tbuckley/cabot-search huggingface dataset:
Abstract 684: Changes in Levels of High Density Lipoprotein Cholesterol Predict the Impact of Torcetrapib on Progression of Coronary Atherosclerosis: Insights from ILLUSTRATE
Authors: Stephen J Nicholls, Danielle M Brennan, Kathy Wolski, Srinivasa R Kalidindi, Keon-Woong Moon, E. Murat Tuzcu, Steven E Nissen
Journal: Circulation (2007)

Background: Administration of the CETP inhibitor torcetrapib does not slow the rate of progression of coronary atherosclerosis. The reason for the lack of therapeutic efficacy remains unknown. This analysis investigated the relationship between changes in HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) and atheroma volume in patients treated with torcetrapib. Methods: 910 patients with angiographic coronary artery disease underwent IVUS imaging within a single coronary artery before and during 24 months of treatment with torcetrapib (n = 464) or placebo (n = 446) on a background of atorvastatin therapy. The relationship between changes in levels of HDL-C and LDL-C and both percent atheroma volume (PAV) and total atheroma volume (TAV) was evaluated in patients treated with torcetrapib. Results: Administration of torcetrapib raised HDL-C by 61% and lowered LDL-C by 20% when compared to atorvastatin alone. An inverse relationship was observed between changes in HDL-C and both PAV (r = −0.17, p &lt; 0.001) and TAV (r = −0.17, p &lt; 0.001). Patients with the highest level of HDL-C (&gt; 87 mg/dL) had the lowest rate of progression of PAV (−0.7 v +0.7%, p = 0.0003) and TAV (−9.2 v −4.6 mm 3 , p = 0.09). The greatest elevation in level of HDL-C (&gt; 80%) was associated with the lowest progression of PAV (−0.3 v +0.9%, p = 0.002) and TAV (−12.6 v −3.4 mm 3 , p = 0.0006). Patients undergoing regression (any reduction in PAV) had greater absolute levels (73 v 66 mg/dL, p = 0.02) and changes (59.5 v 48.3%, p = 0.02) of HDL-C. No difference in the impact of torcetrapib on changes in PAV (+0.3 v +0.1%, p = 0.34) and TAV (−9.1 v −9.3 mm 3 , p = 0.95) was observed in patients with baseline levels below or above 40 mg/dL. No relationship was observed between changes in LDL-C and either PAV (r = 0.06, p = 0.20) or TAV (r = 0.07, p = 0.12) in torcetrapib treated patients. On multivariate analysis, changes in levels of HDL-C independently predicted the impact of torcetrapib on progression of PAV (p = 0.007) and TAV (p = 0.004). Conclusion: Increasing levels of HDL-C from torcetrapib treatment were associated with a beneficial impact of torcetrapib on plaque progression. This is consistent with the generation of functional HDL particles and suggests other effects to be responsible for the lack of benefit of torcetrapib.
Sexual function problems and help seeking behaviour in Britain: national probability sample study
Journal: BMJ (2003)

Stress and infection and the risk of an exacerbationCertain types of psychological stress can suppress immune reactions, leading to an increased susceptibility to infections. 23This would confound the positive association we found between stress and exacerbations.However, we found no evidence of an increase in infections after stressful events in this study.Stress and infection were independently associated with the risk of exacerbation.It will not be easy to tackle these factors in individual patients, because infections and stressful events cannot simply be eradicated from patients' lives.The knowledge that stressful events are associated with disease activity adds important information to the limited insight that patients and their caregivers have on this unpredictable disease.We thank the late Monica van der Hoven, who performed secretarial and organisational tasks for this study, and to D Dippel for critical reading of the manuscript.
Evaluating virological assays and reagents
Authors: E Martinez-Vila
Journal: BMJ (1985)

reiterated my comment' on the treatment of cysticercosis with metriphonate and by means of radioimmunotherapy.Some other advances should be mentioned.In addition to praziquantel2-4 the anthelmninthic flubendazole has recently been used in the management of neurocysticercosis, with apparent success.5 Injection of quinine sulphate in distilled water into subcutaneous cysticerci has also been reported to destroy the bladderworms, thus obviating the need for their surgical excision.6
An educational program in digitalis therapy
Authors: R. I. Ogilvie
Journal: JAMA (1972)

Of 2,334 medical patients surveyed from 1967 to 1968, 22.9% had received digitalis and 21.4% of digitalis courses resulted in intoxication. Risk factors included old age, impaired renal function, myocardial infarction, severe congestive heart failure, cor pulmonale, excessive doses based on body weight, and loading courses. An educational program in digitalis use with dosage guidelines for digoxin was established. In a repeat survey in 1969 to 1970 only 12.3% of 578 digitalis courses resulted in intoxication. The number of loading courses and the total amount of drug administered as a load were reduced. Fewer patients received a daily maintenance dose of digoxin greater than 2.5μg/lb. Deaths in intoxicated patients decreased. These results indicate that an educational program in digitalis use based on clinical pharmacological principles is a valuable addition to medical education.
Abstract 954: SHP2 inhibition overcomes RTK-mediated pathway reactivation in KRAS mutant tumors treated with MEK inhibitors
Authors: Hengyu Lu, Chen Liu, Roberto Velazquez, Hongyun Wang, Lukas M. Dunkl, Malika Kazic-Legueux, Anne Haberkorn, Eric Billy, Eusebio Manchado, Saskia M. Brachmann, Susan Moody, Jeffrey A. Engelman, Peter S. Hammerman, Giordano Caponigro, Morvarid Mohseni, Huaixiang Hao
Journal: Cancer Research (2019)

Abstract Introduction: FGFR1 was recently shown to be activated as part of a compensatory response to prolonged treatment with MEK inhibitor (MEKi) such as trametinib in several KRAS mutant lung and pancreatic cancer cell lines. We hypothesize that other receptor tyrosine kinases (RTKs) are also feedback activated in KRAS mutant cell lines after MEKi treatment. Experimental procedures: We profiled a large panel (n&amp;gt;32) of KRAS mutant cancer cell lines for the contribution of RTKs to the feedback activation of phospho-MEK following MEK inhibition, using a SHP2 inhibitor (SHP099) that blocks RAS activation mediated by multiple RTKs. We then performed in vitro and in vivo combination efficacy studies and pathway analysis in various KRAS mutant cancer models. Results: We find that RTK-driven feedback activation widely exists in KRAS mutant cancer cells and involves several RTKs including EGFR, FGFR, and MET. We further demonstrate that this pathway feedback activation is mediated through mutant KRAS in KRAS G12C or G12D models. Finally, SHP099 and MEK inhibitors exhibit combination benefits inhibiting MAPK pathway and KRAS mutant cancer cell proliferation in vitro and in vivo. Conclusions: Our findings suggest that MAPK inhibition in KRAS mutant cancer provokes feedback re-activation of the pathway that often involves RTK activity and SHP2 inhibition may enhance the efficacy of MEKi in KRAS mutant tumors. These findings provide a rationale for exploration of combining SHP2 and MAPK pathway inhibitors for treating KRAS mutant cancers in the clinic. Citation Format: Hengyu Lu, Chen Liu, Roberto Velazquez, Hongyun Wang, Lukas M. Dunkl, Malika Kazic-Legueux, Anne Haberkorn, Eric Billy, Eusebio Manchado, Saskia M. Brachmann, Susan Moody, Jeffrey A. Engelman, Peter S. Hammerman, Giordano Caponigro, Morvarid Mohseni, Huaixiang Hao. SHP2 inhibition overcomes RTK-mediated pathway reactivation in KRAS mutant tumors treated with MEK inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 954.
CORRECTION
Journal: American Journal of Psychiatry (2017)

We also agree that clinicians, researchers, and policy makers often mistakenly conflate the concepts of physiological dependence, which includes tolerance and withdrawal, and substance use disorder.We are pleased to see this key distinction being taken seriously by medical specialties beyond psychiatry.We hope that this will contribute to improved assessment and treatment of patients with pain, reduced risk of nonmedical opioid use, and a lower incidence of opioid use disorder.To minimize confusion, we chose in our article to use DSM-IV criteria, which was the official classification system when the data were collected.The second issue raised by Dr. Ruan and colleagues is whether use of DSM-IV, rather than DSM-5, compromises our results.Clinical and epidemiological samples have demonstrated a high degree of concordance between DSM-IV and DSM-5 opioid use disorder diagnoses (5,6).The robustness of our analyses to analytic method suggests that the results are unlikely to be sensitive to these changes in nomenclature.We are not aware of nationally representative samples that have been longitudinally evaluated to assess the relationship between pain and prescription opioid use disorder using DSM-5 criteria.We agree with Dr. Ruan and colleagues that, given the importance of this topic, such a study would be an important contribution.
CEA for Monitoring Colon Cancer
Authors: Marvin Corman
Journal: JAMA (1994)

<h3>To the Editor.</h3> —In a recent article Moertel et al<sup>1</sup>question the value of the CEA determination for monitoring patients who had undergone resection for colorectal cancer. They concluded that cancer cures attributable to CEA monitoring are infrequent and suggest that this small gain does not justify the cost and the patient's physical and emotional stress associated with the testing. Such statements raise intriguing questions concerning the allocation of health care dollars for these and other more aggressive medical procedures, which may at least produce only a modest increased survival for a limited number of patients. Although society can justly question the priorities for allocating financial resources, we would expect that an individual who underwent resection for colorectal cancer would take the view that the "small gain" is worth whatever the expense and emotional distress. We agree that cancer cures attributable to CEA monitoring are not frequent. Certainly, this
SOCIETY NEWS.
Journal: JAMA (1893)

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 Journals 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 2024 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
THE HEREDITABILITY OF HEART DISEASE.
Journal: JAMA (1988)

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
In Reply
Authors: Eleanor E.R. Harris
Journal: Journal of Clinical Oncology (2007)

Harris et al 1 have to be commended for their efforts in analyzing the medical records of 961 patients who received radiation therapy (RT) for early breast cancer.They found an increased risk of morbidity for ischemic heart disease after RT for leftsided cancer compared with right-sided RT, especially after more than 10 years post-treatment.There was a trend for increased mortality but their study must have been underpowered to detect a significant mortality difference.Their findings are consistent with some, 2-5 although, not all previous trials, and I agree with Recht who points out in his editorial 6 that it is difficult to know which patients should really worry about this problem. 7 Can anything be done about this potentially life-threatening complication other than optimizing RT techniques and waiting for 10 years to find out whether or not we were right?Advising patients to quit smoking and to have their blood pressure and lipids treated makes perfect sense, but I would recommend a more structured approach.Framingham risk score (FRS) calculations can give a reliable assessment of the patients' 10-year cardiovascular risks and it defines their lipid targets. 8 Based on the aforementioned studies and on the study by Harris et al, it would be reasonable to assume that left-sided chest wall RT is a nonmodifiable risk factor that increases the risk by a factor of 1.5 to 2. Thus, the FRS could be multiplied by this factor and the patients' modifiable cardiac risk factors could be treated accordingly.Alternatively, this may be the right time to initiate a multicenter open-label trial for such patients who could be randomly assigned for an FRS-based approach, including aggressive statin therapy versus usual care.
Darmbrand
Authors: Norman B. Roberg
Journal: JAMA (1962)

<h3>To the Editor:—</h3> In the article "Unusual Gas Bacillus Infections Including Necrotic Enteritis" by Jarkowski and Wolf (<i>JAMA</i><b>181</b>:845 [Sept. 8] 1962) there is this sentence: "The association of<i>Clostridium perfrigens</i>(Welsh's [sic!] bacillus) with hemorrhagic necrosis of the intestine has been referred to in the past as `darmbrand,' which means `fire in the bowel.' " At present, as well as "in the past," "Darmbrand" means "gangrene of the bowel." The medical meaning of "Brand" is "gangrene" (Wildhagen-Heraucourt German-English Dictionary, 1953). Von Gierke (Aschoff's Pathology, 6th ed., pp. 377 and 378, 1923) describes "Brand" as one form of necrosis, and gives "Gangrän" (gangrene) as a synonym: "We speak of 'Brand' when the devitalized parts undergo changes because of contact with the environment and the brown or black colors, due to altered blood pigments and decomposition, create a resemblance to burned tissue." Von Gierke notes that "feuchter, stinkender Brand" (moist, putrid
The Role of Oncogenes in Chemical Carcinogenesis
Authors: S. Jill Stowers, Robert R. Maronpot, Steven H. Reynolds, Marshall W. Anderson
Journal: Environmental Health Perspectives (1987)

Proto-oncogenes are cellular genes that are expressed during normal growth and developmental processes. Altered versions of normal proto-oncogenes have been implicated in the development of human neoplasia. In this report, we show the detection of activated proto-oncogenes in various spontaneous and chemically induced rodent tumors. The majority of activated proto-oncogenes found in these tumors are members of the ras gene family and have been activated by a point mutation. Characterization of the activating mutation may be useful in determining whether this proto-oncogene was activated by direct interaction of the chemical with the DNA. Comparison of activating lesions in spontaneous versus chemically induced tumors should be helpful in determining whether the chemical acts via a genotoxic or a nongenotoxic mechanism. All of this information may be helpful in the assessment of potential carcinogenic hazards of human exposure to chemicals.
Vasculitis in maturity-onset diabetes mellitus
Authors: H. B. Barner
Journal: JAMA (1976)

THE MICROANGIOPATHY that frequently causes death in individuals with juvenile diabetes mellitus is so well recognized and ingrained in our thinking that patients with maturity-onset diabetes are commonly assumed to have similar vascular abnormalities. This misconception is widely held by practicing physicians and is perpetuated in our medical schools, so that emerging physicians continue to believe that microangiopathy precludes vascular reconstruction of larger vessels in the patient with adult-onset diabetes. Basement membrane thickening at the capillary level is associated with aging and, to a greater degree, with maturity-onset diabetes.<sup>1,2</sup>This, however, is a segmental lesion that does not obstruct flow but may limit nutrient exchange across the capillary wall. Occlusive disease at the level of the small arteries and arterioles was not found to be more prevalent in adult diabetics than in nondiabetics by two careful studies.<sup>3,4</sup> Combined with this anatomic evidence<sup>1-4</sup>indicating lack of obliterative diabetic
Pyarthrosis complicating gout
Authors: R. J. Hess
Journal: JAMA (1971)

Pyarthrosis complicating gout is unusual, and not often recognized. An elderly man with chronic tophaceous gout developed staphylococcal septicemia, complicated by multiple areas of sepsis in joints and bursae known to contain sodium biurate crystals. The clinical and laboratory features simulated the acute gout that often accompanies surgery or other severe systemic disease. The true nature of the problem was discovered by meticulous examination of the synovial fluid, including identification of crystals, and appropriate bacteriologic studies.
Evidence for a Renal Vascular Mechanism in Renin Release: New Observations with Graded Stimulation by Aortic Constriction
Authors: EDWARD H. BLAINE, JAMES O. DAVIS
Journal: Circulation Research (1971)

To examine the possibility of a renal intravascular receptor for renin secretion, bilateral ureteral ligation and a two-hour period of renal ischemia were used to produce a nonfiltering kidney model in dogs. In conscious animals with both innervated and denervated, nonfiltering kidneys, hemorrhage and suprarenal aortic constriction produced significant increases in plasma renin activity. To measure renin secretion directly, a unilateral, nonfiltering kidney was produced, and renal blood flow was determined with a square-wave electromagnetic flowmeter in anesthetized dogs. Renin secretion was significantly elevated after a 20 ml/kg hemorrhage in these animals. In another group of dogs, adrenalectomy was combined with renal denervation in the unilateral, nonfiltering kidney model. In these animals hemorrhage produced significant increases in renin secretion. After a recovery period three of these dogs were subjected to graded constriction of the suprarenal aorta. Slight decreases in blood pressure with and without decreases in renal blood flow produced increases in renin secretion. Since increased renin secretion occurred in the absence of sodium delivery to the macula densa, from denervated kidneys, and without the major portion of circulating catecholamines, it is suggested that an intrinsic receptor for renin release is present within the renal vascular tree.
International comparison of treatment and short-term survival for older patients with pancreatic cancer.
Authors: Martine Extermann, Noor M de Leede, Lydia G.M. van der Geest, Kathleen Egan, Anton J.M. de Craen, Gregory M. Springett, Cornelis J. H. Van De Velde, Lodovico Balducci, Bert A Bonsing, Esther Bastiaannet
Journal: Journal of Clinical Oncology (2015)

e20527 Background: A significant proportion of pancreatic cancer patients is aged 70 years or more at diagnosis. The aim of this study was to compare treatment and survival for pancreatic cancer patients aged 70 years and older treated at Moffitt Cancer Center, Tampa (Florida, US) versus in the Netherlands. Methods: All age-eligible patients with invasive pancreatic adenocarcinoma diagnosed between 2008 and 2012 were identified. Results were stratified for stage. Treatment (neo-adjuvant, surgery, adjuvant and palliative treatment) and short-term survival at 1 year were compared, and where appropriate adjusted (sex, age, grade and year) or stratified according to age, period and type of hospital in the Netherlands (academic, teaching or non-teaching). Results: In total, 2728 patients were included (307 Moffitt, 2421 Netherlands). Stratified according to stage, there were no significant differences in age, sex or grade. Neo-adjuvant chemoradiation was more often administrated at Moffitt (17.7% versus 0.6%; p < 0.001) in all non-metastatic stages, as well as adjuvant chemoradiation and chemotherapy (p < 0.001). However, the proportion undergoing surgery was not significantly different (41.0% versus 42.4%; p = 0.8 and 45.9% versus 39.0%; p = 0.1, for stages IA-IIA and IIB, in the Netherlands versus Moffitt, respectively). In patients with metastatic disease, more patients at Moffitt underwent palliative chemotherapy (77.8% versus 17.3%; p < 0.001). Short-term survival at 1 year was better for patients treated at Moffitt (HR 0.46 (95%CI 0.30-0.69), HR 0.65 (0.50-0.80), HR 0.41 (0.33-0.51) for early, advanced and metastatic disease, respectively). In subgroup analyses, there was no significant difference in survival comparing academic hospitals in the Netherlands to Moffitt in patients with early and advanced disease. Conclusions: In the present comparison, a treatment regimen as delivered at Moffitt was associated with a longer short-term survival in older patients with pancreatic cancer. Further detailed analyses of selection criteria for systemic treatment could lead to tailored treatment and improved outcomes in older patients with pancreatic cancer.
"English Bards and Scotch Reviewers."
Journal: JAMA (1904)

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