tbuckley/cabot-search huggingface dataset:
Abstract P4-01-03: HDACi (vorinostat) in metastatic breast cancer to restore sensitivity to ER-directed (AI) therapy: A phase II clinical trial with FES imaging correlates
Authors: HM Linden, BF Kurland, JM Link, A Novakova, X Chai, JM Specht, VK Gadi, JR Gralow, EK Schubert, LM Peterson, J Eary, A Shields, DA Mankoff, KA Krohn
Journal: Cancer Research (2013)

Abstract Background: Histone deacetylase inhibitors (HDACi) have shown pre-clinical promise in estrogen receptor(ER)-modulation and restoring sensitivity to endocrine manipulation, suggesting potential clinical benefit (Sabnis 2011) (Huang 2000) in ER+ breast cancer. Vorinostat is an FDA-approved HDACi for CTCL, and could have a beneficial role in restoring ER-signaling in endocrine-resistant tumors (Munster 2011) (Yardley 2011). [F-18]fluoroestradiol (FES) PET imaging may be used to monitor regional tumor ER expression in patients with breast cancer (Linden 2011). Methods: Patients with metastatic breast cancer with prior clinical benefit from endocrine manipulation who progressed on an AI therapy are eligible for this ongoing trial. In part A, patients were given vorinostat for 2 weeks, then resumed AI for 6 W. In part B (reflecting results of prior HDACi trials) patients are given vorinostat 400mg po daily 5/7 days 3/4 weeks while AI is given continuously. Paired FES and FDG PET are performed at baseline, week 2 and 8; clinical/radiologic assessment of disease is also performed at week 8. Patients with clinical benefit (response or stable disease) may continue on treatment until progressive disease or study withdrawal. Lesion-level analysis of the association between baseline FES uptake (logged) and FES/FDG ratio used generalized estimating equations (GEE) with small-sample adjustments to standard errors. Results: 12/ 20 planned patients have accrued, and the treatment is well tolerated. Enrolled women were postmenopausal, the majority with primary infiltrating ductal tumors, bone/soft tissue dominant with longstanding metastatic disease, exposed to multiple endocrine and chemotherapy regimens. Five patients have had clinical benefit (2/4 on part B with greater HDACi exposure). One patient withdrew from the study due to toxicity. FES and FDG uptake was analyzed in 42 lesions in 11 patients. Average FES uptake was 2.0 (SULmean) for patients with clinical benefit, and 1.2 in patients with progressive disease by 8 weeks (p = 0.09). FES/FDG ratio at baseline was also associated with response (p = 0.04). Conclusions: HDACi therapy is promising in relapsed ER+ breast cancer. Imaging of metabolic pathways in parallel with clinical trials may accelerate understanding of the underlying tumor biology and refine treatment selection. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-01-03.
Pituitary tumors following fallout radiation exposure
Authors: W. H. Adams
Journal: JAMA (1984)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2022 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Selenium supplementation and cancer rates
Authors: L. H. Kuller
Journal: JAMA (1997)

To the Editor.  —The article by Clark et al 1 has very important implications. The results suggest that increased selenium intake results in a substantial reduction in cancer incidence in only 5 years. This is especially remarkable with regard to lung cancer, since the effects of smoking cessation usually require a much longer follow-up. 2 These results can be due to (1) a true beneficial effect of selenium; (2) random variation, ie, type I error; and (3) an unexplained higher rate in the control group; in other words, the differences are not due to the benefit of selenium, but due to a much higher rate in the control group than would be expected. Unfortunately, the authors do not provide information on age- and sex-specific cancer rates in either group or the age distribution of cancer cases. They report a mean age of 63 years at entry, 75% men, and approximately 8000 person-years of observation.
A Multiancestral Genome-Wide Exome Array Study of Alzheimer Disease, Frontotemporal Dementia, and Progressive Supranuclear Palsy
Authors: Jason A. Chen, Qing Wang, Jeremy Davis-Turak, Yun Li, Anna M. Karydas, Sandy C. Hsu, Renee L. Sears, Doxa Chatzopoulou, Alden Y. Huang, Kevin J. Wojta, Eric Klein, Jason Lee, Duane L. Beekly, Adam Boxer, Kelley M. Faber, Claudia M. Haase, Josh Miller, Wayne W. Poon, Ami Rosen, Howard Rosen, Anna Sapozhnikova, Jill Shapira, Arousiak Varpetian, Tatiana M. Foroud, Robert W. Levenson, Allan I. Levey, Walter A. Kukull, Mario F. Mendez, John Ringman, Helena Chui, Carl Cotman, Charles DeCarli, Bruce L. Miller, Daniel H. Geschwind, Giovanni Coppola
Journal: JAMA Neurology (2015)

Previous studies have indicated a heritable component of the etiology of neurodegenerative diseases such as Alzheimer disease (AD), frontotemporal dementia (FTD), and progressive supranuclear palsy (PSP). However, few have examined the contribution of low-frequency coding variants on a genome-wide level.To identify low-frequency coding variants that affect susceptibility to AD, FTD, and PSP.We used the Illumina HumanExome BeadChip array to genotype a large number of variants (most of which are low-frequency coding variants) in a cohort of patients with neurodegenerative disease (224 with AD, 168 with FTD, and 48 with PSP) and in 224 control individuals without dementia enrolled between 2005-2012 from multiple centers participating in the Genetic Investigation in Frontotemporal Dementia and Alzheimer's Disease (GIFT) Study. An additional multiancestral replication cohort of 240 patients with AD and 240 controls without dementia was used to validate suggestive findings. Variant-level association testing and gene-based testing were performed.Statistical association of genetic variants with clinical diagnosis of AD, FTD, and PSP.Genetic variants typed by the exome array explained 44%, 53%, and 57% of the total phenotypic variance of AD, FTD, and PSP, respectively. An association with the known AD gene ABCA7 was replicated in several ancestries (discovery P=.0049, European P=.041, African American P=.043, and Asian P=.027), suggesting that exonic variants within this gene modify AD susceptibility. In addition, 2 suggestive candidate genes, DYSF (P=5.53×10(-5)) and PAXIP1 (P=2.26×10(-4)), were highlighted in patients with AD and differentially expressed in AD brain. Corroborating evidence from other exome array studies and gene expression data points toward potential involvement of these genes in the pathogenesis of AD.Low-frequency coding variants with intermediate effect size may account for a significant fraction of the genetic susceptibility to AD and FTD. Furthermore, we found evidence that coding variants in the known susceptibility gene ABCA7, as well as candidate genes DYSF and PAXIP1, confer risk for AD.
Left Ventricular Hypertrophy Demonstrated by Four-Dimensional Myocardiography by Helical Computed Tomography
Authors: Yasushi Koyama, Hiroshi Matsuoka, Hiroshi Higashino, Teruhito Mochizuki, Hideo Kawakami, Katsuji Inoue, Ichirou Sogabe, Kazuhisa Nishimura, Shigeru Nakata, Masaya Doi, Masato Imai, Hisashi Shinohara, Taketoshi Ito
Journal: Circulation (2001)
THE PHARMACOLOGIC ASSAY OF THE HEART TONICS.
Authors: E. M. HOUGHTON
Journal: JAMA (1898)

It is unnecessary to call attention to the great therapeutic importance of the heart tonics since digitalis, strophanthus and others of the group are now universally employed by physicians in their daily practice. It is my purpose to point out some of the dangers attending the administration of these drugs, and to offer some suggestions in regard to the selection of the crude drug and the processes of manufacture, in order that the danger may be as far as possible circumscribed. We are not generally accustomed to think of the heart tonics as being the most poisonous remedies employed in therapeutics; yet it is true. According to some of the best authorities the maximum dose of extract of digitalis is about one-half as great as the maximum dose of extract of belladonna; while strophanthin, the active principle of strophanthus, is three times as poisonous as atropin, ten times as poisonous
Abstract 4650: Inhibiting oncogenic signaling by sorafenib activates PUMA via GSK3β and NF-κB to suppress tumor cell growth
Authors: Crissy Dudgeon, Monica E. Buchanan, Rui Peng, Peng Wang, Andrea Sebastiani, Jian Yu, Lin Zhang
Journal: Cancer Research (2012)

Abstract Aberrant Ras/Raf/MEK/ERK signaling is one of the most prevalent oncogenic alterations and confers survival advantage to tumor cells. Inhibition of this pathway can effectively suppress tumor cell growth. For example, sorafenib, a multi-kinase inhibitor targeting B-Raf and other oncogenic kinases, has been used clinically for treating advanced liver and kidney tumors, and also has shown efficacy against other malignancies. However, how inhibition of oncogenic signaling by sorafenib and other drugs suppresses tumor cell growth remains unclear. In this study, we found that sorafenib kills cancer cells by activating PUMA, a p53 target and a BH3-only Bcl-2 family protein. Sorafenib treatment induces PUMA in a variety of cancer cells irrespective of their p53 status. Surprisingly, the induction of PUMA by sorafenib is mediated by IαB-independent activation of NF-κB, which directly binds to the PUMA promoter to activate its transcription. NF-κB activation by sorafenib requires GSK3β activation, subsequent to ERK inhibition. Deficiency in PUMA abrogates sorafenib-induced apoptosis and caspase activation, and renders sorafenib resistance in colony formation and xenograft tumor assays. Furthermore, the chemosensitization effect of sorafenib is dependent on PUMA, and involves concurrent PUMA induction through different pathways. Enhanced PUMA expression or BH3 mimetics potentiate the anticancer effects of sorafenib, and restore sorafenib sensitivity in resistant cells. We also developed a high-throughput screening assay for identifying anticancer compounds based on the activation of PUMA by sorafenib. Together, these results demonstrate a key role of PUMA-dependent apoptosis in therapeutic inhibition of Ras/Raf/MEK/ERK signaling. They provide a rationale for manipulating the apoptotic machinery to improve sensitivity and overcome resistance to the therapies that target oncogenic kinase signaling. 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 4650. doi:1538-7445.AM2012-4650
Cough Sounds Can Help Pinpoint Pneumonia Cases
Authors: M. J. Friedrich
Journal: JAMA (2013)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Malabsorption and motor dysfunction in patients with small bowel amyloidosis.
Authors: N L Ectors, K J Geboes, P J Rutgeerts
Journal: Gut (1994)

Lettersfind such a good correlation between motility and ulcer pain8 9 and although in our own studies the use of an anti-spasmodic did not affect the development of acid induced duodenal ulcer pain,6 we feel that duodenal wall tension or dysmotility deserve further study as a possible cause of duodenal ulcer pain and a possible explanation for the imperfect correla- tion between the pH around the ulcer crater and development of ulcer pain in patients with symptomatic duodenal ulcer.
BMA considers asking patients to opt out of using private providers
Authors: Z. Kmietowicz
Journal: BMJ (2012)

The BMA is to consider asking patients to support a boycott of private providers in a bid to disrupt the government’s competition agenda in healthcare.

The campaign would involve a “patient pledge” card that patients would give to their GPs if they would rather not be given the option of private providers when publicly run NHS services can treat them just as well.

The BMA’s governing council will consider the idea in November, after the General Practitioners Committee has explored details of the plan, such as how the …
Randomized, double-blind, placebo-controlled trial of corticosteroids after Kasai portoenterostomy for biliary atresia
Authors: Mark Davenport, Mark D. Stringer, Sarah A. Tizzard, Patricia McClean, Giorgina Mieli-Vergani, Nedim Hadzic
Journal: Hepatology (2007)

The objective of this study was to evaluate adjuvant corticosteroids after Kasai portoenterostomy for biliary atresia. The study consisted of a prospective, 2-center, double-blind, randomized, placebo-controlled trial of post-Kasai portoenterostomy corticosteroids (oral prednisolone: 2 mg/kg/day from day 7 to day 21 and 1 mg/kg/day from day 22 to day 28). The data were compared with chi2 or Mann-Whitney tests, as appropriate. Seventy-one postoperative infants with type 3 biliary atresia were randomized to receive either oral prednisolone (n = 36) or a placebo (n = 37). At 1 month, the median bilirubin level was lower in the steroid group (66 versus 92 micromol/L, P = 0.06), but no difference was evident at 6 (P = 0.56) or 12 (P = 0.3) months. The proportion of infants with a normal bilirubin level (<20 micromol/L) at 6 (47% versus 49%, P = 0.89) and 12 months (50% versus 40%, P = 0.35) was not significantly different. The need for transplantation by 6 (12% versus 13%, P = 0.99) and 12 months (26% versus 35%, P = 0.47) was not significantly different. The steroid effect was more pronounced in younger infants (less than 70 days at Kasai portoenterostomy, n = 51), with a reduced bilirubin level at 1 month (64 versus 117 micromol/L, P = 0.01) and with a greater proportion with a normal bilirubin level at 12 months (54% versus 37%, P = 0.22).There was a beneficial effect on the rate of reduction of bilirubin in the early postoperative period (specifically in infants less than 70 days old at surgery), but this steroid regimen did not reduce the need for liver transplantation.
Reperfusion induced injury: manifestations, mechanisms, and clinical relevance
Authors: D. J Hearse, R. Bolli
Journal: Cardiovascular Research (1992)

Although reperfusion is an absolute prerequisite for the survival of ischaemic tissue, it is not necessarily without hazard. Many (but not all) cardiologists are of the opinion that some component of reperfusion may be detrimental and able to inflict injury over and above that attributable to the ischaemia. In this article we define four sequelae of reperfusion which might be designated as "reperfusion injury", we identify possible underlying mechanisms, and consider whether any of these forms of reperfusion injury are of clinical relevance.
Case 15-1979
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, Phillip G. Stubblefield, William R. Welch
Journal: New England Journal of Medicine (1979)

Presentation of CaseA 41-year-old woman was admitted to the hospital because of a pelvic mass.The patient was gravida 3, para 2, with one miscarriage. She was previously well, with regular menses. An intrauterine coil and later a Dalkon shield were used over an interval of 15 years; repeated pelvic examinations and vaginal cytologic studies at intervals of six to 12 months were negative. Five months before admission lower abdominal cramps and intermenstrual spotting developed, associated with a vaginal discharge and malaise. The intrauterine device was removed, and ampicillin was prescribed. The next menstrual period occurred six weeks later . . .
United States' factor XI-deficiency patients need a safer treatment
Authors: Louis M. Aledort, Jenny Goudemand
Journal: American Journal of Hematology (2005)

A replacement factor for Factor XI with is virally inactivated is not available in the U.S. Elsewhere an inactivated concentrate has been used. A review of the experience over 15 years suggests that this product is safe and effective and suggests its potential use in the U.S. The most serious complication of the factor was a slight increase in DIC and thrombotic events.
Asynchronous left ventricular regional function and impaired global diastolic filling in patients with coronary artery disease: reversal after coronary angioplasty.
Authors: R O Bonow, D F Vitale, S L Bacharach, T M Frederick, K M Kent, M V Green
Journal: Circulation (1985)

Left ventricular diastolic filling is impaired in many patients with coronary artery disease and normal left ventricular systolic function, and is improved in many patients after coronary angioplasty (PTCA). To investigate the mechanisms for this improvement, we studied regional asynchrony by radionuclide angiography in 26 patients with single-vessel coronary artery disease before and after successful PTCA. Before PTCA, all patients had normal ejection fractions at rest and normal qualitative left ventricular regional wall motion, as determined by radionuclide and contrast angiography. Quantitative left ventricular regional function was assessed by dividing the left ventricular region of interest into 20 sectors. Phase analysis was performed on each sector's time-activity curve, and the average intersector phase difference was used as an index of left ventricular regional synchrony. Before PTCA, average intersector phase difference was increased compared with normal (6.0 +/- 2.2 vs 4.0 +/- 1.7 degrees, p less than .005), indicating asynchronous regional function. After PTCA, ejection fraction at rest was unchanged, but peak left ventricular filling rate at rest increased from 2.5 +/- 0.6 to 3.0 +/- 0.6 end-diastolic volume/sec (p less than .001) and was associated with a decrease in average intersector phase difference from 6.0 +/- 2.2 to 5.1 +/- 2.3 degrees (p less than .05). Average intersector phase difference decreased in 16 of 21 patients in whom peak filling rate increased after PTCA (p less than .005), compared with one of five patients in whom peak filling rate was unchanged or decreased. Hence, improved global left ventricular filling after PTCA was associated with more synchronous left ventricular regional behavior. To identify the cause of regional asynchrony before PTCA, we then generated time-activity curves from each of four left ventricular quadrants. These data indicated that the asynchrony was caused by regional variation in timing of diastolic rather than systolic events and that PTCA resulted in reduction in regional diastolic asynchrony. These data suggest that in many patients with coronary artery disease and normal left ventricular systolic function, impaired global diastolic filling may result from asynchronous left ventricular regional diastolic function, which is a reversible manifestation of myocardial ischemia or reduced coronary flow.
ORCHITIS, VARICOCELE, AND TWISTED CORD
Authors: Alex. E. Roche
Journal: BMJ (1939)

The treatment of acute orchitis consists of anodynes, rest in bed, support and raising of the scrotum, with application of heat to it, and finally incision should suppuration occur, as shown by persistence of pyrexia, redness, and oedema, and by attachment of the tender lump to the skin, which becomes smooth and glazed.On incision a necrotic piece of testicle may escape with the pus, as in the following case.
After-Effects of Abdominal Section
Authors: M. Thorne
Journal: BMJ (1899)

Dr. Herbert Spencer pointed out that intestinal obstruc- tion from the adlhesioni of the intestine to the stump after ovariotomy was by no means rare, and a month later at the Harveian Society Mr. Doran drew attention to the fact that hernia of the abdominal cicatrix frequently followed lapar- otomies.
Royal Westminster Ophthalmic Hospital
Authors: J. Rouse
Journal: BMJ (1860)

THE followin, case illuistrates well the beneficial results occa.sionally to be derived from the use of opiate injections in the treatment of neuralgia.Joseph Lewis, aged 27, was admitted into the Hospital on June 6tb, 1800.He liad beeni ill about ninie days, with severe pain in the head, attended with niausea.The pain was seated on the right side, not passing the median line, and proceeded
Changes in the expression of telomere maintenance genes suggest global telomere dysfunction in B-chronic lymphocytic leukemia
Authors: Delphine Poncet, Aurélie Belleville, Claire t'Kint de Roodenbeke, Aude Roborel de Climens, Elsa Ben Simon, Hélène Merle-Beral, Evelyne Callet-Bauchu, Gilles Salles, Laure Sabatier, Jozo Delic, Eric Gilson
Journal: Blood (2007)
Vasoactive and atherogenic effects of cigarette smoking: a study of monozygotic twins discordant for smoking.
Authors: R. Lassila, H. W. Seyberth, A. Haapanen, H. Schweer, M. Koskenvuo, K. E. Laustiola
Journal: BMJ (1988)

The mechanism by which atherosclerotic disease is induced by cigarette smoking has not yet been identified unequivocally. Chronic cigarette smoking and the generation of vasoactive prostanoids and the size of carotid atherosclerotic plaques were studied in nine pairs of identical male twins discordant for smoking for over 20 years. The urinary excretion of 2,3-dinor-thromboxane B2 (thromboxane B2 metabolite) of the smoking twin was significantly higher (on average 1.8 times higher) in every pair and that of 2,3-dinor-6-keto-prostaglandin F1 alpha (prostacyclin metabolite) was significantly higher (on average 1.3 times higher) in eight of the nine pairs. The ratio of excretion of these metabolites was significantly higher, being 4.0 (95% confidence interval 2.7 to 5.4) among the smokers compared with 2.9 (2.1 to 3.8) among the non-smokers, thus favouring a mechanism of vasoconstriction. Excretion of the thromboxane B2 metabolite was related to the urinary concentrations of nicotine metabolites. Atherosclerotic plaques detected by ultrasonography in the carotid arteries were significantly larger among smokers but did not correlate with the urinary excretion of prostacyclin and thromboxane B2 metabolites or intensity of smoking. Smoking was concluded to induce activation of platelets by an effect mediated by nicotine. The increased prostacyclin production, on the other hand, suggested a compensatory mechanism for the general vasoconstrictive properties of cigarette smoking.