tbuckley/cabot-search huggingface dataset:
Abstract 5045: The Hh inhibitor IPI-926 inhibits relapse of a non-small cell lung cancer xenograft model following treatment with an EGF-R targeted tyrosine kinase inhibitor
Authors: Everton Mandley, Kerry White, Kerrie Faia, Veronica Travaglione, Margaret Read, Karen McGovern, John R. MacDougall
Journal: Cancer Research (2010)

Abstract The Hedgehog (Hh) pathway plays a key role in multiple types of cancer, either by mutational activation of the pathway in tumor cells or by ligand-dependent signaling to the tumor cells or paracrine signaling between tumor cells and the tumor microenvironment. We have previously shown in a primary model of SCLC that the Hh pathway inhibitor IPI-926 prevents tumor relapse after regression of the tumor with chemotherapy (Travaglione et al., AACR 2009). To investigate whether tumor regression with a targeted agent could elicit a similar response as that seen with chemotherapy, two NSCLC lines (H1650 and HCC827), with activating mutations in the EGFR were evaluated. NSCLC cell lines bearing mutant EGFR are exquisitely sensitive to EGFR kinase inhibitors. Upon treatment with gefitinib in vitro, HCC827 increased the expression of Indian and Sonic hedgehog ligands 10-fold, as measured by qRT-PCR. When grown in mice as subcutaneous xenografts, H1650 tumors regressed following treatment with the EGFR inhibitor gefitinib (40 mg/kg every day) for 7 days. The gefitinib-treated mice were then administered either vehicle or IPI-926 at 40 mg/kg every other day for three weeks, and in this setting IPI-926 treatment led to a 65% decrease (p=0.0104) in tumor volume compared to vehicle-treated mice. Conversely, tumors that had not been regressed with the EGFR TKI showed no response to the Hh pathway inhibitor, similar to our previous results in SCLC with chemotherapy. Studies are ongoing to define the mechanism of action of IPI-926 in this setting. When grown in mice as subcutaneous xenografts, these tumor cells produce Shh ligand in conjunction with stromal Gli-1 expression in the murine stroma. Stromal Gli-1 expression is inhibited by treatment with IPI-926, indicating that Hh ligand produced by NSCLC tumor cells signals to stroma in a paracrine manner. Together with our previous results in SCLC, these data suggest that therapeutic inhibition of the Hh signaling pathway might be an important strategy to extend progression free survival in patients who initially respond to therapy but later relapse, and that this paradigm is applicable to multiple cancer types and treatment modalities. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5045.
THE NATURE OF NERVOUSNESS IN SOLDIERS
Authors: FOSTER KENNEDY
Journal: JAMA (1918)

For eighteen months the term shell shock has been employed in medical literature and, colloquially also, in the British Army to cover all cases of nervous instability occurring in the course of war.  Under this heading have been massed cases of amnesia, anergic stupor, sleeplessness, nightmare, mutism, functional blindness, tremors, palsies, and further, anxiety neuroses, occurring not only under fighting strain but also in individuals who, failing in self confidence, suffer doubts and apprehensions while still waiting for transport overseas. Further, the term became commonly used in newspaper journalism, whence it passed into common speech, always associated with a train of thought in the mind of the speaker, at once fearful and mysterious.  The general acceptance of this term and the apparent recognition by both medical officers and the public of a concrete, and above all quite novel, condition induced by experiences of unimaginable horror—the moving accidents of flood and
Biologic Correlation of 2-[<sup>18</sup>F]-Fluoro-2-Deoxy-D-Glucose Uptake on Positron Emission Tomography in Thymic Epithelial Tumors
Authors: Kyoichi Kaira, Masahiro Endo, Masato Abe, Kazuo Nakagawa, Yasuhisa Ohde, Takehiro Okumura, Toshiaki Takahashi, Haruyasu Murakami, Asuka Tsuya, Yukiko Nakamura, Tateaki Naito, Isamu Hayashi, Masakuni Serizawa, Yasuhiro Koh, Hirofumi Hanaoka, Hideyuki Tominaga, Noboru Oriuchi, Haruhiko Kondo, Takashi Nakajima, Nobuyuki Yamamoto
Journal: Journal of Clinical Oncology (2010)

The usefulness of 2-[(18)F]-fluoro-2-deoxy-D-glucose ([(18)F]FDG) positron emission tomography (PET) can help predict the grade of malignancy and staging in thymic epithelial tumors. However, no satisfactory biologic explanation exists for this phenomenon. The aim of this study was to investigate the underlying biologic mechanisms of [(18)F]FDG uptake.Forty-nine patients with thymic epithelial tumors who underwent [(18)F]FDG PET were included in this study. Tumor sections were stained by immunohistochemistry for glucose transporter 1 (GLUT1), glucose transporter 3 (GLUT3), hypoxia-inducible factor-1 alpha (HIF-1alpha), vascular endothelial growth factor (VEGF), microvessels (CD31 and CD34), cell cycle control marker (p53), and apoptosis marker (bcl-2). We also conducted an in vitro study of [(18)F]FDG uptake in a thymic tumor cell line.There was a positive correlation between [(18)F]FDG uptake and GLUT1 (P < .0001), HIF-1alpha (P = .0036), VEGF (P < .0001), microvessel density (MVD; P < .0001), and p53 (P = .0002). GLUT3 and bcl-2 showed no positive correlation with [(18)F]FDG uptake. The expression of Glut1, HIF-1alpha, VEGF, CD31, CD34, and p53 was also significantly associated with the grade of malignancy and poor outcome in thymic epithelial tumors, whereas this relationship was not observed in GLUT3 and bcl-2. Our in vitro study demonstrated that upregulation of GLUT1 and HIF-1alpha was closely associated with [(18)F]FDG uptake into thymic tumor cell.[(18)F]FDG uptake in thymic epithelial tumors is determined by the presence of glucose metabolism (GLUT1), hypoxia (HIF-1alpha), angiogenesis (VEGF and MVD), and cell cycle regulator (p53).
Cases in Surgery
Authors: T. Brown
Journal: BMJ (1867)

the ingestion of sulphur began; and, though I cannot positively connect the two facts as cause and effect, I have little doubt of their standing in that relation to each other.Wishing, as far as possible, to clear up the matter, I then and there laid a positive interdict upon the use of "flowers of sulphur," let the complexion suffer ever so much in conse- quence; ordered the bromide mixture to be discontinued, and, recom- mending plenty of out-door exercise, took my leave, convinced in my own mind that I had discovered the mzatcries mnorbi of epilepsy in this case at least.I have only to say, in conclusion, that there has been no recurrence of the attacks since; that Kate -continues in the enjoyment of perfect health, all her functions are performed with healthy regularity, and her complexion is far more brilliant than when she was taking the large doses of sulphur to improve it.
Expression of the Endothelin Axis in Bladder Cancer: Relationship to Clinicopathologic Parameters and Long-term Survival
Authors: Christian Wülfing, Elke Eltze, Johann Yamini, Pia Wülfing, Stefan Bierer, Werner Böcker, Lothar Hertle, Axel Semjonow, Karl-Dietrich Sievert
Journal: European Urology (2005)
Taking a holiday
Authors: W. Sellar
Journal: BMJ (1999)

A few weeks of holiday are invaluable - a chance to relax, recharge the batteries, and return refreshed to work. But often the reality of holidays is of anxious planning, a late and harassed departure, exhausting travel, illness, and frayed tempers. The multiple demands on holiday time can be as stressful as they are at work. Some forward planning can be helpful.

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### Significant others 

Although your own desire for a break and relaxation may seem paramount, you also need to consider the needs of those with whom you share your life. A holiday that suits them may allow you to relax as well, relieve tensions, and allow you to enjoy what may not have been your first choice of destination. Perhaps the most important person to consider is your partner, who may also have strong views on the sort of break he or she needs. It may be helpful to draw up lists of what you each would like on your holiday and where you each would like to go, but be prepared to compromise if necessary. For example, your partner may feel that a break from cooking is paramount while you may prefer being chef de cuisine on holiday.

Children change everything. For small children, long distance journeys and hot climates may be stressful, which tends to have spin off effects on the parents. Most small children are happy with water, sand, hay, bicycles, and trees to climb. Worldly wise parents who argue that overseas holidays will foster cross cultural appreciation in their offspring are surely misguided, especially on a Mediterranean beach where they are only exposed to the dangers of ultraviolet radiation. Caravanning, or an old fashioned week or two by the sea or in a farmhouse in the countryside can offer many interesting learning experiences to small children. These …

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Time-Optimized Carbon-14 Breath Test for Helicobacter Pylori Contamination of the Stomach
Authors: MELTEM CAGLAR, ALLAN S. BELZBERG, BARRY SPRUSTON, GEORGE SEXSMITH
Journal: Clinical Nuclear Medicine (1999)

Evidence that Helicobacter pylori plays an important role in peptic ulcer disease has generated intense interest in the development of various screening strategies. H. pylori can be detected high sensitivity and specificity by the noninvasive carbon-14 (C-14) breath test.The authors assessed the cost-effectiveness of screening patients with dyspepsia before endoscopy. Thirty-four patients with dyspepsia were evaluated by the C-14 breath test, and then the authors reevaluated the criteria for the diagnosis of H. pylori. The discrimination obtained by using values of cumulative radioactivity or specific activity of breath samples collected between 10 and 60 minutes were studied.The main feature of H. pylori colonization in the stomach was a rapid increase of carbon dioxide in expired breath within 10 minutes after oral administration of C-14. Performance of the test was equally excellent for 10-minute values and 60-minute cumulative excretion.The C-14 breath test is a reliable method for diagnosing H. pylori colonization in the stomach, and the accuracy is not compromised by reducing the sample time to maintain better cost-effectiveness and patient acceptance.
On the Use of Nonphysician “Associate Residents” in Overcrowded Specialty-Training Programs
Authors: Henry K. Silver, Patricia A. McAtee
Journal: New England Journal of Medicine (1984)

A number of solutions have been proposed to correct the substantial oversupply of physicians that already exists or will exist by the end of this decade. These include decreasing the number of medical-school entrants, closing some medical schools entirely, eliminating federal support to medical schools for student education, raising fees and tuition for medical students, denying favorable immigration status to foreign-born medical graduates seeking postgraduate medical training, and requiring more thorough evaluation of U.S. citizens who wish to practice here after graduation from foreign medical schools.All these suggestions have merit, but we recommend yet another solution, which depends on . . .
Treatment of knee pain in primary care
Authors: Carmel M Hughes, Chris M Bleakley
Journal: BMJ (2006)

In the United Kingdom, general practitioners have traditionally been seen as the key players in primary care delivery, with support from a multidisciplinary team. As primary care extends its remit into areas such as minor surgery, team members are likely to come from diverse health disciplines. Recent studies show that patients presenting to primary care with knee pain receive little information on pain management, rehabilitation,1 or use of non-steroidal anti-inflammatory drugs and few are referred to specialist services.2 In this week's BMJ , a trial by Hay and colleagues assesses the impact of pharmacy and physiotherapy on the management of older people with pain or stiffness of one or both knees in primary care.3 

The trial compared three interventions: enhanced pharmacy review (pharmacological management in accordance with an algorithm), community physiotherapy (advice about activity and pacing and an individualised …
Only half of people with diabetes receive all the tests they need, report says
Authors: G. Iacobucci
Journal: BMJ (2012)

The NHS in England has systematically failed to meet standards for improving care of people with diabetes, and new systems are unlikely to tackle deficiencies without urgent attention, a new report from MPs has concluded.1

The Department of Health’s 2001 national service framework for diabetes established a set of minimum standards for care, and the department also set out treatment targets for the management of blood glucose, blood pressure, and cholesterol, to try to minimise the risk of associated complications.

But the report from the House of Commons Public Accounts Committee, which looked at data concerning people aged 16 or over with a diagnosis of either type 1 or type 2 diabetes, said that although there was a consensus about what was needed, progress had been “depressingly …
Imiquimod cream 5% for recalcitrant cutaneous warts in immunosuppressed individuals
Authors: C.A. Harwood, C.M. Perrett, V.L. Brown, I.M. Leigh, J.M. Mcgregor, C.M. Proby
Journal: British Journal of Dermatology (2005)

Journal Article Imiquimod cream 5% for recalcitrant cutaneous warts in immunosuppressed individuals Get access C.A. Harwood, C.A. Harwood Centre for Cutaneous Research, Barts and the London School of Medicine and Dentistry, Queen Mary College, University of London, 2 Newark Street, London, E1 2AT, U.K Dr Catherine A. Harwood. E‐mail: caharwood@doctors.org.uk Search for other works by this author on: Oxford Academic Google Scholar C.M. Perrett, C.M. Perrett Centre for Cutaneous Research, Barts and the London School of Medicine and Dentistry, Queen Mary College, University of London, 2 Newark Street, London, E1 2AT, U.K Search for other works by this author on: Oxford Academic Google Scholar V.L. Brown, V.L. Brown Centre for Cutaneous Research, Barts and the London School of Medicine and Dentistry, Queen Mary College, University of London, 2 Newark Street, London, E1 2AT, U.K Search for other works by this author on: Oxford Academic Google Scholar I.M. Leigh, I.M. Leigh Centre for Cutaneous Research, Barts and the London School of Medicine and Dentistry, Queen Mary College, University of London, 2 Newark Street, London, E1 2AT, U.K Search for other works by this author on: Oxford Academic Google Scholar J.M. Mcgregor, J.M. Mcgregor Centre for Cutaneous Research, Barts and the London School of Medicine and Dentistry, Queen Mary College, University of London, 2 Newark Street, London, E1 2AT, U.K Search for other works by this author on: Oxford Academic Google Scholar C.M. Proby C.M. Proby Centre for Cutaneous Research, Barts and the London School of Medicine and Dentistry, Queen Mary College, University of London, 2 Newark Street, London, E1 2AT, U.K Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 152, Issue 1, 1 January 2005, Pages 122–129, https://doi.org/10.1111/j.1365-2133.2005.06322.x Published: 01 January 2005 Article history Accepted: 08 April 2004 Published: 01 January 2005
A new method for the measurement of thyroidal iodine release in man
Authors: John T. Nicoloff
Journal: Journal of Clinical Investigation (1970)

A new method is described for the detection of variations in the release rate of all iodinated products by the thyroid gland in man. (125)I was employed to endogenously label the thyroid gland, and a parenterally administered (131)I thyroxine dose was used to generate a (131)I reference source. Thyroidal iodine release activity was quantitatively assessed by the measurement of variations in (125)I/(131)I ratio values obtained in timed urine samples. Diurnal variation in thyroid release patterns was observed in euthyroid subjects which was promptly suppressed by exogenous triiodothyronine administration and was simulated by the intramuscular injection of 0.25-0.50 U of bovine thyrotropin. The zenith value occurred at 4:00 a.m. +/-3.4 hr (SD) and the nadir at 5:00 p.m. +/-3.6 hr. The absence of a diurnal pattern in patients with thyrotoxicosis and in secondary hypothyroidism indicated that this diurnal fluctuation was under thyrotropin (TSH) regulation. This new method also promises to be a useful tool for the study of the intrathyroidal recycling of iodide from the iodotyrosine pool and the detection of factors which may acutely alter thyroid function.
Interventricular septal motion: biventricular angiographic assessment of its relative contribution to left and right ventricular contraction.
Authors: V S Banka, J B Agarwal, M M Bodenheimer, R H Helfant
Journal: Circulation (1981)

The interventricular septum (IVS) has conventionally been regarded as a functional part of the left ventricle (LV). To determine its normal range of motion, simultaneous biventricular cineangiograms (60 frames/sec) were performed (60 degrees left anterior oblique) in nine subjects without coronary or other heart disease. Arrhythmias were avoided by using a specially designed right ventricular (RV) angiographic catheter. IVS motion was studied qualitatively by three observers and quantitatively by superimposing end-systolic and diastolic frames using intra- and extracardiac reference points. Two transverse chords that trisected the end-systolic length of the IVS were drawn to quantitate IVS, LV and RV free wall motion. Qualitatively, the IVS thickened toward both RV and LV cavities as a result of shortening on its longitudinal axis. LV motion was 39.9 +/- 7.2% on the transverse axis, of which 31.2 +/- 5.2% was contributed by the LV free wall and 8.5 +/- 2.1% by IVS. RV transverse axis motion was 36.9 +/- 3.7%, of which 28.6 +/- 2.1% was contributed by the RV free wall and 8.3 +/- 2.3% by IVS motion. There was no difference between IVS motion toward the LV and that toward the RV. The IVS longitudinal axis shortened by 17.4 +/- 2.8% (p less than 0.001). The mean systolic IVS thickness increased symmetrically from 7.43 +/- 0.55 mm to 12.49 +/- 0.39 mm (p less than 0.001). In brief, the IVS thickens on its transverse axis and shortens on its longitudinal axis, contributing equally to RV and LV function.
SYMPATHECTOMY IN ANGINA PECTORIS
Authors: ELLIOTT C. CUTLER
Journal: JAMA (1926)

The pathologic process that gives rise to the clinical picture angina pectoris is of unknown etiology. Therefore, medical men have attempted symptomatic relief chiefly by rest and nitroglycerin, or by antispecific treatment when the disease has had a syphilitic origin. As these methods have been unavailing in many cases, it was natural to expect an attempt at symptomatic relief by surgical means; i. e., by interrupting nervous pathways carrying the painful stimuli. The belated efforts of surgeons in this field, in contrast to the early interference in comparable diseases, as tic douloureux, are due to our incomplete knowledge of the sensory pathways involved in cardiovascular symptomatology. The surgical treatment of angina pectoris was first proposed by Francois Franck<sup>1</sup>in 1899, but it was not until 1916 that Jonnesco,<sup>2</sup>a Bucharest surgeon, actually operated on a patient with syphilitic aortitis and angina, with complete relief from pain. C. H.
Relative roles of Ca2(+)-dependent and Ca2(+)-independent mechanisms in hypoxic contractile dysfunction.
Authors: Y Koretsune, E Marban
Journal: Circulation (1990)

Contractile function is known to be impaired during hypoxia or metabolic inhibition, but the relative importance of activator Ca2+ deficiency compared with the accumulation of depressant metabolites remains controversial. To distinguish between these possibilities, we used nuclear magnetic resonance (NMR) spectroscopy to measure the most likely mediators--intracellular [Ca2+] [( Ca2+]i), inorganic phosphate concentration [( Pi]), and pH--before and during hypoxia in perfused ferret hearts. Ca2+ transients were quantified by gated fluorine-19 NMR spectroscopy. Left ventricular developed pressure decreased to steady-state levels approximately 60% of control values after 20 minutes of hypoxic perfusion (induced by equilibrating the perfusate with 10% O2-90% N2). With hypoxia, phosphorus NMR revealed an increase in [Pi] and a mild intracellular acidosis. Both [Pi] and intracellular pH correlate well with the extent of decline of developed pressure in each heart, but multiple regression analysis points to the changes in [Pi] as the dominant influence. In contrast, [Ca2+]i at end diastole was not influenced by hypoxia, whereas the peak systolic values were paradoxically increased. The ratio of Ca2+ transient amplitude in hypoxia to that in control had no correlation with percent of developed pressure. These findings indicate that contractile failure during relatively mild, steady-state hypoxia is not due to a critical failure of any of the mechanisms that regulate cytoplasmic activator Ca2+. Instead, the accumulation of Pi (and to a lesser degree, H+) mediates hypoxic contractile dysfunction.
The Esophageal Obturator Airway-Reply
Authors: J. Philip Smith
Journal: JAMA (1984)

<h3>In Reply.—</h3> We agree with Dr Don Michael that the study by Schofferman et al<sup>1</sup>is inadequate to evaluate the EOA. This study was performed in a controlled situation under physician direction in the emergency room. Consequently, the report did not evaluate the capability of the EOA for prehospital ventilation. Two studies have documented that prehospital ventilation with the EOA, as measured by arterial blood gases, is inadequate.<sup>2,3</sup> One study used EMT II rescuers and the other paramedics, so training of rescuers does not appear to be important. Both studies indicated that difficulty in maintaining an effective mouth seal with the EOA contributed to the poor ventilatory results.<sup>2,3</sup> Facility of EOA insertion is a problem. The device offers little or no improvement over properly trained rescuers using endotracheal intubation. In a recent article inThe Journal, Jacobs et al reported that the endotracheal tube was successfully placed
International trade rules "rigged in favour of the rich," Oxfam says
Authors: A. Vass
Journal: BMJ (2002)

International trade rules amount to institutional fraud and are preventing development in poor countries, says a report published this week by a leading charity.

Whereas trade has been the been one of the most powerful driving forces in increasing prosperity for much of the world, millions of the world's poor are being left behind, and there is a widening of inequalities between the rich and poor.

International trade rules, says the Oxfam report, are “rigged in favour of the rich.” When developing countries export to rich country markets, they face tariff barriers that are four times higher then those faced by rich countries. These barriers cost them $100bn (£70bn; €113bn) a year, …
A CONCENTRATED LIVER EXTRACT FOR PARENTERAL ADMINISTRATION IN PERNICIOUS ANAEMIA
Authors: E. F. Scowen, A. W. Spence
Journal: BMJ (1935)

MEDICAL JOURNAL-~~~~~~~~~~~~~~~~~_ for long periods, and be easily sterilized.Two layers of silk and eight double layers of surgical gauze form mechanically efficient masks, but fall short on the other counts.Trials have therefore been made with various patterns of four-layered fine dental gauze masks.