tbuckley/cabot-search huggingface dataset:
Abstract 601: PPARδ mediated p21 induction in aerodigestive preneoplastic cell lines
Authors: Wendy Miller, Beverly Wuertz, Frank G. Ondrey
Journal: Cancer Research (2012)

Abstract PPARδ activating strategies are currently being tested preclinically and clinically in aerodigestive cancer prevention. Thiazolidinedione drugs like pioglitazone are clinically used for the treatment of diabetes and activate PPARδ as a primary target. P21/WAF1 is a cell cycle protein that is a cyclin dependent kinase inhibitor that reguylates cell cycle progression at the G1 phase; therefore its induction may be associated with cell cycle downregulation in precancerous cells experiencing increased proliferation. In our present study we examined the effects of pioglitazone on proliferation in human leukoplakia cells (MSK 1) and transformed lung (BEAS 2B) cells. We found that pioglitazone significantly inhibited cell proliferation in both cell lines in a dose dependent fashion at concentrations between 0 and 40 uM, as judged by MTT assays from 1-5 days. We found p21/WAF 1 induction by western blot within the first eight hours after the intitiation of treatment with pioglitazone, which were preceded by measureable increases in p21 induction on q PCR. In an analysis of an Affymetrix database of human head and neck tumors (41 tumors compared to 13 normal oral mucosa samples), we found significant dysregulation in several p21 activated kinases. We conclude the PPARδ activator, pioglitazone, can activate p21, which is associated with decreased proliferation in 2 aerodigestive preneoplastic cell lines. We also conclude that this gene may be a potential hypothesis driven biomarker in translational studies of pioglitazone as a chemoprevention agent for aerodigestive cancer. 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 601. doi:1538-7445.AM2012-601
Intracellular Potassium Activity in Guinea Pig Papillary Muscle during Prolonged Hypoxia
Authors: Thomas Guarnieri, Harold C. Strauss
Journal: Journal of Clinical Investigation (1982)

During prolonged hypoxia, intracellular potassium concentration, [K]i has been reported to fall by 70% with a concomitant decrease in the calculated potassium equilibrium potential, EK. Nevertheless, resting membrane potential, Vm, declined only slightly. Because Vm depolarized very little in relation to the calculated EK, it was hypothesized that electrogenic Na-K pumping contributed up to 40 mV to Vm during prolonged hypoxia. To further test this hypothesis we studied what changes prolonged hypoxia makes in the thermodynamically active fraction of cellular potassium, intracellular potassium activity, αKi, and how change in αKi affects the relationship between Vm, EK and, by inference, the Na-K pump. Using double-barrel K-selective electrodes, Vm and αKi were measured in quiescent guinea pig right ventricular papillary muscles superfused for 8 h with hypoxic Tyrode's solution. Over the 8-h period both Vm and αKi decreased. However, the decline in Vm was paralleled by a decrease in the EK calculated from αKi. At no time was there hyperpolarization of Vm beyond EK.
An Analysis of Segmental Ischemic Dysfunction Utilizing the Pressure-Length Loop
Authors: JOHN V. TYBERG, JAMES S. FORRESTER, H. L. WYATT, STEVEN J. GOLDNER, WILLIAM W. PARMLEY, H. J. C. SWAN
Journal: Circulation (1974)

Left ventricular (LV) pressure and myocardial segment length, determined by an epicardial mercury-in-silastic length gauge, were plotted simultaneously to obtain a pressure-length loop before and after left anterior descending artery (LAD) occlusion in 11 dogs. Previous studies have indicated that the area within this loop is a sensitive and reproducible means of quantitating regional myocardial performance. Immediately following ligation, systolic performance deteriorated as indicated by progressive reduction in the pressure-length loop area. Within approximately 30 sec a zero area for the pressure-length loop was observed, indicating no effective work was being performed by the ischemic segment. During the ensuing 3-5 min the pressure-length loop moved into a clockwise orientation which indicated work was being done on rather than by the segment. The magnitude was approximately 50% of that amount previously generated by the segment. In addition, during this latter period of repetitive passive stretch, the end-diastolic pressure-length relationship shifted to the right indicating increased diastolic compliance. Restoration of perfusion after 30 min produced variable results. Substantial return of function was observed in two animals, but recovery in the majority of animals was limited to the elimination of paradoxical expansion without restoration of active contraction. Therefore, the pressure-length loop method allows quantitation of regional myocardial performance, and indicates that a predictable pattern of significant changes in both systole and diastole accompanies acute myocardial ischemia.
Lung Changes in Left Heart Failure
Authors: WILLIAM T. MESZAROS
Journal: Circulation (1973)

The lung changes in left heart failure are grouped into four main categories or stages: (1) pulmonary congestion, (2) interstitial edema, (3) alveolar edema, and (4) miscellaneous findings. Some patients, particularly those with mitral stenosis, develop these changes gradually, passing successively through the stages of pulmonary congestion → interstitial edema → alveolar edema. Other patients, particularly those with hypertension or myocardial infarction, often develop rapid left heart failure and tend to show alveolar edema. The roentgen diagnosis of incipient or early heart failure is important since pulmonary auscultatory findings may be minimal or absent.
Guidelines for the Management of Patients with Chronic Stable Angina: Diagnosis and Risk Stratification
Authors: Sankey V. Williams, Stephan D. Fihn, Raymond J. Gibbons
Journal: Annals of Internal Medicine (2001)

Patients with suspected chronic stable angina can be evaluated in three stages. In stage one, the clinician uses information from the history, physical examination, laboratory tests for diabetes and hyperlipidemia, and resting electrocardiography to estimate the patient's probability of coronary artery disease (CAD). In stage two, additional testing for patients with a low probability of CAD focuses on diagnosing noncoronary causes of chest pain. Patients with a high probability of CAD have stress tests to assess their risk from CAD, and patients with an intermediate probability of CAD have stress tests to estimate the probability of CAD and assess their risk from CAD. Most patients with new-onset angina can start stress testing with exercise electrocardiography. The initial stress test should be a stress imaging procedure for patients with rest ST-segment depression greater than 1 mm, complete left bundle-branch block, ventricular paced rhythm, preexcitation syndrome, or previous revascularization with percutaneous coronary angioplasty or coronary artery bypass grafting. Patients who cannot exercise can have an imaging procedure with stress induced by pharmacologic agents. In stage three, patients with a predicted average annual cardiac mortality rate between 1% and 3% should have a stress imaging study or coronary angiography with left ventriculography. Those with a known left ventricular dysfunction should have cardiac catheterization. Patients with CAD who have an estimated annual mortality rate greater than 3% should have cardiac catheterization to determine whether their anatomy is suitable for revascularization. Patients with an estimated annual mortality rate less than 1% can begin to receive medical therapy.
Authors respond to criticism that treatment is ineffective
Authors: P. Aveyard, D. Moore, M. Connock, D. Wang, A. Fry-Smith, P. Barton
Journal: BMJ (2009)

Siegel is surprised that we concluded that nicotine replacement therapy was effective and cannot think of other interventions that would be regarded as effective with such a high failure rate.1 He chooses a secondary outcome from our review to make his point, but as it excludes 76% of all the people who stopped smoking for a long time, this is not an accurate …
Ethical Issues in Community and Research Medicine
Authors: Arthur J. Dyck
Journal: New England Journal of Medicine (1971)

Ramsey's essay in this issue of the Journal identifies two broad areas in which serious ethical issues arise for the practice of medicine — namely, community medicine and medical research. His excellent discussion of these issues suggests that when medicine attempts to make judgments about social well-being and when its practitioners become increasingly dedicated to the advancement of science, important questions must be raised regarding the role, warrant and principles of medical practice. What tasks and what judgments accrue to physicians as physicians? What are they trained to do and what ought they to be trained to do? By what . . .
Metabolic syndrome and liver cancer: Is excess iron the link?
Authors: Luca Mascitelli, Mark R. Goldstein
Journal: Hepatology (2011)

Welzel et al.1 found that preexisting metabolic syndrome conferred a statistically significant increase of primary liver cancers that was independent of other risk factors. We suggest that this pathological association may partially be related to the higher body iron stores often found in such patients. A wealth of evidence has established a link between serum ferritin, insulin resistance, and nonalcoholic fatty liver disease (NAFLD). Body iron excess has frequently been found in patients with metabolic syndrome.2 Furthermore, it has been suggested that the relation between serum ferritin and most of metabolic syndrome features might be mediated by the presence of NAFLD at the population-based level.3 Excessive hepatic iron accumulation in NAFLD can be one of the potential cofactors involved in enhanced oxidative stress, which triggers liver cell necrosis and activation of hepatic stellate cells, both of which lead to fibrosis.4 Indeed, iron depletion by phlebotomy was found to be beneficial in improving insulin resistance in patients with NAFLD and hyperferritinemia.5 On the other hand, it has been shown that individuals with excess total body iron have a higher risk of liver cancer even in the absence of genetic hemochromatosis.6 Interestingly, iron depletion therapy with both phlebotomies and a low-iron diet was shown to significantly lower the risk of hepatocellular carcinoma in patients with chronic hepatitis C.7 Therefore, we hypothesize that iron, metabolic syndrome, NAFLD, and liver cancer may be linked together, and their risk might be modified in parallel by maneuvers that affect either feature. Luca Mascitelli M.D.*, Mark R. Goldstein M.D., FACP , * Medical Service, Comando Brigata Alpina "Julia", Udine, Italy, Fountain Medical Court, Bonita Springs, FL.
CORONARY SCLEROSIS IN HEAD INJURIES
Authors: Walter D. Abbott
Journal: JAMA (1941)

This case is presented because it is pertinent to industrial medicine. Fishberg<sup>1</sup>states that transient monoplegias may be the result of disturbed circulation of the brain, but White<sup>2</sup>mentions that vertigo, faintness and syncope are rarely symptoms associated with heart disease. However, Barnes<sup>3</sup>states that in these cases death may occur on exertion and that previous electrocardiograms may have failed to reveal evidence of coronary disease. In 1937 Willius<sup>4</sup>reviewed 700 cases of coronary sclerosis and stated that in only 7 per cent was paroxysmal dyspnea manifested. The relation of heart disease is not commonly associated with injuries to the head, yet in reviewing a medicolegal case Russem<sup>5</sup>remarks that "the courts were not as much concerned with the pathology present as with the possible relation of the accidental injury to the onset of heart failure regardless of the condition of the heart before the
Gene Therapy With Extracellular Superoxide Dismutase Protects Conscious Rabbits Against Myocardial Infarction
Authors: Qianhong Li, Roberto Bolli, Yumin Qiu, Xian-Liang Tang, Yiru Guo, Brent A. French
Journal: Circulation (2001)

Background —Extracellular superoxide dismutase (Ec-SOD) may protect the heart against myocardial infarction (MI) because of its extended half-life and capacity to bind heparan sulfate proteoglycans on cellular surfaces. Accordingly, we used direct gene transfer to increase systemic levels of Ec-SOD and determined whether this gene therapy could protect against MI. Methods and Results —The cDNA for human Ec-SOD was incorporated into a replication-deficient adenovirus (Ad5/CMV/Ec-SOD). Injection of this virus produced a high level of Ec-SOD in the liver, which was redistributed to the heart and other organs by injection of heparin. Untreated rabbits (group I) underwent a 30-minute coronary occlusion and 3 days of reperfusion. For comparison, preconditioned rabbits (group II) underwent a sequence of six 4-minute-occlusion/4-minute-reperfusion cycles 24 hours before the 30-minute occlusion. Control-treated rabbits (group III) were injected intravenously with Ad5/CMV/nls-LacZ, and gene-therapy rabbits (group IV) were injected with Ad5/CMV/Ec-SOD 3 days before the 30-minute occlusion. Both groups treated with Ad5 received intravenous heparin 2 hours before the 30-minute occlusion. Infarct size (percent risk area) was similar in groups I (57±6%) and III (58±5%). Ec-SOD gene therapy markedly reduced infarct size to 25±4% ( P &lt;0.01, group IV versus group III), a protection comparable to that of the late phase of ischemic preconditioning (29±3%, P &lt;0.01 group II versus group I). Conclusions —Direct gene transfer of the cDNA encoding membrane-bound Ec-SOD affords powerful cardioprotection, providing proof of principle for the effectiveness of antioxidant gene therapy against MI.
THE DROOPING SHOULDER SIGN OF PHTHISIS
Authors: W. C. Rivers
Journal: BMJ (1921)

DROOPING SHOULDRR SIGN OF PHTHIS.treatment of eye injury belongs to a highly specialized branch of surgery,.andshould not be undertaken in a liglht-hearted manner by the general practitioner.If the doctor is in-any doubt he should not hesitate to obtain expert advice.In his evidence before the Workmen's Compensation Committee Mr. Pooley (Q.19,787) states that in Belgium special hospitals or wards, subsidized by the State, undertake the treatment of eye injuries for small fees.In this country the general opinion is against State interference, but both employee and employer have the right to demand adequate medical attendance.
Abstract P1-13-15: Risk of late recurrence of hormone receptor positive breast cancer in cases with no recurrent disease at five years after surgery
Authors: S Ohno, Y Koui, M Oikawa, S Akiyoshi, C Koga, A Igawa, A Saruwatari, S Nishimura, Y Nakamura, K Taguchi, M Ishida
Journal: Cancer Research (2013)

Abstract Background: Among women who take 2-5 years of adjuvant endocrine therapy, more than half of all recurrences of hormone receptor (HR) positive breast cancer occur after the first 5 years. Data from large clinical trials including ATLAS, aTTom,MA17 and NSABP B-30 support extending tamoxifen or aromatase inhibitor beyond 5 year for women with HR positive breast cancer. For decision making according to extending endocrine therapy, the information of the risk of late recurrence is quietly important. Patients and methods: In order to determine ten year disease free survival (DFS) rates, we reviewed medical records and database of patients who were treated at National Kyushu Cancer Center between 1990 and 2001. Among seven hundred fifty seven patients with HR positive breast cancer, 550 received tamoxifen for 2-5 years. Eighty eight patients had recurrence within five years after surgery, and 13 were not followed, with 83.5% of 5-year DFS after surgery. Remaining four hundred twenty six had no recurrence at the time of 5 years after surgery. To evaluate the risk of late recurrence, we analyzed the long-term results in association with clinicopathological factors for these 426 patients. Results: Four hundred twenty six patients had 87.1% of 10-year DFS rate. According to lymph node metastasis (N), ten year DFS rates were 91.4% for 275 N-negative and 80.0% for 155 N-positive cases (P = 0.0037). As for the number of lymph node metastasis, 10-year DFS rates were 82.5%, 74.2%, and 79.1% for N1-3, N4-9, N&amp;gt;9, respectively. Tumor size was correlated with the prognosis, and 10-year DFS rates were 91.5% for 167 T1 (≤2 cm), 86.9% for T2 (2-5 cm), and 67.9% for T3 (&amp;gt;5cm) (P = 0.0334). There were no significant differences between grade and prognosis, and 10-year DFS rates of grade 1, 2 and 3 were 88.9%, 89.8%, and 96.8%, respectively (p = 0.3914). Considering the age at 5 years after surgery, no significant differences were observed as for late recurrence. Ten-year DFS rates of 96 cases of age under 50, 227 between 50 and 65, 113 over 65 was 89.4%, 85.1%, and 86.0%, respectively. Ten-year DFS rates of N-negative and N-positive were 94.3% and 81.2%, 88.1% and 80.1%, and 90.4% and 76.7% for these age criteria, respectively. Conclusion: Patients with HR positive breast cancer require optimal information for decision making whether to receive extending endocrine therapy or not. Our data demonstrated the risk of late recurrence in relation to clinic-pathological factors, which may support the consideration about extending endocrine therapy. Relatively high risks of late recurrence with over 10% of 10 year DFS rates are there in cases with N-positive or T2-3 HR positive breast cancer. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-13-15.
Type I collagen content is increased in lungs of patients with adult respiratory distress syndrome.
Authors: J A Last, A D Siefkin, K M Reiser
Journal: Thorax (1983)

Collagen in lung tissue was examined from patients with adult respiratory distress syndrome, from patients who did not have this disease but required mechanical ventilation and oxygen treatment, and from patients without overt lung disease. Cyanogen bromide peptide mapping techniques were used to determine the ratio of type I to type III collagen present in these lungs. In the fibrotic lungs from patients with adult respiratory distress syndrome a shift was found in the ratio of type I to type III from the normal value of 2:1 to a mean value of 3.4:1. In patients with normal lungs and those with other lung diseases collagen type ratios were normal. Our data suggest that (i) changes in lung collagen of patients with adult respiratory distress syndrome resemble those previously described in patients with idiopathic pulmonary fibrosis, although the changes occur much more rapidly in the former; (ii) the increased content of collagen in lungs of patients with adult respiratory distress syndrome shown by others is predominantly of type I collagen; and (iii) the stimulus to the lung to produce excess type I collagen relative to type III is not solely of iatrogenic origin--that is, resulting from oxygen or ventilator treatment.
Use of Aspirin as Primary Prevention of Cardiovascular Events
Authors: James E. Dalen
Journal: JAMA (2006)

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
Refused and granted requests for euthanasia and assisted suicide in the Netherlands: interview study with structured questionnaire
Authors: I. Haverkate
Journal: BMJ (2000)

In 1995, physicians in the Netherlands received 9700 explicit requests for euthanasia or physician assisted suicide, of which 37% were granted and carried out.1 Among the remaining requests, about half were refused by the physician; in the rest of the cases either the patient died before a decision had been reached or the physician's promise of help could be effected, or the patient withdrew the request.2 Knowledge of specific characteristics of refused and granted requests for euthanasia or physician assisted suicide may give insight into physicians' decision making and into the role of criteria for prudent practice. We therefore compared the characteristics of refused and granted requests.

In 1995 and 1996, 405 Dutch physicians, randomly sampled nationwide and stratified by specialty and region, were interviewed by over 30 specifically trained and experienced physicians using a structured questionnaire. The response rate was …
Management of the Asymptomatic Patient With an Abnormal Exercise Electrocardiogram
Authors: Steven W. Lewis
Journal: JAMA (1985)

<h3>To the Editor.—</h3> The article by Laslett and Amsterdam,<sup>1</sup>"Management of the Asymptomatic Patient With an Abnormal Exercise ECG," is an extremely important one, because it so clearly demonstrates a common error in clinical decision making. Despite taking the reader through a clear and correct discussion of Bayes' theorem and then correctly applying this theorem to exercise testing of the asymptomatic patient, the authors reach the wrong conclusion. They properly demonstrate the low predictive accuracy of the exercise tolerance test in the asymptomatic patient. They then, however, conclude that not only should the exercise tolerance test be done in the asymptomatic situation, but that in the event that the result is positive, an array of further testing is suggested. The error is twofold. First of all, it is very difficult to improve on the asymptomatic state. This is particularly true as relates to coronary artery disease. True, in two
GPs need training in care programme approach more than in supervised discharge
Authors: J. Bindman, A. Beck, G. Thornicroft
Journal: BMJ (1997)

Editor—In her editorial on patients in the community Julie K Johnston suggests that up to two thirds of the 5000 psychiatric patients compulsorily admitted at any one time could be suitable for community supervision under the Mental Health (Patients in the Community) Act 1995, which introduced a new power of “supervised discharge.”1 She outlines the implications of the act for, among others, general practitioners, …
The breast cancer lottery
Authors: M. Kissin
Journal: BMJ (1994)

Iin this week's Panorama Steve Bradshaw set out to determine why Britain is near the bottom of the European breast cancer survival league (60% 5 year survival). His basic premise was that women with this disease are getting a bad deal because many are referred to a general surgeon and not to a breast specialist. The theme was humanised reference to three young women who are estined to die of metastatic disease. Lesley had a breast lump that was dismissed by two general practitioners and presented with an axillary lymph node four months later. …