tbuckley/cabot-search huggingface dataset:
HIF-1α of Bone Marrow Endothelial Cells Implies Relapse and Drug Resistance in Patients with Multiple Myeloma and May Act as a Therapeutic Target
Authors: Roberto Ria, Ivana Catacchio, Simona Berardi, Annunziata De Luisi, Antonella Caivano, Claudia Piccoli, Vitalba Ruggieri, Maria Antonia Frassanito, Domenico Ribatti, Beatrice Nico, Tiziana Annese, Simona Ruggieri, Attilio Guarini, Carla Minoia, Paolo Ditonno, Emanuele Angelucci, Daniele Derudas, Michele Moschetta, Franco Dammacco, Angelo Vacca
Journal: Clinical Cancer Research (2013)

Abstract Purpose: To investigate the role of hypoxia-inducible factor-1α (HIF-1α) in angiogenesis and drug resistance of bone marrow endothelial cells of patients with multiple myeloma. Experimental Design: HIF-1α mRNA and protein were evaluated in patients with multiple myeloma endothelial cells (MMEC) at diagnosis, at relapse after bortezomib- or lenalidomide-based therapies or on refractory phase to these drugs, at remission; in endothelial cells of patients with monoclonal gammapathies of undetermined significance (MGUS; MGECs), and of those with benign anemia (controls). The effects of HIF-1α inhibition by siRNA or panobinostat (an indirect HIF-1α inhibitor) on the expression of HIF-1α proangiogenic targets, on MMEC angiogenic activities in vitro and in vivo, and on overcoming MMEC resistance to bortezomib and lenalidomide were studied. The overall survival of the patients was also observed. Results: Compared with the other endothelial cell types, only MMECs from 45% of relapsed/refractory patients showed a normoxic HIF-1α protein stabilization and activation that were induced by reactive oxygen species (ROS). The HIF-1α protein correlated with the expression of its proangiogenic targets. The HIF-1α inhibition by either siRNA or panobinostat impaired the MMECs angiogenesis–related functions both in vitro and in vivo and restored MMEC sensitivity to bortezomib and lenalidomide. Patients with MMECs expressing the HIF-1α protein had shorter overall survival. Conclusions: The HIF-1α protein in MMECs may induce angiogenesis and resistance to bortezomib and lenalidomide and may be a plausible target for the antiangiogenic management of patients with well-defined relapsed/refractory multiple myeloma. It may also have prognostic significance. Clin Cancer Res; 20(4); 847–58. ©2013 AACR.
Smoking Habits of High-School Students in Newton, Massachusetts
Authors: Eva J. Salber, Elisabeth Goldman, Magda Buka, Barbara Welsh
Journal: New England Journal of Medicine (1961)

THERE have now been a number of studies of the prevalence of tobacco smoking among young people in Great Britain and other European countries. However, the only substantial studies of this problem in North America are those conducted in Portland, Oregon, by Horn et al.1 and in Winnipeg, Canada, by Morison and Medovy.2 Studies are under way in Newton, Massachusetts, to derive frequency data for a community in the eastern United States and also to investigate the demographic and psychologic correlates of cigarette smoking among high-school students. The present paper presents initial data on the prevalence and distribution of smoking . . .
Case Study of Tc-99m HMPAO Brain SPECT Imaging in a Patient With Hepatic Encephalopathy and Carotid Artery Stenosis
Authors: Michael J. Blend, Mehdi Rohany, Nicole Jones-Martinez, Ovidio A. De Leon
Journal: Clinical Nuclear Medicine (2010)

A patient with hepatic encephalopathy is described. An initial SPECT using Tc-99m HMPAO was performed to evaluate relative brain perfusion. The initial brain SPECT images revealed decreased perfusion in the left frontal temporal lobe region. A subsequent carotid Doppler study revealed left-sided carotid artery stenosis. After appropriate medical treatment for elevated NH3 levels and reversal of the patient's symptoms, repeat SPECT brain images showed a normal pattern of activity. The possible causes and significance for these image findings are discussed.
Odonto-onycho-dermal dysplasia
Authors: G.M. ZIRBEL, M.S. RUTTUM, A.C. POST, N.B. ESTERLY
Journal: British Journal of Dermatology (2006)

Odonto‐onycho‐dermal dysplasia is an ectodermal dysplasia (ED) described once previously in two families who exhibited atrophic malar patches, sparse hair, conical teeth, dystrophic nails and hyperkeratosis of the palms and soles. We describe a boy who developed a blistering malar rash soon after birth. When examined at 11 months, and then at 27 months of age, he had persistent atrophic malar plaques that reddened with heat. He also showed nail dystrophy, sparse hair. lingual concavity of the incisors, a bifid maxillary incisor, a five‐cusped molar, and hyperhidrosis of the palms and soles. In addition he had chronic tearing, photophobia, blepharitis, and a mild keratitis. After reviewing EDs with atrophic or scar‐like skin changes, we believe this child most resembles the patients with odonlo‐onycho‐dermal dysplasia, although his eye findings are unique.
Growth of Foetal Head
Authors: P. Cave
Journal: BMJ (1949)

Of 166 consecutive patients with histologically confirmed giant cell (temporal) arteritis (GCA) seen during a 3-year period, 23 (14%) had clinically diagnosed peripheral neuropathic syndromes temporally coincident with clinically active GCA. Electromyography and nerve conduction studies were performed in 16, confirming abnormalities in all. Of the 23 patients, 11 had a generalized peripheral neuropathy, nine had multiple mononeuropathies, and three had a mononeuropathy. The nerves affected as mononeuropathies were the median, ulnar, peroneal, tibial, and sural nerves, and the C-5 and L-5 nerve roots. Angiography, performed in two patients, demonstrated widespread arteritis involving the lower limbs and, after 3 months of oral corticosteroid treatment in one of these patients, an amputation specimen showed chronic arteritis.
Abstract P2-14-02: Preclinical Evaluation of Enzalutamide in Breast Cancer Models
Authors: DR Cochrane, S Bernales, BM Jacobsen, NC D'Amato, J Guerrero, F Gómez, AA Protter, AD Elias, JK Richer
Journal: Cancer Research (2012)

Abstract Background: The vast majority of breast cancers express the androgen receptor (AR) with ∼80% of ER+ and 30% to50% of ER− tumors being positive for AR by immunohistochemistry (IHC). Approximately 30% of breast cancer patients with estrogen receptor positive (ER+) tumors do not respond to tamoxifen or aromatase inhibitors and AR signaling has been implicated as a possible mechanism of this insensitivity. AR overexpression has also been associated with resistance to either tamoxifen or aromatase inhibitors in cell line models. Hypothesis: ER+ breast cancers can switch from estrogen to androgen-dependent growth as they become resistant to traditional endocrine therapies and AR can serve as a therapeutic target in AR+ breast cancers, irrespective of ER status. Methods: The proliferative effect of dihydrotestosterone (DHT) and estradiol (E2) in the presence enzalutamide (formerly MDV3100) was examined in vitro and in xenograft studies using models of both ER+ and ER− breast cancer that express AR. Furthermore, AR and ER were examined by IHC in clinical specimens from breast cancer patients treated with neoadjuvant exemestane and adjuvant tamoxifen. Tumor tissue was compared to adjacent normal breast epithelium. Results: In ER+ models, bicalutamide and enzalutamide both inhibited DHT-mediated proliferation, while enzalutamide uniquely inhibited E2-mediated proliferation. In vivo, enzalutamide significantly reduced estrogen- and androgen-mediated growth of MCF7 (ER+/AR+) xenograft tumors. Remarkably, enzalutamide demonstrated an anti-proliferative effect comparable to tamoxifen. in vitro, enzalutamide inhibits E2-stimulated tumor cell proliferation and E2 bound ER activation of genes such as PR and SDF-1, despite no observed binding of enzalutamide to ER alpha or beta. In ER−/AR+ MDA-MB-453 xenografts, enzalutamide treatment resulted in decreased nuclear AR localization, increased apoptosis and tumor growth inhibition. Conclusions: Enzalutamide demonstrated significant anti-tumor activity in preclinical models of breast cancers that express AR, regardless of ER status. When enzalutamide opposes DHT, it functions by excluding AR from the nucleus, thereby reversing the anti-apoptotic effect of AR. In contrast, when opposing E2, it causes a decrease in tumor cell proliferation. Profiling of ER+ xenografts is underway to further elucidate the mechanism by which this occurs. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-14-02.
Stimulation of inositol trisphosphate and diacylglycerol production in renal tubular cells by parathyroid hormone.
Authors: K A Hruska, D Moskowitz, P Esbrit, R Civitelli, S Westbrook, M Huskey
Journal: Journal of Clinical Investigation (1987)

Parathyroid hormone (PTH) produced a dose-dependent immediate stimulation of inositol triphosphate and diacylglycerol production in the opossum kidney cell line, primary culture proximal tubular cells, and basolateral membranes from canine proximal tubular segments. The increase in inositol triphosphate production was accompanied by a minor increase in inositol phosphate and no significant increase in inositol bisphosphate production. Associated with the changes in inositol triphosphate and diacylglycerol, there was an immediate hydrolysis of phosphatidylinositol 4'5-bisphosphate. The effect on phospholipid hydrolysis was followed by stimulation of phosphorylation of phosphatidylinositol 4' monophosphate and phosphatidylinositol. PTH produced a sudden increase in cytoplasmic Ca2+ in opossum kidney cells that persisted for approximately 1 min. Inositol triphosphate transiently increased cytoplasmic Ca2+ in saponin-treated opossum kidney and primary culture proximal tubule cells. The effects of PTH were not mimicked by cyclic nucleotides. In fact, cyclic AMP appeared to diminish inositol triphosphate production. These results demonstrate that PTH may activate renal tubular epithelial cells by the production of inositol triphosphate and diacylglycerol.
Surgical Trainees' Attitudes to Laparoscopic Cholecystectomy: A Regional Survey
Authors: R. Baker, D. Gilroy, D. McCrory
Journal: Endoscopy (2001)

Since the introduction of laparoscopic cholecystectomy (LC), numerous articles have been written emphasising its many advantages over open cholecystectomy (OC). However, reports also highlight increased complications following LC such as bile-duct, vascular and bowel injuries. We aimed to study surgical trainees as a defined population of individuals who, with increasing exposure to cholecystectomy, would become fully aware of LC's advantages and controversies. We wished to test the hypothesis that, with increasing in-depth knowledge, they might opt for OC rather than LC if they themselves required cholecystectomy.We conducted a postal survey of all 133 Northern Ireland surgical trainees identified as having exposure to LC during their training. Trainees were asked whether they would undergo LC and if so with which preconditions. Similarly, if they stated a preference for open cholecystectomy they were asked to state the reason. A minimum time period of 18 months was considered adequate for trainees to become relatively more experienced in this field compared with their more junior counterparts.A response rate of 80.5% (107/133) was achieved. A total of 51 of 107 trainees had at least 18 months' experience. Of the 107 who replied, 88.8% (95/107) would be willing to undergo LC. A total of 12 of 107 trainees would opt for OC, with twice as many experienced trainees (8 vs. 4) opting for this approach (n.s. [not significant]). Significantly more experienced trainees cited the use of laparoscopic cholangiography as a precondition for LC compared with their inexperienced counterparts (7 vs. 1, p = 0.020). Of 107 trainees, 19 would request use of the open first port (Hasson) technique; 14 of these had at least 18 months' experience (p = 0.009).Our survey confirms that the majority of trainees would be willing to undergo LC. However, increased experience of LC may alter an individual's expectations about how LC should ideally be performed.
Management of Polypoid Lesions
Authors: Horatio T. Enterline
Journal: JAMA (1975)

POLYPS of the colon and rectum have been the subject of a voluminous and discordant literature ever since the publication of the article by Spratt et al in 1958.<sup>1</sup>The practicing physician, with good reason, may be confused and uncertain about the appropriate course of action when a patient is discovered to have one or more such lesions. However, because of this controversy, much has been learned of the biology and diversity of these lesions. Although there may still be disagreement about the mode of origin of colonic carcinoma, there is surprisingly little disagreement on the care of the patient with one or more polyps. A major problem has been the tendency to equate "polyp" with "adenoma" in thinking and writing about polypoid lesions. Polypoid lesions of the colon form a diverse group; they may be of inflammatory, "hamartomatous," hyperplastic, or neoplastic origin. Unfortunately, although most types of polyps
An International Foodborne Outbreak of Shigellosis Associated With a Commercial Airline
Authors: Craig W. Hedberg
Journal: JAMA (1992)

To determine the source of an international outbreak of shigellosis associated with consumption of food served by a Minnesota-based airline.Cohort studies of players and staff of a Minnesota-based professional football team and passengers on flights with a confirmed case of outbreak-associated Shigella sonnei infection.Community- and industry-based studies conducted from October through November 1988.Sixty-five football team players and staff, and 725 airline passengers in the cohort studies.Twenty-one (32%) of 65 football players and staff developed shigellosis that was associated with consumption of cold sandwiches prepared at the airline flight kitchen (relative risk [RR], 17.1; 95% confidence interval [Cl], 2.4 to 120; P < .001). Confirmed or probable shigellosis was identified among 240 passengers on 219 flights to 24 states, the District of Columbia, and four countries between September 14 and October 13. An outbreak-associated strain of S sonnei was isolated from football players and staff, airline passengers, and flight attendants. Thirty (4.1%) of 725 passengers on 13 flights with confirmed cases had confirmed or probable shigellosis. Illness was associated with consumption of cold food items served on the flights and prepared by hand at the airline flight kitchen (RR, 5.7; 95% Cl, 1.4 to 23.5; P < .01).This international outbreak of shigellosis was identified only because of the occurrence of an index outbreak involving a professional football team. Prevention of Shigella transmission in mass catering establishments may require reduction of hand contact in the preparation of cold food items or elimination of these items from menus.
HIV Testing of Pregnant Women and Newborns
Authors: Ronald Bayer
Journal: JAMA (1991)

<h3>To the Editor. —</h3> The Working Group on HIV Testing of Pregnant Women and Newborns<sup>1</sup>provides a thoughtful analysis of the ethical and policy issues posed by the challenge of HIV infection in pregnant women and newborns. In the course of that analysis, the authors make reference to my work in a way that does considerable violence to what I have written. In my own article,<sup>2</sup>I argued that the human misery represented by HIV infection in newborns provided a strong moral argument for discouraging pregnancy in infected women. I was, however, careful to insist that counseling against pregnancy was not the moral equivalent of prohibiting pregnancy: "There are many occasions when coercion for pragmatic, constitutional and ethical reasons is unacceptable as a means of gaining adherence to morally desirable standards, and decisions regarding procreation present such an occasion." Furthermore, I made a radical distinction between counseling about
Medicine in Colorado—An Overcrowded Field.
Authors: John Inglis
Journal: JAMA (1904)

Pueblo, Col., May 16, 1904. <h3>To the Editor:</h3> —So far as medicine is concerned, the cry of "Go west, young man," has changed in Colorado to "Go east." No state in the Union and no country in the world is so well supplied with physicians as Colorado. Hundreds of medical men have sought the mountain air of Colorado on account of their own health or the health of some one belonging to them. This has produced just one result—an overstocked market of physicians, good, bad and indifferent. Denver has a population of 133,859, but has almost 600 physicians. Colorado Springs has about one physician to every 200 of population. In Pueblo the same condition of affairs prevails, with this exception—which has lured many a young doctor to stop in Pueblo long enough to spend all his capital before he realized why practice was not coming his way. Pueblo has a
Effect of activation of the H1 receptor on coronary hemodynamics in man.
Authors: C Vigorito, S Poto, G B Picotti, M Triggiani, G Marone
Journal: Circulation (1986)

We evaluated the effects of selective activation of H1 receptors on coronary hemodynamics in 16 patients divided into two groups: group A, 11 patients with atypical angina or valvular heart disease and normal coronary arteries, and group B, five patients with spontaneous angina, four of whom had significant (greater than 70% stenosis) coronary artery disease and one with normal coronaries. Selective H1 receptor stimulation was achieved by infusing 0.5 microgram/kg/min of histamine intravenously for 5 min after pretreatment with cimetidine (25 mg/kg). Heart rate was maintained constant (100 beats/min) by coronary sinus pacing and coronary blood flow (CBF) was measured by thermodilution. In group A, during histamine infusion mean aortic pressure fell from 99 +/- 5 to 77 +/- 4 mm Hg (mean +/- SEM, p less than .001), coronary vascular resistance (CVR) decreased from 1.07 +/- 0.17 to 0.82 +/- 0.14 mm Hg/ml/min (p less than .02), and CBF and myocardial oxygen consumption remained unchanged. None of the patients in this subgroup developed angina during histamine infusion. In group B, while no significant average changes in mean arterial pressure, CVR, or CBF were observed, two of the five patients (40%) developed angina during histamine infusion, accompanied by ST-T elevation, a decrease in CBF, and an increase in CVR. In one of these two patients circumflex coronary arterial spasm was angiographically demonstrated during histamine-induced angina. Our results suggest that stimulation of the H1 receptor induces a reduction of CVR, probably resulting from vasodilation of small coronary resistance vessels.(ABSTRACT TRUNCATED AT 250 WORDS)
Comparison of human skeletal myoblasts and bone marrow-derived CD133+progenitors for the repair of infarcted myocardium
Authors: Onnik Agbulut, Susanne Vandervelde, Nawwar Al Attar, Jérôme Larghero, Said Ghostine, Bertrand Léobon, Estelle Robidel, Paolo Borsani, Marc Le Lorc'h, Alvine Bissery, Christine Chomienne, Patrick Bruneval, Jean-Pierre Marolleau, Jean-Thomas Vilquin, Albert Hagège, Jane-Lyse Samuel, Philippe Menasché
Journal: Journal of the American College of Cardiology (2004)
A Case Report of Transfusion-Induced Babesiosis
Authors: Leonard C. Marcus
Journal: JAMA (1982)

An elderly woman contracted transfusion-induced babesiosis, accompanied by disseminated intravascular coagulopathy. Her parasitemia cleared after treatment with several antibiotic and antimalarial drugs, but she died of cardiopulmonary failure. One of the transfusion donors had a high indirect fluorescent antibody titer against<i>Babesia microti</i>but was asymptomatic; his parasitemia was detected only by hamster inoculation, illustrating the difficulty in detecting the carrier state. (<i>JAMA</i>1982;248:465-467)
Developing skills in consulting with the public
Authors: D. Jakubowska
Journal: BMJ (1999)

Career focus is now integrated with the rest of the eBMJ, which enables customised @lerts (http://www.bmj.com), textword searches, and themed collections of articles. Content will continue to appear through the Synergy site (http://classified.bmj.com/) for the time being.

The issue of involving the public in healthcare decision making has a complex history. Debates have raged about challenges to professional judgment and the weighting given to public views.1Questions of whom to consult and when can be equally perplexing.

There are clear expectations that each layer of the NHS will seek the views of the public on the services it provides. A number of documents explain the rationale behind involving the public and the applicability of different methods.2–4What has not been explored is the role that medical practitioners must play in this exercise given their background, knowledge, and professional experience, and what sort of skills might be needed.

The relaunch of the Patient Partnership Strategy earlier this year with its announcement of £2.5m being earmarked for research into public involvement methods has signalled the government's intentions. This is not about political sensitivity but an acknowledgement that the quality of services can be improved by gaining the experience of patients. Every PCG member will need skills in involving the public.5 NHS professionals will need to know how to participate in such exercises and how to understand the processes adopted. But underpinning this is the need for a change in attitude. As the NHS accepts the reality that it is only part of the health equation so it will not be enough to assume that doctors have the sum total of knowledge where a patient's treatment is concerned. Other parties such as the voluntary sector, carers, and users of the service have valuable roles to play and expertise …
Ischemic Forms of Venous Thrombosis: Phlegmasia Cerulea Dolens, Venous Gangrene
Authors: Geza de Takats
Journal: JAMA (1971)

A critical analysis of 175 collected cases including 50 personal observations is given in this monograph, which describes a truly frightening, ignored, and poorly understood syndrome. The incidence ranges from 1.7% to 10% of all deep venous thromboses, the frequency depending on the observer and the time of observation. The nurses' notes and the observations of the house-staff, describing the onset of a massive venous thrombosis, may record a blue purple cyanotic extremity vastly improved next morning on elevation or hot packs. There is much controversy about the mechanism of decreased or absent arterial inflow when venous pressure rises above a critical point. The author writes an excellent chapter on the perverted physiology of ischemic thrombosis, but it follows instead of preceding the chapters on clinical manifestations and diagnosis. The text is noncommittal on the exact indications for anticoagulants, fibrinolytics, sympathetic blockade, thrombectomy, and fasciotomy. All in all, an unbiased