tbuckley/cabot-search huggingface dataset:
Chelating agents and cadmium toxicity: problems and prospects.
Authors: G F Nordberg
Journal: Environmental Health Perspectives (1984)

Symptoms and signs in humans after excessive exposure to cadmium usually involve the gastrointestinal tract after single oral intake, the lung after acute inhalation, and the kidney after long-term exposure. These organs are usually considered to be the "critical" organs, i.e., the organs most sensitive at a certain type of exposure. The type of Cd-related damage that is most common in humans is probably the renal toxicity after long-term exposure. Most animal experiments, including the most recently published ones, have involved study of gross toxicity and tissue distribution after injection of cadmium in acute experiments. The observations in the older literature that the influence of chelating agents on Cd distribution and excretion is confined to the early period after acute Cd exposure has been confirmed and extended, and the relationship to the time course of metallothionein synthesis has been demonstrated. Although the injection experiments concerning cadmium distribution, particularly those employing repeated exposure, may furnish information that can form a basis for speculation about long-term toxicity to the kidney, there is a lack of direct studies in animals of possible beneficial effects of chelating agents on renal toxicity of cadmium after prolonged exposure. Among the few studies reported, either an increased renal toxicity or a lack of influence on renal toxicity has been observed. The problems in finding a treatment scheme that can be beneficial for the renal toxicity resulting from long-term cadmium exposure thus remain; however, the prospects of finding such schemes in the future seem favorable in view of some of the recent observations.
UK public calls for legislation over living wills
Authors: C. Dyer
Journal: BMJ (1998)

Two out of three Britons favour an act of parliament making living wills legally binding on doctors, according to a survey by the polling company MORI for the Patients Association.

The poll of 1960 adults, published last week, found 65% in favour of legislation and only 21% against. The rest either answered “don't know” or wanted more information before deciding. Living wills (or advance directives) allow patients to express their wishes in advance about what treatment they will accept …
The ECG Made Easy
Authors: D. Warriner
Journal: BMJ (2009)

<h3>Objective</h3> The significance of the liver-microbiome axis has been increasingly recognised as a major modulator of autoimmunity. The aim of this study was to take advantage of a large well-defined corticosteroids treatment-naïve group of patients with autoimmune hepatitis (AIH) to rigorously characterise gut dysbiosis compared with healthy controls. <h3>Design</h3> We performed a cross-sectional study of individuals with AIH (n=91) and matched healthy controls (n=98) by 16S rRNA gene sequencing. An independent cohort of 28 patients and 34 controls was analysed to validate the results. All the patients were collected before corticosteroids therapy. <h3>Results</h3> The gut microbiome of steroid treatment-naïve AIH was characterised with lower alpha-diversity (Shannon and observed operational taxonomic units, both p&lt;0.01) and distinct overall microbial composition compared with healthy controls (p=0.002). Depletion of obligate anaerobes and expansion of potential pathobionts including <i>Veillonella</i> were associated with disease status. Of note, <i>Veillonella dispar</i>, the most strongly disease-associated taxa (p=8.85E–8), positively correlated with serum level of aspartate aminotransferase and liver inflammation. Furthermore, the combination of four patients with AIH-associated genera distinguished AIH from controls with an area under curves of approximately 0.8 in both exploration and validation cohorts. In addition, multiple predicted functional modules were altered in the AIH gut microbiome, including lipopolysaccharide biosynthesis as well as metabolism of amino acids that can be processed by bacteria to produce immunomodulatory metabolites. <h3>Conclusion</h3> Our study establishes compositional and functional alterations of gut microbiome in AIH and suggests the potential for using gut microbiota as non-invasive biomarkers to assess disease activity.
Identification of low HBV-DNA levels by nucleic acid amplification test (NAT) in blood donors
Authors: Stefano Dettori, Angela Candido, Loreta A. Kondili, Paola Chionne, Stefania Taffon, Domenico Genovese, Paola Iudicone, Michelina Miceli, Maria Rapicetta
Journal: Journal of Infection (2009)
MCP-1 is up-regulated in unstressed and stressed HO-1 knockout mice: Pathophysiologic correlates1
Authors: Siobhan T. Pittock, Suzanne M. Norby, Joseph P. Grande, Anthony J. Croatt, Gary D. Bren, Andrew D. Badley, Noel M. Caplice, Matthew D. Griffin, Karl A. Nath
Journal: Kidney International (2005)
A specific neutrophil elastase inhibitor (ONO-5046.Na) attenuates LPS-induced acute lung inflammation in the hamster
Authors: S Yasui, A Nagai, K Aoshiba, Y Ozawa, Y Kakuta, K Konno
Journal: European Respiratory Journal (1995)

We have examined the effect of ONO-5046.Na, a synthetic specific inhibitor of neutrophil elastase, on lipopolysaccharide (LPS)-induced acute lung inflammation. Syrian golden hamsters were injected intraperitoneally with either 300 mg.kg-1 of ONO-5046.Na or saline, 30 min before and 1 h after intratracheal administration of 0.1 mg.kg-1 LPS. Animals were sacrificed 2 and 24 h later and the wet-to-dry lung weight ratio (W/D) was determined. Bronchoalveolar lavage (BAL) was performed, and tissue sections were examined histologically. The effect of ONO-5046.Na on migration of isolated neutrophils was determined. W/D was not significantly different at 2 h, but was increased at 24 h in the LPS-treated animals. This increase was attenuated in the LPS-treated animals injected with ONO-5046.Na. Analysis of BAL fluid revealed that both at 2 and 24 h after LPS administration the total cell number and neutrophil number, albumin concentration, and elastase-like activity were significantly lower in the LPS-treated animals injected with ONO-5046.Na than in those given LPS alone. Histological examination of the lungs of the animals treated with LPS alone showed intra-alveolar haemorrhages and inflammatory cell infiltration 24 h after LPS administration, whereas the lungs of the LPS-treated ONO-5046.Na injected animals were only sparsely infiltrated by inflammatory cells, as indicated by the inflammation score.(ABSTRACT TRUNCATED AT 250 WORDS)
Suppression of angiogenesis and tumor growth by adenoviral-mediated gene transfer of pigment epithelium-derived factor
Authors: Lin Wang, Volker Schmitz, Alberto Perez-Mediavilla, Iñigo Izal, Jesus Prieto, Cheng Qian
Journal: Molecular Therapy (2003)

Pigment epithelium-derived factor (PEDF) was identified from retinal pigment epithelial cells and has been shown to display neurotrophic effects. In addition it has been found to induce a potent inhibition of angiogenesis. In this study we have explored whether overexpression of PEDF by a gene transfer approach can block tumor angiogenesis and reduce tumor growth. We found that cells infected with an adenovirus encoding PEDF under the control of the CMV promoter (AdPEDF) secreted PEDF protein into the medium that exhibited strong inhibitory effects on migration and tube formation of endothelial cells cultured in the presence of vascular endothelial growth factor. Moreover, the systemic administration of AdPEDF was able to inhibit angiogenesis in Matrigel assay in vivo, and treatment with this adenovirus of established hepatocellular carcinoma tumor in nude mice resulted in strong suppression of tumor growth. This anti-tumor effect could also be seen in a mouse lung carcinoma model by systemic administration of vector. In that model, treatment of tumor by intratumoral injection of AdPEDF also caused significant inhibition of tumor growth. The anti-tumor effect was related to a decrease in density of microvessels in tumors after treatment with AdPEDF. These data suggest that the antiangiogenic properties of PEDF can be exploited to inhibit the establishment of tumor neovasculature and reduce tumor growth.
Contributions of societal and geographical environments to "chronic Lyme disease": the psychopathogenesis and aporology of a new "medically unexplained symptoms" syndrome.
Authors: Leonard H Sigal, Afton L Hassett
Journal: Environmental Health Perspectives (2002)

Lyme disease is a relatively well-described infectious disease with multisystem manifestations. Because of confusion over conflicting reports, anxiety related to vulnerability to disease, and sensationalized and inaccurate lay media coverage, a new syndrome, "chronic Lyme disease," has become established. Chronic Lyme disease is the most recent in a continuing series of "medically unexplained symptoms" syndromes. These syndromes, such as fibromyalgia, chronic fatigue syndrome, and multiple chemical sensitivity, meet the need for a societally and morally acceptable explanation for ill-defined symptoms in the absence of objective physical and laboratory findings. We describe factors involved in the psychopathogenesis of chronic Lyme disease and focus on the confusion and insecurity these patients feel, which gives rise to an inability to adequately formulate and articulate their health concerns and to deal adequately with their medical needs, a state of disorganization termed aporia.
Interaction of Cardiopulmonary and Somatic Reflexes in Humans
Authors: John L. Walker, Francois M. Abboud, Allyn L. Mark, Marc D. Thames
Journal: Journal of Clinical Investigation (1980)

Activation of cardiopulmonary receptors with vagal afferents results predominantly in reflex inhibition of efferent sympathetic activity, whereas activation of somatic receptors reflexly increases sympathetic activity to the heart and circulation. Previous studies in experimental animals indicate that there is an important interaction between these excitatory and inhibitory reflexes in the control of the renal circulation.
Long QT Syndrome–Associated Mutations in Intrauterine Fetal Death
Authors: Lia Crotti, David J. Tester, Wendy M. White, Daniel C. Bartos, Roberto Insolia, Alessandra Besana, Jennifer D. Kunic, Melissa L. Will, Ellyn J. Velasco, Jennifer J. Bair, Alice Ghidoni, Irene Cetin, Daniel L. Van Dyke, Myra J. Wick, Brian Brost, Brian P. Delisle, Fabio Facchinetti, Alfred L. George, Peter J. Schwartz, Michael J. Ackerman
Journal: JAMA (2013)

Intrauterine fetal death or stillbirth occurs in approximately 1 out of every 160 pregnancies and accounts for 50% of all perinatal deaths. Postmortem evaluation fails to elucidate an underlying cause in many cases. Long QT syndrome (LQTS) may contribute to this problem.To determine the spectrum and prevalence of mutations in the 3 most common LQTS susceptible genes (KCNQ1, KCNH2, and SCN5A) for a cohort of unexplained cases.In this case series, retrospective postmortem genetic testing was conducted on a convenience sample of 91 unexplained intrauterine fetal deaths (mean [SD] estimated gestational age at fetal death, 26.3 [8.7] weeks) that were collected from 2006-2012 by the Mayo Clinic, Rochester, Minnesota, or the Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. More than 1300 ostensibly healthy individuals served as controls. In addition, publicly available exome databases were assessed for the general population frequency of identified genetic variants.Comprehensive mutational analyses of KCNQ1 (KV7.1, LQTS type 1), KCNH2 (HERG/KV11.1, LQTS type 2), and SCN5A (NaV1.5, LQTS type 3) were performed using denaturing high-performance liquid chromatography and direct DNA sequencing on genomic DNA extracted from decedent tissue. Functional analyses of novel mutations were performed using heterologous expression and patch-clamp recording.The 3 putative LQTS susceptibility missense mutations (KCNQ1, p.A283T; KCNQ1, p.R397W; and KCNH2 [1b], p.R25W), with a heterozygous frequency of less than 0.05% in more than 10 000 publicly available exomes and absent in more than 1000 ethnically similar control patients, were discovered in 3 intrauterine fetal deaths (3.3% [95% CI, 0.68%-9.3%]). Both KV7.1-A283T (16-week male) and KV7.1-R397W (16-week female) mutations were associated with marked KV7.1 loss-of-function consistent with in utero LQTS type 1, whereas the HERG1b-R25W mutation (33.2-week male) exhibited a loss of function consistent with in utero LQTS type 2. In addition, 5 intrauterine fetal deaths hosted SCN5A rare nonsynonymous genetic variants (p.T220I, p.R1193Q, involving 2 cases, and p.P2006A, involving 2 cases) that conferred in vitro electrophysiological characteristics consistent with potentially proarrhythmic phenotypes.In this molecular genetic evaluation of 91 cases of intrauterine fetal death, missense mutations associated with LQTS susceptibility were discovered in 3 cases (3.3%) and overall, genetic variants leading to dysfunctional LQTS-associated ion channels in vitro were discovered in 8 cases (8.8%). These preliminary findings may provide insights into mechanisms of some cases of stillbirth.
Super-Resolution Dissection of Coordinated Events during Malaria Parasite Invasion of the Human Erythrocyte
Authors: David T. Riglar, Dave Richard, Danny W. Wilson, Michelle J. Boyle, Chaitali Dekiwadia, Lynne Turnbull, Fiona Angrisano, Danushka S. Marapana, Kelly L. Rogers, Cynthia B. Whitchurch, James G. Beeson, Alan F. Cowman, Stuart A. Ralph, Jake Baum
Journal: Cell Host & Microbe (2011)
THE MEDIATOR OF CELLULAR IMMUNITY
Authors: D. D. McGregor, Pamela S. Logie
Journal: The Journal of Experimental Medicine (1974)

Peritoneal exudates induced in rats infected with Listeria monocytogenes contain sensitized lymphocytes which can protect normal recipients against a Listeria challenge. The protective cells arise in lymphoid tissue remote from the peritoneal cavity. Those formed in the caudal lymph nodes of subcutaneously infected rats are delivered to the thoracic duct and hence to the blood from where they are drawn into exudates. Immunoblasts are the most immature members of this protective cell population and they alone among the cells in central lymph localize in exudates induced by killed bacteria. They do so in substantial numbers, but only during the early postinduction period. The "homing" of immunoblasts to inflammatory foci seems to be determined by a general property of the cells rather than their immunological commitment; however, the intense inflammation induced by organisms to which an animal has been specifically sensitized is accompanied by an exuberant influx of immunoblasts into lesions. Sensitized lymphocytes that extravasate in the inflamed peritoneal may generate more of their own kind, but some give rise to small lymphocytes. The latter also have protective properties and, with time, comprise an increasing portion of the protective cell population. The results imply that the tissue disposition of sensitized lymphocytes in the body is determined by a complementary relationship between blood-borne immunoblasts and vascular endothelium in inflamed tissue. The results also provide a plausible explanation for the concentration of sensitized lymphocytes at sites of microbial implantation where they alone would be expected to collaborate with monocyte-derived macrophages in the control of infection.
Long-term results of a randomized phase 3 trial comparing idarubicin and daunorubicin in younger patients with acute myeloid leukaemia
Authors: C Récher, M C Béné, B Lioure, A Pigneux, N Vey, J Delaunay, I Luquet, M Hunault, D Guyotat, D Bouscary, N Fegueux, E Jourdan, S Lissandre, M Escoffre-Barbe, C Bonmati, E Randriamalala, R Guièze, M Ojeda-Uribe, F Dreyfus, J L Harousseau, J Y Cahn, N Ifrah, P Guardiola
Journal: Leukemia (2013)
TCT-107 TAVI in patients with bicuspid aortic stenosis - preliminary results from multicenter registry
Authors: Janusz Kochman, Zenon Huczek, Piotr Ścisło, Maciej Dabrowski, Zbigniew Chmielak, Piotr Szymański, Adam Witkowski, Radosław Parma, Andrzej Ochala, Piotr Chodór, Krzysztof Wilczek, Krzysztof W. Reczuch, Piotr Kubler, Bartosz Rymuza, Lukasz Koltowski, Anna Ścibisz, Radosław Wilimski, Grzegorz Opolski
Journal: Journal of the American College of Cardiology (2013)
Older Age — Not a Barrier to Cancer Treatment
Authors: Hyman Bernard Muss
Journal: New England Journal of Medicine (2001)

More than half of all new cancers in the United States occur in patients 65 years of age or older.1 The incidence of cancer in this age group is 11 times that in the population under 65 (2261 per 100,000 population, as compared with 207 per 100,000 population), and more than half of all deaths due to cancer occur in patients 65 or older. This age group accounts for two thirds to three fourths of colorectal cancers and at least three fourths of deaths from colorectal cancer. The increasing longevity of our population makes these statistics especially sobering; by 2030 . . .
Clinical Lectures Delivered at University College Hospital
Authors: J. Erichsen
Journal: BMJ (1860)

LECTURE II.O()N EPITHELIOMA.GENTLEIIEN,-WO have had under our care during the last few weeks several cases of epithelioma of the lip, tongue, fauces, and penis.I will to-day direct your attention to the nature of this disease, as developed under our observation in these cases.TIle case to which I shall particularly refer, illus- trates in a marked manner the nature, course, and distinctive characters of the disease.It is that of a soldier, sent up to me at this Hospital from Aldershot, a few weeks since, with the following history.He had served twenty-one years in the army, during a great part of which time he had been stationed in hot clirmiates, and whilst there had suffered from the ordin.ary tropical diseases, as dysentery, etc.; otherwise, his health appeared to have been excellent.On admission, he was sallow, and somewhat emaciated; but otherwise in tolerably good healtlh, and in excellent spirits, quite prepared, and indeed anxious, to uindergo any operation which might be deemed advisable.About two years ago, he observed an ulcer on the tongue, about midway between the apex and base on the left side.This ulcer, small at first, yielded to no treatment that had been applied to it, and gradually increased in size and depth up to the present time.It was now irregular in shape, with induration of the tongue-substance beneath and around, and it was hollowed out, so that it would contain half a walnut.The patient never smoked, but recollected that he had a decayed and ragged tooth on the left side of the jaw at about the time of the appearance of the ulcer.In addition, there was on the left side of the neck a swelling, of the size of a goose's egg, first noticed about seven weeks before admission, firm, adhe- rent, passing beneath the sterno-mastoid, and extending back to the trapezius on the sheath of the great vessels of the neck, in close connection with the carotid artery.There was also on the right side and in the anterior half of the submaxillary region, a second mass, of similar character, about as large as a
Study to predict which elderly patients will fall shows difficulties in deriving and validating a model
Authors: D. G Altman
Journal: BMJ (1997)

More widespread public debate on rationing is essentialEditor-We find it significant that none of the clinicians who contributed to the conference "Rationing in the NHS: Time to Get Real" signed the open letter to Frank Dobson. 1 In the letter, rationing is defined as occurring when not all health services can be provided to everybody who might benefit from them, a definition so broad that it can be said always to have existed.Yet most British clinicians would not recognise the examples given as rationing.A young woman with high cholesterol as a single risk factor for coronary heart disease may be "denied" drug treatment and given dietary advice instead simply because the risks of side effects outweigh the marginal benefit; this is rational, not rationing.Again, "denying" magnetic resonance imaging for uncomplicated migraine in a young person has nothing to do with cost: the risks of iatrogenic anxiety and distress are far greater than any possible benefit from such intervention.The authors do the cause of so called smart rationing a disservice by these examples.This debate is too important to be "dumbed down" in this way.Whenever rationing is discussed there is a tension between those whose professional discipline (health economics, medical ethics, or policy analysis) allows them to work with broad underlying principles and those who are constantly brought face to face with the limitations of these principles through daily contact with patients.The former are much more likely to believe that it is possible and appropriate to base all rationing decisions on a series of well argued principles.Life for the latter is far messier: it is often impossible to apply broad principle to individual cases, let alone find a "currency of comparison" 2 that will enable the claims of, for example, a dying older person on an understaffed geriatric ward to be ranked against those of a patient with multiple sclerosis who might benefit from interferon beta.Struggling to make these sorts of comparisons is painful; the examples given in the open letter tax no one and thereby offer false hope of easy solutions.It is because the choices are difficult that more widespread public debate is essential.Only through such a debate can we all, as citizens, realise what is happening to the NHS, consider if that is the NHS that we want, and decide how much of our taxes an NHS worthy of the name deserves.
Breast Metastasis as the First Clinical Manifestation of Ileal Neuroendocrine Tumor. A Challenging Diagnosis with Relevant Clinical Implications
Authors: Stefano La Rosa, Selenia Casnedi, Roberta Maragliano, Gilles Goyault, Jean-Christophe Weber, Bernard Louis, Elvire Schlund, Fausto Sessa
Journal: Endocrine Pathology (2015)
Non-steroidal anti-inflammatory drugs and oral lichenoid reactions.
Authors: J Hamburger, A J Potts
Journal: BMJ (1983)

behaves differently from that in other parts of Britain.Seasonal trends have important implications in the planning of therapeutic trials and may help to identify environmental trigger factors in childhood asthma.A further study of national data is warranted.We thank the Hospital Activity Analysis and statistical staff of the South East Thames region for their help.