tbuckley/cabot-search huggingface dataset:
Macrophage migration inhibitory factor polymorphisms do not predict therapeutic response to glucocorticoids or to tumour necrosis factor -neutralising treatments in rheumatoid arthritis
Authors: T. R D J Radstake, J. Fransen, E. J M Toonen, M. J H Coenen, A. E Eijsbouts, R. Donn, F. H J van den Hoogen, P. L C M van Riel
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Background:</h3> Macrophage migration inhibitory factor (MIF) is an inflammatory mediator associated with RA severity. In various diseases, MIF polymorphisms are associated with clinical response glucocorticoid (GC) treatment. It is unclear whether MIF polymorphisms determine GC response in rheumatoid arthritis (RA) and to other RA treatments. Therefore, the question of whether two functional variants in MIF are associated with the response to tumour necrosis factor (TNF)α-neutralising and GC treatments in RA was investigated. <h3>Methods:</h3> Data from two cohorts of an RA registry were used. For patients who started with TNFα-neutralising (infliximab) or GC treatment, courses with a duration of at least 3 months were included and response to TNFα blockers or GC was calculated according to the European League Against Rheumatism response criteria. MIF −173G→C genotyping was achieved using an assay-on-demand allelic discrimination assay, and alleles of the CATT repeat element were identified using a fluorescently labelled PCR primer and capillary electrophoresis. Logistic-regression modelling was used for the statistical analysis. <h3>Results:</h3> In total, 192 courses of oral prednisone or methylprednisolone injections in 98 patients with RA and 90 patients with RA who were on TNFα-neutralising treatments were documented. In all, 27% of the patients with RA were found to be heterozygous for seven CATT repeats (CATT<sub>7</sub>) and 31% were heterozygous for −173C. Respectively, 4% and 6% of the patients with RA were homozygous for the MIF CATT<sub>7</sub> repeat or the MIF −173C allele. Carrier status and homozygosity for CATT<sub>7 </sub>repeat and the MIF −173C allele were not associated with response to GC (odds ratios (ORs) close to 1) or to TNFα-neutralising treatment (ORs close to 2). <h3>Conclusion:</h3> The MIF-CATT<sub>7</sub> repeat and the MIF−173G→C functional variant are not strongly associated with a decreased clinical response to TNFα-neutralising or GC treatment in RA.
An Ambitious Needle and a Benign Bullet.
Authors: J. B. Greene
Journal: JAMA (1889)

<h3>To the Editor:</h3> —Dr. Kime, in the issue of January 19, reports a case of the "Migration of a Needle." I offer a companion case. Some time during the winter of 1885-6 I was called to see the 3-year old son of Mr. Henry Cook, of this place. I found the child busy with his toys and not complaining of anything. His mother informed me that, while creeping over the floor, he had suddenly cried out, and going to him she found a needle protruding,<i>point out</i>, from the inner aspect of the knee. I made a careful examination and, aside from a small prick-point of the skin, I found nothing to indicate any foreign body being imbedded, and so informed Mrs. C. She said she knew it was there, for she had, in her effort to remove it, broken off the point. As the child suffered no more, I
The primary health care team: history and contractual farces.
Authors: J. Hasler
Journal: BMJ (1992)

Risk factor weightingsRandall et al suggest that an error may arise through using weightings derived from men seen 18-20 years ago.The Dundee score is based on data of similar age to that of almost all other British ' and American scoring systems.""' Risk assessment must be based on historical comparison (unless it is spurious), and for that reason it will take a similar length of time to know whether the error actually exists.
Exhaled 8-Isoprostane as an <i>In Vivo</i> Biomarker of Lung Oxidative Stress in Patients with COPD and Healthy Smokers
Authors: PAOLO MONTUSCHI, JOHN V. COLLINS, GIOVANNI CIABATTONI, NICOLA LAZZERI, MASSIMO CORRADI, SERGEI A. KHARITONOV, PETER J. BARNES
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Most of the studies linking chronic obstructive pulmonary disease (COPD) with oxidative stress are in vitro, using invasive techniques, or measuring systemic oxidative stress. The aim of this study was to quantify oxidative stress in the lungs in patients with COPD and in healthy smokers, as reflected by 8-isoprostane concentrations in breath condensate. This is a noninvasive method to collect airway secretions. 8-Isoprostane is a prostaglandin-F(2alpha) isomer that is formed in vivo by free radical-catalyzed peroxidation of arachidonic acid. We also studied the acute effect of smoking on exhaled 8-isoprostane in healthy smokers. Exhaled 8-isoprostane was measured by a specific enzyme immunoassay in 10 healthy nonsmokers and 12 smokers, 25 COPD ex-smokers, and 15 COPD current smokers. 8-Isoprostane concentrations were similar in COPD ex-smokers (40 +/- 3.1 pg/ml) and current smokers (45 +/- 3.6 pg/ ml) and were increased about 1.8-fold compared with healthy smokers (24 +/- 2.6 pg/ml, p < 0.001), who had 2.2-fold higher 8-isoprostane than healthy nonsmokers (10.8 +/- 0.8 pg/ml, p < 0.05). Smoking caused an acute increase in exhaled 8-isoprostane by about 50%. Our study shows that free radical production is increased in patients with COPD and that smoking causes an acute increase in oxidative stress.
Transgene Expression Levels Determine the Immunogenicity of Transduced Hematopoietic Grafts in Partially Myeloablated Mice
Authors: Herena Eixarch, Alba Gómez, Elisabeth Kádár, Mónica George, Nuria Martínez, Carmen Espejo, Jordi Pétriz, Ramon Gimeno, Jordi Barquinero
Journal: Molecular Therapy (2009)

We investigated whether transgene expression levels influence the immunogenicity of transduced hematopoietic grafts upon transplantation into partially myeloablated mice. To this aim, bone marrow cells (BMCs) transduced with retroviral vectors driving green fluorescent protein (GFP) expression either at high (high-EGFP) or low levels (low-EGFP) were transplanted into congenic recipients conditioned with sublethal doses of total body irradiation (TBI) or busulfan. Virtually all recipients showed evidence of donor engraftment 4 weeks after transplantation. However, as opposed to recipients receiving low-EGFP transduced grafts, the risk of rejecting the EGFP(+) cells by 30 days after transplantation was significantly higher in mice conditioned with busulfan and receiving high-EGFP transduced grafts. Anti-EGFP cellular immune responses were demonstrated in high-EGFP-treated mice conditioned with busulfan by interferon-gamma (IFN-gamma), enzyme-linked immunospot assay (ELISPOT), and cytotoxic T lymphocyte (CTL) assays, in contrast to that observed in mice transplanted with low-EGFP BMC. These results show for the first time that transgene expression levels can be critical for the immunogenicity of gene-modified hematopoietic grafts, especially in immunocompetent or in partially immunosuppressed recipients. These results have profound implications in vector choice and in the design of gene therapy (GT) protocols.
Charles Dickens on "Town and Gown"
Authors: Roy C. Gumpel
Journal: JAMA (1964)

<h3>To the Editor:—</h3> For this Journal reader seeking respite from a current tide of medical literature, perusing a copy of<i>Household Words</i>, a weekly journal conducted by Charles Dickens, proved to be an adventure of contemporary interest. With the hope of eliminating profession-linked problems of academic and practicing medicine, W. C. Wescoe in aJournalSpecial Communication, "The Town-Gown Syndrome: Pathology" (<b>186</b>:785 [Nov 23] 1963), examined the "symptomcomplex" of the titled syndrome, outlining etiological factors, course, prognosis, diagnosis, and treatment. Dickens, in an 1852 contribution to<i>Household Words</i>titled "Town and Gown,"<sup>1</sup>with the same intent approached the controversies of university students and citizens of another century, the fictitious gowned members of the University of Bulferry and the tradesmen of the town of Bulferry. In keeping with the Journal comparison of conflict of "town and gown" to a clinical syndrome, the English novelist also draws such an analogy,
Abstract 5502: Absence of ERCC1 expression is predictive of complete pathologic response to platinum-based therapy for women with triple negative breast cancer
Authors: Maureen Cioffi-Lavina, Jude Hurley, Merce Jorda, Gail Walker, Carmen Gomez-Fernandez
Journal: Cancer Research (2011)

Abstract Background: Platinum-based chemotherapy exerts its cytotoxic effects by forming intra-strand DNA adducts that inhibit replication. Excision Repair Cross Complementing group 1 protein (ERCC1) plays a critical, yet undesirable, role in repair of DNA damage induced by platinum. Absence of immunohistochemical expression of ERCC1 has been shown to be associated with response to platinum-based chemotherapy regimens in non small cell lung carcinomas. Experimental data suggests that triple negative breast cancers may have increased sensitivity to platinum-based chemotherapy, particularly in BRCA1 mutation carriers, whose cancers cluster among the basal-like subtype, as defined by gene expression profiling. We investigated the immunohistochemical expression of ERCC1 in relation to response to neoadjuvant platinum-based chemotherapy in a cohort of patients with triple negative breast cancers. Materials and Methods: We reviewed the diagnostic core biopsies of 32 triple-negative breast cancer patients treated with neoadjuvant docetaxel plus platinum-based salts at our institution between 1999 and 2007. Fifteen (46.9%) study patients had pathologic complete response (pCR), defined by the absence of invasive carcinoma in the breast and axilla. Immunohistochemistry for ERRC1 (ABCAM) was performed in all cases using the LSAB method. A nuclear immunohistochemical reaction in &amp;gt;1% of the tumor cells was scored as positive for ERCC1. Fisher's exact test was used to compare pCR rates by ERCC1 status. Results: Sixteen of 32 (50%) triple negative breast carcinomas were positive for ERCC1 by immunohistochemistry. Reactivity was present in 10 to 50% of the tumor cell nuclei. The remaining 16/32 (50%) carcinomas were definitively negative for ERCC1. Significantly higher pCR rates were found in patients with ERCC1(−) tumors, 11/16 (68.8%), compared to 4/16 (25%) patients with ERCC1(+) tumors, p=0.032. Findings were similar for pCR confined to the breast (75.0 v 31.3%, p=0.032), and for pCR in the axilla (75.0 v 43.8%), although the latter result lost statistical significance, p=−0.149. Conclusion: Absence of immunohistochemical expression for ERCC1 is predictive of pathologic complete response to platinum-based neoadjuvant chemotherapy for patients with triple negative breast cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5502. doi:10.1158/1538-7445.AM2011-5502
Educational Programs in US Medical Schools, 2003-2004
Authors: Barbara Barzansky, Sylvia I. Etzel
Journal: JAMA (2004)

US medical schools continue to change their organizational structures, staffing patterns, and educational programs.To review the status of US medical school educational programs in the 2003-2004 academic year, compared with 1993-1994.The Liaison Committee on Medical Education (LCME) Annual Medical School Questionnaire for 2003-2004 and the Association of American Medical Colleges Directory of American Medical Education for the years 1983-1984, 1993-1994, and 2003-2004.The number of full-time faculty members in the 126 LCME-accredited medical schools increased from 90 975 in 1993-1994 to 114 549 in 2003-2004 (+26%), whereas the number of enrolled students remained essentially unchanged (66 453 in 1993-1994 and 67 166 in 2003-2004). In 2003-2004, 48% of medical school deans held another title at the medical center or university level, such as vice president for health affairs. There are 94 medical schools that have a comprehensive clinical examination using the standardized patient/objective structured clinical examination format; 59 schools require students to pass this examination for graduation. As of spring 2004, 58 schools will require students in the class of 2005 to pass the new US Medical Licensing Examination Step 2 Clinical Skills examination.The role of the medical school dean has expanded over time and is associated with the creation of a discrete administrative structure for the educational program. The number of full-time medical school faculty continues to increase, whereas the number of enrolled students remains steady. Considerable variability exists among medical schools in their use of standardized clinical evaluations.
Ferritin metabolism in reticulated-siderocytes
Authors: Andrew Deiss, G. E. Cartwright
Journal: Journal of Clinical Investigation (1970)

Reticulated-siderocytes (reticulocytes which contain siderotic granules), obtained from the circulation of pigs after vigorous phlebotomy, were incubated in vitro. A rapid disappearance of granules from the reticulocytes was observed over 24 hr. Simultaneously with the decrease in granules, soluble ferritin accumulated in the media and siderotic granules developed in monocytes. The disappearance of the granules from the reticulated-siderocytes was oxygen-dependent and the loss of granules and the accumulation of ferritin in the media were both prevented by the addition of cyanide or dinitrophenol. It is concluded that the ferritin aggregates in the granules of reticulated-siderocytes are dispersed intracellularly into soluble ferritin, that soluble ferritin is excreted from the cell, and that one or both of these steps is dependent upon oxidative metabolism. Blood monocytes are capable of taking up soluble ferritin from the media and converting this into siderotic granules. Thus, a reticulocyte to plasma to monocyte ferritin pathway has been described.
The alpha-smooth muscle actin promoter: a useful tool to analyse autocrine and paracrine roles of mesenchymal cells in normal and diseased bowel
Authors: P K LUND
Journal: Gut (1998)

Smooth muscle cells (SMC) of the vascular wall, bladder, myometrium, and gastrointestinal and respiratory tracts retain the ability to proliferate postnatally, which enables adaptive responses to injury, hormonal, or mechanical stimulation. SMC growth is regulated by a number of mesenchymal growth factors, including insulin-like growth factor I (IGF-I). To explore the function of IGF-I on SMC in vivo, the mouse SMC alpha-actin promotor fragment SMP8 (-1074 bp, 63 bp of 5'UT and 2.5 kb of intron 1) was cloned upstream of rat IGF-I cDNA, and the fusion gene microinjected into fertilized eggs of the FVB-N mouse strain. Mating of hemizygous mice with controls produced about 50% transgenic offspring, with equal sex distribution. Transgenic IGF-I mRNA expression was confined to SMC-containing tissue, with the following hierarchy: bladder > stomach > aorta = uterus > intestine. There was no transgene expression in skeletal muscle, heart, or liver. Radioimmunoassayable IGF-I content was increased by 3.5- to 4-fold in aorta, and by almost 10-fold in bladder of transgenic mice at 5 and 10 wk, with no change in plasma IGF-I levels. Wet weight of bladder, stomach, intestine, uterus, and aorta was selectively increased, with no change in total body or carcass weight of transgenic animals. In situ hybridization showed that transgene expression was exquisitely targeted to the smooth muscle layers of the arteries, veins, bladder, ureter, stomach, intestine, and uterus. Paracine overproduction of IGF-I resulted in hyperplasia of the muscular layers of these tissues, manifesting in remarkably different phenotypes in the various SMC beds. Whereas the muscular layer of the bladder and stomach exhibited a concentric thickening, the SMC of the intestine and uterus grew in a longitudinal fashion, resulting in a marked lengthening of the small bowel and of the uterine horns. This report describes the first successful targeting of expression of any functional protein capable of modifying the phenotype of SMC in transgenic mice. IGF-I stimulates SMC hyperplasia, leading to distinct patterns of organ remodeling in the different tissue environments.
Rescue Use of Beclomethasone and Albuterol in a Single Inhaler for Mild Asthma
Authors: Alberto Papi, Giorgio W. Canonica, Piero Maestrelli, Pierluigi Paggiaro, Dario Olivieri, Ernesto Pozzi, Nunzio Crimi, Antonio M. Vignola, Paolo Morelli, Gabriele Nicolini, Leonardo M. Fabbri
Journal: New England Journal of Medicine (2007)

Treatment guidelines recommend the regular use of inhaled corticosteroids for patients with mild persistent asthma. We investigated whether the symptom-driven use of a combination of beclomethasone dipropionate and albuterol (also known as salbutamol) in a single inhaler would be as effective as the regular use of inhaled beclomethasone and superior to the as-needed use of inhaled albuterol.We conducted a 6-month, double-blind, double-dummy, randomized, parallel-group trial. After a 4-week run-in, patients with mild asthma were randomly assigned to receive one of four inhaled treatments: placebo twice daily plus 250 microg of beclomethasone and 100 microg of albuterol in a single inhaler as needed (as-needed combination therapy); placebo twice daily plus 100 microg of albuterol as needed (as-needed albuterol therapy); 250 microg of beclomethasone twice daily and 100 microg of albuterol as needed (regular beclomethasone therapy); or 250 microg of beclomethasone and 100 microg of albuterol in a single inhaler twice daily plus 100 microg of albuterol as needed (regular combination therapy). The primary outcome was the morning peak expiratory flow rate.In 455 patients with mild asthma who had a forced expiratory volume in 1 second of 2.96 liters (88.36% of the predicted value), the morning peak expiratory flow rate during the last 2 weeks of the 6-month treatment was higher (P=0.04) and the number of exacerbations during the 6-month treatment was lower (P=0.002) in the as-needed combination therapy group than in the as-needed albuterol therapy group, but the values in the as-needed combination therapy group were not significantly different from those in the groups receiving regular beclomethasone therapy or regular combination therapy. The cumulative dose of inhaled beclomethasone was lower in the as-needed combination therapy group than in the groups receiving regular beclomethasone therapy or regular combination therapy (P<0.001 for both comparisons).In patients with mild asthma, the symptom-driven use of inhaled beclomethasone (250 microg) and albuterol (100 microg) in a single inhaler is as effective as regular use of inhaled beclomethasone (250 microg twice daily) and is associated with a lower 6-month cumulative dose of the inhaled corticosteroid. (ClinicalTrials.gov number, NCT00382889 [ClinicalTrials.gov].).
Index Medicus
Authors: Jeffrey Kunz
Journal: JAMA (1979)

IN ITS initial year of publication,<i>Index Medicus</i>, which purported to catalog "all current medical journals and transactions of value," listed some 20,000 medical articles from around the world. One hundred years later, it is expected to list more than 250,000 articles—mute testimony to the impressive growth in medical science during the past century, growth that<i>Index Medicus</i>has helped to stimulate as well as to chronicle. When its principal founder, John Shaw Billings, MD, died in 1913, William H. Welch of Johns Hopkins included<i>Index Medicus</i>with Billings' other bibliographic achievements as America's "greatest contribution to medicine."1 Today, judging from the prestige of the National Library of Medicine (NLM) and its best known publication, the<i>Index Medicus</i>has maintained its premiere position. Despite its parallel growth with American medical discoveries and continued international acclaim, the future of<i>Index Medicus</i>has not always been bright. More than once it has
Goodness and the good doctor
Authors: P. Benn
Journal: BMJ (2002)

Philosophers since Plato have wondered what goodness is, but what does the term mean when ascribed to doctors? Notice that if I call Dr Jones a good doctor I am not saying that Jones is a doctor who also happens to be good. I am saying that as a doctor Jones is good—good by the standards for judging doctors. In this respect, calling something good is like calling something big or small. A small boil is usually larger than a large pimple. The boil is small relative to the average size for boils.

Thus the good doctor does not have all …
Traumatic Biliopleural Communication Detected by Hepatobiliary Scintigraphy
Authors: Anish Bhattacharya, Rajesh Gupta, Bhagwant Rai Mittal
Journal: Clinical Nuclear Medicine (2006)

A 24-year-old man presented with a recent history of a stab injury followed by dyspnea and a right-sided pleural fluid collection. Tc-99m mebrofenin hepatobiliary scintigraphy demonstrated passage of bile from the liver across the diaphragm, into the right pleural cavity, confirming a biliopleural communication.
Calcium transport in canine renal basolateral membrane vesicles. Effects of parathyroid hormone.
Authors: J E Scoble, S Mills, K A Hruska
Journal: Journal of Clinical Investigation (1985)

The effects of parathyroid hormone were studied on Ca2+ fluxes in canine renal proximal tubular basolateral membrane vesicles (BLMV). Efflux of Ca2+ from preloaded BLMV was found to be stimulated by an external Na+ gradient, and this was inhibited by the Na+ ionophore, monensin, and enhanced by intravesicular negative electrical potentials, which indicated electrogenic Na+/Ca2+ exchange activity. There was a Na+ gradient independent Ca2+ flux, but membrane binding of Ca2+ was excluded from contributing to the Na+ gradient-dependent efflux. The Na+ gradient-dependent flux of Ca2+ was very rapid, and even 2- and 5-s points may not fully represent absolute initial rates. It was saturable with respect to the interaction of Ca2+ and Na+ with an apparent (5 s) Km for Na+-dependent Ca2+ uptake of 10 microM, and an apparent (5 s) Vmax of 0.33 nmol/mg protein per 5 s. The Na+ concentration that yielded half maximal Ca2+ efflux (2 s) was 11 mM, and the Hill coefficient was two or greater. Both Na+ gradient dependent and independent Ca2+ efflux were decreased in BLMV prepared from kidneys of thyroparathyroidectomized (TPTX) dogs, and both were stimulated by parathyroid hormone (PTH) infusion to TPTX dogs. BLMV from TPTX dogs exhibited significantly reduced maximal stimulation of Na+ gradient-dependent Ca2+ uptake with an apparent (5 s) Vmax of 0.23 nmol/mg protein per 5 s, but the apparent Km was 8 microM, which was unchanged from normal. The Na+ gradient independent Ca2+ uptake was also reduced in BLMV from TPTX dogs compared with normal. Thus, PTH stimulated both Na+/Ca2+ exchange activity and Na+ independent Ca2+ flux. In vivo, the latter could result in an elevation of cytosolic Ca2+ by PTH, and this might contribute to the observed decrease in solute transport in the proximal tubule.