tbuckley/cabot-search huggingface dataset:
Breast cancer and the pill
Authors: A A Kubba
Journal: Journal of the Royal Society of Medicine (2003)

In the UK 11% of women will develop breast cancer by age 85. Breast cancer is the most frequently diagnosed cancer in women.1 However, compared with lifetime risk, the age-specific risk of breast cancer is low. At age 50 the risk is 2% and at 25 it is 0.05% (1 in 2000). Whatever the actual risk, the notion of getting breast cancer is terrifying, and women overestimate the likelihood of acquiring and dying from this disease by a factor of 25.2 Less than 5% of deaths in women are attributed to breast cancer; more than half of all women die of cardiovascular disease. Public anxiety about breast cancer tends to be fuelled by the media. Qualitative research suggests that cancer stories are overreported in the popular press, and both broadsheets and tabloid newspapers are 70% more likely to publish bad news than good news. They are also more inclined to report observational studies than randomized trials.3 In American magazines throughout the 1990s there was disproportionate reporting of breast cancer in a 2:1 ratio to cardiovascular disease.4
Clinical Interpretation of Laboratory Tests
Authors: William R. Barclay
Journal: JAMA (1979)

This is the eighth edition of a book that first appeared in 1949. However, laboratory tests have multiplied so rapidly and their interpretation has undergone such great changes that a new edition of an old and successful book is really a new book. This is not a laboratory manual of instruction on how to perform tests, nor is it a simple recitation of how diseases alter biochemical measurements. It is a series of discussions on how to use certain laboratory measurements to diagnose and follow the course of disease. It is not a profound treatise but a simply straightforward description of how tests are done, what they mean, and how they can be in error or misleading. It is an easy book to read and can be used as a reference or digested in small portions in preparation for passing examinations at several levels—medical school to board examinations and recertification.
V <sub>max</sub> as an Index of Contractile State in Man
Authors: HERMAN L. FALSETTI, ROBERT E. MATES, DAVID G. GREENE, IVAN L. BUNNELL
Journal: Circulation (1971)

The maximal, no-load, velocity for the contractile element (V max ) was estimated in 45 patients. The patients included: 17 with normal left ventricular dynamics; eight with volume overload, compensated; 11 with volume overload, decompensated; three with pressure overload; and six with cardiomyopathy. Contractile element velocity (V CE ) during isovolumic contraction was estimated in two ways: (1) from left ventricular pressure data alone, where V CE =(1/28.8p) (dp/dt), and (2) pressure data combined with measurement of left ventricular geometry (right anterior oblique cine). V max obtained in these two ways agreed well for most patients (r = 0.82). In the normal patients, V max varied from 1.46 to 2.64 muscle lengths per sec; in contrast that of the patients with cardiomyopathy varied between 0.71 and 1.34 muscle lengths per sec. Other indices of contractility (ejection fraction, peak dp/dt, peak velocity of circumferential fiber [peak V CF ], peak V CE , and V CE at zero stress) were compared on the basis of statistical correlation and consistency of other clinical evidence (presence or absence of congestive failure). Good correlation was obtained between V max and peak V SE (r = 0.68). Ejection fraction and peak V CF were less sensitive. Neither the peak rate of pressure rise or V CE at peak stress show any significant correlation with V max or clinical state. Previous studies have shown that V max can be evaluated from pressure data alone; this study confirms this finding in patients with mitral regurgitation as well as in those with normal outflow impedance.
Evaluating Health Risks from Inhaled Polychlorinated Biphenyls: Research Needs for Addressing Uncertainty
Authors: Geniece M. Lehmann, Krista Christensen, Mark Maddaloni, Linda J. Phillips
Journal: Environmental Health Perspectives (2014)

Indoor air concentrations of polychlorinated biphenyls (PCBs) in some buildings are one or more orders of magnitude higher than background levels. In response to this, efforts have been made to assess the potential health risk posed by inhaled PCBs. These efforts are hindered by uncertainties related to the characterization and assessment of source, exposure, and exposure-response.We briefly describe some common sources of PCBs in indoor air and estimate the contribution of inhalation exposure to total PCB exposure for select age groups. Next, we identify critical areas of research needed to improve assessment of exposure and exposure response for inhaled PCBs.Although the manufacture of PCBs was banned in the United States in 1979, many buildings constructed before then still contain potential sources of indoor air PCB contamination. In some indoor settings and for some age groups, inhalation may contribute more to total PCB exposure than any other route of exposure. PCB exposure has been associated with human health effects, but data specific to the inhalation route are scarce. To support exposure-response assessment, it is critical that future investigations of the health impacts of PCB inhalation carefully consider certain aspects of study design, including characterization of the PCB mixture present.In certain contexts, inhalation exposure to PCBs may contribute more to total PCB exposure than previously assumed. New epidemiological and toxicological studies addressing the potential health impacts of inhaled PCBs may be useful for quantifying exposure-response relationships and evaluating risks.
Testicular Dysgenesis Syndrome and the Estrogen Hypothesis: A Quantitative Meta-Analysis
Authors: Olwenn V. Martin, Tassos Shialis, John N. Lester, Mark D. Scrimshaw, Alan R. Boobis, Nikolaos Voulvoulis
Journal: Environmental Health Perspectives (2007)

Male reproductive tract abnormalities such as hypospadias and cryptorchidism, and testicular cancer have been proposed to comprise a common syndrome together with impaired spermatogenesis with a common etiology resulting from the disruption of gonadal development during fetal life, the testicular dysgenesis syndrome (TDS). The hypothesis that in utero exposure to estrogenic agents could induce these disorders was first proposed in 1993. The only quantitative summary estimate of the association between prenatal exposure to estrogenic agents and testicular cancer was published over 10 years ago, and other systematic reviews of the association between estrogenic compounds, other than the potent pharmaceutical estrogen diethylstilbestrol (DES), and TDS end points have remained inconclusive.
Positional cloning of the APECED gene
Authors: Kentaro Nagamine, Pärt Peterson, Hamish S. Scott, Jun Kudoh, Shinsei Minoshima, Maarit Heino, Kai J. E. Krohn, Maria D. Lalioti, Primus E. Mullis, Stylianos E. Antonarakis, Kazuhiko Kawasaki, Shuichi Asakawa, Fumiaki Ito, Nobuyoshi Shimizu
Journal: Nature Genetics (1997)
Revalidation: a missed opportunity
Authors: K. Patel
Journal: BMJ (2012)

What do a washing machine and a tyre have in common? No: this is not a bad joke, although I’m sure I have been responsible for a fair few of those in my time. It is the quality labelling. When you buy a washing machine, it has a label that gives information independent of the manufacturer that tells you how good it is at washing and how much energy it uses. From this month, car tyres are subject to the same European regulations, so that you’ll know before you buy how good the …
Airway Inflammation and Infection in Congenital Bilateral Absence of the Vas Deferens
Authors: Marita Gilljam, Yuri Moltyaner, Gregory P. Downey, Roslyn Devlin, Peter Durie, André M. Cantin, Julian Zielenski, D. Elizabeth Tullis
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

In cystic fibrosis (CF), airway disease begins early in life. Bacteria and elevated levels of neutrophils and inflammatory mediators have been detected in bronchoalveolar lavage (BAL) fluid from infants with CF. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) are common in men with congenital bilateral absence of the vas deferens (CBAVD) and it has been suggested that this syndrome represents a mild form of CF. We hypothesized that men with CBAVD also have subclinical pulmonary disease. Bronchoscopy with BAL, viral and quantitative bacterial cultures, and analyses of total and differential cell count, cytokines, and free neutrophil elastase was performed in eight men with CBAVD, who had mutations in the CFTR and intermediate or elevated sweat chloride levels, and in four healthy control subjects. There was light growth of Staphylococcus aureus in one of eight men with CBAVD, and small numbers of opportunistic gram-negative bacteria in six of eight men with CBAVD and in one control subject. BAL cell counts and neutrophil elastase were within the normal range. Interleukin-8 and tumor necrosis factor-α levels were higher for men with CBAVD than for control subjects. These data suggest that mutations in the CFTR in men with CBAVD, in addition to causing infertility, lead to subclinical bacterial pulmonary infection and inflammation consistent with mild CF.
Current Concepts of the Aging Process
Authors: Nathan W. Shock
Journal: JAMA (1961)

The decrements in physiological functions that take place with increasing age become manifest primarily when the environment places extra demands on the individual. The age-dependent reductions in reserve capacities result in part from a gradual loss of functioning tissue. Since complex and coordinated functions are more influenced by age than are simple cellular changes, it is concluded that age decrements in performance are also a result of a breakdown of neural and endocrine regulatory processes.
CYCLIC 3',5'ADENOSINE MONOPHOSPHATE-DEPENDENT PROTEIN KINASE OF SKIN.
Authors: P. D. MIER, J. HURK, S. W. J. HOLLA, E. P. M. J. HOLLMAN, J. E. PORTERS, M. B. M. WEEMERS
Journal: British Journal of Dermatology (1972)

Summary.— cAMP-dependent protein kinase activity has been measured in skin biopsies from atopic patients, psoriatic patients, and from healthy volunteers. No significant differences were observed either in the presence or absence of cAMP.
A Haplotype-Based Case-Control Study of <i>BRCA1</i> and Sporadic Breast Cancer Risk
Authors: Matthew L. Freedman, Kathryn L. Penney, Daniel O. Stram, Stephanie Riley, Roberta McKean-Cowdin, Loïc Le Marchand, David Altshuler, Christopher A. Haiman
Journal: Cancer Research (2005)

Abstract Rare, highly penetrant germ line mutations in BRCA1 strongly predispose women to a familial form of breast and ovarian cancer. Whether common variants (either coding or noncoding) at this locus contribute to the more common form of the disease is not yet known. We tested common variation across the BRCA1 locus in African American, Native Hawaiian, Japanese, Latino, and White women in the Multiethnic Cohort Study. Specifically, 28 single nucleotide polymorphisms (SNPs) spanning the BRCA1 gene were used to define patterns of common variation in these populations. The majority of SNPs were in strong linkage disequilibrium with one another, indicating that our survey captured most of the common inherited variation across this gene. Nine tagging SNPs, including five missense SNPs, were selected to predict the common BRCA1 variants and haplotypes among the non–African American groups (five additional SNPs were required for African Americans) and genotyped in a breast cancer case-control study nested in the Multiethnic Cohort Study (cases, n = 1,715; controls, n = 2,502). We found no evidence for significant associations between common variation in BRCA1 and risk of breast cancer. Given the large size of our study population and detailed analysis of the locus, this result indicates either that common variants in BRCA1 do not substantially influence sporadic breast cancer risk, or that unmeasured heterogeneity in the breast cancer phenotype or unmeasured interactions with genetic or environmental exposures obscure our ability to detect any influence that may be present.
Duodenal ulcer: a model of impaired mucosal defence.
Authors: R H Gompertz, A S Michalowski, W K Man, J Spencer, J H Baron
Journal: Gut (1992)

There is a new model of chronic duodenal ulcer in which the ulcer is generated by irradiating the lower mediastinum of mice with a single dose of 18 Gy 250 kV x rays. Single ulcers develop in the proximal duodenum of about half the animals. Previous studies have shown a remarkable morphological and behavioural similarity to duodenal ulcer in man. Ulceration occurs because of an imbalance between aggressive and defensive forces within the duodenum and an attempt has been made to elucidate the pathomechanism of this ulcer by determining acid and pepsin secretion. The basal and pentagastrin stimulated secretion of acid, pepsin, and histamine were measured and no changes in acid or pepsin secretion were shown to occur (risk of type II error &lt; 1%). It is therefore concluded that this chronic ulcer is a model of impaired duodenal defence.
Declining Autopsy Rates and Diagnosis of Myocardial Infarction-Reply
Authors: Thomas J. Thom
Journal: JAMA (1984)

In Reply.—  Dr Altman's letter raises the question of whether the decline in autopsy rate that has taken place since 1965 might account for the decline in mortality from myocardial infarction and cardiovascular diseases that has been observed since 1968. The report by Zarling et al, 1 showing that a substantial fraction of autopsy-demonstrated myocardial infarctions were not diagnosed antemortem, may provoke this question, but it does not shed much light on the answer. As recognized in the report, autopsies are not done on a representative fraction of hospital deaths or deaths in the community. Furthermore, the report is vague in clarifying how often the pathologically identified myocardial infarction was the cause of death rather than a secondary or incidental finding. Nor were the clinically judged causes of death reported, so one can only speculate how frequently they were one of the other subcategories within the ischemic heart disease category
Initiation of hypertension in utero and its amplification throughout life.
Authors: C M Law, M de Swiet, C Osmond, P M Fayers, D J Barker, A M Cruddas, C H Fall
Journal: BMJ (1993)

<h3>Background</h3> There is little data on injuries in elite U18 field hockey players, which limits development of appropriate evidence-based injury prevention strategies. <h3>Objective</h3> Quantify incidence and characteristics of injuries in elite U18 field hockey players at a major tournament. <h3>Design</h3> Prospective injury surveillance. <h3>Setting</h3> 2016 EuroHockey Youth Championships, Ireland. <h3>Participants</h3> Sixteen national representative teams; 8 in each of the boys and girls competitions. <h3>Main Outcome Measurements</h3> Number of, type, mechanism and site of injuries occurring on the pitch where play was stopped for the player to receive attention. <h3>Results</h3> Across the six-day tournament, 39 injuries were reported (20 in boys competition, 19 in girls; average: 0.98 injuries per match). In the boys competition, fifteen contusions were observed primarily due to being hit by the ball/stick, with fractures (2), being winded (2) and sprains (1) also reported. Most injuries (15) occurred in the lower limb or torso, with three in the upper limb and two to the head/face where players collided with each other. Three injuries occurred when struck by the ball defending penalty corners, resulting in two lower limb contusions and one fractured finger. In the girls competition, 10 of 19 injuries were contusions, also primarily due to being hit by the ball/stick. Sprains (3), lacerations (2), being winded (2), strains (1) and cramp (1) were also reported. Ten occurred in the lower limb, five to the head/face (four due to being hit by the stick), one to the upper limb and three to the torso. Two injuries occurred defending penalty corners, resulting in contusions to the thigh and hand. <h3>Conclusions</h3> Injury incidence in elite U18 field hockey is low but the high number of injuries due to being struck by the ball or stick highlights the importance of design and use of appropriate protective equipment for youth athletes.
Earliest electrocardiographic evidence of myocardial infarction: implications for thrombolytic treatment. The GREAT Group.
Authors: J Adams, R Trent, J Rawles
Journal: BMJ (1993)

To determine the incidence of the earliest electrocardiographic changes in patients with suspected myocardial infarction and their sensitivity and specificity for predicting the final diagnosis of acute myocardial infarction.Retrospective study of paired electrocardiograms recorded at home and on admission to hospital.29 rural practices in Grampian and teaching hospitals in Aberdeen.137 patients participating in the early anistreplase trial in the Grampian region, who received placebo at home and for whom paired electrocardiograms were available.Classified electrocardiographic abnormalities and diagnosis at discharge.Electrocardiograms were recorded immediately before injection of placebo at home and anistreplase in hospital at median times of 110 and 240 minutes after the onset of symptoms. Definite or probable myocardial infarction was later confirmed in 93 (68%) patients. Of these, 66 (71%) had the same findings on both electrocardiograms of either ST elevation, bundle branch block, or a non-specific abnormality, while 27 (29%) showed a major change of classification between home and hospital recordings; 21 (23%) had ST elevation or bundle branch block on only one of the paired recordings. Although ST elevation was the commonest abnormality in the 93 patients with myocardial infarction, in only 51 was it recorded at home (sensitivity 55%) and in 49 on admission (sensitivity 53%). Of 57 patients with ST elevation at home, six did not have infarction (specificity 86%), while of 51 with ST elevation on admission, two did not have infarction (specificity 95%).Elevation of the ST segment is a transient electrocardiographic abnormality that has high specificity but low sensitivity for predicting the diagnosis of acute myocardial infarction; it is an unsatisfactory precondition for giving thrombolytic treatment to patients with suspected acute myocardial infarction.
Epithelial–Mesenchymal Transition and Tumor Suppression Are Controlled by a Reciprocal Feedback Loop between ZEB1 and Grainyhead-like-2
Authors: Benjamin Cieply, Joshua Farris, James Denvir, Heide L. Ford, Steven M. Frisch
Journal: Cancer Research (2013)

Epithelial-mesenchymal transition (EMT) in carcinoma cells enhances malignant progression by promoting invasion and survival. EMT is induced by microenvironmental factors, including TGF-β and Wnt agonists, and by the E-box-binding transcription factors Twist, Snail, and ZEB. Grainyhead-like-2 (GRHL2), a member of the mammalian Grainyhead family of wound-healing regulatory transcription factors, suppresses EMT and restores sensitivity to anoikis by repressing ZEB1 expression and inhibiting TGF-β signaling. In this study, we elucidate the functional relationship between GRHL2 and ZEB1 in EMT/MET and tumor biology. At least three homeodomain proteins, Six1, LBX1, and HoxA5, transactivated the ZEB1 promoter, in the case of Six1, through direct protein-promoter interaction. GRHL2 altered the Six1-DNA complex, inhibiting this transactivation. Correspondingly, GRHL2 expression prevented tumor initiation in xenograft assays, sensitized breast cancer cells to paclitaxel, and suppressed the emergence of CD44(high)CD24(low) cells (defining the cancer stem cell phenotype in the cell type studied). GRHL2 was downregulated in recurrent mouse tumors that had evolved to an oncogene-independent, EMT-like state, supporting a role for GRHL2 downregulation in this phenotypic transition, modeling disease recurrence. The combination of TGF-β and Wnt activation repressed GRHL2 expression by direct interaction of ZEB1 with the GRHL2 promoter, inducing EMT. Together, our observations indicate that a reciprocal feedback loop between GRHL2 and ZEB1 controls epithelial versus mesenchymal phenotypes and EMT-driven tumor progression.
Functional analysis of the marginating pool of human polymorphonuclear leukocytes
Authors: Roger L. Berkow, Robert W. Dodson
Journal: American Journal of Hematology (1987)

Abstract The intravascular pool of human polymorphonuclear leukocytes (PMN) is composed of one compartment which is circulating and another that is marginated to the vascular endothelium. Administration of B‐adrenergic agonists leads to a rapid demargination with an increase in the circulating PMN pool. The marginating PMN has previously been stated to represent an older PMN based on a higher cytochemical alkaline phosphatase activity. With the understanding that circulating PMN are heterogeneous with respect to function and size we undertook the present study to evaluate the contribution of the marginating PMN to functional and volume‐dependent heterogeneity. We found that PMN isolated 7 min after epinephrine administration, presumably enriched by marginating PMN, were not different in volume, biochemically measured alkaline phosphatase activity, stimulated superoxide anion release, degranulation, or phagocytosis. These data suggest that the circulating and marginating pools of PMN are interchangeable and that the marginating PMN are not enriched by a particular subpopulation of PMN.
Induction of severe granulomatous experimental autoimmune thyroiditis in mice by effector cells activated in the presence of anti-interleukin 2 receptor antibody.
Authors: H Braley-Mullen, G C Sharp, J T Bickel, M Kyriakos
Journal: The Journal of Experimental Medicine (1991)

Spleen cells from CBA/J mice immunized with mouse thyroglobulin (MTg) and the adjuvant lipopolysaccharide induce experimental autoimmune thyroiditis (EAT) after transfer to recipient mice if they are first activated in vitro with MTg. EAT induced by cells cultured with MTg is generally moderate in severity and is characterized by a thyroid infiltration consisting primarily of mononuclear cells. Addition of the anti-interleukin 2 receptor (IL-2R) monoclonal antibodies (mAbs) M7/20, 3C7, or 7D4 to spleen cell cultures with MTg resulted in a cell population capable of inducing a more severe type of EAT characterized by extensive follicular destruction, granuloma formation, and the presence of multinucleated giant cells. Recipients of cells cultured with MTg and anti-IL-2R mAb also had higher anti-MTg autoantibody responses than recipients of cells cultured with MTg alone. Activation of cells capable of transferring severe granulomatous EAT and increased anti-MTg autoantibody responses required both MTg and M7/20 in culture and required addition of M7/20 within the first 8 h of the 72-h culture period. CD4+ T cells were required for the expression of both the severe granulomatous EAT lesions and the mononuclear cell infiltrates typically observed in murine EAT. The increased anti-MTg autoantibody responses in recipients of cells cultured with MTg and anti-IL-2R mAbs were not restricted to a particular immunoglobulin G (IgG) subclass and included antibody of the IgG1, IgG2A, and IgG2B subclasses. These results suggest that a subset of CD4+ T cells capable of inducing severe granulomatous EAT and increased anti-MTg autoantibody responses is preferentially activated when cells are cultured in the presence of anti-IL-2R mAb. Anti-IL-2R mAb may either prevent activation of cells that induce classical lymphocytic EAT or prevent activation of cells that normally function to downregulate EAT effector T cell activity.