tbuckley/cabot-search huggingface dataset:
M2 Bone mineral density changes in patients in the severe asthma clinic on oral corticosteroids
Authors: HGT Brice, DJ Wilkinson, R Daly, G Tavernier, RM Niven
Journal: Thorax (2013)

<h3>Objectives</h3> How effective are bone sparing medications (BSM)? Is bone mineral density (BMD) change related to other clinical variables? <h3>Background</h3> Regular oral corticosteroids (OCSs) cause several side effects including BMD loss, occurring at varying rates in different patients. <h3>Method</h3> Patients attending the specialist severe asthma clinic with two available bone densitometry scans since 2007 were identified and the hip and spine BMD change calculated. The cumulative steroid dose (pre and post first scan) and risk factors for osteoporosis were also recorded, including current bone protection. <h3>Results</h3> Yearly hip BMD change and average cumulative steroid dose did not correlate for all patients (n = 59 Pearson = -0.083 p0.53) or for patients not on BSM (n = 27 Pearson = -0.26 p0.19). Yearly spine BMD change also did not correlate for all patients (n = 59 Pearson = 0.012 p0.19) or for patients not on BSM (n = 27 Pearson = -0.22 p0.28). Body mass index (BMI) predicted a higher t-score on the first DXA scan; hip (n = 59) (Pearson = 0.59 p &lt; 0.001) and spine (n = 59) (Pearson = 0.53 p &lt; 0.001). However between scans, although not statistically significant, a higher BMI correlated with a greater decrease in BMD. Analysing the effect of BSM (see figure: spine BMD change) showed spine BMD improved over time for patients taking a bisphosphonate (n = 59) p0.029. However when compared to patients on calcium/vitamin D or no BSM, patients on a bisphosphonate and calcium/vitamin D had a greater improvement ( + 1.5% average BMD change, p0.039) than patients on a bisphosphonate alone ( + 1.19% average BMD change, p0.21). <h3>Conclusion</h3> OCS use causes a decrease in BMD which is greater in the spine. In this small population, cumulative steroid dose did not correlate to BMD change over time. Bisphosphonate and calcium/vitamin D demonstrated benefit in spine BMD between scans, whereas the benefit of bisphosphonate alone was not statistically significant.
Cost-effectiveness of peginterferon alpha-2b plus ribavirin compared with interferon alpha-2b plus ribavirin for initial treatment of chronic hepatitis C
Authors: Uwe Siebert, Gaby Sroczynski, Siegbert Rossol, Juergen Wasem, Ulrike Ravens-Sieberer, Baerbel M. Kurth, Michael P. Manns, John G. Hutchison, John B. Wong
Journal: Journal of Hepatology (2002)
P4-01-11: Autocrine Human Growth Hormone (hGH) Reduces the Sensitivity of Breast Cancer Cells to Treatment with Tamoxifen and Fulvestrant.
Authors: JK Perry, H Chen, NM Bougen, D-X Liu, PE Lobie
Journal: Cancer Research (2011)

Abstract Despite recent advances in breast cancer treatment regimes, intrinsic or development of resistance to conventional breast cancer therapies is still a significant clinical challenge. Expression of growth factors by tumour cells has been proposed as one mechanism for developing resistance to radiotherapy and chemotherapeutic agents. The growth hormone/insulin-like growth factor-1 axis is emerging as an important mediator of tumour development in human breast cancer. Recent studies have demonstrated that humans with growth hormone receptor deficiency are protected from developing cancer. Studies investigating human growth hormone (hGH) expression in human breast cancer have demonstrated that hGH expression is associated with specific histopathological features and survival outcomes for patients. Increased hGH expression is significantly associated with lymph node metastasis, tumour stage, proliferative index, worse relapse free survival and reduced overall survival in mammary carcinoma. In recent studies we have demonstrated that autocrine hGH promotes cell proliferation, cell survival and oncogenicity of human mammary carcinoma cells, enhancing anchorage independent cell growth, and supporting tumour formation in immunodeficient mice. Autocrine hGH also promotes mammary carcinoma cell migration/invasion and epithelial to mesenchymal transition and tumour vascularisation in xenograft studies. In this study we investigated whether autocrine hGH promotes resistance to anti-estrogen therapeutic drugs, sensitivity to tamoxifen and fulvestrent using the human breast cancer cell lines MCF-7, T47D and BT474. Stable transfection with an expression vector containing the hGH gene enhanced MCF-7, T47D and BT474 cell viability, total cell number and anchorage independent growth following treatment with tamoxifen or fulvestrant when compared to control transfected cells. Conversely, treatment of BT474 cells with an hGH receptor antagonist (B2036), increased BT474 cell sensitivity to treatment with tamoxifen or fulvestrant. Using an estrogen response element (ERE) luciferase assay, we observed that autocrine hGH enhanced basal estrogen receptor (ER)-mediated transcriptional activity. Our results demonstrate that forced expression of hGH in mammary carcinoma cells enhances ER-mediated signal tranduction and promotes resistance to tamoxifen and fulvestrant, while functional antagnonism of hGH increased cell sensitivity. Consequently, antagonism of the hGH receptor may help maintain sensitivity to anti-estrogen therapy and improve the prognosis of patients with hormone sensitive breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-01-11.
Acute Coronary Findings at Autopsy in Heart Failure Patients With Sudden Death
Authors: Barry F. Uretsky, Kristian Thygesen, Paul W. Armstrong, John G. Cleland, John D. Horowitz, Barry M. Massie, Milton Packer, Philip A. Poole-Wilson, Lars Ryden
Journal: Circulation (2000)

Background —Sudden unexpected death frequently occurs in chronic heart failure. The importance of acute coronary events in triggering sudden death (SD) is unclear. Methods and Results —We evaluated at autopsy the prevalence of acute coronary findings (coronary thrombus, ruptured plaque, or myocardial infarction [MI]) and their relation to SD. Autopsy results in 171 patients in the randomized ATLAS trial were reviewed. The prevalence of acute coronary findings was 33%: in 54% of patients with significant coronary artery disease (CAD) who died suddenly, 32% who died of myocardial failure, but in non-CAD patients, they were present in only 5% and 10% respectively. The percentage of patients classified as dying of MI was 28% in the autopsy group versus 4% in the nonautopsied group ( P &lt;0.0001). Of the autopsied group with acute MI, 97% (31 of 32 patients) with SD and 40% (6 of 15 patients) with myocardial failure did not have the MI diagnosed during life. When undiagnosed MI was classified as “sudden unexpected” or “myocardial failure” from clinical information only, the distribution of death causes was similar in the autopsy and nonautopsied groups. Conclusions —Acute coronary findings are frequent and usually not clinically diagnosed in heart failure patients with CAD, particularly in those dying suddenly, suggesting the importance of acute coronary events as a trigger for SD in this setting.
UNILATERAL SYMPTOMS IN MENINGITIS
Authors: ABRAHAM LEVINSON
Journal: JAMA (1928)

The classic signs of meningitis, such as the Brudzinski, Kernig and Babinski, are usually bilateral. When unilateral symptoms occur, one is often inclined to rule out the presence of meningitis and to think of brain abscess, brain tumor, encephalitis or poliomyelitis.  I have encountered cases that manifested unilateral Brudzinski, Kernig and Babinski signs, in which the character of the cerebrospinal fluid, and, in some instances, the necropsy, proved the presence of a meningitis, either tuberculous, pneumococcic or meningococcic. This shows that, although the classic signs of meningitis are usually bilateral, unilateral manifestations of meningeal irritation do not exclude the diagnosis of meningitis. This knowledge is particularly important in the diagnosis of meningococcic meningitis, in which reliance on unilateral symptoms to exclude meningitis may lead to delay in the removal of cerebrospinal fluid and the administration of serum with consequent disastrous results.  Unilateral manifestations during the course of meningitis may be
The judge makes hospital rounds
Authors: G Dunea
Journal: BMJ (1994)

It is 9 am and the doctors in starched white coats are waiting in the lobby for the judge to make his ward rounds at the hospital. The judge arrives and parks his big Mercedes in his reserved place. He then puts on his sterile wig and a disposable black robe. The doctors all stand up.

“Good morning, your honour,” say the doctors.

“Good morning, boys,” replies the judge. “What do you have for me today?”

“There is a 23 year old woman with a failing placenta, sir. We believe that if the baby is not delivered at once it will die or become mentally retarded. The mother refuses to have a …
Changes in plasma 1,25 and 24,25-dihydroxyvitamin D after renal transplantation in children
Authors: Michèle Garabedian, Caroline Silve, David Levy-Bentolila, Agnès Bourdeau, André Ulmann, T. Minh Nguyen, Michèle Lieberherr, Michel Broyer, Sonia Balsan
Journal: Kidney International (1981)
Infectious Mononucleosis In an Elderly Farmer
Authors: J. H. Ransom
Journal: JAMA (1966)

To the Editor:—  When the letter of William P. Corr, MD, concerning infectious mononucleosis in the aged appeared ( 195 :1158, 1966) I had just hospitalized a 72-year-old farmer with the same disease.  The patient had noted general malaise, dry cough, fever, chills, and a gradually increasing sore throat for seven to ten days before admission to the hospital. When seen March 24, 1966, his body temperature was 101.6 F, the blood pressure was 110/80 mm Hg, and the pulse rate was 100 beats per minute. His throat was beefy red, with markedly enlarged tonsils which were covered with grayish-white exudates. The posterior cervical lymph nodes were markedly enlarged. His spleen and liver were not palpable, but he did have a few scattered rales in both lung fields.  His white blood cell count (WBC) was 17,400/cu mm; the hemoglobin level was 13.5 gm/100 cc; the hematocrit reading, 42%. The differential WBC
THERAPEUTICS OF KOLA.
Authors: CHARLES C. YARBROUGH
Journal: JAMA (1899)

In presenting this paper, I do not claim to offer anything strikingly new, but it is my purpose to direct anew your attention for thoughtful consideration to one of the most valuable drugs of our newer materia medica. This drug has been known to the profession of this country now for nearly twenty years, but notwithstanding this fact, its medicinal virtues are not generally known among general practitioners, and few of those who use it fully appreciate its capabilities. The drug to which I refer is kola—the seed, or nut, of<i>Sterculia acuminata</i>. Kola, being, as is now fully established, a general tonic stimulant acting primarily on the cerebrospinal centers, has a wide field of usefulness. Its stimulation is peculiar in that it is tonic in effect and does not leave the secondary depression and "all-gone" feeling which, like the after-effects of the ordinary stimulants, is calculated to gradually develop
Dependence of T Cell Antigen Recognition on the Dimensions of an Accessory Receptor–Ligand Complex
Authors: Martin K. Wild, Anna Cambiaggi, Marion H. Brown, Elizabeth A. Davies, Hiroshi Ohno, Takashi Saito, P. Anton van der Merwe
Journal: The Journal of Experimental Medicine (1999)

The T cell antigen receptor (TCR) and its ligand peptide–major histocompatibility complex (MHC) are small (∼7 nm) compared with other abundant cell surface molecules such as integrins, CD43, and CD45 (23–50 nm). We have proposed that molecules at the T cell/antigen-presenting cell (APC) interface segregate according to size, with small “accessory” molecules (e.g., CD2, CD4, CD8, CD28, and CD154) contributing to the formation of a close-contact zone, within which the TCR engages peptide–MHC, and from which large molecules are excluded (Davis, S.J., and P.A. van der Merwe. 1996. Immunol. Today. 17:177–187). One prediction of this model is that increasing the size of these small accessory molecules will disrupt their function. Here, we test this prediction by varying the dimensions of the CD2 ligand, CD48, and examining how this affects T cell antigen recognition. Although the interaction of CD2 on T cells with wild-type or shortened forms of CD48 on APCs enhances T cell antigen recognition, the interaction of CD2 with elongated forms of CD48 is strongly inhibitory. Further experiments indicated that elongation of the CD2/CD48 complex inhibited TCR engagement of peptide–MHC, presumably by preventing the formation of sufficiently intimate contacts at the T cell/APC interface. These findings demonstrate the importance of small size in CD2/CD48 function, and support the hypothesis that T cell antigen recognition requires segregation of cell surface molecules according to size.
Measurement of desarginine fibrinopeptide B in human blood.
Authors: T Eckhardt, H L Nossel, A Hurlet-Jensen, K S La Gamma, J Owen, M Auerbach
Journal: Journal of Clinical Investigation (1981)

Thrombin converts fibrinogen to fibrin in two steps. First fibrinopeptide A and fibrin I are formed and then fibrinopeptide B (B beta 1-14) and fibrin II. Since it is postulated that fibrin II is important in the genesis of thrombosis, it is of interest to measure fibrinopeptide B in peripheral blood samples. Previous difficulties in interpreting fibrinopeptide B immunoreactivity in plasma resulted from crossreaction of fibrinogen and of plasmin digest peptides B beta 1-42 and B beta 1-21 and from rapid loss of fibrinopeptide B immunoreactivity resulting from cleavage of arginine 14 by blood carboxypeptidase B. We have obviated these difficulties by removing fibrinogen from plasma by precipitation with ethanol and peptides B beta 1-21 and B beta 1-42 by adsorption on bentonite. Fibrinopeptide B is then converted to a desarginine fibrinopeptide B, which is measured in a new specific assay. Studies of the kinetics of fibrinopeptide cleavage showed that when whole blood was allowed to clot in vitro, fibrinopeptide A was cleaved more rapidly than fibrinopeptide B. In 18 patients on an acute care medical ward, desarginine fibrinopeptide B levels were lower than fibrinopeptide A levels and did not correlate with the levels of fibrinopeptide A or B beta 1-42. Desarginine fibrinopeptide B levels were less than 1 pmol/ml in all but two patients. In six patients receiving intraamniotic infusions of hypertonic saline to induce abortion, desarginine fibrinopeptide B levels increased 10-fold from the preinfusion mean level of 0.4 pmol/ml and then decreased. The pattern of changes resembled that of the fibrinopeptide A levels rather than of the B beta 1-42 levels. On the basis of these data it is suggested that plasma desarginine fibrinopeptide B levels reflect fibrin II formation in vivo.
Localizing Functioning Thyroid Following Total Thyroidectomy by Use of a Combination Scanning Technique
Authors: MARTHA SCHMIDT, DOUGLAS M. KLOTCH, JOHN LOR??
Journal: Clinical Nuclear Medicine (1980)

A technique is described using l-131-sodium iodine and Tc-99m-sodium pertechnetate for localizing functioning thyroid tissue in the neck following total thyroidectomy. The procedure consists of obtaining a 1-131 thyroid scan. If functioning thyroid tissue is found, it can be localized by means of skin markers as well as a swallow using Tc-99m-sodium pertechnetate. The procedure is safe, simple, and cost efficient and provides a means of localizing functioning thyroid that may influence subsequent therapy.
Description of a Nonselective Cation Current in Human Atrium
Authors: William J. Crumb, John D. Pigott, Craig W. Clarkson
Journal: Circulation Research (1995)

Abstract Ion currents were examined in isolated human atrial myocytes by using the whole-cell patch-clamp technique. When currents were recorded with a K + -containing pipette solution, depolarizing voltage pulses elicited a rapidly activating outward current that decayed to an apparent steady state. Exposure of cells to 10 mmol/L 4-aminopyridine markedly reduced current amplitude; however, a rapidly activating current that was ≈30% of the steady state current amplitude remained. When pipette K + was replaced with Cs + , a similar rapidly activating current that reversed polarity at ≈0 mV was recorded. This current was seen in 100% of the cells tested from 17 different hearts (n=142), and its amplitude was ≈40% of the amplitude of the steady state current recorded in the presence of pipette K + . The current amplitude was not significantly different in cells isolated from adult (6.31±1.35 pA/pF, n=8) and pediatric (5.54±1.04 pA/pF, n=9) hearts. Studies designed to determine the charge-carrying species indicated that changes in bath Cl − concentration had no effect on either the amplitude or the reversal potential of this current, whereas removal of pipette Cs + and bath Na + dramatically reduced this current. In addition, this current was not modulated by either isoproterenol (1 μmol/L, 22°C) or cell swelling. This study provides the first description of a nonselective cation current in human atrial myocytes, which may play an important role in repolarization in human atria.
Research governance: Research governance approval is putting people off research
Authors: Niall Galbraith, Carol Hawley, Valerie De-Souza
Journal: BMJ (2006)

Editor—The BMJ has highlighted the bureaucratic burden placed on health researchers by the research governance approval process. 1 2 Our own study sought only to interview health professionals in 12 trusts about giving advice, with a few patient telephone interviews, but the process of seeking approval from one research and development consortium delayed our project by 11 weeks.

If this sort of approval process does not put …
Unstable Angina Pectoris
Authors: RISTEARD MULCAHY
Journal: Annals of Internal Medicine (1983)

Letters and Corrections1 May 1983Unstable Angina PectorisRISTEARD MULCAHY, M.D.RISTEARD MULCAHY, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-98-5-670_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Brown and Dodge (1) state in their editorial on unstable angina that our conclusions (2) about the benefits of a conservative approach to the management of unstable angina are unwarranted due to lack of comparability with the accepted definition of this syndrome, because we stated that 77 of our patients remained "free of significant symptoms" during the follow-up period.This quotation was an error in our paper. It should have read "free of significant complications." Twenty-eight of our 77 patients without complications had angina of effort during some or all of the follow-up period. All our patients...References1. BROWNDODGE BH. Unstable angina: guidelines for therapy based on the last decade of clinical observations [Editorial]. Ann Intern Med. 1982;97:921-3. LinkGoogle Scholar2. MULCAHYDALYGRAHAM RLI. Unstable angina: natural history and determinants of prognosis. Am J Cardiol. 1981;48:525-8. CrossrefMedlineGoogle Scholar3. KANNEL W. The Framingham Study: An Epidemiological Investigation of Cardiovascular Disease. Hyattsville, Maryland: National Center for Health Statistics; 1974; DHEW Publication No. 74-599. Google Scholar4. . Unstable angina pectoris. National cooperative study group to compare medical and surgical therapy: I. Report of protocol in patient population. Am J Cardiol. 1976;37:896-902. Google Scholar5. DE FEYTERMAJIDWARDEHROOS PPRJ. Observations on unstable angina pectoris with particular respect to management. Am Heart J. 1979;98:431-9. CrossrefMedlineGoogle Scholar6. PACKERFRISHMAN MW. Verapamil therapy for stable and unstable angina pectoris: calcium channel antagonists in perspective. Am J Cardiol. 1982;50:881-5. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1983Volume 98, Issue 5_Part_1Page: 670-670KeywordsAnginaUnstable angina Issue Published: 1 May 1983 PDF DownloadLoading ...
Absorption, Elimination and Excretion of Orally Administered Vitamin B<sub>12</sub>in Normal Subjects and in Patients with Pernicious Anemia
Authors: Myron Pollycove, Leonard Apt, Mary Pratt, Joan Donovan, Jack Sullivan
Journal: New England Journal of Medicine (1956)

A SELECTIVE defect of Vitamin B12 absorption is pathogenic of Addisonian pernicious anemia. The parenteral administration of crystalline vitamin B12 in daily doses of 1 to 5 microgm. to patients with pernicious anemia in relapse has been shown to produce a characteristic, optimal hematopoietic response.1 2 3 4 5 Oral administration of crystalline vitamin B12 in daily doses of 5 microgm. to patients with pernicious anemia in relapse produces little or no hematopoietic response unless a source of intrinsic factor is administered either simultaneously or within six hours.6 , 7 This persistent inability of patients with Addisonian pernicious anemia to absorb from the . . .
Expression of IL-5 alters bone metabolism and induces ossification of the spleen in transgenic mice
Authors: MiMi P. Macias, Lorraine A. Fitzpatrick, Ina Brenneise, Michael P. McGarry, James J. Lee, Nancy A. Lee
Journal: Journal of Clinical Investigation (2001)

We have developed a transgenic mouse line, NJ.1638, which expresses high levels of IL-5 from T cells, with profound hematological consequences. Eosinophils comprise more than 60% of circulating white blood cells in these animals, with the total peripheral white blood cell counts increasing more than 40-fold relative to wild-type littermates. This extraordinary proliferative capacity is sustained by expanded sites of extramedullary hematopoiesis and is accompanied by multifocal, ectopic bone formation in the spleen. Histology of the splenic nodules revealed the presence of osteoid matrices and osteocytes trapped within mineralized trabecular plates. In addition, polarized light microscopy of calcified tissue sections revealed both woven bone and areas of organized lamellar bone. Morphometric assessments demonstrated that both the growth and mineralization of splenic bone occurred at rates nearly an order of magnitude higher than in skeletal bone. Skeletal bone metabolic parameters were also perturbed. We also observed heterotopic ossification of the spleen and perturbation of skeletal bone homeostasis following adoptive engraftment of transgenic marrow to wild-type recipients. These data suggest that IL-5 overexpression mediates bone formation through the mobilization of marrow-derived osteogenic progenitors and/or the inhibition of recruited osteoclasts.
Retargeting mobile group II introns to repair mutant genes
Authors: John Patrick Jones, Monique N. Kierlin, Robert G. Coon, Jiri Perutka, Alan M. Lambowitz, Bruce A. Sullenger
Journal: Molecular Therapy (2005)

Retroposable elements such as retroviral and lentiviral vectors have been employed for many gene therapy applications. Unfortunately, such gene transfer vectors integrate genes into many different DNA sequences and unintended integration of the vector near a growth-promoting gene can engender pathological consequences. For example, retroviral vector-mediated gene transfer induced leukemia in 2 of 11 children treated for severe combined immunodeficiency, raising significant safety issues for gene transfer strategies that cannot be targeted to specific sequences. Here, we examine the use of a mobile retroposable genetic element that can be targeted to introduce therapeutic sequences site specifically into mutant genes. The data demonstrate that the mobile group II intron from Lactococcus lactis can be targeted to insert into and repair mutant lacZ (approved gene symbol GLB1) and beta-globin (approved gene symbol HBB) genes with high efficiency and fidelity in model systems in bacteria. These results suggest that these mobile genetic elements represent a novel class of agents for performing targeted genetic repair.