tbuckley/cabot-search huggingface dataset:
Constrictive pericarditis. Clinical clues to diagnosis
Authors: E. W. Hancock
Journal: JAMA (1975)

CONSTRICTIVE pericarditis is an uncommon condition that occurs in varied forms. Errors and uncertainties in diagnosis are frequent. Invasive studies and even exploratory thoracotomy are considered to be the only sure methods of diagnosis. Careful observation and correct interpretation of a number of clinical clues should, however, permit a correct clinical diagnosis in nearly all cases. <h3>Confusion With Noncardiac Disease</h3> Patients with constrictive pericarditis frequently receive diagnoses of and treatment for chronic liver disease, presumed abdominal carcinomatosis, or pleural effusion of suspected infectious or neoplastic cause. Why constrictive pericarditis has such a tendency to cause right pleural effusion, hepatomegaly, and ascites with little or no peripheral edema is not fully understood, but it is characteristic, particularly in young patients. However, this kind of diagnostic error would not be made if the neck veins were examined carefully in such patients. The central venous pressure is normal in liver disease and in
Insulin-like growth factor binding protein-1 in PCOS: a systematic review and meta-analysis
Authors: C. J. Kelly, S. R. Stenton, H. Lashen
Journal: Human Reproduction Update (2010)

BACKGROUNDDespite extensive research, the pathogenesis of polycystic ovary syndrome (PCOS) remains unclear. Putatively, an elevated circulating concentration of insulin inhibits the production of insulin-like growth factor binding protein-1 (IGFBP-1), thus increasing the level of free IGF-I in serum and stimulating ovarian androgen production. Decreased IGFBP-1 has been reported in PCOS and in obesity; however, there are inconsistencies in the evidence. This systematic review and meta-analysis aimed to determine whether IGFBP-1 is decreased in PCOS when controlling for the influence of BMI.
Hypertension Prevalence and Blood Pressure Levels in 6 European Countries, Canada, and the United States
Authors: Katharina Wolf-Maier
Journal: JAMA (2003)

Geographic variations in cardiovascular disease (CVD) and associated risk factors have been recognized worldwide. However, little attention has been directed to potential differences in hypertension between Europe and North America.To determine whether higher blood pressure (BP) levels and hypertension are more prevalent in Europe than in the United States and Canada.Sample surveys that were national in scope and conducted in the 1990s were identified in Germany, Finland, Sweden, England, Spain, Italy, Canada, and the United States. Collaborating investigators provided tabular data in a consistent format by age and sex for persons at least 35 years of age. Population registries were the main basis for sampling. Survey sizes ranged from 1800 to 23 100, with response rates of 61% to 87.5%. The data were analyzed to provide age-specific and age-adjusted estimates of BP and hypertension prevalence by country and region (eg, European vs North American).Blood pressure levels and prevalence of hypertension in Europe, the United States, and Canada.Average BP was 136/83 mm Hg in the European countries and 127/77 mm Hg in Canada and the United States among men and women combined who were 35 to 74 years of age. This difference already existed among younger persons (35-39 years) in whom treatment was uncommon (ie, 124/78 mm Hg and 115/75 mm Hg, respectively), and the slope with age was steeper in the European countries. For all age groups, BP measurements were lowest in the United States and highest in Germany. The age- and sex-adjusted prevalence of hypertension was 28% in the North American countries and 44% in the European countries at the 140/90 mm Hg threshold. The findings for men and women by region were similar. Hypertension prevalence was strongly correlated with stroke mortality (r = 0.78) and more modestly with total CVD (r = 0.44).Despite extensive research on geographic patterns of CVD, the 60% higher prevalence of hypertension in Europe compared with the United States and Canada has not been generally appreciated. The implication of this finding for national prevention strategies should be vigorously explored.
Absence of Maternal Contamination of Chorionic Villi Used for Fetal-Gene Analysis
Authors: Robert G. Elles, Robert Williamson, Meena Niazi, Dulcie V. Coleman, David Horwell
Journal: New England Journal of Medicine (1983)

Chorionic villi can be obtained by direct transcervical aspiration at 9 to 10 weeks' gestation and used for analysis of fetal DNA. However, for the method to be reliable, there must be no detectable contamination by maternal DNA. To investigate the question of contamination, we compared the DNA of chorionic villi from five fetuses with that obtained from maternal lymphocytes, using the restriction endonuclease TaqI and specific DNA probes for a pair of alleles on the X chromosome. The alleles yield fragments of different lengths when digested with TaqI (length polymorphism), which can be demonstrated by electrophoresis and hybridization with the radioactive DNA probes. If the pattern obtained with the chorionic DNA is different from that obtained with the maternal DNA, contamination is not present. In two cases the fetal DNA of the chorionic villi was shown to be uncontaminated by maternal tissue. In one of these cases the mother was heterozygous and the fetus was homozygous; in the other the mother was homozygous and the fetus was heterozygous. In three other cases no definitive conclusions could be drawn, because the genotypes of the fetus and mother were identical. We conclude that chorionic villi at 9 to 10 weeks' gestation are a source of fetal DNA that can be used for gene analysis, with no detectable contamination by maternal DNA. (N Engl J Med 1983; 308:1433–5.)
George Hebbington Field John Rowland Hughes Denis Leary McDermott Kelly William Bell Knapman Albert Alexander ("Sandy") Lawrence Kenneth Lewis Lipp Clifford Wilson McKee John Michael Kenneth Marsh Anthony Hugh Marshall Denis Smith Poole-Wilson Ian Clifford Campbell Todd Jean Mary Webster
Authors: A A Clark, E. Jeffreys, D. Jones, G. Davies, W Lawrence, D E Walker, M. McKee, H. McKee, H B. Wright, J. Smith, J. Mitchell, C. Todd, H N C Gunther
Journal: BMJ (1998)

He transformed the Oswestry hospital into a teaching centre of excellence and built up the orthopaedic children's department, besides establishing a
Control of Tumorigenesis and Chemoresistance by the DEK Oncogene
Authors: Erica Riveiro-Falkenbach, María S. Soengas
Journal: Clinical Cancer Research (2010)

Slight modifications of chromatin dynamics can translate into small- and large-scale changes in DNA replication and DNA repair. Similarly, promoter usage and accessibility are tightly dependent on chromatin architecture. Consequently, it is perhaps not surprising that factors controlling chromatin organization are frequently deregulated (directly or indirectly) in cancer cells. DEK is emerging as a novel class of DNA topology modulators that can be both targets and effectors of protumorigenic events. The locus containing DEK at chromosome 6p22.3 is amplified or reorganized in multiple cancer types. In addition, DEK can be subject to a variety of tumor-associated transcriptional and post-translational modifications. In turn, DEK can favor cell transformation, at least in part by inhibiting cell differentiation and premature senescence. More recently, DEK has also been linked to the resistance of malignant cells to apoptotic inducers. Interestingly, a fraction of DEK can also bind RNA and affect alternative splicing, further illustrating the pleiotropic roles that this protein may exert in cancer cells. Here we will summarize the current literature about the regulation and function(s) of DEK as a proto-oncogene. In addition, the translational relevance of DEK as a putative diagnostic marker and candidate for drug development will be discussed.
Reduced physical activity and the retired athlete: a dangerous combination?
Authors: S Witkowski, E E Spangenburg
Journal: British Journal of Sports Medicine (2008)

Physical activity is a key component of our environment that is a major contributor to the prevention of many chronic diseases that plague our society. Dr Frank Booth and colleagues have argued on numerous occasions that the human body evolved to expect and respond to high levels of physical activity, whereas currently our society provides us with technical innovations that encourage low levels of physical activity.1 The unfortunate result is that people are less physically active than ever and there are epidemic elevations in various chronic diseases. Numerous publications have shown that reduced physical activity significantly and unequivocally increases an individual’s risk for developing conditions such as type 2 diabetes, cardiovascular disease, and obesity.2–6 The data are so convincing that the Center for Disease Control lists physical inactivity as a potential cause for a number of chronic diseases.7 Contrary to the viewpoints of some, there …
Rate-dependence of atrial tachycardia effects on atrial refractoriness and atrial fibrillation maintenance
Authors: A. Shiroshita-Takeshita, H. Mitamura, S. Ogawa, S. Nattel
Journal: Cardiovascular Research (2008)

AimsAlthough atrial-tachycardia remodelling is a significant atrial fibrillation (AF) promoting factor, little information is available about how atrial-tachycardia rate determines remodelling effects. This study assessed the effects of atrial tachypacing (ATP) over a range of clinically relevant rates on atrial electrophysiology and AF.
Novel coronavirus: how much of a threat?
Authors: R. Pebody, M. Zambon, J. M. Watson
Journal: BMJ (2013)

We know the questions to ask; we don’t yet have many answers

A third case of novel coronavirus (NCoV) infection was reported by the Health Protection Agency (HPA) on 15 February 2013, part of a family cluster of three cases in the West Midlands, England.1 This means that 13 cases have been laboratory confirmed worldwide since September 2012. Four cases have been diagnosed in the United Kingdom, and seven patients, including one in the UK, have died.2 The index patient in the recent UK cluster had travelled to Saudi Arabia and Pakistan in the 10 days before the onset of disease, whereas the second and third cases were family members who had not been abroad and probably acquired their infection after contact with the index case. The earlier UK case was a previously well adult transferred to intensive care in London from Qatar with severe respiratory illness in September 2012.3 What have we discovered about this new pathogen from the few cases so far reported? Is this likely to represent a global public health threat akin to that from severe acute respiratory syndrome (SARS) coronavirus?

Human coronaviruses, first identified in the 1960s, are part of a diverse group of viruses found in humans and animals. In humans these RNA viruses typically cause respiratory illnesses ranging from …
Management-based risk prediction in community-acquired pneumonia by scores and biomarkers
Authors: Martin Kolditz, Santiago Ewig, Gert Höffken
Journal: European Respiratory Journal (2012)

Community-acquired pneumonia (CAP) represents a major life-threatening infection, but disease course and outcome is highly variable. Major drivers of prognosis are respiratory failure, sepsis-related organ dysfunction and unstable comorbidities. Current risk stratification tools have been primarily designed to predict mortality and identify low risk patients potentially suitable for ambulatory management. Detection of patients at high risk for clinical deterioration by current scores remains suboptimal. Therefore, management-related risk stratification tools designed to predict benefit from early intensified monitoring and treatment strategies in hospitalised CAP are advocated. An approach including early and repeatedly evaluated clinical markers of respiratory failure, sepsis-related organ dysfunction or decompensating comorbidity combined with individual definition of treatment goals is suggested. Inflammatory biomarkers can add prognostic information. New cardiovascular or stress-related biomarkers like copeptin, midregional proadrenomedullin and cortisol have been repeatedly linked with outcome and disease course in CAP and improved clinical scoring in observational studies. Thus they represent promising tools for individualised risk stratification. A major task in future CAP research will be the evaluation of their additional value in large interventional trials with control groups incorporating strict management guidance by clinical criteria.
ErbB2 Promotes Src Synthesis and Stability: Novel Mechanisms of Src Activation That Confer Breast Cancer Metastasis
Authors: Ming Tan, Ping Li, Kristine S. Klos, Jing Lu, Keng-Hsueh Lan, Yoichi Nagata, Dexing Fang, Tong Jing, Dihua Yu
Journal: Cancer Research (2005)

Activation of Src kinase plays important roles in the development of many neoplasias. Most of the previous Src studies focused on the deregulation of Src kinase activity. The deregulated Src protein synthesis and stability in mediating malignant phenotypes of cancer cells, however, have been neglected. While investigating the signal transduction pathways contributing to ErbB2-mediated metastasis, we found that ErbB2-activated breast cancer cells that had higher metastatic potentials also had increased Src activity compared with ErbB2 low-expressing cells. The increased Src activity in ErbB2-activated cells paralleled higher Src protein levels, whereas Src RNA levels were not significantly altered. Our studies revealed two novel mechanisms that are involved in Src protein up-regulation and activation by ErbB2: (a) ErbB2 increased Src translation through activation of the Akt/mammalian target of rapamycin/4E-BP1 pathway and (b) ErbB2 increased Src stability most likely through the inhibition of the calpain protease. Furthermore, inhibition of Src activity by a Src-specific inhibitor, PP2, or a Src dominant-negative mutant dramatically reduced ErbB2-mediated cancer cell invasion in vitro and metastasis in an experimental metastasis animal model. Together, activation of ErbB2 and downstream signaling pathways can lead to increased Src protein synthesis and decreased Src protein degradation resulting in Src up-regulation and activation, which play critical roles in ErbB2-mediated breast cancer invasion and metastasis.
Importance of -Carotene, beta-Carotene, and Other Phytochemicals in the Etiology of Lung Cancer
Authors: R. G. Ziegler, E. A. Colavito, P. Hartge, M. J. McAdams, J. B. Schoenberg, T. J. Mason, J. F. Fraumeni
Journal: JNCI Journal of the National Cancer Institute (1996)

Of all proposed cancer chemopreven-tive agents, p-carotene seemed the mostpromising (7)—until recently. Numer-ous retrospective and prospective studieshave demonstrated that a reduced risk oflung and other cancers is associatedwith an increased intake of provitaminA carotenoids, the vitamin A precursorsin vegetables and fruits (2-7). Inprospective studies, elevated prediag-nostic blood P-carotene levels havebeen consistently predictive of a re-duced incidence of lung and other can-cers (2-5,7,8). However, in a large,randomized, placebo-controlled trial inFinland (9), male smokers took P-carotene daily for 5-8 years at a dosesubstantially higher than that linked toreduced risk in observational studies,and lung cancer incidence was increased18% (95% confidence interval [CI] -3%-36%), contributing substantially toan 8% excess in total mortality. Interimresults from a second large, randomizedtrial conducted in the United States withmale and female smokers and men ex-posed to asbestos have corroborated thatlung cancer incidence and total mor-tality are increased in subjects taking P-carotene supplements.'The observational studies of diet andcancer relied on food composition tablesto estimate consumption of total pro-vitamin A carotenoids, which include p-carotene, a-carotene, and chemicallysimilar carotenoids. Recently, adatabase detailing the levels of themajor individual carotenoids in U.S.foods was published (10,11). Conse-quently, we reanalyzed data from thefirst case-control study to evaluate thehypothesis that P-carotene could protectagainst cancer—a population-basedstudy of diet and lung cancer conductedin New Jersey during 1980-1981(12,13).Eligible case subjects were whitemen
Remissions of Mammary Adenocarcinoma in Hypothyroid Mice Given 5-Fluorouracil and Chloroquine Phosphate
Authors: Jon P. Shoemaker, Rifaat K. Dagher
Journal: JNCI Journal of the National Cancer Institute (1979)

In two separate experiments, treatment of C3H/He mice bearing transplantable mammary adenocarcinomas (C3HBA) with a regimen of 6-propylthiouracil (PTUra) and 5-fluorouracil (FUra) plus chloroquine phosphate (CP) resulted in complete remissions of 77 and 65%, respectively. Treatment with PTUra alone resulted in 41% remissions in experiment 1 and 35% remissions in experiment 2. None of the nontreated control mice in either experiment had spontaneous remissions, and all controls died in each experiment. The principal effect was apparently due to the treatment with PTUra, inasmuch as most of the tumors disappeared during the 21-day treatment period. This observation indicated that the proper timing of the thyroid treatment with PTUra was crucial to achieve the best results. The combined FUra+CP regimen augmented the effects of the thyroid treatment and resulted in an increase in remissions.
N-Terminal Pro-B–Type Natriuretic Peptide and Long-Term Mortality in Acute Coronary Syndromes
Authors: Torbjørn Omland, Anita Persson, Leong Ng, Russel O’Brien, Thomas Karlsson, Johan Herlitz, Marianne Hartford, Kenneth Caidahl
Journal: Circulation (2002)

Background— B-type natriuretic peptide (BNP) is a predictor of short- and medium-term prognosis across the spectrum of acute coronary syndromes (ACS). The N-terminal fragment of the BNP prohormone, N-BNP, may be an even stronger prognostic marker. We assessed the relation between subacute plasma N-BNP levels and long-term, all-cause mortality in a large, contemporary cohort of patients with ACS. Methods and Results— Blood samples for N-BNP determination were obtained in the subacute phase in 204 patients with ST-elevation myocardial infarction (MI): 220 with non-ST segment elevation MI and 185 with unstable angina in the subacute phase. After a median follow-up of 51 months, 86 patients (14%) had died. Median N-BNP levels were significantly lower in long-term survivors than in patients dying (442 versus 1306 pmol/L; P &lt;0.0001). The unadjusted risk ratio of patients with supramedian N-BNP levels was 3.9 (95% confidence interval, 2.4 to 6.5). In a multivariate Cox regression model, N-BNP (risk ratio 2.1 [95% confidence interval, 1.1 to 3.9]) added prognostic information above and beyond Killip class, patient age, and left ventricular ejection fraction. Adjustment for peak troponin T levels did not markedly alter the relation between N-BNP and mortality. In patients with no evidence of clinical heart failure, N-BNP remained a significant predictor of mortality after adjustment for age and ejection fraction (risk ratio, 2.4 [95% confidence interval, 1.1 to 5.4]). Conclusions— N-BNP is a powerful indicator of long-term mortality in patients with ACS and provides prognostic information above and beyond conventional risk markers.
Phase I Study of BMS-214662, a Farnesyl Transferase Inhibitor in Patients With Acute Leukemias and High-Risk Myelodysplastic Syndromes
Authors: Jorge Cortes, Stefan Faderl, Elihu Estey, Razelle Kurzrock, Deborah Thomas, Miloslav Beran, Guillermo Garcia-Manero, Alessandra Ferrajoli, Francis Giles, Charles Koller, Susan O'Brien, John Wright, Stephen A. Bai, Hagop Kantarjian
Journal: Journal of Clinical Oncology (2005)

Purpose To investigate the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of BMS-214662, a farnesyl transferase (FTase) inhibitor, in patients with acute leukemias and high-risk myelodysplastic syndromes (MDS). Patients and Methods Patients with relapsed or refractory acute leukemias or MDS, or previously untreated but poor candidates for chemotherapy, were included in this phase I study with a 3 + 3 dose escalation design. BMS-214662 was administered as a 1-hour bolus once weekly at doses of 42 to 157 mg/m 2 . Once the MTD was identified, the schedule was changed to a 24-hour continuous infusion once weekly (starting dose, 300 mg/m 2 ). Results Thirty patients were treated at a dose of 42 (n = 1), 56 (n = 3), 84 (n = 3), 118 (n = 13), 157 (n = 6) or 300 mg/m 2 (n = 4). DLT occurred in 3 patients at 157 mg/m 2 , including nausea, vomiting, diarrhea, hypokalemia and cardiovascular problems. No DLT occurred with 24-hour continuous infusion. MTD with a 1-hour infusion was 118 mg/m 2 , with no MTD identified with the 24-hour infusion. Plasma concentrations of BMS-214662 correlated with the dose. Inhibition of FTase activity of approximately 60% occurred after the infusion with recovery to near baseline after 24 hours. Five patients had evidence of antileukemia activity, including two with complete remission with incomplete platelet recovery, one with hematologic improvement, and two with morphologic leukemia-free state. Conclusion BMS-214662 is well tolerated at doses of up to 118 mg/m 2 as a 1-hour infusion. The toxicity profile and efficacy may be improved with prolonged exposure. Further investigation of this agent in leukemia is warranted.
The global challenge for skin health
Authors: R.J. Hay, M. Augustin, C.E.M. Griffiths, W. Sterry
Journal: British Journal of Dermatology (2015)

See Appendix for more details. The human skin is the largest of the body's organs, with functions that encompass sensation, heat regulation, water conservation and immunological surveillance. It is also the single most important determinant of human appearance and identity, and the interface for much of our physical and social contact with our environment. It is not difficult, therefore, to understand how events that compromise its integrity and health have a profound, and potentially devastating, impact on general well‐being and self‐respect. Furthermore, illness that directly affects the skin is the fourth most frequent cause of all human disease, affecting some 1·9 billion people at any time, almost one‐third of the world's population.1 It is therefore a leading reason for seeking medical help in all societies. Skin diseases may be infectious, congenital, degenerative, inflammatory and cancerous, and they affect all ages from cradle to grave, but a disproportionate burden falls on the elderly and young children.1 2 One of the more common popular fallacies in the perception of human illness is that, because a disease is very common, it may be of little consequence. Yet intolerable itching and disfigurement are severe consequences of damage to the skin. Furthermore, many of these conditions have long‐standing, serious repercussions that impair internal organs from the joints to the kidneys, as well as posing a real threat of mental illness leading to severe depression and even suicide.3