tbuckley/cabot-search huggingface dataset:
Innovative phase I study of concomitant and consecutive treatment with dasatinib and MK-0457 in refractory Ph+ CML and ALL patients
Authors: C. Papayannidis, I. Iacobucci, S. Soverini, S. Paolini, D. Cilloni, F. Messa, F. Pane, E. Ottaviani, M. Baccarani, G. Martinelli
Journal: Journal of Clinical Oncology (2009)

7080 Background: MK-0457 is a pan-aurora kinase inhibitor with activity against wild-type and mutated BCR-ABL, including the T315I form, FLT3, and JAK-2. Methods: We conducted an innovative Phase I clinical study of sequential and concomitant treatment with dasatinib, previously administered for 3 months, and MK-0457. This combined activity suggests that MK-0457, in association with dasatinib, would suppress the emergence of T315I and other resistant clone, improving upon the response rate for dasatinib and the durability of response. The trial investigated two schedules of therapy: patients who achieved and maintained a major hematologic response (MHR) after 3 months of therapy with dasatinib (70 mg twice daily) received a 6-hour biweekly infusion of MK-0457 at 64 mg/m2/hr, whereas patients who failed to achieve a MHR received a 5-days continuous infusion of MK-0457 at 10 mg/m2/hr, every 4 weeks. Results: Two patients with Ph+ ALL and one patient with CML in myeloid blast crisis, previously unsuccessfully treated with imatinib, were enrolled. The first two patients, both in hematologic response after three months of treatment with dasatinib, subsequently received the 6-hour biweekly schedule, maintaining the hematological response. No hematological toxicity was described. The third patient, in progression disease, received the 5 days MK-0457 schedule. His peripheral blood count showed a severe pancytopenia, and his bad clinical conditions were compromised by a severe hemorrhagic pleural effusion. After one cycle of MK-0457, a complete recovery of the pulmonary disease and a complete hematologic response were obtained. Conclusions: The sequential and concomitant administration of dasatinib and MK-0457 represents a promising therapeutic strategy for refractory Ph+ CML and ALL. Supported by: European LeukemiaNet, AIL, AIRC, FIRB 2006, Fondazione del Monte di Bologna e Ravenna, Merck Sharp &amp; Dohme. No significant financial relationships to disclose.
Abstract 9560: Clinical Trial Simulations of Dyslipidemic Patients in a Mechanistic Model of Cardiovascular Disease Predict Little Impact on CHD Events by CETP Inhibitors
Authors: Karim Wahba, Arthur Lo, Ananth Kadambi, Lyn M Powell
Journal: Circulation (2011)

The Entelos® CV PhysioLab® platform, a mechanistic model of CHD, quantitatively predicts cholesterol metabolism and plaque growth in the coronary artery over time through the dynamic simulation of relevant biological pathways. Statistical methodologies are used to translate predicted changes in circulating lipids and plaque characteristics to predictions of CHD risk. Such predictions can be made for approved or novel therapeutics over time in virtual populations representing a diverse set of patient populations that can be created. PK and PD effects of cholesteryl ester transfer protein (CETP) inhibitors, torcetrapib (60 mg qd), dalcetrapib (600 mg qd) and anacetrapib (100mg qd) were implemented in the platform, calibrated to published data and administered to simulated patients to predict effects on lipoprotein profile and the mean hazard ratio (HR) relative to the same simulated patients on a statin treated background (statin treated mean LDL-C 84 ± 15 mg/dL, HDL-C 44 ± 9 mg/dL). An additional effect of the reported increase on blood pressure was implemented for torcetrapib simulations only. Predicted changes in lipoproteins and 4 year HRare shown in the table. When the mechanistic effects of the reported increase in systolic blood pressure with torcetrapib are added to the lipoprotein changes that result from appropriate CETP inhibition, simulations predict an increased HR similar to that seen in the ILLUMINATE study. Dalcetrapib simulations do not predict any clinically meaningful changes in HR. Finally, despite an additional decrease in LDL-C and the largest increase in HDL-C, anacetrapib simulations predict a very small reduction in HR. Simulations also define a subpopulation within whom the inhibition of CETP activity is more beneficial with the general characteristics of high TG and low HDL-C. 1Additional effect on blood pressure was included in simulations
Abstract 9792: Chrontropic Incompetence in Heart Failure and the Relationship of Minute Ventilation and Chronotropic Response During Exercise
Authors: Donald L Hopper, JoEllyn M Abraham, Michael A Samara, Bruce Wilkoff
Journal: Circulation (2012)

BACKGROUND: Cardiac pulmonary mismatch is prevalent in heart failure patients that exhibit chronotropic incompetence (CI). Wilkoff’s model provides evaluation of metabolic chronotropic response (MCR) during exercise. In addition to CI we evaluated a new measure of the normalized heart rate to normalized minute ventilation relationship during exercise (HRn/VEn) which,in combination with the MCR slope, may provide discriminating information in regards to identifying those normal subjects and heart failure patients who would most likely benefit from adaptive rate pacing. Normalization allows comparison of subjects and identification of patients with CI regardless of Age, functional capacity, and during submaximal workloads. METHOD: We studied the resulting MCR slopes and the HRn/VEn slopes in 40 normal subjects (N) (age 37±9) and 40 heart failure patients (HF) implanted with BiV CRT-D devices (age 62±9) during graded exercise testing by using standard cardiopulmonary exercise testing techniques. Exercise tests were performed to peak exercise (as quantified by the respiratory exchange ratio (RER) RER = 1.13±0.09 N and 1.11±0.07 HF) and the end stage heart rate and minute ventilation data was used in the calculations of the MCR slope and HRn/VEn slopes. RESULTS: Mean MCR slopes were 1.0±0.14 (N) and 0.52±0.23 (HF). The mean HRn/VEn slope were 1.34±0.26 (N) and 0.66±0.28 (HF). Details are presented in the table. DISSCUSION/CONCLUSSION: When CI is present there is also a significant derangement in the heart rate to pulmonary relationship as shown by the HRn/VEn slopes. A MCR slope of 0.7 which is considered to be severely CI corresponds to a decreased HRn/VEn slope of 0.881 (95% confidence interval of the normal relationship). HF CI patients (MCR slopes &lt;0.7) also exhibit low HRn/VEn measures (&gt; 2 standard deviations from the mean of normal group).
Industrial Microscopy: A Book Dealing with the Use of the Microscope and the Preparation of Specimens for All Who Use the Microscope in Industry.
Authors: Walter. Garner
Journal: JAMA (1933)

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
Physiological Aspects of the Liquor Problem.
Authors: Wilbur Olin Atwater, John Shaw Billings
Journal: JAMA (1903)

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
Chikungunya infection in a French traveller returning from the Maldives, October, 2009
Authors: M Receveur, K Ezzedine, T Pistone, D Malvy
Journal: Eurosurveillance (2010)

In the last years, cases of chikungunya fever have been reported in international travellers returning from the Indian Ocean region. The cases have been linked to the re-emergence of chikungunya fever on Indian Ocean islands in 2006. We describe the first case of chikungunya fever in a French traveller returning from Malé, an island of the Maldives islands, confirming the permanence of virus circulation by the end of 2009.
Intensified shigellosis epidemic associated with sexual transmission in men who have sex with men - Shigella flexneri and S. sonnei in England, 2004 to end of February 2015
Authors: I Simms, N Field, C Jenkins, T Childs, V L Gilbart, T J Dallman, P Mook, P D Crook, G Hughes
Journal: Eurosurveillance (2015)

Surveillance data suggest an intensification of the shigellosis epidemic associated with sexual transmission in men who have sex with men (MSM) in England with separate introductions into the population. In 2014, sexual transmission between MSM might have accounted for 97%, 89%, and 43% of non-travel associated Shigella flexneri 3a and S. flexneri 2a, and S. sonnei diagnoses. Clinicians should sensitively ascertain sexual history for men with enteric infections to facilitate prompt diagnosis and appropriate management.
CD4+ctla-4+ t Lymphocytes Inversely Correlate With CD4+CD127+ T Cells In Brazilian Patients With Classical Hodgkin Lymphoma
Authors: Joyce M. K. Silva, Adriana M. Damasco Penna, Maria Mirtes Sales, Elma Maria Chaves, Priscilla Brito Silva, Mariane Cristina Gennari Assis, Otavio C.G. Baiocchi
Journal: Blood (2013)
Allergy: Immunological and Clinical Aspects.
Authors: Maurice H. Lessof
Journal: Annals of Internal Medicine (1985)

best, appears as single paragraphs or footnotes in most ENT or neurology textbooks.Vertigo in children, acrophobia (vertigo as understood by Hitchcock's film), migrainous vertigo, motion sickness, barotrauma and vertigo in neck disorders are all reviewed in depth with plenty of references.
Abstract 8244: Inhibition of Ca2+ Entry Mode of Na+/Ca2+ Exchanger Improves Survival Rate of Rat Model for Heart Failure with Preserved Ejection Fraction
Authors: Daisuke Kamimura, Tomohito Ohtani, Yasushi Sakata, Toshiaki Mano, Yasuharu Takeda, Shunsuke Tamaki, Yosuke Omori, Yasumasa Tsukamoto, Kazuharu Furutani, Yutaka Komiyama, Masamichi Yoshika, Hakuo Takahashi, Toshio Matsuda, Akemichi Baba, Satoshi Umemura, Takeshi Miwa, Issei Komuro, Kazuhiro Yamamoto
Journal: Circulation (2011)

Background: Heart failure with preserved ejection fraction (HFPEF) has a poor prognosis as well as heart failure with reduced ejection fraction and its therapeutic strategy has not been established. Left ventricular (LV) fibrosis and stiffening play crucial roles in the development of HFPEF. Plasma level of digitalis-like factors (DLFs) is increased in about a half of patients with hypertension, a principal underlying cardiovascular disease of HFPEF. DLFs inhibit ion-pumping function of Na+/K+-ATPase and activate the Ca2+ entry mode of Na+/Ca2+ exchanger (NCX). It is also known that DLFs promote collagen production in fibroblasts. Objective: The objective of this study was to explore whether the pharmacological inhibition of the NCX entry mode is effective in preventing LV fibrosis and the development of HFPEF. Methods and Results: (1) Dahl salt-sensitive rats fed 8% NaCl diet from age 6 weeks served as hypertensive HFPEF model. In this model, 24-hour urine excretion of DLFs was greater than that in the age-matched control at compensatory hypertrophic and heart failure stages. (2) Continuous administration of ouabain for 14 weeks developed LV fibrosis without the changes in blood pressure in Sprague-Dawley rats irrespective of NaCl loading. (3) Ouabain elevated intracellular Ca2+ concentration through the entry of extracellular Ca2+, increased the phosphorylation level of p42/44 mitogen-activated protein kinases, and enhanced 3H-proline incorporation in cardiac fibroblast, and SEA0400, the inhibitor of the NCX entry mode, suppressed these in vitro effects of ouabain. (4) In the HFPEF model, chronic administration of SEA0400 at subdepressor dose prevented the elevation of LV filling pressure and improved the survival rate in association with the attenuation of LV fibrosis and stiffening. Conclusion: DLFs and the subsequently activated NCX entry mode may play an important role in the development of hypertensive HFPEF, and the blockade of the NCX entry mode may be a new therapeutic strategy for this phenotype of heart failure.
Targeted liposomal daunorubicin (LDauno) dose escalation is feasible with filgrastim (F): Improved tumor response in colon cancer (CoC), prostate cancer (PrC), and non-small cell lung cancer (NSCLC)
Authors: C. A. Presant, M. Mesisca
Journal: Journal of Clinical Oncology (2005)

2107 Background: In animal models, response to targeted LDauno (DaunoXome) is dose dependent. DE has not been possible with liposomal doxorubicin due to cutaneous toxicity. In order to determine if DE is possible with LDauno, a DE study was performed in patients (pt) with stage 4 CoC, PrC, or NSCLC. Methods: Pts were eligible if they had 0–1 prior chemotherapy regimen, no significant hematologic, cardiac, or hepatorenal dyusfunction, and ps>60. Pt received LDauno IV Q3wk starting at 100 mg/m2 (NSCLC, CoC) or 80 mg/m2 (PrC), doses escalated by 20 mg/m2 after 2 cycles with no dose limiting toxicity (DLT), and initial doses escalated after no DLT in 3 pt per cohort. After LDauno, F was given at 5 mcg/kg daily for 10 d. Cardiac ejection fraction was measured at 0, 500, 750, and 1000 mg/m2 LDauno and at study completion. Toxicity was measured by SWOG criteria. Partial tumor response (PR) was defined as over 50% reduction in tumor area or PSA for at least 4 wk with improved symptoms and no new cancer. Results: 20/21 pt were evaluable. DLT grade 4 neutropenia (n) was observed in 4/5 and 5/6 pt at 140 and 150 mg/m2 LDauno. Duration of n was 3d or less and 2 pt had febrile n. Grade 4 thrombocytopenia was observed in 3/4 and 2/6 pt at 140 and 150 mg/m2. Other grade 3–4 adverse events were fatigue 5 pt, back pain 2, vomiting 1, dyspnea 2, dizziness 1, flushing 1, allergic reaction 1, confusion 1, hypokalemia 1, pneumothorax 1, and congestive heart failure 1. PR were observed in 1/8 CoC pt (duration 4 mo), 2/4 PrC (3,7 mo), and 2/9 NSCLC (3,5 mo). Improvements (>25%, <50%) were observed in 1/8 CoC (10 mo), 0/4 PrC, and 1/9 NSCLC (3 mo). Mean survival from time on study was 12.6 mo in CoC (range 6–19 mo), 8 mo in PrC (5–10), and 16.8 in NSCLC (2–84). Conclusions: We conclude that compared to standard dose LDauno of 80–100 mg/m2, DE up to 140 mg/m2 is feasible using standard dose F. Compared to historical controls, targeted LDauno may improve response rates and survival in previously treated CoC, PrC, and NSCLC. Targeted LDauno at escalated doses with F may be useful as a single agent or in combination with other drugs. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen Amgen
Assessment of prognostic factors in pancreatic ductal adenocarcinoma: Focus on the retroperitoneal margin
Authors: A. M. Bellizzi, M. Bloomston, S. M. Bellizzi, W. L. Marsh, W. L. Frankel
Journal: Journal of Clinical Oncology (2009)

e15670 Background: Pancreatic ductal adenocarcinoma (PDA) is a leading cause of cancer death in the West, with a nearly superimposable incidence and mortality. Resection is the only chance for cure, and various features in resection specimens correlate with outcome. While most consider the uncinate margin (UM) to be the true retroperitoneal margin, it has been suggested that the posterior pancreatic surface (PPS) may also be important. At another site with a retroperitoneal margin (i.e. rectum), 1 mm margins are significant. We thus evaluated margin status in various ways, focusing on the retroperitoneal region and emphasizing outcome. Methods: We identified all pancreaticoduodenectomies for PDA over a 6 year period in which the PPS was histologically evaluable. Tumors were assessed for the following: size, stage, grade, lymph node (LN) status, vascular and perineural invasion, and margin status. Margin status was evaluated in 3 ways: traditional margins (tumor at pancreatic neck, bile duct, and/or uncinate margins), 1 mm margins (traditional + tumor within 1 mm of UM), and PPS margins (traditional + tumor within 1 mm of PPS or UM). Kaplan-Meier survival curves were constructed with univariate factors compared by log rank analysis; multivariate analysis was done using the Cox proportional hazard model. Results: Fifty-one tumors exhibited the following features: size (mean 3.3 cm), stage (48 T3), grade (27 low, 24 high), LN status (11 neg, 40 pos), positive margins (13 traditional, 23 1 mm, and 32 PPS). Nearly all tumors exhibited at least focal vascular and perineural invasion. Grade influenced survival (p=0.0001), while size (p=0.417) and traditional and PPS margins did not (p=0.5 and 0.95). LN status and 1 mm margins trended toward significance (p=0.17 and 0.2). Conclusions: Use of a two-tiered grading system is highly correlated with survival. Neither tumor size, LN status, nor traditional or PPS margins are significant, while 1 mm margins trend toward significance. Although lack of significance of some features (i.e. size, LN status, and traditional margin status) may be attributable to modest sample size, lack of significance of the PPS may reflect its anatomic nature (i.e. not a true surgical margin). Additional study of 1 mm margins in a larger tumor set is warranted. No significant financial relationships to disclose.
Die Entzündung des Magens
Authors: Norbert Henning
Journal: JAMA (1934)

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
Lehrbuch und Atlas der Röntgendiagnostik in der inneren Medizin und ihren Grenzgebieten.
Authors: Franz M. Groedel
Journal: JAMA (1924)

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
Abstract 670: Immediate And Sustained Blood Pressure Lowering by CRF-receptor Stimulation: A Novel Approach To Antihypertensive Therapy?
Authors: Thomas Dieterle, Silvia Meili-Butz, Katrin Buehler, Christian Morandi, Dietlinde John, Matthias Pfisterer, Peter T Buser, Wylie W Vale, Kirk L Peterson, Marijke Brink
Journal: Circulation (2007)

Background: Recently, novel corticotropin-releasing factor (CRF)-related peptides, named urocortin I (UcnI), UcnII, and UcnIII were described. Available data suggest that the Ucns are part of a peripheral CRF system modulating cardiovascular function and mediating cardiovascular responses to stress. Blood pressure (BP) lowering effects have been described after administration of UcnI. However, no data are available on effects of UcnII on BP in an animal model of systemic arterial hypertension. Methods: Experiments were performed in Dahl salt-sensitive (DSS) and salt-resistant rats (DSR, control). Animals were fed a diet containing 4% NaCl (high salt) to induce arterial hypertension in DSS rats. At the end of week 2 of high salt diet, both DSS and DSR rats were randomly assigned to i.p. injections of either UcnII (2.5 μg/kg body weight) or vehicle b.i.d. for five weeks. Animals underwent repetitive tail cuff BP measurements at baseline (prior to first injection), at 5 and 15 minutes after the first injection and at week 1, 2, and 5 of b.i.d. treatment. At week 5 animals were sacrificed to determine heart weight /body weight ratio. Results: Systolic BP (SBP, mmHg) and heart rate (HR, min −1 ) are given in the following table as mean ± SD (n=10 per group). Conclusions: In hypertensive DSS rats, acute CRF-receptor stimulation by UcnII immediately lowered BP to the range observed in DSR rats. Compared to vehicle-treated DSS rats, sustained BP reduction was observed with further chronic administration of UcnII. No severe reflex tachycardia was observed after administration of UcnII. Thus, CRF-receptor stimulation might represent a novel approach to the treatment of arterial hypertension.