tbuckley/cabot-search huggingface dataset:
Cyclooxygenase-2 Expression Is an Independent Predictor of Poor Prognosis in Colon Cancer
Authors: Shuji Ogino, Gregory J. Kirkner, Katsuhiko Nosho, Natsumi Irahara, Shoko Kure, Kaori Shima, Aditi Hazra, Andrew T. Chan, Reiko Dehari, Edward L. Giovannucci, Charles S. Fuchs
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Cyclooxygenase-2 (COX-2; PTGS2) is considered to play an important role in colorectal carcinogenesis and is often up-regulated in colon cancers. However, previous data on the influence of COX-2 expression on patient outcome have been conflicting. Experimental Design: Using 662 colon cancers (stage I-IV) in two independent prospective cohorts (the Nurses' Health Study and the Health Professionals Follow-up Study), we detected COX-2 overexpression in 548 (83%) tumors by immunohistochemistry. Cox proportional hazards models were used to compute hazard ratios (HR) of colon cancer-specific and overall mortalities, adjusted for patient characteristics and related molecular events, including the CpG island methylation phenotype, microsatellite instability, and p53, CIMP, KRAS, and BRAF mutations. Results: During follow-up of the 662 cases, there were 283 deaths, including 163 colon cancer-specific deaths. Patients with COX-2-positive tumors showed a trend towards an inferior colon cancer-specific mortality [HR, 1.37; 95% confidence interval (95% CI), 0.87-2.14], which became significant after adjusting for tumor stage and other predictors of clinical outcome (multivariate HR, 1.70; 95% CI, 1.06-2.74; P = 0.029). Notably, the prognostic effect of COX-2 expression might differ according to p53 status (Pinteraction = 0.04). Compared with tumors with both COX-2 and p53 negative, COX-2-positive tumors were significantly associated with an increased cancer-specific mortality (multivariate HR, 2.12; 95% CI, 1.23-3.65) regardless of p53 status. A similar trend was observed when overall mortality was used as an outcome. Conclusion: COX-2 overexpression is associated with worse survival among colon cancer patients. The effect of COX-2 on clinical outcome may be modified by p53 status.
Book Review Cardiac Surgery of the Neonate and Infant Edited by Aldo R. Castañeda, Richard A. Jonas, John E. Mayer, Jr., and Frank L. Hanley. 506 pp., illustrated. Philadelphia, W.B. Saunders, 1994. $169. 0-7216-4301-9
Authors: Jonah Odim
Journal: New England Journal of Medicine (1995)
Accelerated Infusion of Streptokinase for the Treatment of Left-Sided Prosthetic Valve Thrombosis
Authors: Ganesan Karthikeyan, Ravi S. Math, Navin Mathew, Bhima Shankar, Mani Kalaivani, Sandeep Singh, Vinay K. Bahl, Jack Hirsh, John W. Eikelboom
Journal: Circulation (2009)

No large prospective studies have evaluated the efficacy of fibrinolytic therapy for left-sided prosthetic valve thrombosis, yet it remains the first line of treatment in developing countries.We performed a randomized controlled trial comparing an accelerated infusion with the conventional infusion of streptokinase in 120 patients with a first episode of left-sided prosthetic valve thrombosis. The primary outcome measure was the occurrence of a complete clinical response, defined as objectively documented complete restoration of valve function in the absence of major complications. The secondary outcome was a composite of death, major bleeding, embolic stroke, or non-central nervous system systemic embolism. Patients were recruited over a 2.5-year period at a single center in India. Complete clinical response occurred in 38 (64.4%) of 59 patients with the accelerated infusion compared with 32 (53.3%) of 60 with the conventional infusion (hazard ratio 1.6, 95% confidence interval 0.9 to 2.5, P=0.055). There was no significant difference in the occurrence of the composite secondary outcome (hazard ratio 1.4, 95% confidence interval 0.5 to 3.5, P=0.50) or major bleeding (hazard ratio 2.2, 95% confidence interval 0.6 to 7.7, P=0.24) with the accelerated infusion. The success rate with fibrinolytic therapy was low overall (59%) and very low in patients in New York Heart Association functional class III/IV (24%).The large number of patients recruited from a single center underscores the massive burden of prosthetic valve thrombosis in developing countries. Fibrinolytic therapy with streptokinase is less efficacious than previously believed. The accelerated streptokinase infusion is not better than the standard infusion for left-sided prosthetic valve thrombosis. Developing countries urgently need more effective strategies to prevent and treat prosthetic valve thrombosis.
Knowledge and Use of Placebos by House Officers and Nurses
Authors: JAMES S. GOODWIN
Journal: Annals of Internal Medicine (1979)

Sixty house officers and 39 registered nurses in a university teaching hospital were surveyed to ascertain their knowledge of placebo action and their patterns of placebo use. The majority of physicians and nurses greatly underestimated the percentage of patients who experience pain relief when given placebo. Placebos typically were given to disliked patients who were suspected of exaggerating their pain or had failed to respond to usual medical regimens, or both. Positive responses to placebo medication were then interpreted by the physicians as evidence that the pain had no physiologic basis. Many studies have shown that overdemanding and complaining patients are, if anything, less likely to respond to placebo than patients well liked by the hospital staff. Nevertheless the results of our survey suggest that this is precisely the type of patient "at risk" for placebo treatment.
The joint disease of sarcoidosis.
Authors: J M Gumpel, C J Johns, L E Shulman
Journal: Annals of the Rheumatic Diseases (1967)

Although the first description of sarcoidosis by Jonathan Hutchinson (1877) was of a patient who "suffered from gout", only recently has it been appreciated that joint manifestations are an important part of sarcoidosis.Myers, Gottlieb, Mattman, Eckley, and Chason (1952) first described migratory polyarthritis as a presenting feature of sarcoidosis in four cases, and Gendel, Young, and Greiner (1952) reported a high incidence of joint symptoms in sarcoidosis in six of 24 patients.Subsequently the arthritis occurring in sarcoidosis has been studied by others, but these reports all concern patients selected because of their joint disease.Sokoloff and Bunim (1959) investigated five cases of sarcoidosis with arthritis, and found granulomata in the synovium of affected joints in three of the five.Williams (1961) described seven patients presenting with arthritis, in whom systemic manifestations and erythema nodo- sum were common, and Bianchi and Keech (1964) discussed the features of twelve cases of sarcoidosis presenting in a rheumatology clinic.The increased prevalence of a rheumatoid factor in patients with sarcoidosis was reported by Kunkel, Simon, and Fudenberg (1958), and the possibility that rheumatoid factor may play a role in the patho- genesis of pulmonary fibrosis in sarcoidosis was considered by Israel, Patterson, and Smukler (1964).Rheumatoid factor has on occasion been found in patients with sarcoidosis and joint disease (Kaplan, 1963a) but the frequency of its presence in unselected patients, with or without arthritis, is not known.Hyperuricaemia in sarcoidosis was noted in six of 25 patients by Kaplan and Klatskin (1960) and they described the co-existence and possible association of psoriasis, sarcoidosis, and gout in three.
Abstract 1454: MiR-517a mediates cisplatin sensitivity in bladder cell carcinoma
Authors: Ahmed Ibrahim, Arnab Chakravarti, Tim Lautenschlaeger
Journal: Cancer Research (2014)

Abstract Cisplatin-containing neoadjuvant chemotherapy is the standard of care treatment for patients with muscle-invasive bladder cancer. We sought out to assess if miR-517a modulates sensitivity to cisplatin in bladder cancer cell lines. We used four transitional cell carcinoma cell lines T24, J82, UM-UC3 and TCCSUP. Cells were transfected with miR-517a mimic or inhibitor using lipofectaime according to manufacturer's instruction. Mtt assay was performed to assess viability after 96 hrs and clonogenic survival assays were performed to assess colony forming ability of cell lines. We found that miR-517a reduced proliferation and increased cisplatin sensitivity. Overexpression of miR-517a resulted in reduction of proliferation by 53%, 45%, 62% and 67% respectively (t-test p&amp;lt;0.05 for comparison with respective control cell lines). Transfection with miR-517a followed by cisplatin treatment resulted in a dramatic reduction in viability and colony forming ability of cells compared to cisplatin treatment alone. This reduction in viability was not observed after transfection with the miR-517a inhibitor. To our knowledge, this is the first report indicating that miR-517a functions as a sensitizer to cisplatin therapy in bladder cancer. Bioinformatics and microRNA target prediction databases identified several candidate genes. Note: This abstract was not presented at the meeting. Citation Format: Ahmed Ibrahim, Arnab Chakravarti, Tim Lautenschlaeger. MiR-517a mediates cisplatin sensitivity in bladder cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1454. doi:10.1158/1538-7445.AM2014-1454
EFFECTS OF ALIROCUMAB, A FULLY HUMAN MONOCLONAL ANTIBODY TO PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9, ON LIPOPROTEIN PARTICLE CONCENTRATIONS DETERMINED BY NUCLEAR MAGNETIC RESONANCE: SUBSTUDY OF A RANDOMIZED DOUBLE-BLIND PHASE II CLINICAL TRIAL
Authors: Michael J. Koren, Dean Kereiakes, Ray Pourfarzib, Deborah Winegar, Poulabi Banerjee, Sara Hamon, Corinne Hanotin, James M. McKenney
Journal: Journal of the American College of Cardiology (2014)
929-61 Contrast Wash-in During MRI Myocardial Perfusion Imaging in Patients with Q-Wave Myocardial Infarction
Authors: Mark A. Lawson, H. Ross Singleton, Edward G. Walsh, Mark Doyle, Maryann Roney, Gerald G. Blackwell, Gerald M. Pohost
Journal: Journal of the American College of Cardiology (1995)
The Troubled Helix: Social and Psychological Implications of the New Human Genetics
Authors: D J Weatherall
Journal: BMJ (1996)

M Marteau, M P M Richards Cambridge University Press, £35, pp 355 ISBN 0 521 46288 6

Books about the “new genetics” continue to pour into medical book-sellers. Never, it seems, has any advance in human biology brought with it such high hopes for the future mixed with so many dire concerns about its misuse. When The Troubled Helix arrived on my desk I wondered how there possibly could be anything new to be said about the past, present, or future of medical genetics.

Despite its title, however, The Troubled Helix is not yet another compendium of doom and gloom. Rather, it is a serious attempt to present both the …
Effects of tonicity on tension and intracellular sodium and calcium activities in sheep heart.
Authors: M G Lado, S S Sheu, H A Fozzard
Journal: Circulation Research (1984)

We have measured the effects of changing tonicity of the bathing solution on intracellular sodium and calcium activities and tension of sheep cardiac Purkinje strands and ventricular muscle. For Purkinje strands in solutions of normal tonicity, resting membrane potential was -77.4 +/- 0.4 mV (mean +/- SE), sodium activity was 7.9 +/- 0.4 mM, and calcium activity was 98 +/- 9 nM. For ventricular muscle in solutions of normal tonicity, resting membrane potential was -86.4 +/- 1.2 mV, sodium activity was 6.9 +/- 0.5 mM, and calcium activity was 70 +/- 4 nM. Reduction of tonicity to 75% of normal in both tissues produced depolarization of a few millivolts, and sodium activity fell almost to the level predicted for simple osmotic dilution. In Purkinje strands, calcium activity fell much more than that predicted for simple osmotic dilution. Twitch contraction was reduced in the hypotonic solution. Increase of tonicity to 150% and 200% caused the resting membrane potential to become more negative. In both tissues, sodium activity increased somewhat less than predicted from simple water movement, and calcium activity increased proportionately much more than sodium activity. The much larger change of calcium activity in both hypo- and hypertonic solutions could be explained by water movement plus the effect of sodium-calcium exchange. In hypertonic solutions, tonic tension was increased, along with the rise in calcium activity; however, the twitch tension was reduced. This reduction of twitch tension may be due to a direct effect of hypertonicity on cross-bridge behavior, as has been reported for skeletal muscle.
"Poorest of the poor" cannot access contraceptive services, report finds
Authors: A. Gulland
Journal: BMJ (2012)

Progress in ensuring that women in poor countries have access to modern methods of contraception has stalled, says a new report.

A study by the United Nations Population Fund and the Guttmacher Institute, a US organisation that carries out research on reproductive and sexual health, found that this year 645 million women of reproductive age (15 to 49 years) are using modern methods of contraception in the developing world, 42 million more than in 2008. But this rise is less than half the increase of 100 million between 2003 and 2008.1

Half of the rise between 2008 and 2012 is the result of an increase in the population, rather than in the number of women using contraception, says …
Smoking Reduction and Lung Cancer Risk—Reply
Authors: Nina S. Godtfredsen
Journal: JAMA (2006)

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STUDIES ON ENDOTHELIAL REACTIONS
Authors: Nathan Chandler Foot
Journal: The Journal of Experimental Medicine (1923)

THE CHANGES IN THE DISTRIBUTION OF INTRAVENOUSLY ADMINISTERED COLLOIDAL INK IN SPLENECTOMIZED RABBITS MAY BE INTERPRETED SOMEWHAT AS FOLLOWS: The removal of the spleen throws an increased amount of ink into the other hematopoietic organs and the lung and liver. While we should expect the liver or the bone marrow to compensate for the loss of the spleen and to take up this ink and remove it from the circulation, that is not the case. The lungs appear to play the chief part in the process, slowly passing on the removed material, contained in macrophages, to the liver, or retaining these ink-laden cells in their tissues and capillaries. By an increase in the capillary endothelium and by a process of engorgement of the capillaries with cells presumably derived therefrom, the lungs remove by far the greater part of the foreign material that has been introduced into the circulation. At the same time there is an increase in the number of ink-bearing macrophages in the lymphatics and capillaries of the lung, indicating that these cells are entering the circulation and the lymph stream (Fig. 8). The only organ where they lodge in any quantities, outside of the peribronchial lymph nodes, is the liver, the sinusoids of which contain an increasing number of macrophages as time goes on. It is possible that these cells are destroyed in the sinusoids and the carbon transferred to the liver epithelium; there is evidence to support this assumption. After the lungs, the liver comes next in degree of intensity of pigmentation; the bone marrow contains far less than either of these organs.
Hospital Central Sterile Supply Departments
Authors: V. D. Allison
Journal: BMJ (1960)

PROBLEMSBDICAJOURNA building of an informal character.Fig. 1 shows a portion of the new Swindon hospital with one-and two- story buildings for the departments of pathology and physical medicine.Fig. 2 shows a small garden planned in a courtyard within the single-story out-patient depart- ment at the same hospital.Fig. 3, also taken from the new Swindon hospital, shows the low buildings for the out-patient and casualty departments, with the future, higher, ward building sketched in the background.Fig. 4 shows the ward block at the Nuffield experimental hospital building at Belfast.Here the treatment of the facade reflects the interior organization of the ward into small nursing units, two on each floor.These examples suggest that the hospital of the future may perhaps draw architectural inspiration from the size and shape of the functional units within it, whether they be nursing units, out-patient clinics, or other units of care.By expressing these working units in the architecture we can break up the very large masses of building which go to make a modern hospital, and create a more human scale, and an environment more compre- hensible and reassuring for the patient.
Ambulance Transport in Rural Areas
Authors: M. Bradford
Journal: BMJ (1949)

occurrence of which, it may be mentioned in passing, had been suggested by me (Edinb.med.J., 1929, 36, 654).Because of some confusion, especially in regard to the terms " carcinogen " and " carcinogenic " and their implications, I am unable to comprehend fully Sir Ernest Kennaway's remarks in his letter in the Journal of April 16 (p.679).I imagine, however, that one thing which would determine the development of a Shope tumour in a cottontail rabbit would be whether or not it had been scratched when fighting by another rabbit, the bearer of such a tumour.In such a case the claws of the latter would almost certainly be contaminated with the virus through scratching its skin papillomata in order to relieve irritation.The onus of proof that " the first abnormal change in the fowl which produced the Chicken Sarcoma I of Murphy and Rous" (and, indeed, in animals treated with carcinogenic substances strictly so called) is the liberation in the tissue cells of commensal viruses rests with those who hold this view.No valid evidence has so far been submitted in support of such an out-of-the-way assumption: while on the other hand the one tumour definitely shown to be caused by a virus-namely, the Shope papilloma-when it becomes malignant, behaves in a manner very difficult to reconcile with such a view, since the virus, easily demonstrable in the non-malignant papilloma, ceases to be so at all in the malignant transformation.-Iam, etc., Aberdeen.
Failure of Postnatal Ductus Arteriosus Closure in Prostaglandin Transporter–Deficient Mice
Authors: Hee-Yoon Chang, Joseph Locker, Run Lu, Victor L. Schuster
Journal: Circulation (2010)

Background— Prostaglandin E 2 (PGE 2 ) plays a major role both in maintaining patency of the fetal ductus arteriosus and in closure of the ductus arteriosus after birth. The rate-limiting step in PGE 2 signal termination is PGE 2 uptake by the transporter PGT. Methods and Results— To determine the role of PGT in ductus arteriosus closure, we used a gene-targeting strategy to produce mice in which PGT exon 1 was flanked by loxP sites. Successful targeting was obtained because neither mice hypomorphic at the PGT allele (PGT Neo/Neo) nor global PGT knockout mice (PGT −/− ) exhibited PGT protein expression; moreover, embryonic fibroblasts isolated from targeted mice failed to exhibit carrier-mediated PGE 2 uptake. Although born in a normal mendelian ratio, no PGT −/− mice survived past postnatal day 1, and no PGT Neo/Neo mice survived past postnatal day 2. Necropsy revealed patent ductus arteriosus with normal intimal thickening but dilated cardiac chambers. Both PGT Neo/Neo and PGT −/− mice could be rescued through the postnatal period by giving the mother indomethacin before birth. Rescued mice grew normally and had no abnormalities by gross and microscopic postmortem analyses. In accordance with the known role of PGT in metabolizing PGE 2 , rescued adult PGT −/− mice had lower plasma PGE 2 metabolite levels and higher urinary PGE 2 excretion rates than wild-type mice. Conclusion— PGT plays a critical role in closure of the ductus arteriosus after birth by ensuring a reduction in local and/or circulating PGE 2 concentrations.
Abstract 5390: Anti-IL10-R1 monoclonal antibody with concomitant bacillus calmette-Guérin (BCG) prevents metastatic bladder cancer in an <i>in vivo</i> mouse model
Authors: Eric Askeland, Mark Newton, Nathan Bockholt, Matthew Knudson, Jonathan Henning, Xu Wang, Ryan Askeland, Peter Weady, George Smith, Michael Eisenbraun, James Fraser, Michael O'Donnell, Yi Luo
Journal: Cancer Research (2012)

Abstract Introduction: Induction of Th1 immunity is required for effective intravesical BCG immunotherapy of bladder cancer. IL-10 down-regulates the Th1 response and is associated with BCG failure. We previously demonstrated that blocking IL-10 receptor (IL-10R) by systemic administration of anti-IL-10R1 mAb enhanced intravesical BCG (living Pasteur strain) treatment of bladder cancer in an orthotopic mouse model. Here we investigated the effect of anti-IL-10R1 mAb on clinically used BCG (lyophilized TICE strain) for induction of anti-bladder cancer immunity. Methods: Splenocytes were incubated with BCG alone or plus control IgG or ant-IL-10R1 mAb for 24 hours, followed by ELISA analysis of IFN-γ production. Bladder RNA was extracted after 6 treatments (twice weekly) with intravesical (i.b.) BCG plus intraperitoneal (i.p.) control IgG or anti-IL-10R1 mAb, followed by qPCR analysis of IFN-γ mRNA expression. Three groups of 20 mice were inoculated with luciferase-expressing MB49 bladder cancer cells and treated with i.b. PBS plus i.p. PBS (Group 1), i.b. BCG plus i.p. control IgG (Group 2), or i.b. BCG plus i.p. anti-IL-10R1 mAb (Group 3) 2x/wk for 6 total treatments. Mice were monitored weekly using IVIS luminescence and followed for 76 days. A bioluminesence cutoff of 5X104 p/s was used to establish the presence of bladder cancer. At animal death bladders were collected, weighed and processed for histological analysis. In suspected cases of metastatic disease the affected organs were also collected for histological analysis. Results: BCG plus anti-IL-10R1 mAb induced increased IFN-γ production by splenocytes in a dose-dependent manner. BCG plus anti-IL-10R1 mAb substantially increased IFN-γ mRNA. Eleven, 17 and 9 mice from Groups 1, 2 and 3, respectively, developed bladder cancer. One mouse in Group 2 and 2 mice in Group 3 showed cancer regression. 36%, 53% and 0% of Groups 1, 2 and 3 developed metastatic bladder cancer, respectively (p=0.020). While bladder weights for the groups were different, the differences did not reach statistical significance. Conclusions: Anti-IL-10R1 mAb enhances BCG-induced Th1 immune responses both in vitro and in vivo. Intravesical BCG plus anti-IL-10R1 mAb shows statistical significance in preventing metastasis of bladder cancer in an orthotopic bladder tumor mouse model. Anti-IL-10R1 mAb may prove useful in clinical practice for the prevention of metastatic bladder cancer in high-risk patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5390. doi:1538-7445.AM2012-5390