tbuckley/cabot-search huggingface dataset:
Clinical and Hemodynamic Observations After Combined Aortic and Mitral Replacement
Authors: J. DAVID BRISTOW, CYRUS FARREHI, COLIN W. MCCORD, ALBERT STARR, HERBERT E. GRISWOLD
Journal: Circulation (1965)

Twelve patients have been observed from 6 to 19 months after combined aortic and mitral valvular replacement with Starr-Edwards prostheses. Eleven patients have had postoperative right- and left-heart catheterizations. The clinical and hemodynamic findings are described. Nine patients are well. Three others have less than satisfactory results, although one of these is improved. It is concluded that bivalvular replacement is now practical in selected patients and provides gratifying results in most individuals so treated.
Omega-3 Free Fatty Acids for the Maintenance of Remission in Crohn Disease
Authors: Brian G. Feagan, William J. Sandborn, Ulrich Mittmann, Simon Bar-Meir, Geert D’Haens, Marc Bradette, Albert Cohen, Chrystian Dallaire, Terry P. Ponich, John W. D. McDonald, Xavier Hébuterne, Pierre Paré, Pavel Klvana, Yaron Niv, Sandro Ardizzone, Olga Alexeeva, Alaa Rostom, Gediminas Kiudelis, Johannes Spleiss, Denise Gilgen, Margaret K. Vandervoort, Cindy J. Wong, Guang Yong Zou, Allan Donner, Paul Rutgeerts
Journal: JAMA (2008)

Maintenance therapy for Crohn disease features the use of immunosuppressive drugs, which are associated with an increased risk of infection. Identification of safe and effective maintenance strategies is a priority.To determine whether the oral administration of omega-3 free fatty acids is more effective than placebo for prevention of relapse of Crohn disease.Two randomized, double-blind, placebo-controlled studies (Epanova Program in Crohn's Study 1 [EPIC-1] and EPIC-2) conducted between January 2003 and February 2007 at 98 centers in Canada, Europe, Israel, and the United States. Data from 363 and 375 patients with quiescent Crohn disease were evaluated in EPIC-1 and EPIC-2, respectively.Patients with a Crohn's Disease Activity Index (CDAI) score of less than 150 were randomly assigned to receive either 4 g/d of omega-3 free fatty acids or placebo for up to 58 weeks. No other treatments for Crohn disease were permitted.Clinical relapse, as defined by a CDAI score of 150 points or greater and an increase of more than 70 points from the baseline value, or initiation of treatment for active Crohn disease.For EPIC-1, 188 patients were assigned to receive omega-3 free fatty acids and 186 patients to receive placebo. Corresponding numbers for EPIC-2 were 189 and 190 patients, respectively. The rate of relapse at 1 year in EPIC-1 was 31.6% in patients who received omega-3 free fatty acids and 35.7% in those who received placebo (hazard ratio, 0.82; 95% confidence interval, 0.51-1.19; P = .30). Corresponding values for EPIC-2 were 47.8% and 48.8% (hazard ratio, 0.90; 95% confidence interval, 0.67-1.21; P = .48). Serious adverse events were uncommon and mostly related to Crohn disease.In these trials, treatment with omega-3 free fatty acids was not effective for the prevention of relapse in Crohn disease.clinicaltrials.gov Identifiers: EPIC-1: NCT00613197, EPIC-2: NCT00074542.
Cerebral Syphilis: Two Cases in One Family
Authors: F. Warner
Journal: BMJ (1888)

7Wpressed tlae speaker with the efforts of Nature to heal these chronic lung diseases through the deposition of fibroid tissue.This re- sulted in the contraction of the affected portions of lung, and the compensative dilatation of the unaffected portions.Hence, the medicaments went with the air to the healthy portions almost wholly.Then again the nebulisation of fluids in inhalation was, as usually done, accompanied by a lowering of temperature; and this taken cold, the moisture became diffused during breathing, and was not deposited within either the bronchial or alveolar tracts.2. The residual and usual amount of air within the lungs became mixed with the inhalants, and thus these medicaments become diluted and not deposited.Futrther evidence was mentioned in the speaker's calculations, showing a far greater exhalation of moisture in a cold, dry, Qa compared with that in a warm, moist
Control of marrow production by the level of iron supply
Authors: Robert S. Hillman, Perry A. Henderson
Journal: Journal of Clinical Investigation (1969)

The level of erythroid marrow production varies widely in different erythropoietic disorders. In part, this reflects the level of erythropoietin stimulation as determined by the severity of the anemia. However, iron supply plays an equally important role in the control of erythropoiesis. As demonstrated in normal individuals subjected to prolonged periods of phlebotomy-induced anemia, the erythroid marrow will increase production by as little as twice to as much as eight times normal, depending on the iron supply available from different iron pools. Whereas the iron delivered from normal reticuloendothelial stores or orally administered iron is sufficient for a marrow production response of only two to three times normal, the increased iron supply from nonviable red cells, hemolysis, or iron dextran infusions permits marrow production to rise acutely to levels of four to eight times normal.
How to Implement Evidence Into Practice to Improve Diabetes Care
Authors: Liza L. Ilag, William H. Herman
Journal: Diabetes Care (2004)

We appreciate Dr. Saleem’s (1) interest and comments and thank the editor for the opportunity to clarify the points raised about our study (2).

Our study was an effectiveness trial. The target population for the Annual Diabetes Assessment Program (ADAP) included all managed care members with diabetes assigned to the participating provider groups. The enrollment criteria were pragmatic, excluding those without diabetes, those who were no longer being followed by the primary care physician, and those …
The Open Medical School
Authors: Herbert Bauer
Journal: JAMA (1966)

<h3>To the Editor:—</h3> The "Open Medical School" described by Dr. Dimond offers an ideal compromise in our perennial "town and gown conflict." It eliminates largely the difference between the "in" and the "out" groups, by bringing the medical school into the community and the community back into the medical school. I can only hope that Dr. Dimond's thoughts will find widespread application.
Disease progression and patient survival are significantly influenced by BRAF protein expression in primary melanoma
Authors: G. Safaee Ardekani, S.M. Jafarnejad, S. Khosravi, M. Martinka, V. Ho, G. Li
Journal: British Journal of Dermatology (2013)

Mutation of BRAF is a prevalent event in melanoma. Despite much attention to the role of BRAF mutation in melanoma, the status of BRAF protein expression and its significance in melanoma progression are unknown.We investigated the BRAF expression level in different stages of melanocytic lesions and evaluated its correlation with clinicopathological features and patient survival.Using tissue microarray, BRAF expression and its correlation with patient outcome was evaluated in 49 naevi samples and 370 patients with melanoma. We also evaluated the correlation of BRAF protein expression and V600E mutation using direct sequencing.Compared with naevi samples, BRAF expression was remarkably increased in primary melanomas and further increased in metastatic melanomas (P = 1·8 × 10(-11) ). High BRAF expression was significantly correlated with thicker tumours, ulceration and higher American Joint Committee on Cancer stages (P = 1·5 × 10(-7) , 1·5 × 10(-5) and 3·6 × 10(-13) , respectively). In cases of primary melanoma, patients with high BRAF expression had significantly worse overall (P = 0·009) and disease-specific 5-year survival (P = 0·007). While there was a trend for higher prevalence of BRAF V600E mutation in patients with high BRAF protein expression, no significant correlation was observed between protein expression and BRAF mutation. Furthermore, univariate Cox regression analysis confirmed high BRAF protein expression as a strong risk factor for poor patient survival in primary melanoma [hazard ratio (HR) 2·08 for overall survival; HR 2·39 for disease-specific survival].Our data demonstrate that BRAF protein expression is significantly increased during melanoma progression. In addition, we revealed a novel prognostic value for BRAF protein expression in primary melanoma as it is significantly correlated with poor patient survival.
Pathways followed by membrane recovered from the surface of plasma cells and myeloma cells
Authors: PD Ottosen, PJ Courtoy, MG Farquhar
Journal: The Journal of Experimental Medicine (1980)

Evidence for recovery of surface membrane and its fusion with Golgi cisternae has been obtained previously in several glandular cells. This study was conducted to determine whether or not membrane is similarly retrieved from the surfaces of plasma cells from lymph nodes (of rats immunized with horseradish peroxidase [HRP]) and mouse myeloma cells (RPC 5.4 and X63 Ag 8 cell lines). Electron-dense tracers (cationic and anionic ferritin, HRP) were used to trace the pathways followed by surface membrane recovered by endocytosis, and immunocytochemistry was used to identify the secretory compartments. When plasma cells or myeloma cells were incubated with cationized ferritin (CF), it bound to the cell surfaces and was taken up in endocytic vesicles, for the most part bound to the vesicle membrane. After 30-60 min, it was found increasingly within lysosomes and in several secretory compartments- notably in multiple stacked Golgi cisternae and secretory vacuoles. By immunocytochemistry the secretory product (immunoglobulins) and CF could be demonstrated in the same Golgi components. When myeloma cells were incubated with native (anionic) ferritin or in HRP, these tracers were taken up in much smaller amounts, primarily within the contents of endocytic vesicles. With continued incubation, they appeared only in lysosomes. When cells were doubly incubated, first in CF and then in HRP, both tracers were taken up (often within the same endocytic vesicle), but they maintained their same destinations as when incubated in a single tracer alone: the content marker, HRP, was localized exclusively within the lysosomal system, whereas the membrane marker, CF, was found within elements along the secretory pathway as well as within lysosomes. The findings demonstrate the existence of considerable membrane traffic between the cell membrane and the Golgi cisternae and lysosomes in both normal plasma cells and myeloma cells. Because myeloma cells behave like the glandular cells studied previously with regard to pathways of retrieved surface membrane, they represent a suitable and promising system for further studies of mechanisms and pathways of membrane retrieval and recycling in secretory cells.
Adult bone-marrow stem cells
Authors: S. Kochhar
Journal: Journal of the Royal Society of Medicine (2004)

In their paper about the therapeutic potential of adult bone-marrow stem cells (October 2004 JRSM1) Professor Hassan and Dr El-Sheemy refer to ethical controversies over use of embryonic stem cells. Apart from the ethical objections, cell replacement therapy from embryos and fetal tissue is complicated by difficulties with standardizing the procedure, ensuring viability of tissue and obtaining tissue at optimal time points. By induction of fate-specific cells from an in-vitro-expanded population of isolated progenitor/stem cells, bone marrow stem cells may be more readily exploited. Differentiation of expanded cells can be induced by mitogen withdrawal or by exposure to cytokines, hormones or vitamins that cause lineage restriction.

Cytokines involved in the clonal expansion and lineage restriction of stem/progenitor cells in the haematopoietic system may play an important analogous role in the developing nervous system. For example, interleukin-1 can induce expression of the dopaminergic marker tyrosine hydroxylase. Furthermore, in a study by Carpenter et al.2 leukaemia inhibitory factor, a member of the interleukin-6 cytokine family, when combined with other mitogens was shown to enhance proliferation of human forebrain neural stem cells. Importantly, we need to consider the possibility that bone marrow stem cells are able to redifferentiate. Already there is evidence that neural stem cells can become bone-marrow-like: they were shown capable of reconstituting the haematopoietic systems of mice that had undergone marrow ablation.3 These studies suggest that the lineage path taken by multipotent cells is influenced by the environments to which they are exposed.
WHEN SHOULD ANTIBIOTICS BE USED IN COMBINATION?
Authors: Harry F. Dowling
Journal: JAMA (1953)

The steady increase in the number of antibiotics that are therapeutically active presents the practicing physician with a perplexing problem: if one antibiotic will do a good job, will two do a better one? Should the clinician employ more than one antibiotic frequently, occasionally, or never? We shall attempt to answer these questions on the basis of the evidence available in the literature and from our own experience.  There are several situations in which the use of combinations of antibiotics can be justified on theoretical grounds. The first of these is the presence of a mixed infection in which one organism is sensitive to one antibiotic and a second organism is sensitive only to a different antibiotic. Some of the common mixed infections are peritonitis due to a ruptured viscus, bronchiectasis, lung abscess, otitis media (if the tympanic membrane has ruptured), and urinary tract infections. In many of these conditions
The simple sequence contingency loci of Haemophilus influenzae and Neisseria meningitidis
Authors: Christopher D. Bayliss, Dawn Field, E. Richard Moxon
Journal: Journal of Clinical Investigation (2001)

Many pathogens have evolved the ability to alter surface-exposed molecules, most often in response to selective pressures associated with the host immune system (1). Pathogenic bacteria exhibit numerous examples of this adaptive strategy, and a range of molecular mechanisms has evolved in these bacteria for generating genetic variation at individual loci termed “contingency loci” (2). Many contingency genes are controlled by simple sequence DNA repeats that accumulate reversible, rec-independent mutations at high frequency. A striking feature of the complete genome sequences of the human pathogens Haemophilus influenzae and Neisseria meningitidis is the abundance of loci containing simple sequences (3, 4). Intriguingly, both of these bacteria are obligate commensals of the upper respiratory tract of humans but can, in some hosts, cause life-threatening invasive disease. In this Perspective we provide a synthesis of our current understanding of how polymorphisms in simple sequence contingency loci produce phenotypic variation. We also evaluate the role of this variation in pathogenesis and the evolution of virulent bacterial strains.
Abstract IA13: A hypoxic microenvironment influences pancreatic cancer progression
Authors: M. Celeste Simon
Journal: Cancer Research (2015)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer related deaths in the United States and one of the most lethal human cancers. Chronic pancreatitis, which is characterized by inflammation of the pancreas, is a well-known risk factor for PDAC in humans. However, the precise mechanisms whereby chronic pancreatitis promotes pancreatic tumorigenesis remain elusive. Hypoxia, a condition of insufficient oxygen availability, occurs in the context of pancreatic cancer as well as chronic pancreatitis, suggesting that hypoxia is a link between chronic inflammation of the pancreas and carcinogenesis. Hypoxia inducible factor 1α (HIF-1α) is a principal mediator of hypoxic responses. HIF-1α has also been shown to tightly regulate inflammatory responses of myeloid cells. To elucidate the effects of HIF-1α on chronic inflammatory injury and regeneration of the pancreas, and define the role of HIF-1α in pancreatic cancer development, we generated mice that spontaneously develop PDAC with HIF-1α ablated. Our results indicate that HIF-1α impacts both the resolution of pancreatitis as well as the progression of pancreatic neoplasia and inflammatory cell recruitment. Citation Format: M. Celeste Simon. A hypoxic microenvironment influences pancreatic cancer progression. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr IA13. doi:10.1158/1538-7445.CHTME14-IA13
Continuity, displaced reference, and deception
Authors: Lee Cronk
Journal: Behavioral and Brain Sciences (2004)

Falk's contribution to a continuity theory of the origins of language would be complemented by an account of the origins of displaced reference, a key characteristic distinguishing human language from animal signaling systems. Because deception is one situation in which nonhumans may use signals in the absence of their referents, deception may have been the starting point for displaced reference.
High-Flow Oxygen for Treatment of Cluster Headache
Authors: Anna S. Cohen, Brian Burns, Peter J. Goadsby
Journal: JAMA (2009)

<h3>Context</h3>Cluster headache is an excruciatingly painful primary headache syndrome, with attacks of unilateral pain and cranial autonomic symptoms. The current licensed treatment for acute attacks is subcutaneous sumatriptan.<h3>Objective</h3>To ascertain whether high-flow inhaled oxygen was superior to placebo in the acute treatment of cluster headache.<h3>Design, Setting, and Patients</h3>A double-blind, randomized, placebo-controlled crossover trial of 109 adults (aged 18-70 years) with cluster headache as defined by the International Headache Society. Patients treated 4 headache episodes with high-flow inhaled oxygen or placebo, alternately. Patients were randomized to the order in which they received the active treatment or placebo. Patients were recruited and followed up between 2002 and 2007 at the National Hospital for Neurology and Neurosurgery, London, England.<h3>Intervention</h3>Inhaled oxygen at 100%, 12 L/min, delivered by face mask, for 15 minutes at the start of an attack of cluster headache or high-flow air placebo delivered alternately for 4 attacks.<h3>Main Outcome Measures</h3>The primary end point was to render the patient pain free, or in the absence of a diary to have adequate relief, at 15 minutes. Secondary end points included rendering the patient pain free at 30 minutes, reduction in pain up to 60 minutes, need for rescue medication 15 minutes after treatment, overall response to the treatment and overall functional disability, and effect on associated symptoms.<h3>Results</h3>Fifty-seven patients with episodic cluster headache and 19 with chronic cluster headache were available for the analysis. For the primary end point the difference between oxygen, 78% (95% confidence interval, 71%-85% for 150 attacks) and air, 20% (95% confidence interval, 14%-26%; for 148 attacks) was significant (Wald test, χ<sup>2</sup><sub>5</sub> = 66.7, P &lt; .001). There were no important adverse events.<h3>Conclusion</h3>Treatment of patients with cluster headache at symptom onset using inhaled high-flow oxygen compared with placebo was more likely to result in being pain-free at 15 minutes.<h3>Trial Registration</h3>isrctn.org Identifier: ISRCTN94092997
MicroRNA-7 inhibits tumor growth and metastasis by targeting the phosphoinositide 3-kinase/Akt pathway in hepatocellular carcinoma
Authors: YuXiang Fang, Jing-Lun Xue, Qi Shen, Jinzhong Chen, Ling Tian
Journal: Hepatology (2012)

MicroRNAs (miRNAs) are known to be involved in carcinogenesis and tumor progression in hepatocellular carcinoma (HCC). Recently, microRNA-7 (miR-7) has been proven to play a substantial role in glioblastoma and breast cancer, but its functions in the context of HCC remain unknown. Here, we demonstrate that miR-7 inhibits HCC cell growth and metastasis in vitro and in vivo . We first screened and identified a novel miR-7 target, phosphoinositide 3-kinase catalytic subunit delta (PIK3CD). Overexpression of miR-7 would specifically and markedly down-regulate its expression. miR-7-overexpressing subclones showed significant cell growth inhibition by G0/G1-phase cell-cycle arrest and significant impairment of cell migration in vitro . To identify the mechanisms, we investigated the phosphoinositide 3-kinase (PI3K)/Akt pathway and found that Akt, mammalian target of rapamycin (mTOR), and p70S6K were down-regulated, whereas 4EBP1 was up-regulated in miR-7-overexpressing subclones. We also identified two novel, putative miR-7 target genes, mTOR and p70S6K, which further suggests that miR-7 may be a key regulator of the PI3K/Akt pathway. In xenograft animal experiments, we found that overexpressed miR-7 effectively repressed tumor growth (3.5-fold decrease in mean tumor volume; n = 5) and abolished extrahepatic migration from liver to lung in a nude mouse model of metastasis (n = 5). The number of visible nodules on the lung surface was reduced by 32-fold. A correlation between miR-7 and PIK3CD expression was also confirmed in clinical samples of HCC. Conclusion: These findings indicate that miR-7 functions as a tumor suppressor and plays a substantial role in inhibiting the tumorigenesis and reversing the metastasis of HCC through the PI3K/Akt/mTOR-signaling pathway in vitro and in vivo . By targeting PIK3CD, mTOR, and p70S6K, miR-7 efficiently regulates the PI3K/Akt pathway. Given these results, miR-7 may be a potential therapeutic or diagnostic/prognostic target for treating HCC.
Cardiac Outcomes After Screening for Asymptomatic Coronary Artery Disease in Patients With Type 2 Diabetes
Authors: Lawrence H. Young, Frans J. Th. Wackers, Deborah A. Chyun, Janice A. Davey, Eugene J. Barrett, Raymond Taillefer, Gary V. Heller, Ami E. Iskandrian, Steven D. Wittlin, Neil Filipchuk, Robert E. Ratner, Silvio E. Inzucchi, for the DIAD Investigators
Journal: JAMA (2009)

Coronary artery disease (CAD) is the major cause of mortality and morbidity in patients with type 2 diabetes. But the utility of screening patients with type 2 diabetes for asymptomatic CAD is controversial.
Abnormal Chemoreceptor Response to Hypoxia in Patients with Tabes Dorsalis
Authors: R. J. C. Evans, M. K. Benson, D. T. D. Hughes
Journal: BMJ (1971)

Nine patients with tabes dorsalis and one patient with diabetic autonomic neuropathy were subjected to hypoxia to test the integrity of their carotid chemoreceptors. Ventilation and pulse rate changes were monitored and compared with those of a group of normal subjects of comparable age and sex. Four patients had a completely negative response to hypoxia, and the changes in ventilation in the group of patients as a whole were significantly less than in the control subjects. The results indicate that some patients with autonomic denervation are unable to adjust their respiratory system in response to hypoxia.
CFH and LOC387715/ARMS2 Genotypes and Treatment with Antioxidants and Zinc for Age-Related Macular Degeneration
Authors: Michael L. Klein, Peter J. Francis, Bernard Rosner, Robyn Reynolds, Sara C. Hamon, Dennis W. Schultz, Jurg Ott, Johanna M. Seddon
Journal: Ophthalmology (2008)
Seroepidemiology of Hepatitis B virus infection in Saudi children 8 years after a mass hepatitis B vaccination programme
Authors: Faleh Z. AI-Faleh, Mohammad AI-Jeffri, Sami Ramia, Rashed AI-Rashed, Mohammad Arif, Mohammed Rezeig, Ibrahim AI-Toraif, Mohammad Bakhsh, Amin Mishkkhas, Omer Makki, Hussein AI-Freihi, Soleman Mirdad, Abdulrahman AlJuma, T. Yasin, Abdulmohsen Al-Swailem, Ayobanji Ayoola
Journal: Journal of Infection (1999)