophils also reduce mucosal inflammatory cells and MUC5A expression, but do not change subepithelial collagen deposition in mild to moderate asthma.
There's Many a Slip 'twixt Implantation and the Crib
Authors: A. Brian Little
Journal: New England Journal of Medicine (1988)

Between fertilization and implantation and the clinical identification of pregnancy there is a period of hazard and potential pregnancy loss. Pregnancy loss during this period is usually classified as occult abortion or "chemical beta human chorionic gonadotropin (ß hCG) abortion" (implying a positive pregnancy test with or without delayed bleeding). The study by Wilcox et al.1 in this issue of the Journal assesses such pregnancy loss with a sensitive urinary immunoradiometric assay2 in 230 healthy women. The assay is a test with exquisite specificity and sensitivity that measures intact hCG plus some free beta-subunit radicals without cross-reaction with luteinizing hormone. . . .