tbuckley/cabot-search huggingface dataset:
Vemurafenib in Multiple Nonmelanoma Cancers with <i>BRAF</i> V600 Mutations
Authors: David M. Hyman, Igor Puzanov, Vivek Subbiah, Jason E. Faris, Ian Chau, Jean-Yves Blay, Jürgen Wolf, Noopur S. Raje, Eli L. Diamond, Antoine Hollebecque, Radj Gervais, Maria Elena Elez-Fernandez, Antoine Italiano, Ralf-Dieter Hofheinz, Manuel Hidalgo, Emily Chan, Martin Schuler, Susan Frances Lasserre, Martina Makrutzki, Florin Sirzen, Maria Luisa Veronese, Josep Tabernero, José Baselga
Journal: New England Journal of Medicine (2015)

BRAF V600 mutations occur in various nonmelanoma cancers. We undertook a histology-independent phase 2 "basket" study of vemurafenib in BRAF V600 mutation-positive nonmelanoma cancers.We enrolled patients in six prespecified cancer cohorts; patients with all other tumor types were enrolled in a seventh cohort. A total of 122 patients with BRAF V600 mutation-positive cancer were treated, including 27 patients with colorectal cancer who received vemurafenib and cetuximab. The primary end point was the response rate; secondary end points included progression-free and overall survival.In the cohort with non-small-cell lung cancer, the response rate was 42% (95% confidence interval [CI], 20 to 67) and median progression-free survival was 7.3 months (95% CI, 3.5 to 10.8). In the cohort with Erdheim-Chester disease or Langerhans'-cell histiocytosis, the response rate was 43% (95% CI, 18 to 71); the median treatment duration was 5.9 months (range, 0.6 to 18.6), and no patients had disease progression during therapy. There were anecdotal responses among patients with pleomorphic xanthoastrocytoma, anaplastic thyroid cancer, cholangiocarcinoma, salivary-duct cancer, ovarian cancer, and clear-cell sarcoma and among patients with colorectal cancer who received vemurafenib and cetuximab. Safety was similar to that in prior studies of vemurafenib for melanoma.BRAF V600 appears to be a targetable oncogene in some, but not all, nonmelanoma cancers. Preliminary vemurafenib activity was observed in non-small-cell lung cancer and in Erdheim-Chester disease and Langerhans'-cell histiocytosis. The histologic context is an important determinant of response in BRAF V600-mutated cancers. (Funded by F. Hoffmann-La Roche/Genentech; ClinicalTrials.gov number, NCT01524978.).
Medical castration produced by the GnRH analogue leuprolide to treat metastatic breast cancer.
Authors: H A Harvey, A Lipton, D T Max, H G Pearlman, R Diaz-Perches, J de la Garza
Journal: Journal of Clinical Oncology (1985)

Leuprolide (Lupron, TAP Pharmaceuticals, North Chicago), a gonadotropin-releasing hormone analogue, was administered to 26 premenopausal women with metastatic breast cancer. Of 25 evaluable patients, 11 (44%) had a partial response with a median duration of 39 weeks and five (20%) remained stable. Six patients showed early rapid progression of their disease. Toxicity was mild and included hot flashes, nausea, vomiting, and headache. Leuprolide induced amenorrhea in all patients who received treatment for ten weeks or longer. We conclude that this GnRH analogue provides a safe and effective means of producing medical castration in premenopausal patients with metastatic breast carcinoma.
Brain Activity During Emotional States
Authors: ROBERT G. HEATH, ARIS W. COX, LEONARD S. LUSTICK
Journal: American Journal of Psychiatry (1974)

When a patient capable of articulate reporting was prepared with deep and surface electrodes, correlations were demonstrated between activity at certain brain sites and pleasurable or painful affect. Moreover, a functional relationship was shown between these sites for emotional expression and some sensory relay nuclei. These findings substantiate previous observations made in the Tulane University depth electrode series and add meaning to anatomic and physiologic data from animal studies that have shown an integral relationship between brain sites involved in sensory perception and those for emotional expression.
Prevalence of established and exercise induced pulmonary hypertension in COPD
Authors: Janne Hilde, Ingunn Skjorten, Sjur Humerfelt, Viggo Hansteen, Morten Melsom, Jonny Hisdal, Kjetil Steine
Journal: European Respiratory Journal (2011)

Aim: To describe prevalence of pre-capillary pulmonary hypertension (PH) and exercise induced pulmonary hypertension (EIPH) in COPD without left sided heart diseases, and to relate PH to GOLD stages II- IV.  Methods: 98 patients, 64±7 yrs and 50% men, were recruited. Right heart catheterization with exercise was done. Pulmonary vascular resistance (PVR) was calculated. Pulmonary artery compliance (PAC) was defined as stroke volume/puls presssure. Pre-capillary PH was defined as mean pulmonary artery pressure (mPAP) ≥ 25 mmHg and pulmonary capillary wedge pressure (PCWP) ≤ 15 mmHg. Pre-capillary EIPH was defined as an increase in mPCWPexc ≤ 20 mmHg, and increase in mPAPexc, combined with abnormal exercise responses both in PVR (unchanged or increased from rest to exercise) and PAC (reduced from rest to exercise).  Results: Prevalence of pre-capillary PH was 27% with mPAP 29±4 mmHg. Categorized by GOLD stages, PH was found in 5% in GOLD II (mPAP 27±1), 28% in III (mPAP 28±4), and 52% in IV (mPAP 29±5). PCWP was normal at rest, 11±3 mmHg. During exercise 17% showed pathological increase in mPCWP (23±2mmHg). EIPH was found in 31%, mPAP rest and exercise 18±3 and 38±7mmHg, respectively. There were significant differences in mPAP for EIPH vs no EIPH, p  Conclusion: PH and EIPH of pre-capillary type were a common finding in this COPD population. In lack of upper normal limit for mPAP during exercise, we suggest a combined evaluation of PAC and PVR during exercise to determine if increase in mPAP is a pathologic or an expected physiologic response to exercise.
Eyebrow regrowth in patients with frontal fibrosing alopecia treated with intralesional triamcinolone acetonide
Authors: J.C. Donovan, A. Samrao, B.S. Ruben, V.H. Price
Journal: British Journal of Dermatology (2010)

Conflicts of interest: none declared. Madam, Frontal fibrosing alopecia (FFA) is a primary lymphocytic cicatricial alopecia which causes recession of the frontotemporal hairline.1 Partial or complete eyebrow hair loss is seen in a majority of patients.2–9 Treatments are aimed at reducing symptoms and signs of disease and slowing disease progression, but rarely stimulate hair regrowth. The goal of this study was to retrospectively evaluate the benefit of intralesional triamcinolone acetonide in the treatment of eyebrow hair loss in patients with FFA. Institutional Review Board approval was obtained to review the medical records of patients with a clinical diagnosis of FFA seen at the University of California San Francisco Hair Clinic over the 6‐year period October 2003–September 2009. Patients with FFA with partial or complete eyebrow hair loss who received at least one treatment session with triamcinolone acetonide injections were included in the final study group. With the exception of one patient, all patients had a scalp biopsy showing a lymphocyte‐predominant scarring alopecia that was consistent with a clinical diagnosis of FFA. Patient medical records were evaluated to identify basic demographic information (age, sex, menopausal status and ethnicity), current and prior treatments including number of eyebrow treatment sessions, eyebrow biopsy results (if available), and documentation of eyebrow regrowth or loss at follow‐up.
Abstract 14626: Evidence of Progressive Subclinical Right Ventricular Dysfunction in Patients with Chronic Obstructive Pulmonary Disease: A Prospective Study by Tissue Doppler Imaging
Authors: Jun-Min Xie, Ran Guo, Fanny W Ko, Jing-Ping Sun, Qing Zhang, David S Hui, Alex P Lee, Yat-Yin Lam, Bryan P Yan, Cheuk-Man Yu
Journal: Circulation (2011)

Background: In patients with chronic obstructive pulmonary disease (COPD), right ventricular (RV) function could be adversely affected as the disease progresses. We hypothesize that subclinical det...
Peri-procedural management of patients taking oral anticoagulants
Authors: Paul R Daniels
Journal: BMJ (2015)

The use of oral anticoagulants is becoming increasingly common. For many years warfarin was the main oral anticoagulant available, but therapeutic options have expanded with the introduction of oral direct thrombin (dabigatran) and factor Xa inhibitors (apixaban, rivaroxaban, and edoxaban). Management of patients taking any oral anticoagulant in the peri-procedural period poses a challenge to medical and surgical providers because of the competing risks of thrombosis and hemorrhage. Bridging therapy has been used to minimize time without anticoagulation when warfarin is interrupted for invasive procedures, but validated strategies based on high quality data are lacking. Existing data suggest that the use of bridging therapy may increase the risk of bleeding for some patients without reducing the risk of thrombosis. Clinical trials are currently under way to answer these questions. Because the half lives and time to anticoagulant activity of newer oral anticoagulants are shorter than for warfarin, bridging therapy is not thought to be necessary with these agents. Peri-procedural management of patients taking these agents is complicated by the lack of demonstrated reversal agents in emergency situations, although specific antidotes are being developed and tested. Existing guidelines for peri-procedural management of patients on oral anticoagulants highlight the importance of individualized patient decision making and suggest strategies to minimize complications. From a patient’s perspective, given the uncertainties surrounding optimal management, explicit discussions regarding risks and benefits of treatment options and demonstration of effective communication among medical and surgical providers are essential.
Is dynamic hyperinflation a major concern in patients with pseudotumoral silicosis
Authors: Mafalda van Zeller, Manuel Vaz, Filipa Soares Pires, Paula Martins, Luís Gaspar, Paulo Viana, Isabel Gomes
Journal: European Respiratory Journal (2013)

Introduction - In patients with severe airway obstruction exercise might induce dynamic hyperinflation, nevertheless pulmonary rehabilitation (PR) is an essential component of care for patients with chronic pulmonary disease. Information regarding the effects of PR in pseudotumoral silicosis is scant in the literature.  Aim – evaluate the effects of a twelve weeks PR program in pulmonary function (PF) and arterial blood gases (ABG) of pseudotumoral silicosis patients.  Methods - a retrospective evaluation of pseudo-tumoral silicosis patients who attended PR which included cycle-ergometer exercise for 30 minutes, 3 times per week, with additional upper and lower limbs training. PF and ABG were evaluated before and after the PR.  Results - 10 patients were included, all were male with median age 56 years. Initial PF testes reveled that all but one patient had severe obstruction: median FVC- 57.1%, FEV1 – 36, 7 % and RV-132,5% of predicted values and ABG analysis showed median pO2-64.3 mmHg, pCO2-42.1 mmHg, pH-7.44. After PR median final FVC- 53.4%, FEV1 – 33,75 % and RV-136,0% of predicted values and ABG analysis showed median pO2-69.4 mmHg, pCO2-40.0 mmHg, pH-7.45. PF was stable and an increase on pO2 was noted, but without any statistically significance (p=0.767).  Conclusion – PR in these patients with pseudotumoral silicosis did not significantly change PF or ABG. Although patients were severely obstructed, no significant change suggesting exercise deleterious effects in RV was present at the end of the PR program.
Abstract 16841: Cardiac Deletion of Aryl Hydrocarbon Nuclear Translocator (Hypoxia Inducible Factor 1-beta) in the Adult Heart Leads to Cardiomyopathy Due to Lipid Accumulation via Peroxisome Proliferator Activated Receptor Activation
Authors: Rongxue Wu, Kusum Chawla, Mohsen Ghanefar, Hossein Ardehali
Journal: Circulation (2011)

Background: Aryl hydrocarbon receptor nuclear translocator (ARNT), also known as hypoxia-inducible factor 1-beta (HIF1-beta), serves as a binding partner for numerous basic helix-loop-helix Per/ARNT/Sim proteins, including HIF1alpha. Although HIF1alpha is known to be required for normal cardiac development, the role of ARNT in basal cardiac function in the adult is not known. We hypothesized that ARNT is required for normal cardiac physiology, and that ARNT deletion in the adult heart results in cardiomyopathy. Methods and Results: Cardiac-specific ARNT deletion was achieved by crossing ARNT flox/flox with αMHC-MCM (tamoxifen-inducible heart specific Cre) transgenic mice, followed by oral administration of tamoxifen. MCM/ARNT +/+ (WT) littermates were used as a control. Echocardiography of the ARNT knockout (KO) mice showed enlarged left ventricle with a reduction in ejection fraction (KO vs. WT: 35.8 ± 3.6% vs. 61.2 ± 2.8%, n=12, p&lt;0.01). Closed-chest catheterization indicated that +dP/dt (KO vs. WT: 4355 ± 538 vs. 9426 ± 180 mmHg, p&lt;0.01) was reduced in KO mice but not in WT mice. Electron microscopy revealed lipid droplets in ARNT KO heart tissues that were confirmed by oil-red staining. Furthermore, genes involved in fatty acid oxidation were up-regulated in KO hearts, as shown by microarray analysis and qRT-PCR. We further confirmed these results in vitro with siRNA-mediated knock down of ARNT in H9c2 cardiac myoblasts. Compared to control siRNA transfection, ARNT knockdown led to increases in PPAR-alpha (1.7-fold, p&lt;0.001), fatty acid translocase (1.4-fold, P&lt;0.01), and acyl-coenzyme A dehydrogenase (1.6-fold, p&lt;0.0001) mRNA levels and to enhanced triglyceride accumulation (p&lt;0.05). Moreover, insulin resistance was noted in ARNT knockdown cells, as demonstrated by significantly reduced glucose uptake in response to insulin stimulation. These results suggest that impaired fatty acid oxidation leads to lipid accumulation in response to a reduction in ARNT levels. Conclusion: ARNT is essential for normal cardiac function, and a reduction in ARNT levels leads to cardiomyopathy by increasing triglyceride accumulation through a PPAR-alpha pathway.
Temporal Trends in Mortality in the United States, 1969-2013
Authors: Jiemin Ma, Elizabeth M. Ward, Rebecca L. Siegel, Ahmedin Jemal
Journal: JAMA (2015)

A systematic and comprehensive evaluation of long-term trends in mortality is important for health planning and priority setting and for identifying modifiable factors that may contribute to the trends.To examine temporal trends in deaths in the United States for all causes and for the 6 leading causes.Joinpoint analysis of US national vital statistics data from 1969 through 2013.Causes of death.Total and annual percent change in age-standardized death rates and years of potential life lost before age 75 years for all causes combined and for heart disease, cancer, chronic obstructive pulmonary disease (COPD), stroke, unintentional injuries, and diabetes mellitus.Between 1969 and 2013, the age-standardized death rate per 100,000 decreased from 1278.8 to 729.8 for all causes (42.9% reduction; 95% CI, 42.8%-43.0%), from 156.8 to 36.0 for stroke (77.0% reduction; 95% CI, 76.9%-77.2%), from 520.4 to 169.1 for heart disease (67.5% reduction; 95% CI, 67.4%-67.6%), from 65.1 to 39.2 for unintentional injuries (39.8% reduction; 95% CI, 39.3%-40.3%), from 198.6 to 163.1 for cancer (17.9% reduction; 95% CI, 17.5%-18.2%), and from 25.3 to 21.1 for diabetes (16.5% reduction; 95% CI, 15.4%-17.5%). In contrast, the rate for COPD increased from 21.0 to 42.2 (100.6% increase; 95% CI, 98.2%-103.1%). However, during the last time segment detected by joinpoint analysis, death rate for COPD in men began to decrease and the declines in rates slowed for heart disease, stroke, and diabetes. For example, the annual decline for heart disease slowed from 3.9% (95% CI, 3.5%-4.2%) during the 2000-2010 period to 1.4% (95% CI, -3.4% to 0.6%) during the 2010-2013 period (P = .02 for slope difference). Between 1969 and 2013, age-standardized years of potential life lost per 1000 decreased from 1.9 to 1.6 for diabetes (14.5% reduction; 95% CI, 12.6%-16.4%), from 21.4 to 12.7 for cancer (40.6%; 95% CI, 40.2%-41.1%), from 19.9 to 10.4 for unintentional injuries (47.5%; 95% CI, 47.0%-48.0%), from 28.8 to 9.1 for heart disease (68.3%; 95% CI, 68.1%-68.5%), and from 6.0 to 1.5 for stroke (74.8%; 95% CI, 74.4%-75.3%). For COPD, the rate for years of potential life lost did not decrease over this time interval.According to death certificate data between 1969 and 2013, an overall decreasing trend in age-standardized death rate was observed for all causes combined, heart disease, cancer, stroke, unintentional injuries, and diabetes, although the rate of decrease appears to have slowed for heart disease, stroke, and diabetes. The death rate for COPD increased during this period.
Twenty‐four‐hour heart rate lowering with ivabradine in chronic heart failure: insights from the <scp>SHIFT</scp> Holter substudy
Authors: Michael Böhm, Jeffrey S. Borer, John Camm, Ian Ford, Suzanne M. Lloyd, Michel Komajda, Luigi Tavazzi, Mario Talajic, Mitja Lainscak, Jan‐Christian Reil, Christian Ukena, Karl Swedberg
Journal: European Journal of Heart Failure (2015)
Cyclophosphamide, carmustine, and etoposide with autologous bone marrow transplantation in refractory Hodgkin's disease and non-Hodgkin's lymphoma: a dose-finding study.
Authors: C Wheeler, J H Antin, W H Churchill, S E Come, B R Smith, G J Bubley, D S Rosenthal, J M Rappaport, K A Ault, L E Schnipper
Journal: Journal of Clinical Oncology (1990)

Cyclophosphamide, carmustine (BCNU), and etoposide (VP-16) (CBV) is a widely used conditioning regimen in autologous bone marrow transplantation (ABMT) of patients with refractory and relapsed lymphoma. However, the maximum-tolerated dose (MTD) of these agents when used in combination has not been systematically explored. We treated 58 patients (28 with non-Hodgkin's lymphoma [NHL], 30 with Hodgkin's disease [HD]) at seven dose levels of CBV. Doses were cyclophosphamide 4,500 to 7,200 mg/m2, BCNU 450 to 600 g/m2, and VP-16 1,200 to 2,000 mg/m2. The MTD was cyclophosphamide 7,200 mg/m2, BCNU 450 mg/m2, and VP-16 2,000 mg/m2. Six hundred milligrams per square meter of BCNU was associated with five of 18 cases of interstitial pneumonitis versus two of 40 at 450 mg/m2 (P = .02). Treatment-related mortality was 5% at dose levels less than or equal to the MTD and 22% at the highest dose. In this heavily pretreated patient population, most of whom had high volume residual disease, complete responses (CRs) to CBV and ABMT occurred in 25% of assessable patients with NHL and 43% of patients with HD. Thirteen of 28 patients with NHL and 14 of 30 with HD remain free from disease progression with median follow-up of 212 and 215 days, respectively. CBV can be administered with acceptable toxicity over a wide range of doses to patients with refractory and relapsed lymphoma.
Nomograms Predict Overall Survival for Patients with Small-Cell Lung Cancer Incorporating Pretreatment Peripheral Blood Markers
Authors: Dong Xie, Randolph Marks, Mingrui Zhang, Gening Jiang, Aminah Jatoi, Yolanda I. Garces, Aaron Mansfield, Julian Molina, Ping Yang
Journal: Journal of Thoracic Oncology (2015)
Preoperative Testing—A Bridge to Nowhere
Authors: Sanjiv M. Baxi, Joshua R. Lakin
Journal: JAMA Internal Medicine (2015)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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 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 Internal Medicine journal
Interleukin-4 Receptor in Moderate Atopic Asthma
Authors: LARRY C. BORISH, HAROLD S. NELSON, MIGUEL J. LANZ, LORI CLAUSSEN, JAMES B. WHITMORE, JAN M. AGOSTI, LESLIE GARRISON
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Interleukin-4 mediates important proinflammatory functions in asthma, including induction of the IgE isotype switch, expression of VCAM-1 on endothelium, mucin production, 15-lipoxygenase activity, and Th2 lymphocyte stimulation leading to the secondary synthesis of IL-4, IL-5, and IL-13. Soluble recombinant human IL-4 receptor (IL-4R; Nuvance; altrakincept) inactivates naturally occurring IL-4 without mediating cellular activation. Nebulized IL-4R has a serum half-life of approximately 1 wk. In this double-blind, placebo-controlled trial, 25 patients with moderate asthma requiring inhaled corticosteroids were randomly assigned to receive a single nebulized dose of IL-4R 1,500 μ g, IL-4R 500 μ g, or placebo after stopping inhaled corticosteroids. No drug-related toxicity was observed. Treatment with IL-4R produced significant improvement in FEV1 on Day 4 (1,500 μ g versus placebo; p < 0.05) and in FEF25–75 on Days 2 and 4 (1,500 μ g versus placebo; p < 0.05). Asthma symptom scores stabilized among patients treated with IL-4R 1,500 μ g, despite abrupt withdrawal of corticosteroids, but not in the IL-4R 500 μ g group or the placebo group (p < 0.05). Patients in the IL-4R 1,500 μ g group also required significantly less β2-agonist rescue use (p < 0.05). Anti-inflammatory effects were further demonstrated by significantly reduced exhaled nitric oxide (p < 0.05). Conclusions: A single dose of IL-4R appears safe and effective in moderate asthma. The 1,500 μ g dose appears as safe but significantly more effective than the 500 μ g dose. Borish LC, Nelson HS, Lanz MJ, Claussen L, Whitmore JB, Agosti JM, Garrison L. Interleukin-4 receptor in moderate atopic asthma: a phase I/II randomized, placebo-controlled trial.
Assessment of chest pain in a low risk patient: is the exercise tolerance test obsolete?
Authors: K. Barraclough, C. P. Gale, R. Hall
Journal: BMJ (2015)

#### The bottom line

A 55 year old man presents with chest pain that he has had for a few months. He is a keen cyclist and a non-smoker with normal blood pressure. He has a serum total cholesterol concentration of 6.1 mmol/L (with an high density lipoprotein cholesterol concentration of 1.5 mmol/L). The chest pain is anterior, poorly localised, mild, and intermittent, though sometimes associated with exercise. It generally resolves after a few minutes whether or not the patient continues to exercise. Examination and his resting 12 lead electrocardiograph are normal.

Three international guidelines for the assessment of new onset of chest pain provide different advice about how an individual at low or medium likelihood of coronary artery disease should be investigated (table 1⇓). The American Heart Association1 and European Society of Cardiology2 advocate the exercise tolerance test or functional cardiac imaging. However, in 2010, the UK National Institute for Health and Care Excellence (NICE) took a new approach and recommended that, for patients who had a low likelihood of coronary artery disease, coronary artery calcium scoring should be the first line investigation, replacing the …