tbuckley/cabot-search huggingface dataset:
Global migration and the changing distribution of sickle haemoglobin: a quantitative study of temporal trends between 1960 and 2000
Authors: Frédéric B Piel, Andrew J Tatem, Zhuojie Huang, Sunetra Gupta, Thomas N Williams, David J Weatherall
Journal: The Lancet Global Health (2014)

BackgroundChanges in the geographical distribution of genetic disorders are often thought to happen slowly, especially when compared with infectious diseases. Whereas mutations, genetic drift, and natural selection take place over many generations, epidemics can spread through large populations within a few days or weeks. Nevertheless, population movements can interfere with these processes, and few studies have been done of their effect on genetic disorders. We aimed to investigate the effect of global migration on the distribution of the sickle-cell gene—the most common and clinically significant haemoglobin structural variant.MethodsFor each country, we extracted data from the World Bank's Global Bilateral Migration Database about international human migrations between 1960 and 2000. We combined this information with evidence-based estimates of national HbS allele frequencies, generated within a Bayesian geostatistical framework, to analyse temporal changes in the net numbers of migrants, and classified countries with an index summarising these temporal trends.FindingsThe number of international migrants increased from 92·6 million in 1960, to 165·2 million in 2000. The estimated global number of migrants with HbS increased from about 1·6 million in 1960, to 3·6 million in 2000. This increase was largely due to an increase in the number of migrants from countries with HbS allele frequencies higher than 10%, from 3·1 million in 1960, to 14·2 million in 2000. Additionally, the mean number of countries of origin for each destination country increased from 70 (SE 46) in 1960, to 98 (48) in 2000, showing an increasing diversity in the network of international migrations between countries. Our index of change map shows a patchy distribution of the magnitude of temporal changes, with the highest positive and negative values scattered across all continents.InterpretationGlobal human population movements have had a substantial effect on the distribution of the HbS gene. Population movements can create a long-term burden on health-care systems. Our findings, which emphasise countries in which migration fluxes are changing the most, should increase awareness about the global burden of haemoglobinopathies and encourage policy makers to implement specific public health interventions, such as screening programmes and genetic counselling.FundingWellcome Trust, European Research Council, Bill & Melinda Gates Foundation, National Institute of Allergy and Infectious Diseases–National Institutes of Health, the Research and Policy for Infectious Disease Dynamics program, Fogarty International Center.
Pericarditis With Effusion
Authors: William Dressler
Journal: JAMA (1966)

<h3>To the Editor:—</h3> In "Huge Pericardial Effusion of 15 Years' Duration," inThe Journal(<b>195</b>:1064, 1966), the first few lines of Comment read: "Although chronic pericardial effusion is not very rare,<sup>1</sup>it is not even mentioned in some leading texts. Spodick<sup>2</sup>quotes a report by Froment and associates who observed pericardial effusion of the chronic type in five out of 100 patients suffering from pericarditis with effusion." Dr. Spodick drew my attention to the fact that this juxtaposition of two statements might be interpreted as if the topic of chronic pericardial effusion was only imperfectly treated in his text on<i>Chronic and Constrictive Pericarditis</i>which was cited as reference 2. I should like to stress that such an interpretation would do great injustice to Dr. Spodick's text, which, indeed, offers a clear and comprehensive discussion of the topic of chronic pericardial effusion.
Associations of Toenail Arsenic, Cadmium, Mercury, Manganese, and Lead with Blood Pressure in the Normative Aging Study
Authors: Irina Mordukhovich, Robert O. Wright, Howard Hu, Chitra Amarasiriwardena, Andrea Baccarelli, Augusto Litonjua, David Sparrow, Pantel Vokonas, Joel Schwartz
Journal: Environmental Health Perspectives (2011)

Arsenic, cadmium, mercury, and lead are associated with cardiovascular disease in epidemiologic research. These associations may be mediated by direct effects of the metals on blood pressure (BP) elevation. Manganese is associated with cardiovascular dysfunction and hypotension in occupational cohorts.We hypothesized that chronic arsenic, cadmium, mercury, and lead exposures elevate BP and that manganese lowers BP.We conducted a cross-sectional analysis of associations between toenail metals and BP among older men from the Normative Aging Study (n = 639), using linear regression and adjusting for potential confounders.An interquartile range increase in toenail arsenic was associated with higher systolic BP [0.93 mmHg; 95% confidence interval (CI): 0.25, 1.62] and pulse pressure (0.76 mmHg; 95% CI: 0.22, 1.30). Positive associations between arsenic and BP and negative associations between manganese and BP were strengthened in models adjusted for other toenail metals.Our findings suggest associations between BP and arsenic and manganese. This may be of public health importance because of prevalence of both metal exposure and cardiovascular disease. Results should be interpreted cautiously given potential limitations of toenails as biomarkers of metal exposure.
Microbiological safety of drinking water: United States and global perspectives.
Authors: T E Ford
Journal: Environmental Health Perspectives (1999)

Waterborne disease statistics only begin to estimate the global burden of infectious diseases from contaminated drinking water. Diarrheal disease is dramatically underreported and etiologies seldom diagnosed. This review examines available data on waterborne disease incidence both in the United States and globally together with its limitations. The waterborne route of transmission is examined for bacterial, protozoal, and viral pathogens that either are frequently associated with drinking water (e.g., Shigella spp.), or for which there is strong evidence implicating the waterborne route of transmission (e.g., Leptospira spp.). In addition, crucial areas of research are discussed, including risks from selection of treatment-resistant pathogens, importance of environmental reservoirs, and new methodologies for pathogen-specific monitoring. To accurately assess risks from waterborne disease, it is necessary to understand pathogen distribution and survival strategies within water distribution systems and to apply methodologies that can detect not only the presence, but also the viability and infectivity of the pathogen.
Remodeling of In-Stent Neointima, Which Became Thinner and Transparent Over 3 Years
Authors: Masanori Asakura, Yasunori Ueda, Shinsuke Nanto, Atsushi Hirayama, Takayoshi Adachi, Masafumi Kitakaze, Masatsugu Hori, Kazuhisa Kodama
Journal: Circulation (1998)

Recently, it has been reported that the luminal diameter shows phasic changes after stenting: the progression of luminal narrowing followed by its regression. To elucidate the mechanisms involved in the phasic changes in luminal diameter after stenting, we examined the changes in neointimal thickness and the appearance of neointima by a series of angiographic and angioscopic observations for 3 years after stent implantation.In 12 patients who received a Wiktor coronary stent, serial angiographic and angioscopic examinations were performed immediately, 2 to 4 weeks, 3 months, 6 months, and 3 years after the stenting without repetition of angioplasty. Neointimal thickness was determined by angiography as the difference between stent and luminal diameters. The angioscopic appearance of neointima over the stent was classified as transparent or nontransparent according to the visibility of the majority of the stent. Neointimal thickness increased significantly at 3 months (0.75+/-0.32 mm) without further changes at 6 months (0.74+/-0.32 mm). Thereafter, however, it decreased significantly over 3 years (0.51+/-0.26 mm). The angioscopic appearance was classified as transparent in 8 patients (100) immediately after stenting, 6 patients (100%) at 2 to 4 weeks, 2 patients (17%) at 3 months, 2 patients (20%) at 6 months, and 7 patients (58%) at 3 years.The neointima became thick and nontransparent until 6 months and then became thin and transparent by 3 years. We conclude that neointimal remodeling exists after stenting and plays a major role in the alteration of coronary luminal diameter after stenting.
Premenstrual Syndrome and Anxiety Disorders: A Psychobiological Link
Authors: F. Facchinetti, M. Tarabusi, G. Nappi
Journal: Psychotherapy and Psychosomatics (1998)

The term premenstrual syndrome (PMS) has been used for many years to describe disturbances of mood or physical symptoms occurring regularly 7–10 days before menses and remitting during menses. The Diagnostic and Statistical Manual of Mental Disorders (DSM III-R) included PMS among the ‘proposed Diagnostic Categories Needing Further Study’ under the name of Late Luteal Phase Dysphoric Disorder (LLPDD), and established among its diagnostic criteria the need for daily prospective symptoms self-ratings during at least two cycles, for confirmation [1]. The more recent fourth edition of DSM maintained PMS among the categories needing further study, adding the new category of Premenstrual Dysphoric Disorder (PMDD) [2]. PMDD is distinguished from PMS in several respects: It requires at least one mood symptom; the symptoms must be severe enough to cause functional impairment, and they must not be a mere exacerbation of another psychiatric disorder. Since no other diagnostic criteria have been proposed, many studies have compared the scores from the premenstrual and follicular phases: a 30–50% increase found in prospectively administered diaries is now normally accepted as an indicator of the diagnosis of PMS [3], no attention being paid to the quality of symptoms. On the other hand, no specific hormone changes or other biological markers are able to distinguish between PMS sufferers and normal women [4]. Therefore, the absence of both a universally accepted definition and an objective biological or clinical marker makes it impossible to study the etiology of PMS. Accordingly, the therapeutic approach is presently indefinite. Steinberg [5] correctly stated that the time-honored medical adage maintaining that ‘in the absence of cure, treatments multiply’ seems to be appropriate to PMS. Nevertheless, it is well accepted that the severe form of PMS, i.e. the one characterized by psychosocial impairment and thus requiring medical treatment, is present in 5–8% of women during their 40s. This implies that we should multiply our efforts toward the understanding of the disorder.
Use of the somatostatin analogue octreotide to localise and manage somatostatin-producing tumours
Authors: S Angeletti, V D Corleto, O Schillaci, M Marignani, B Annibale, A Moretti, G Silecchia, F Scopinaro, N Basso, C Bordi, G Delle Fave
Journal: Gut (1998)

Background —Somatostatin receptor scintigraphy (SRS) and octreotide therapy have both changed the management of gastroenteropancreatic endocrine tumours, but very few data are available on the use of SRS and octreotide to visualise and treat somatostatinomas. Method —The results of SRS and octreotide treatment in three somatostatinoma patients were examined. Results —SRS was able to detect extensive hepatic involvement in patient 1, one hepatic and one pancreatic lesion in patient 2, and one hepatic lesion in patient 3. Octreotide therapy (0.5 mg/day subcutaneously) was effective in decreasing plasma levels of somatostatin in all three patients. Symptoms (diabetes and diarrhoea) were greatly improved in the two patients with “somatostatinoma syndrome”. Conclusion —The study shows that somatostatinoma, like most other gastroenteropancreatic endocrine tumours, possesses functioning somatostatin receptors.
S141 A disintegrin and metalloprotease (ADAM) 33 protein in patients with pulmonary sarcoidosis
Authors: A. S. Shaffiq, H. M. H. Haitchi, Y. Y. P. Pang, A. A. Alangari, M. G. J. Jones, B. G. M. Marshall, K. M. A. O. O'Reilly, D. E. D. Davies
Journal: Thorax (2010)

<h3>Background</h3> The asthma and chronic obstructive pulmonary disease (COPD) gene, <i>A Disintegrin And Metalloproteinase (ADAM)33</i>, is selectively expressed in mesenchymal cells and its metalloprotease activity has been linked to angiogenesis and airway remodelling. A soluble form of ADAM33 (sADAM33) has been identified in the bronchoalveolar lavage fluid (BALF) of asthmatic patients and its levels inversely correlate with lung function and disease severity. Because tissue remodelling also occurs in pulmonary sarcoid, we hypothesised that sADAM33 is elevated in BALF of patients with this disease which, like asthma, is heterogeneous. <h3>Methods</h3> BALF was obtained from healthy controls (n=11) and patients with sarcoid (n=13) using fibre optic bronchoscopy according to current guidelines. After removal of immunoglobulins using Protein A/G and enrichment using Concanavalin A beads, sADAM33 was identified in BALF by Western blotting. A FRET peptide cleavage assay was used to assess ADAM33-like activity in BALF. Lung function (FVC%) and gas transfer (TLCO%) were measured at time of first diagnostic workup. <h3>Results</h3> sADAM33 protein in BALF was detected as a 25kDa fragment and levels were significantly increased in samples from sarcoid patients when compared to healthy controls (p&lt;0.05) (Abstract S141 Figure 1A). Levels of sADAM33 were inversely correlated with lung function (FVC % predicted) (p&lt;0.05) and gas transfer (TLCO% predicted) (p&lt;0.01) (Abstract S141 Figure 1B). No difference in sADAM33 enzymatic activity was observed between healthy and sarcoid BALF samples. <h3>Conclusion</h3> Release of sADAM33 is increased in sarcoid in association with abnormal lung function. Further studies will be required to determine whether the release of sADAM33 results in dysregulated metalloprotease activity, leading to angiogenesis and pulmonary parenchymal remodelling in pulmonary sarcoid. Since <i>ADAM33</i> polymorphism is related to reduced lung function in asthma and COPD, this study raises the possibility that there may also be genetic associations between <i>ADAM33</i> and some forms of pulmonary sarcoid. Finally, the occurrence of sADAM33 in asthma and sarcoidosis and its relation to reduced lung function suggests that it may be a biomarker of pulmonary remodelling in these diseases.
Inpatient management of sickle cell pain: A ‘snapshot’ of current practice
Authors: Scott T. Miller, Hae‐Young Kim, Debra Weiner, Carrie G. Wager, Dianne Gallagher, Lori Styles, Carlton D. Dampier
Journal: American Journal of Hematology (2011)

The Sickle Cell Disease Clinical Research Network (SCDCRN) designed the PROACTIVE Feasibility Study (ClinicalTrials.gov NCT00951808) to determine whether elevated serum levels of secretory phospholipase A2 (sPLA2) during hospitalization for pain would permit preemptive therapy of sickle cell acute chest syndrome (ACS) by blood transfusion. While PROACTIVE was not designed to assess pain management and was terminated early due to inadequate patient accrual, collection of clinical data allowed a "snapshot" of current care by expert providers. Nearly half the patients admitted for pain were taking hydroxyurea; hydroxyurea did not affect length of stay. Providers commonly administered parenteral opioid analgesia, usually morphine or hydromorphone, to adults and children, generally by patient-controlled analgesia (PCA). Adult providers were more likely to prescribe hydromorphone and did so at substantially higher morphine equivalent doses than were given to adults receiving morphine; the latter received doses similar to children who received either medication. All subjects treated with PCA received higher daily doses of opioids than those treated by time-contingent dosing. Physicians often restricted intravenous fluids to less than a maintenance rate and underutilized incentive spirometry, which reduces ACS in patients hospitalized for pain.
1078 MECHANIC-BASED REPROGRAMMING OF HEPATIC SELF-RENEWING TUMOR-INITIATING CELLS THROUGH DNMT1-INHIBITION
Authors: C. Raggi, V.M. Factor, S. Daekwan, G.C. Matthew, A. Holczbauer, J.U. Marquardt, S.S. Thorgeirsson
Journal: Journal of Hepatology (2013)
Mutations in AXIN2 cause colorectal cancer with defective mismatch repair by activating β-catenin/TCF signalling
Authors: Liu W, Dong X, Mai M, Seelan Rs, Taniguchi K, Krishnadath Kk, Halling Kc, Cunningham Jm, Boardman La, Qian C, Christensen E, Schmidt Ss, Roche Pc, Smith Di, Thibodeau Sn
Journal: Nature Genetics (2000)
In vivo gene transfer of parvalbumin improves diastolic function in aged rat hearts
Authors: U SCHMIDT, X ZHU, D LEBECHE, F HUQ, J GUERRERO, R HAJJAR
Journal: Cardiovascular Research (2004)

Diastolic dysfunction is a characteristic finding of the aged mammalian heart. Parvalbumin acts as a Ca2+ sink and enhances relaxation in skeletal muscle, and overexpression of parvalbumin in myocardium increased cardiac relaxation in vitro as well as in vivo. Therefore, the objective of this study is to test the hypothesis that in vivo gene transfer of parvalbumin will improve diastolic dysfunction in aged rat heart.We used adenovirus to transfer parvalbumin into two different rat models of aging: the Fischer 344 (F344) and the Fischer 344 x Brown Norway F1 hybrid (F344 x BN). Cardiac function was measured and compared after gene transfer.In vivo overexpression of parvalbumin in both rat aging models had no effect on systolic parameters but reduced left ventricular diastolic pressure and the time course of pressure decline. Overexpression of parvalbumin also improved the force frequency relationship in senescent rats.In vivo overexpression of parvalbumin improves diastolic dysfunction in two rat models of senescence, and this effect is independent of the rat strain investigated. The results show promise that gene therapy of parvalbumin may address the impaired Ca2+ homeostasis and diastolic dysfunction without an increase in energy expenditure.
Phosphorylation of p53 protein in A549 human pulmonary epithelial cells exposed to asbestos fibers.
Authors: Masato Matsuoka, Hideki Igisu, Yasuo Morimoto
Journal: Environmental Health Perspectives (2002)

We examined effects of asbestos exposure on the phosphorylation of p53 protein in human pulmonary epithelial type II cells (A549), which express wild-type p53. In cells exposed to two different types of asbestos, chrysotile (approximately 1-6% iron content) and crocidolite (approximately 27% iron content) fibers, at the doses of 1, 5, and 10 microg/cm2 for 24 hr, the levels of p53 phosphorylated at Ser15 and p53 protein were correlated with the dose. On a per-weight basis, chrysotile was more potent in inducing Ser15 phosphorylation and accumulation of p53 protein than was crocidolite. After exposure to 10 micro g/cm2 chrysotile, the levels of p53 phosphorylated at Ser15 and of p53 protein increased after 18 hr. Among serines in p53 protein immunoprecipitated from A549 cells treated with chrysotile, only Ser15 was markedly phosphorylated. In contrast, no clear phosphorylation was observed at Ser6, Ser9, Ser20, Ser37, Ser46, or Ser392. Blocking of the extracellular signal-regulated protein kinase pathway with U0126 or inhibition of p38 activity with SB203580 did not suppress chrysotile-induced Ser15 phosphorylation. On the other hand, treatment with wortmannin, an inhibitor of DNA-activated protein kinase and ataxia-telangiectasia mutated, suppressed both chrysotile-induced Ser15 phosphorylation and accumulation of p53 protein. Treatment with either catalase or N-acetylcysteine failed to suppress chrysotile-induced Ser15 phosphorylation, suggesting that reactive oxygen species do not play a major role in the phosphorylation of p53 protein. The present results show that asbestos, particularly chrysotile, induces phosphorylation of p53 protein at Ser15 in A549 cells depending on a DNA damage-signaling pathway.
Targeted transfection and expression of hepatitis B viral DNA in human hepatoma cells.
Authors: T J Liang, W J Makdisi, S Sun, K Hasegawa, Y Zhang, J R Wands, C H Wu, G Y Wu
Journal: Journal of Clinical Investigation (1993)

A soluble DNA carrier system consisting of an asialoglycoprotein covalently linked to poly-L-lysine was used to bind DNA and deliver hepatitis B virus (HBV) DNA constructs to asialoglycoprotein receptor-positive human hepatoma cells. 4 d after transfection with surface or core gene expression constructs, HBsAg and HBeAg in the media were measured to be 16 ng/ml and 32 U/ml per 10(7) cells, respectively. Antigen production was completely inhibited by the addition of an excess of asialoorosomucoid. On the other hand, asialoglycoprotein receptor-negative human hepatoma cells, SK-Hep1, did not produce any viral antigens under identical conditions after incubation with HBV DNA complexed to a conjugate composed of asialoorosomucoid and poly-L-lysine. Using a complete HBV genome construct, HBsAg and HBeAg levels reached 16 ng/ml and 16 U/ml per 10(7) cells, respectively. Northern blots revealed characteristic HBV RNA transcripts including 3.5-, 2.4-, and 2.1-kb fragments. Intracellular and extracellular HBV DNA sequences including relaxed circular, linear and single stranded forms were detected by Southern blot hybridization. Finally, 42-nm Dane particles purified from the spent cultures medium were visualized by electron microscopy. This study demonstrates that a targetable DNA carrier system can transfect HBV DNA in vitro resulting in the production of complete HBV virions.
The value of a university department of general practice.
Authors: I M Richardson
Journal: BMJ (1975)

I am proud to be an academic, a value judgement that I hope in some measure to substantiate in this paper, but I have no illusions about the continuing need to re-examine the case for medicine as a university subject.Especially now the credentials for clinical medical education remaining within the university system need to be reaffirmed, so let me briefly mention some views of the purpose of higher education. Purpose of university educationOver a century ago Cardinal Newman argued the case for a non-vocational institution of learning'; he likened the univer- sity to a mental gymnasium, in which, unhampered by practical considerations, the powers of the mind should be generally developed and, thus equipped with principles, be able to tackle problems of the future.Just 20 years ago in a notable essay on the university and medicine Himsworth2 opined that higher education was principally concerned with developing the power to form judgements.He argued that, whereas technological training aims to develop competence in the application of existing specialist knowledge and procedures, university education aims to equip people to deal with problems and situations as yet undefined.He added that, as the unknown cannot be particularised, this higher education must necessarily be broad and representative.A third view is that of Livingstone, the educationist, whose philosophy of the first rate strongly
Evaluation of the Circlecuf for Measurement of Human Blood Pressure
Authors: George P. Fulton, Donald I. Patt, Elmer B. Mode
Journal: New England Journal of Medicine (1954)

THE Circlecuf¶ (Fig. 1) is a new device for the indirect measurement of blood pressure in man. It differs in principle from similar instruments because of the distinctive property of a circumferential air bladder providing for the uniform application of pressure around the upper arm. Consequently, the Circlecuf is merely drawn over the arm like a sleeve and becomes "self-fitting" with inflation. This feature of the instrument makes it practical for self-measurement of blood pressure.Experimental ProceduresThe Circlecuf was compared with a standard "wrap-around" cuff for blood-pressure measurements during "rest" in a group of 48 normal college students (32 . . .