tbuckley/cabot-search huggingface dataset:
Abstract PD03-01: Significant Reduction of Triple-Negative Breast Cancers in Diabetic Women on Metformin
Authors: PJ Meiers, E Sharon, W DongYu, A Pooni, DR McCready, WL. Leong
Journal: Cancer Research (2010)

Abstract Background: Diabetes is an increasingly prevalent chronic disease. Many of these patients may develop breast cancer (BC). A meta-analysis by Larsson (2007)demonstrated that diabetic women have an increased risk (RR: 1.2) of BC particularly for estrogen receptor positive (ER+) subtypes (RR: 1.22). However, a recent study by Bodmer (2010) showed that women on long-term metformin have a reduced incidence of BC (OR 0.44, 95% CI 0.24-0.82). Metformin has antiproliferative effects on BC based on studies using proliferative marker Ki67. BC patients on metformin have better cancer-specific survival based on Landman (2010). We hypothesize that when compared to other diabetic medications; including exogenous insulin and other oral hypoglycemics; metformin specifically reduces the incidence of triple negative BCs (TNBC or ER-/PR-/Her2-). Methods: We conducted a retrospective chart review of an unselected cohort of patients who underwent surgical interventions for their primary BC to correlate the history of pre-existing diabetes and metformin use to the BC subtypes based on the immunohistochemistry of the surgical specimens. P-values were calculated using Chi-square and Fisher exact tests. Results: There were 99 TNBC in the 1005 patients reviewed. Of the 90 diabetic patients, none of the 44 patients took metformin had TNBC, compared to 7 of the 46 diabetic patients not taking metformin had TNBC (0% vs. 15.2% p=0.007). Discussion: Studies that examined the incidence of BC in diabetics were not able to differentiate the effects of various diabetic treatments on the subtypes of BC. The reported increase in ER+ BC in diabetics is likely multifactorial but may be attributed to the proliferative effects of hyperinsulinemia. Interesting, of all the diabetic medications, Bodmer (2010) reported only metformin reduced the incidence of BC. In this study, we reported a statistical significant reduction in the incidence of TNBC. In fact, in our study population, there was no TNBC in patients who took metformin. Hirsch (2009) reported a selective inhibition of BC stem cells with metformin. Of interest, many studies have shown that BC stem cells were ER-/PR-/Her2-. This study supports the view that the phenotype of the BCs can be influenced by drug. At this point, we cannot differentiate if metformin can “protect” patients from developing TNBC, or “convert” TNBC to other subtypes of BC, further study is underway to address this question. Figure available in online version. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD03-01.
Alpha heavy chain disease (report of 18 cases from Iraq).
Authors: Z Al-Bahrani, T Al-Saleem, H Al-Mondhiry, F Bakir, H Yahia, I Taha, J King
Journal: Gut (1978)

The clinical and pathological features of 18 new patients with alpha heavy chain disease seen at two referral centres in Baghdad, Iraq, are described. The series included 14 males and four females ranging in age from 14 to 47 years. Almost all patients presented because of long-standing abdominal pain and diarrhoea. The tissue diagnosis and extent of the disease were established at laparotomy in most patients. Peroral jejunal biospy was used in a number of patients, mainly for follow-up. The serological abnormality was confirmed by immunoselection technique. Most of the patients had extensive thickening of the bowel wall and/or tumour masses of the small intestine and mesenteric nodes. Histopathological sections showed muscularis. Preliminary results of the treatment, including two long remissions, are reported. In general, our observations agree with those made by other authors, mostly from the Middle East and Africa. We believe that a high index of clinical suspicion, routine use of the immunoselection, and recognition of the early pathological changes may hopefully lead to the detection of more cases before the frank neoplastic phase of the disease.
Functional dissociation of cellular activation as a mechanism of Mobitz type II atrioventricular block.
Authors: M D Gonzalez, B J Scherlag, P Mabo, R Lazzara
Journal: Circulation (1993)

BACKGROUND Several mechanisms have been advanced to explain Mobitz type II atrioventricular block in the ischemically damaged His-Purkinje system. Only recently, however, has an animal model been developed to study this form of conduction defect in vivo and in vitro. METHODS AND RESULTS Conduction defects were induced in anesthetized dogs by ischemic damage to the proximal His-Purkinje system after anterior septal artery ligation. Stable 2:1 atrioventricular block, localized within the His bundle or in the proximal bundle branches, was obtained in each dog by atrial pacing at an average rate of 239 +/- 20 beats per minute (n = 12). In vitro studies were then performed from the same hearts. Action potentials and electrograms were simultaneously recorded from the His bundle and the proximal right bundle branch at the site of damage. At slow rates of pacing (40-60 beats per minute), the action potential amplitude was 85 +/- 4 mV, and some cells (10 +/- 3%) showed dissociation from the electrical activity in the bundle. At fast rates (149 +/- 11 beats per minute), during 1:1 conduction, the frequency of cellular dissociation increased to 57 +/- 6% (p &lt; 0.001), and the action potential amplitude decreased (-31 +/- 4%, p &lt; 0.001). The frequency of dissociation closely correlated with the reduction in action potential amplitude (r = 0.87, p &lt; 0.001). These changes were markedly attenuated once 2:1 block developed. The site of block was not constant but rather showed a dynamic behavior with spatial shifting in response to changes in pacing rate or the introduction of extrastimuli. CONCLUSIONS These results indicate that in the ischemically damaged proximal His-Purkinje system, an increase in rate leads to reduced and asynchronous cellular activation before 2:1 block. The latter provides a more stable activation pattern, because the frequency of dissociation is markedly reduced.
A New Era for Anticoagulation in Atrial Fibrillation
Authors: Jessica L. Mega
Journal: New England Journal of Medicine (2011)

For more than 50 years, warfarin has been the primary medication used to reduce the risk of thromboembolic events in patients with atrial fibrillation. Despite its clinical efficacy, warfarin has multiple, well-known limitations, including numerous interactions with other drugs and the need for regular blood monitoring and dose adjustments. Thus, clinicians and patients have been eager to embrace alternative oral anticoagulants that are equally efficacious but easier to administer.In this issue of the Journal, Granger and colleagues report the impressive primary results of the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial (ARISTOTLE; ClinicalTrials.gov . . .
Specific Secondary Genetic Alterations in Mantle Cell Lymphoma Provide Prognostic Information Independent of the Gene Expression–Based Proliferation Signature
Authors: Itziar Salaverria, Andreas Zettl, Sílvia Beà, Victor Moreno, Joan Valls, Elena Hartmann, German Ott, George Wright, Armando Lopez-Guillermo, Wing C. Chan, Dennis D. Weisenburger, Randy D. Gascoyne, Thomas M. Grogan, Jan Delabie, Elaine S. Jaffe, Emili Montserrat, Hans-Konrad Muller-Hermelink, Louis M. Staudt, Andreas Rosenwald, Elias Campo
Journal: Journal of Clinical Oncology (2007)

To compare the genetic relationship between cyclin D1-positive and cyclin D1-negative mantle cell lymphomas (MCLs) and to determine whether specific genetic alterations may add prognostic information to survival prediction based on the proliferation signature of MCLs.Seventy-one cyclin D1-positive and six cyclin D1-negative MCLs previously characterized by gene expression profiling were examined by comparative genomic hybridization (CGH).Cyclin D1-negative MCLs were genetically characterized by gains of 3q, 8q, and 15q, and losses of 1p, 8p23-pter, 9p21-pter, 11q21-q23, and 13q that were also the most common alterations in conventional MCLs. Parallel analysis of CGH aberrations and locus-specific gene expression profiles in cyclin D1-positive patients showed that chromosomal imbalances had a substantial impact on the expression levels of the genes located in the altered regions. The analysis of prognostic factors revealed that the proliferation signature, the number of chromosomal aberrations, gains of 3q, and losses of 8p, 9p, and 9q predicted survival of MCL patients. A multivariate analysis showed that the gene expression-based proliferation signature was the strongest predictor for shorter survival. However, 3q gains and 9q losses provided prognostic information that was independent of the proliferative activity.Cyclin D1-positive and -negative MCLs share the same secondary genetic aberrations, supporting the concept that they correspond to the same genetic entity. The integration of genetic information on chromosome 3q and 9q alterations into a proliferation signature-based model may improve the ability to predict survival in patients with MCL.
CHEMO-IMMUNOLOGICAL STUDIES ON CONJUGATED CARBOHYDRATE-PROTEINS
Authors: Walther F. Goebel, Oswald T. Avery
Journal: The Journal of Experimental Medicine (1931)

1. The p-amino and p-nitromonobenzyl ethers of the specific polysaccharide of Type III Pneumococcus have been prepared. 2. The diazonium ether of the specific polysaccharide has been coupled with serum globulin to yield a specific polysaccharide-protein complex and this complex has been used for immunization. The results of the immunological studies are presented in the following paper.
To binge or not to binge: Binge drinking disrupts glucose homeostasis by impairing hypothalamic but not liver insulin signaling
Authors: Carmen Garcia-Ruiz, José C. Fernandez-Checa
Journal: Hepatology (2013)

Abstract Individuals with a history of binge drinking have an increased risk of developing the metabolic syndrome and type 2 diabetes. Whether binge drinking impairs glucose homeostasis and insulin action is unknown. To test this, we treated Sprague-Dawley rats daily with alcohol (3 g/kg) for three consecutive days to simulate human binge drinking and found that these rats developed and exhibited insulin resistance even after blood alcohol concentrations had become undetectable. The animals were resistant to insulin for up to 54 hours after the last dose of ethanol, chiefly a result of impaired hepatic and adipose tissue insulin action. Because insulin regulates hepatic glucose production and white adipose tissue lipolysis, in part through signaling in the central nervous system, we tested whether binge drinking impaired brain control of nutrient partitioning. Rats that had consumed alcohol exhibited impaired hypothalamic insulin action, defined as the ability of insulin infused into the mediobasal hypothalamus to suppress hepatic glucose production and white adipose tissue lipolysis. Insulin signaling in the hypothalamus, as assessed by insulin receptor and AKT phosphorylation, decreased after binge drinking. Quantitative polymerase chain reaction showed increased hypothalamic inflammation and expression of protein tyrosine phosphatase 1B (PTP1B), a negative regulator of insulin signaling. Intracerebroventricular infusion of CPT-157633, a small-molecule inhibitor of PTP1B, prevented binge drinking-induced glucose intolerance. These results show that, in rats, binge drinking induces systemic insulin resistance by impairing hypothalamic insulin action and that this effect can be prevented by inhibition of brain PTP1B.
HYAL-1 Hyaluronidase: A Potential Prognostic Indicator for Progression to Muscle Invasion and Recurrence in Bladder Cancer
Authors: Mario W. Kramer, Roozbeh Golshani, Axel S. Merseburger, Judith Knapp, Alfredo Garcia, Joerg Hennenlotter, Robert C. Duncan, Mark S. Soloway, Merce Jorda, Marcus A. Kuczyk, Arnulf Stenzl, Vinata B. Lokeshwar
Journal: European Urology (2009)
Sympathectomy and Claudication
Authors: W. Reid, J. K. Watt
Journal: BMJ (1966)

<h3>Summary</h3> We describe a method for rapid in silico selection of diagnostic peptides from newly described viral pathogens and applied this approach to SARS-CoV-2/COVID-19. This approach is multi-tiered, beginning with compiling the theoretical protein sequences from genomic derived data. In the case of SARS-CoV-2 we begin with 496 peptides that would be produced by proteolytic digestion of the viral proteins. To eliminate peptides that would cause cross-reactivity and false positives we remove peptides from consideration that have sequence homology or similar chemical characteristics using a progressively larger database of background peptides. Using this pipeline, we can remove 47 peptides from consideration as diagnostic due to the presence of peptides derived from the human proteome. To address the complexity of the human microbiome, we describe a method to create a database of all proteins of relevant abundance in the saliva microbiome. By utilizing a protein-based approach to the microbiome we can more accurately identify peptides that will be problematic in COVID-19 studies which removes 12 peptides from consideration. To identify diagnostic peptides, another 7 peptides are flagged for removal following comparison to the proteome backgrounds of viral and bacterial pathogens of similar clinical presentation. By aligning the protein sequences of SARS-CoV-2 field isolates deposited to date we can identify peptides for removal due to their presence in highly variable regions that may lead to false negatives as the pathogen evolves. We provide maps of these regions and highlight 3 peptides that should be avoided as potential diagnostic or vaccine targets. Finally, we leverage publicly deposited proteomics data from human cells infected with SARS-CoV-2, as well as a second study with the closely related MERS-CoV to identify the two proteins of highest abundance in human infections. The resulting final list contains the 24 peptides most unique and diagnostic of SARS-CoV-2 infections. These peptides represent the best targets for the development of antibodies are clinical diagnostics. To demonstrate one application of this we model peptide fragmentation using a deep learning tool to rapidly generate targeted LCMS assays and data processing method for detecting CoVID-19 infected patient samples. <h3>Graphical Abstract</h3>
DEVELOPMENT OF HEAT PYREXIA
Authors: Joseph Gold
Journal: JAMA (1960)

In a study of heat stroke, more than 250 observations were made on healthy adult human subjects. Data were obtained on body heat storage, sweat rate, sweat replacement, blood pressure, venous pressure, oxygen consumption, blood gas analyses, hemoconcentration, and osmolarity; and on cardiac output, cardiac shadows, and auscultatory and electrocardiographic findings. During extreme heat exposure there was an increased venous pressure and operational arteriovenous shunt (or its functional equivalent) in the presence of cardiac failure. It is postulated that (1) the primary event in the circulatory collapse of heat pyrexia is highoutput cardiac failure, (2) the cessation of sweating is a result of rising venous pressure, (3) older persons are more susceptible because of irreversible circulatory changes, and (4) an effective treatment may be the intravenous administration of saline solution together with rapid digitalization.
How to Deal With Poor Medical Care
Authors: William E. Mitchell
Journal: JAMA (1976)

THE COURSE of a medical audit prompted by poor medical care may depend on the specific problem, but the approach discussed here has proved useful in almost all instances, the only exception being the rare situation in which a problem of ethics or falsification is involved. <h3>RECOGNITION OF POSSIBLE PROBLEM</h3> Presented with allegations that a staff member is rendering poor care, the hospital governing body should first consider whether facts rather than hearsay support the allegation. The sources should have personal knowledge or professional experience to raise questions of professional performance, and problems should involve substantial potential for harm to patients and be amenable to correction. <h3>UNNECESSARY SURGERY</h3> Informed that a staff physician, "Dr A," is performing too many unnecessary appendectomies, how should the governing body instruct the surgical audit committee to proceed? A frontal assault on the problem, ie, auditing all the appendectomies performed by the physician, may be
Interaction between Doxycycline and some Antiepileptic Drugs
Authors: O. Penttila, P. J. Neuvonen, K. Aho, R. Lehtovaara
Journal: BMJ (1974)

The mean half life of doxycycline given to seven patients on long-term diphenylhydantoin treatment was 7·2 ± 0·4 hours. In five patients on long-term carbamazepine treatment the half life was 8·4 ± 1·4 hours. In four patients on combined diphenylhydantoin and carbamazepine treatment the half life was 7·4 ± 0·7 hours. All these were significantly shorter than a mean half life of 15·1 ± 1·0 hours when doxycycline was given to nine control patients. Therefore doxycycline in normal doses given to patients taking diphenylhydantoin or carbamazepine may fail to maintain the minimum inhibitory concentration necessary for proper bacteriostasis. When doxycycline is given in association with agents known to induce drug metabolism the serum concentration of the antibiotic should be watched to see that bacteriostatic levels are maintained.
THE ANTITOXIN OF TETANUS.
Authors: SAMUEL S. KNEASS
Journal: JAMA (1896)

Among the many principles on which are based our modern theories of the etiology and therapeutics of disease is that of the vaccinating or immunizing power of attenuated cultures of specific microörganisms. Although this principle is forecast by Jenner's discovery of the vaccine against variola, it is to the great Frenchman, Pasteur, that should be ascribed its first scientific development. In 1880 this investigator showed that an attenuated culture of the microbe of chicken cholera, injected into animals, would produce a mild attack of the septicemia, and would leave them immune against a second attack. This was the first experimental fact to which numerous laboratory workers have been adding during the last fifteen years. Disease after disease has been added to the list, anthrax, hog cholera, malignant edema, hydrophobia, diphtheria, the infections due to the staphylococcus, the streptococcus and the pneumococcus, typhoid fever and tetanus. It is not the purpose
First American Electrocardiography
Authors: Carleton B. Chapman
Journal: JAMA (1966)

To the Editor:—  I recently had occasion to read the very fine history of electrocardiography written by Burch and DePasquale1and wish that more authorities of such eminence would devote time to producing scholarly accounts of the development of medical concepts and techniques. It seems, however, that they have overlooked the very early work done by Lewellys Barker and colleagues at Johns Hopkins Hospital from 1909 onward, and it seems fair to call attention to it.  In their excellent book, Professor Burch and Dr. DePasquale assign credit for introducing the first electrocardiograph into this country to Dr. Alfred Cohn, then working at Mount Sinai Hospital in New York. The year was 1909 and there is little reason to question Cohn's statement, quoted in the book, that he brought an Edelmann electrocardiograph, made in Munich, to New York in the early autumn of that year. But if it was actually
More women (and men) that never evolved
Authors: R. Elisabeth Cornwell, Craig T. Palmer, Hasker P. Davis
Journal: Behavioral and Brain Sciences (2000)

We are not convinced by Gangestad &amp; Simpson that differential mating strategies within each sex would be greater than such strategies between sexes. The target article does not provide actual evidence of human males who do not desire mating with multiple females, or evidence that the benefits for females of short-term matings with multiple males have ever outweighed the associated costs.
Coexistence of Alzheimer??s Disease and Multi-lnfarct Dementia Diagnosed by Functional Brain Imaging with SPECT
Authors: JAMES H. TIMMONS, JAMES D. HEIRONIMUS
Journal: Clinical Nuclear Medicine (1990)

The ability of I-123 lodoamphetamine (IMP) SPECT brain imaging to differentiate senile dementia of the Alzheimer's type (SDAT) and multi-infarct dementia (MID) is well established. The present case demonstrates the coexistence of SDAT and MID in a patient with atherosclerotic peripheral vascular disease and a clinical history of strokes that were not visualized on a prior CT image. The value of IMP SPECT in diagnosing these conditions is not diminished by their coexistence, though the process responsible for the patient's gradually progressive dementia cannot be determined with certainty.
An Improved Method for the Intravenous Administration of Heparin
Authors: Stanford Wessler, Jerome W. Fischbein
Journal: New England Journal of Medicine (1954)

EXTENSIVE clinical and experimental studies have demonstrated that heparin is an effective anticoagulant. Although the drug has been injected subcutaneously and intramuscularly in different menstruums with varying success1 2 3 4 5 6 7 some investigators believe that it can be administered with the greatest safety and the dosage regulated most effectively when it is injected intravenously.8 , 9 Its use by the intravenous route, however, has been limited by the necessity of frequent venipunctures. The present report describes a method whereby this problem has now been solved through the use of indwelling catheters attached to rubber-capped Tuohy–Borst adapters.MethodPolyethylene tubing in 15-cm. lengths and 0.965 mm. . . .
The Impact of Interscreening Interval and Age on Prostate Cancer Screening With Prostate-Specific Antigen
Authors: Grace Hui-Min Wu, Anssi Auvinen, Amy Ming-Fang Yen, Matti Hakama, Teuvo L. Tammela, Ulf-Håkan Stenman, Paula Kujala, Mirja Ruutu, Hsiu-Hsi Chen
Journal: European Urology (2012)
Businesses, Federal Government Move to Pick Up AIDS Gauntlet
Authors: Marsha F. Goldsmith
Journal: JAMA (1987)

RESPONSE TO SOME challenges posed by acquired immunodeficiency syndrome (AIDS) began to appear a little more attainable after two meetings in Chicago in October, AIDS Awareness Month. One was an unprecedented nationwide effort to direct private sector initiatives toward managing a public health problem. The other heralded a long-awaited, broadbased approach to disease containment via information and education ordered by Washington. <h3>AIDS: Corporate America Responds:</h3> What's good for General Motors may help this country cope more effectively with AIDS. That's the feeling engendered by the two-day gathering, called "AIDS: Corporate America Responds," sponsored by Allstate Insurance Company, Northbrook, Ill. Senior executives from more than 125 Fortune 500 companies appeared not to flinch when Mervyn F. Silverman, MD, MPH, president of the American Foundation for AIDS Research, greeted them with: "Welcome to the war." The purpose of the forum was to develop policy guidelines for dealing with AIDS in the workplace—only
PATIENT AND SCAN VARIABLES CONTRIBUTING TO DIAGNOSTIC ACCURACY OF CORONARY COMPUTED TOMOGRAPHY ANGIOGRAPHY AS INTERPRETED ON AN IPHONE: RESULTS FROM THE MULTICENTER ACCURACY TRIAL
Authors: Troy LaBounty, Robert J. Kim, Fay Y. Lin, Matthew J. Budoff, Jonathan W. Weinsaft, James K. Min
Journal: Journal of the American College of Cardiology (2010)