tbuckley/cabot-search huggingface dataset:
New Approaches to Assessing and Treating Early-Stage Colon and Rectal Cancer: Summary Statement from 2007 Santa Monica Conference
Authors: Lee S. Rosen, Anton J. Bilchik, Robert W. Beart, Al B. Benson, Kenneth J. Chang, Carolyn C. Compton, Axel Grothey, Daniel G. Haller, Clifford Y. Ko, Patrick M. Lynch, Heidi Nelson, Michael J. Stamos, Roderick R. Turner, Christopher G. Willett
Journal: Clinical Cancer Research (2007)

Abstract The 2007 Santa Monica Conference on Assessing and Treating Early-Stage Colon and Rectal Cancer, a multidisciplinary meeting of leaders in surgery, medical and radiation oncology, and pathology, was convened on January 12 to 13, 2007. The purpose of the meeting was to assess current data and issues in the field and to develop recommendations for advancing patient care and clinical research. Topics included pathologic assessment and staging, transanal versus laparoscopic versus open resection, adjuvant therapy, genetic testing and counseling, cooperative group strategies, and the use of biological therapies and novel agents. A review of the key issues discussed, as well as conclusions and recommendations considered significant to the field, is summarized below and presented at greater length in the individual manuscripts and accompanying discussion that comprise the full conference proceedings. Although the management of early-stage colon and rectal cancers remains a challenge for all of us, the development and use of new technologies and methods of assessment and treatment over the past several decades is yielding encouraging results. A variety of opportunities to further improve outcomes were addressed in this forum, including recommendations that specific protocols be adopted regarding surgical and pathologic dissection and reporting, particularly for stage II disease; the corollary need to increase active multidisciplinary collaboration; and the development of comprehensive consensus guidelines and recommendations to standardize care in early-stage colorectal cancer.
1118-102 Baseline white blood cell count and interleukin-6 levels provide complementary prognostic information in acute myocardial infarction: Results from the CARDINAL trial
Authors: Manesh R Patel, Kenneth W Mahaffey, Paul W Armstrong, W.Douglas Weaver, Gudaye Tasissa, Judith S Hochman, Thomas G Todaro, Kevin J Malloy, Thomas H Parish, Scottt Rollins, Pierre Theroux, Wiltold Ruzyllo, Jose C Nicolau, Christopher B Granger
Journal: Journal of the American College of Cardiology (2004)
Direct effects of gemfibrozil on the fibrinolytic system. Diminution of synthesis of plasminogen activator inhibitor type 1.
Authors: S Fujii, B E Sobel
Journal: Circulation (1992)

BACKGROUND Platelet-associated epidermal growth factor (EGF) and transforming growth factor-beta (TGF-beta) can augment synthesis of plasminogen activator inhibitor type 1 (PAI-1). Accordingly, exacerbation of atherogenesis may accompany release of platelet-associated growth factors (or mitogens) occurring in association with occult, repetitive thrombosis and thrombolysis. In the Helsinki primary prevention trial, gemfibrozil decreased coronary events but did so essentially only in initially hypertriglyceridemic subjects. Such subjects are known to exhibit high concentrations of PAI-1 in plasma. METHODS AND RESULTS To determine whether pharmacological concentrations of gemfibrozil directly affect PAI-1 synthesis, we characterized its effects on a human hepatoma cell line (Hep G2) in vitro. Gemfibrozil decreased basal PAI-1 secretion by 43% and attenuated the augmentation of PAI-1 synthesis over 24 hours induced by EGF and TGF-beta by 37% and 39% without altering overall protein synthesis. Furthermore, it blocked the EGF and TGF-beta-induced increases in PAI-1 mRNA over 6 hours by 65% and 60%. Increases in plasma PAI activity induced by infusion of purified growth factors or by autologous platelet lysates in rabbits were inhibited by gemfibrozil by more than 50%. CONCLUSIONS Beneficial effects of gemfibrozil in reducing coronary events in hypertriglyceridemic patients may depend, in part, on potentiation of fibrinolysis by direct diminution of synthesis of endogenous PAI-1.
Preservation of Physiological Responses to Hypoglycemia 2 Days After Antecedent Hypoglycemia in Patients With IDDM
Authors: Emad George, Jefferson L Marques, Nigel D Harris, Ian A Macdonald, Colin A Hardisty, Simon R Heller
Journal: Diabetes Care (1997)

OBJECTIVE To assess the effects of short-term antecedent hypoglycemia on responses to further hypoglycemia 2 days later in patients with IDDM. RESEARCH DESIGN AND METHODS We studied eight type I diabetic patients without hypoglycemia unawareness or autonomic neuropathy during two periods at least 4 weeks apart. On day 1, 2 h of either clamped hyperinsulinemic (60 mU · m−2 · min−1) hypoglycemia at 2.8 mmol/l or euglycemia at 5.0 mmol/l were induced. Hyperinsulinemic hypoglycemia was induced 2 days later with 40 min glucose steps of 5.0, 4.0, 3.5, 3.0, and 2.5 mmol/l. Catecholamine levels and symptomatic and physiological responses were measured every 10–20 min. RESULTS When compared with the responses measured following euglycemia, the responses of norepinephrine 2 days after hypoglycemia were reduced (peak, 1.4 ± 0.4 [mean ± SE] vs.1.0 ± 0.3 nmol/l [P &amp;lt; 0.05]; threshold, 3.4 ± 0.1 vs. 2.9 ± 0.1 mmol/l glucose [P &amp;lt; 0.01]). The responses of epinephrine (peak, 4.0 ± 1.4 vs. 3.5 ± 0.8 nmol/l [P = 0.84]; threshold, 3.8 ± 0.1 vs. 3.6 ± 0.1 mmol/l glucose [P = 0.38]), water loss (peak, 194 ± 34 vs. 179 ± 47 g−1 · m−2 · h−1 [P = 0.73]; threshold, 2.9 ± 0.2 vs. 2.9 ± 0.2 mmol/l glucose [P = 0.90]), tremor (peak, 0.28 ± 0.05 vs. 0.37 ± 0.06 root mean square volts (RMS V) [P = 0.19]; threshold, 3.2 ± 0.2 vs. 3.1 ± 0.2 mmol/l glucose [P = 0.70]), total symptom scores (peak, 10.6 ± 2.1 vs. 10.8 ± 1.9 [P = 0.95]; threshold, 3.3 ± 0.2 vs. 3.6 ± 0.1 mmol/l glucose [P = 0.15]), and cognitive function (four-choice reaction time: threshold, 2.9 ± 0.2 vs. 3.0 ± 0.2 mmol/l glucose [P = 0.69]) were unaffected. CONCLUSIONS The effect on hypoglycemic physiological responses of 2 h of experimental hypoglycemia lasts for 1–2 days in these patients with IDDM . The pathophysiological effect of antecedent hypoglycemia may be of shorter duration in IDDM patients, compared with nondiabetic subjects.
THE THYMUS AND RECOVERY FROM CYCLOPHOSPHAMIDE-INDUCED TOLERANCE TO SHEEP ERYTHROCYTES
Authors: Alan C. Aisenberg, Caroline Davis
Journal: The Journal of Experimental Medicine (1968)

Recovery from specific immunological tolerance to sheep erythrocytes induced with the drug cyclophosphamide was studied with the hemolytic plaque technique of Jerne. The base line plaque (19S antibody-forming cell of the unstimulated spleen) and the proliferative response to antigen, both of which had disappeared during tolerance induction, returned with the recovery of specific immunological reactivity. When cyclophosphamide is injected without sheep cells there is temporary immunological unreactivity and lymphoid depletion of the spleen, but specific tolerance is not induced. Recovery is largely complete at the end of 2 wk and does not require the participation of the thymus. When cyclophosphamide is injected together with sheep cells, 18 days after drug injection, tolerance is still complete. In nonthymectomized mice there is rapid recovery during the next 10 wk, followed by much slower restoration over the remaining 20-30 wk of observation. The entire recovery process evidently takes 40-50 wk. In thymectomized CBA mice only minimal recovery takes place in the first 10 wk and no further restoration occurs thereafter. Thymectomy performed 18 days after tolerance is induced, when tolerance is complete, is equally effective in preventing this recovery.
RADIUM APPLICATOR FOR TREATMENT OF LESIONS ABOUT THE HEAD, FACE AND NECK
Authors: William H. Kennedy
Journal: JAMA (1926)

Great difficulty has been experienced with methods of applying radium to the face, head and neck. This applicator, while very simple in construction, is adjustable to any angle by bending the copper wire, and when once adjusted remains in perfect contact with the lesion, allowing the patient to move his head in any direction. Another important consideration is distance without the use of blocks or gauze. This method eliminates the handling of radium, as it can be placed in the rubber tube with forceps and removed in the same manner. It consists of a leather head-band, copper wire and universal ball joint made to be used with one-fourth inch rubber tubing, in which the radium is placed. The applicator is manufactured by the Akron Surgical Instrument Company, Indianapolis.
Biochemical Parameters of Guinea Pig Perilymph Sampled According to Scala and Following Sound Presentation
Authors: Leon L. Gershbein, Dennis T. Manshio, Phil S. Shurrager
Journal: Environmental Health Perspectives (1974)

Guinea pigs were exposed to sound varying from 2 to 8 kHz in frequency and 80-100 dB (SPL) in intensity for periods of 1 hr. The biochemical parameters, glucose, sodium, total protein, and the glycolytic enzymes, aldolase, phosphohexose isomerase, and total LDH as well as isozymes of the latter were ascertained for blood serum, perilymph, and, in some instances, cerebrospinal fluid. The three enzymes occurred at lower levels in perilymph as compared to blood serum. Except for a small difference in serum total protein, sound presentation incurred no significant effect on any of the above parameters. Definite differences in several metabolites were discerned for perilymph sampled according to scala and which were independent of the respective acoustical treatments. Thus, as compared to the scale tympani, the scala vestibuli perilymph displayed a higher glucose content and a diminished total LDH level and of the latter isozymes, LDH(1) ranged lower and LDH(2), higher. As further evidence pointing to cerebrospinal fluid as the possible origin of perilymph, similarities in glucose contents and LDH isozyme patterns were noted for both fluids.
F-18 FDG PET/CT for Detecting Bone and Bone Marrow Involvement in Sarcoidosis Patients
Authors: Rémy L. Mostard, Léonne Prompers, Rene E. Weijers, Marinus J. van Kroonenburgh, Petal A. Wijnen, Piet P. Geusens, Marjolein Drent
Journal: Clinical Nuclear Medicine (2011)

Background: The prevalence of bone involvement in sarcoidosis has been estimated to be 3% to 5%, mostly affecting the phalanges. The aim of this study was to assess the prevalence and distribution pattern of bone and bone marrow involvement as detected by positron emission tomography/computed tomography (PET/CT) in sarcoidosis patients. Methods: Between June 2006 and September 2010, 122 patients suffering from severe sarcoidosis who underwent a PET/CT and met the inclusion criteria were studied. In 94 (77%) patients, the PET/CT demonstrated positive findings associated with sarcoidosis. The 94 PET/CTs were screened for the presence of bone/bone marrow localizations. Additionally, low-dose CT scans were screened for other causes of increased bone uptake. Relevant clinical data were gathered retrospectively. Results: Evidence for bone/bone marrow localizations was found in 34% of the 94 patients with PET/CT-positive findings. Of these patients, 60% showed obvious focal bone lesions at various localizations: axial skeleton (47%), pelvis (40%), extremities (34%), and skull (2%). In 40% of patients, diffuse increased uptake in both axial and peripheral bone marrow, without focal lesions, was found. Both diffuse and focal uptake were seen in 34%, whereas only focal lesions were observed in 25%. In all but 2 (6%) patients, no bone abnormalities on low-dose CT were found. Conclusions: More than one-third of PET/CT-positive sarcoidosis patients had osseous abnormalities on PET/CT. The majority of these lesions (94%) could not be detected on low-dose CT. No single localization of preference was found. These preliminary results stress the value of PET/CT imaging in the assessment of bone/bone marrow involvement in sarcoidosis patients.
Experimental non-O group 1 Vibrio cholerae gastroenteritis in humans.
Authors: J G Morris, T Takeda, B D Tall, G A Losonsky, S K Bhattacharya, B D Forrest, B A Kay, M Nishibuchi
Journal: Journal of Clinical Investigation (1990)

In this study, 27 volunteers received one of three non-O group 1 Vibrio cholerae strains in doses as high as 10(9) CFU. Only one strain (strain C) caused diarrhea: this strain was able to colonize the gastrointestinal tract, and produced a heat-stable enterotoxin (NAG-ST). Diarrhea was not seen with a strain (strain A) that colonized the intestine but did not produce NAG-ST, nor with a strain (strain B) that produced NAG-ST but did not colonize. Persons receiving strain C had diarrhea and abdominal cramps. Diarrheal stool volumes ranged from 154 to 5,397 ml; stool samples from the patient having 5,397 ml of diarrhea were tested and found to contain NAG-ST. The median incubation period for illness was 10 h. There was a suggestion that occurrence of diarrhea was dependent on inoculum size. Immune responses to homologous outer membrane proteins, lipopolysaccharide, and whole-cell lysates were demonstrable with all three strains. Our data demonstrate that V. cholerae of O groups other than 1 are able to cause severe diarrheal disease. However, not all strains are pathogenic for humans: virulence of strain C may be dependent on its ability both to colonize the intestine and to produce a toxin such as NAG-ST.
New medium used in the differentiation of human pluripotent stem cells to retinal cells is comparable to fetal human eye tissue
Authors: Xiaobing Wang, Kai Xiong, Cong Lin, Lei Lv, Jing Chen, Chongchong Xu, Songtao Wang, Dandan Gu, Hua Zheng, Hurong Yu, Yan Li, Honglei Xiao, Guomin Zhou
Journal: Biomaterials (2015)
Abstract 3803: Anti-cancer activity of Capridine, a novel nitroacridine chemotherapeutic, in glioblastoma
Authors: Arulkumaran Shanmugam, Shilpi Rajoria, Andrea L. George, Casey Jussim, Robert Suriano, Jerzy Konopa, Abraham Mittelman, Raj K. Tiwari
Journal: Cancer Research (2012)

Abstract Glioblastoma is characterized by highly proliferative tumor cells, increased cellularity, necrosis, and proliferation of capillary endothelial cells. The incidence rate of glioma in adults is 50% greater in men than in women suggesting that there may be a male hormonal component that modulates glioblastoma progression. Our preclinical developmental program identified Capridine as a chemotherapeutic agent that had specificity towards prostate cancer with minimal bone marrow toxicity. Since the DNA intercalating activity of Capridine does not completely correlate with its cytotoxic activity, we examined other alternative cellular targets. Our investigation identified the androgen receptor (AR) and its dependent signal transduction mechanism as a possible cellular mediator of its cytotoxic activity. In this study, our analysis revealed that glioblastoma cell lines T98G and MO59K expressed AR and their growth was responsive to the AR-mediated signal transduction. Capridine inhibited the growth of glioblastoma cells by down regulating the AR and inhibiting the phosphorylation of Focal adhesion kinase (FAK). Since FAK is associated with integrin and neuropeptide mediated signaling, critical for cell migration and invasion, we examined the activity of Capridine on cell invasion and migration using a Boyden Chamber assay. Capridine inhibited the migration and invasion of the glioblastoma cell lines T98G and MO59K. Our data not only validate AR as a target of Capridine as with prostate cancer but also implicate a novel target, FAK in glioblastoma. Combination approaches using Capridine and anti-hormonal therapy may prove to be viable chemotherapeutic regimen for primary glioblastoma as well as an inhibitor of metastatic propensity. These preclinical studies are being extended in an in vivo animal model with combination treatment approaches with a view to develop novel chemotherapy based treatment for glioblastoma. 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 3803. doi:1538-7445.AM2012-3803
Disseminated Mammary Carcinoma
Authors: Ian Macdonald
Journal: JAMA (1963)

To the Editor:  —The discussion of the therapy of disseminated mammary carcinoma ( JAMA  184 :306 [April 27] 1963) is based on a concept which has become untenable in the light of accumulated evidence in the past 5 or more years. It amounts to an expression of the idea of estrogen-dependence of the neoplasm, and assigns an unjustified importance to a chronological landmark rather than, correctly, to the woman's endocrinologic age as gauged by the menopause. If estrogen-dependence were the key, the best results of hormonal, additive treatment should be secured by the use of androgens in menstruants. Actually, the proportion of responsive patients with treatment either by androgens or estrogens increases with succeeding decades beyond the menopause. For several years I have used estrogens as the initial treatment of choice in disseminated disease in women who are more than 1 year postmenopausal, with no single observation of augmentation.  Although done
Seventeen-Year Survival of Small-Cell Lung Carcinoma Presenting As Carcinoma-Associated Retinopathy
Authors: Dinu Stanescu-Segall, Clare Wilson, Sebastien Bonnel, Jean-Paul Heligon
Journal: Journal of Clinical Oncology (2011)

Case ReportA 51-year-old man with bilateral rapid loss of vision and photopsia was referred.He smoked 20 cigarettes a day for 25 years and gave up smoking in 1989.His past medical and ophthalmologic histories were both unremarkable.Visual acuity was 20/50 in the right eye and 20/25 in the left eye.Pupillary reactions to light were normal.Eye movements were full in both eyes.Ishihara color plates were read fully in both eyes.Anterior segments and intraocular pressures were normal in both eyes.Funduscopy revealed retinal pigment epithelium changes in the macular region of both eyes and slight narrowing of retinal arteries.Goldman visual field testing was performed a few weeks later and disclosed generalized field loss with ring scotomas in the midperiphery (Fig 1, Goldman visual field of right eye [RE] and [LE] disclosing typical ring scotomas with preservation of islands of vision in the periphery in the right and left panels, respectively).Full-field (Ganzfeld) electroretinograms were abnormal, with a reduction in both rod and cone functions.Orbit and brain magnetic resonance imaging scans were also normal.The ophthalmic constellation of findings in this patient raised the suspicion of carcinoma-associated retinopathy (CAR).A computed tomographic scan of the chest demonstrated multiple hilar masses in the right hemithorax suggestive of a primary lung neoplasm.Both transbronchial fine-needle aspiration cytology and endobronchial biopsy confirmed a small-cell lung cancer (SCLC).A work-up for metastases yielded negative results.Blood marrow biopsy, computed tomography and ultrasound of the abdomen, CSF e566
Evidence based vets
Authors: T. Greenhalgh
Journal: BMJ (2003)

This time last week, I was at the Royal Veterinary College running a workshop on evidence based medicine. I came with some credibility, since whoever prepared the chairman's brief had gleaned a story from this column of how I had once managed an obstetric emergency in a ewe.

There's a bit of a crisis on. Most jobbing vets, I am told, make decisions on the basis of what worked on the last animal. Their journals …
Sugar should make up less than 5% of total energy consumption, says WHO
Authors: A. Gulland
Journal: BMJ (2015)

Free sugar should make up less than 5% of a person’s total energy consumption, new guidance from the World Health Organization states.1

In the new guidance WHO is backing a 2002 recommendation that monosaccharides and disaccharides—that is, sugar added to food or found in honey, fruit syrups, fruit juice, and fruit concentrate—should make up no more than 10% of a person’s energy intake. However, WHO is now urging that the total consumption drop to less than 5% “if possible.” Last year the authors of a study recommended that intake should be …
A survey of golf injuries in amateur golfers.
Authors: M E Batt
Journal: British Journal of Sports Medicine (1992)

A survey of 461 amateur golfers was undertaken to assess golf injuries. There were 193 respondents of whom 57% reported injuries. Wrist, back, muscle, elbow and knee problems were the most likely ailments to compromise a player's game. Overuse and poor technique were the main aetiological factors. Attention to those factors in addition to maintenance of physique would reduce the incidence of these problems.
Transmembrane signals and protooncogene induction evoked by carcinogenic metals and prevented by zinc.
Authors: J B Smith, L Smith, V Pijuan, Y Zhuang, Y C Chen
Journal: Environmental Health Perspectives (1994)

Cd2+ provokes an immediate production of inositol trisphosphate and the release of Ca2+ from internal stores in human fibroblasts and some other mammalian cells. Ni2+, Co2+, Fe2+, and Mn2+ evoke the release of stored Ca2+, but are less potent than Cd2+ (apparent K0.5 = 40 nM). Zn2+ and Cu2+ competitively inhibit Ca2+ release evoked by Cd2+ without affecting Ca2+ release by hormones such as bradykinin. Zn2+ has the same apparent Ki value (80-90 nM) towards the five agonist metals, which suggests that the metals interact with the same site. Many other divalent cations neither released stored Ca2+ nor affected Cd(2+)-evoked Ca2+ release. The agonist metals appear to activate phospholipase C via a G protein rather than a tyrosine kinase. The production of reactive oxygen species is probably not involved in Ca2+ release by the metals. Cd2+ and other stimuli that raise cytosolic-free Ca2+ induce cyclic (AMP) production, apparently by activating a calmodulin-dependent adenylyl cyclase. We suggest that an orphan receptor mediates the hormonelike responses to Cd2+ and the other agonist metals. The receptor is referred to as an orphan because its physiological stimulus is unknown. Growth of the fibroblasts in high Zn2+ desensitizes them to the five agonist metals without affecting Ca2+ release by bradykinin or histamine. A several hour incubation in culture medium with normal Zn2+ fully restores responsiveness to the five active metals. Growth in high Zn2+ appears to repress the synthesis of the putative orphan receptor because inhibitors of RNA or protein synthesis, or asparagine-linked glycosylation, prevented the restoration of metal responsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)