tbuckley/cabot-search huggingface dataset:
A Phase I, First-in-Human Study of AMG 780, an Angiopoietin-1 and -2 Inhibitor, in Patients with Advanced Solid Tumors
Authors: Afshin Dowlati, Gordana Vlahovic, Ronald B. Natale, Erik Rasmussen, Indrajeet Singh, Yuying C. Hwang, John Rossi, Michael B. Bass, Gregory Friberg, Cheryl A. Pickett
Journal: Clinical Cancer Research (2016)

Abstract Purpose: To assess the toxicity, pharmacokinetics, tumor vascular response, tumor response, and pharmacodynamics of AMG 780, a mAb designed to inhibit the interaction between angiopoietin-1 and -2 and the Tie2 receptor. Experimental Design: This was a phase I dose-escalation study of patients with advanced solid tumors refractory to standard treatment without previous antiangiogenic treatment. AMG 780 was administered by intravenous infusion every 2 weeks in doses from 0.1 to 30 mg/kg. The primary endpoints were incidences of dose-limiting toxicity (DLT) and adverse events (AE), and pharmacokinetics. Secondary endpoints included tumor response, changes in tumor volume and vascularity, and anti-AMG 780 antibody formation. Results: Forty-five patients were enrolled across nine dose cohorts. Three patients had DLTs (0.6, 10, and 30 mg/kg), none of which prevented dose escalation. At 30 mg/kg, no MTD was reached. Pharmacokinetics of AMG 780 were dose proportional; median terminal elimination half-life was 8 to 13 days. No anti-AMG 780 antibodies were detected. At week 5, 6 of 16 evaluable patients had a &amp;gt;20% decrease in volume transfer constant (Ktrans), suggesting reduced capillary blood flow/permeability. The most frequent AEs were hypoalbuminemia (33%), peripheral edema (29%), decreased appetite (27%), and fatigue (27%). Among 35 evaluable patients, none had an objective response; 8 achieved stable disease. Conclusions: AMG 780 could be administered at doses up to 30 mg/kg every 2 weeks in patients with advanced solid tumors. AMG 780 treatment resulted in tumor vascular effects in some patients. AEs were in line with toxicity associated with antiangiopoietin treatment. Clin Cancer Res; 22(18); 4574–84. ©2016 AACR.
Case 25-1991
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Leonard Sicilian, Eugene J. Mark
Journal: New England Journal of Medicine (1991)

Presentation of CaseA 21-year-old man was admitted to the hospital because of a massive pulmonary embolus.The patient was well until six weeks earlier, when lumbosacral pain developed, became concentrated in the left gluteal area, and subsided after about one month. Three weeks before entry the patient experienced two bouts of painless hematuria. On the following day a physician confirmed the presence of microscopic hematuria. A culture of urine yielded no microorganisms. The patient was then well until two days before admission, when he abruptly felt lightheaded while playing volleyball and collapsed to the ground. He did not lose . . .
Spatial Ability in Androgen-Deficient Men
Authors: Daniel B. Hier, William F. Crowley
Journal: New England Journal of Medicine (1982)

Several lines of previous evidence have suggested that androgens affect cognitive abilities. In an effort to characterize this defect, we compared 19 men with idiopathic hypogonadotropic hypogonadism with 19 control men and with five men with acquired hypergonadotropic hypogonadism that had developed after puberty. The 19 patients with idiopathic hypogonadism had markedly impaired spatial ability in comparison to either controls or subjects with acquired hypogonadism (P less than 0.05). Moreover, the spatial ability of the patients correlated positively with their testicular volume (P less than 0.05). Androgen-replacement therapy in six of the patients did not improve their spatial ability. The impairment in spatial ability in men with the idiopathic form of hypogonadotropic hypogonadism, the lack of such an impairment in men with the acquired form, and the failure to exogenous androgens to correct the deficits in the idiopathic form suggest that androgens exert a permanent organizing influence on the brain before or at puberty in boys.
Depletion of Butyrate-Producing Clostridia from the Gut Microbiota Drives an Aerobic Luminal Expansion of Salmonella
Authors: Fabian Rivera-Chávez, Lillian F. Zhang, Franziska Faber, Christopher A. Lopez, Mariana X. Byndloss, Erin E. Olsan, Gege Xu, Eric M. Velazquez, Carlito B. Lebrilla, Sebastian E. Winter, Andreas J. Bäumler
Journal: Cell Host & Microbe (2016)
NIMG-56IMMUNOTHERAPY RESPONSE ASSESSMENT IN NEURO-ONCOLOGY (iRANO): A REPORT OF THE RANO WORKING GROUP
Authors: Hideho Okada, Michael Weller, Raymond Huang, Gaetano Finocchiaro, Mark Gilbert, Wolfgang Wick, Benjamin Ellingson, Naoya Hashimoto, Ian Pollack, Alba Brandes, Enrico Franceschi, Christel Herold-Mende, Lakshmi Nayak, Ashok Panigrahy, Whitney Pope, Robert Prins, John Sampson, Patrick Wen, David Reardon
Journal: Neuro-Oncology (2015)

Immunotherapy represents a promising area of therapy among neuro-oncology patients. However, early phase studies reveal unique challenges associated with assessment of radiological changes reflecting delayed responses or therapy-induced inflammation. Clinical benefit, including long-term survival and tumor regression, can still occur following initial apparent progression or appearance of new lesions. Refinement of response assessment criteria for neuro-oncology patients undergoing immunotherapy is therefore warranted. A multinational and multidisciplinary panel of neuro-oncology immunotherapy experts describes immunotherapy response assessment for neuro-oncology (iRANO) criteria that are based on guidance for determination of tumor progression outlined by the immune-related response criteria (irRC) and the response assessment in neuro-oncology (RANO) working group. Among patients who demonstrate imaging findings meeting RANO criteria for progressive disease (PD) within six months of initiating immunotherapy including the development of new lesions, confirmation of radiographic progression on follow-up imaging is recommended provided that the patient is not significantly worse clinically. The proposed criteria also include guidelines for use of corticosteroids. The role of advanced imaging techniques and measurement of clinical benefit endpoints including neurologic and immunologic functions are reviewed. The iRANO guidelines put forth herein will evolve successively to improve their utility as further experience from immunotherapy trials in neuro-oncology accumulate.
Efficacy and Safety of Oxycodone/Naloxone Controlled Release in Comparison with Oxycodone Controlled Release in Korean Patients with Cancer Pain
Authors: S. Park, K.H. Lee, T.W. Kim, J.H. Kang, J. Kim, J.S. Ahn, S. Kim, H.J. Yun, H.Y. Kim
Journal: Annals of Oncology (2014)
Prophylactic Antimicrobial Drugs in Surgery
Authors: Richard C. Karl, James J. Mertz, Frank J. Veith, Peter Dineen
Journal: New England Journal of Medicine (1966)

MANY studies have assessed the value of prophylactic chemotherapy in the prevention of surgical wound infections.1 2 3 4 5 6 7 8 9 Most of these have indicated that there has been no beneficial effect, and some have suggested that surgical sepsis has actually been increased by such measures. In 1964, Bernard and Cole10 reported a controlled study of a regimen that impressively reduced infection rates in patients undergoing surgery of the alimentary tract. Their technic involved administration of a mixture of antimicrobial drugs in only 3 doses, shortly before, during and after surgery. The present investigation was conducted largely because of their reported promising results, with . . .
Knowledge and Use of Folic Acid by Women of Childbearing Age—United States, 1995
Journal: JAMA (1995)

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
Resequencing analysis of five Mendelian genes and the top genes from genome-wide association studies in Parkinson’s Disease
Authors: Bruno A. Benitez, Albert A. Davis, Sheng Chih Jin, Laura Ibanez, Sara Ortega-Cubero, Pau Pastor, Jiyoon Choi, Breanna Cooper, Joel S. Perlmutter, Carlos Cruchaga
Journal: Molecular Neurodegeneration (2016)

Most sequencing studies in Parkinson’s disease (PD) have focused on either a particular gene, primarily in familial and early onset PD samples, or on screening single variants in sporadic PD cases. To date, there is no systematic study that sequences the most common PD causing genes with Mendelian inheritance [α-synuclein (SNCA), leucine-rich repeat kinase 2 (LRRK2), PARKIN, PTEN-induced putative kinase 1 (PINK1) and DJ-1 (Daisuke-Junko-1)] and susceptibility genes [glucocerebrosidase beta acid (GBA) and microtubule-associated protein tau (MAPT)] identified through genome-wide association studies (GWAS) in a European-American case-control sample (n=815). Disease-causing variants in the SNCA, LRRK2 and PARK2 genes were found in 2 % of PD patients. The LRRK2, p.G2019S mutation was found in 0.6 % of sporadic PD and 4.8 % of familial PD cases. Gene-based analysis suggests that additional variants in the LRRK2 gene also contribute to PD risk. The SNCA duplication was found in 0.8 % of familial PD patients. Novel variants were found in 0.8 % of PD cases and 0.6 % of controls. Heterozygous Gaucher disease-causing mutations in the GBA gene were found in 7.1 % of PD patients. Here, we established that the GBA variant (p.T408M) is associated with PD risk and age at onset. Additionally, gene-based and single-variant analyses demostrated that GBA gene variants (p.L483P, p.R83C, p.N409S, p.H294Q and p.E365K) increase PD risk. Our data suggest that the impact of additional untested coding variants in the GBA and LRRK2 genes is higher than previously estimated. Our data also provide compelling evidence of the existence of additional untested variants in the primary Mendelian and PD GWAS genes that contribute to the genetic etiology of sporadic PD.
Updated results of a phase II trial of AP23573, a novel mTOR inhibitor, in patients (pts) with advanced soft tissue or bone sarcomas
Authors: S. P. Chawla, A. W. Tolcher, A. P. Staddon, S. M. Schuetze, G. Z. D’Amato, J. Y. Blay, K. K. Sankhala, S. T. Daly, V. M. Rivera, G. D. Demetri
Journal: Journal of Clinical Oncology (2006)

9505 Background: AP23573 is an mTOR inhibitor that has shown anti-tumor activity in phase 1 clinical trials, particularly in patients with advanced sarcomas. Given this observation, this phase 2 trial was undertaken to assess further the efficacy and safety of AP23573 across various sarcoma subtypes. Methods: Advanced sarcoma pts, with no restrictions on prior therapies, were enrolled into 4 cohorts based on histologic subtype, in a phase 2 trial with Simon’s 2-stage design. AP23573 (12.5 mg, i.v.) is administered for 5 days every 2 wks. Efficacy is assessed using RECIST guidelines, with clinical benefit response (CBR) defined as complete or partial response (PR) or stable disease (SD) for at least 16 wks duration. For each cohort, treatment was defined as successful if the proportion of patients with CBR was ≥ 25%. Studies of potential predictive markers of response include 18 FDG-PET imaging, analysis of mTOR pathway proteins in tumoral tissue, and measurement of plasma cytokines and angiogenic factors. Results: In total, 216 pts were enrolled as all cohorts met criteria to enter Stage 2 of the trial. Of these pts, 213 were treated (106 M/107 F) (age 17–79 yrs, median 50 yrs). Most frequent related adverse events included mucositis, rash, hyperlipidemia, fatigue, and thrombocytopenia. Preliminary response data for 193 evaluable pts are available: overall 54 (28%) had CBRs, including 5 PRs (3 pts with osteo, 1 with spindle cell of bone, and 1 with MFH). Twenty of 76 pts (26%) imaged with PET had rapid induction of partial metabolic responses following 3 to 5 days of study treatment. Conclusions: Initial assessments from this trial show that single-agent AP23573 is well tolerated and has efficacy in pts with advanced sarcomas that warrants evaluation in phase 3. Analysis of the potential utility of FDG-PET and a broad set of candidate biomarkers continues. Enrollment is complete, and pt treatment and follow-up are ongoing. [Table: see text] [Table: see text]
Stabilization of Plasma Glucose during Fasting
Authors: Thomas J. Merimee, John E. Tyson
Journal: New England Journal of Medicine (1974)

To establish more reliable criteria for the diagnosis of hypoglycemia during fasting, studies of plasma glucose concentrations during 72 hours of fasting were conducted independently at two institutions. Premenopausal women did not stabilize glucose at a level comparable to men. Twenty-four subjects, both men and women, were fasted in Study I. The mean (± S.E.M.) lowest glucose recorded was 66.4 ± 2.9 mg per 100 ml in men of normal weight and 47.8 ± 2.9 mg per 100 ml in women. In Study II the mean lowest glucose in 40 fasts by women was 41.3 ± 1.9 mg per 100 ml. No variation was noted in the early and late phases of the menstrual cycle. Three prepubertal children had glucose responses during fasting comparable to those of women. To be considered abnormal, plasma glucose must decrease in women to less than 35 mg per 100 ml within 24 hours, and in men,55 mg per 100 ml. After 36 hours of fasting, it is virtually impossible to judge the diagnostic implications of plasma or blood glucose values in premenopausal women. (N Engl J Med 291:1275–1278, 1974)
Herpes Simplex Virus Proctitis in Homosexual Men
Authors: Steven E. Goodell, Thomas C. Quinn, Emmanuel Mkrtichian, Michael D. Schuffler, King K. Holmes, Lawrence Corey
Journal: New England Journal of Medicine (1983)

Acute herpes simplex virus (HSV) infection was detected in 23 of 102 consecutively examined, sexually active male homosexuals who presented with anorectal pain, discharge, tenesmus, or hematochezia, as compared with 3 of 75 homosexual men without gastrointestinal symptoms (P<0.01). Findings that were significantly more frequent in men with HSV proctitis than in men with proctitis due to other infectious causes included fever (48 per cent), difficulty in urinating (48 per cent), sacral paresthesias (26 per cent), inguinal lymphadenopathy (57 per cent), severe anorectal pain (100 per cent), tenesmus (100 per cent), constipation (78 per cent), perianal ulcerations (70 per cent), and the presence of diffuse ulcerative or discrete vesicular or pustular lesions in the distal 5 cm of the rectum (50 per cent). Serologic evidence indicated that 85 per cent of the men with symptomatic HSV proctitis were having their first episode of HSV-2 infection. The diagnosis of HSV proctitis is suggested by the presence of severe anorectal pain, difficulty in urinating, sacral paresthesias or pain, and diffuse ulceration of the distal rectal mucosa. (N Engl J Med. 1983; 308:868–71.)
Role of Surgery for Locally Advanced and Metastatic Renal Cell Carcinoma
Authors: Robert Torrey, Philippe E. Spiess, Sumanta K. Pal, David Josephson
Journal: Journal of the National Comprehensive Cancer Network (2011)

Both locally advanced and metastatic renal cell carcinoma (RCC) present a challenge in terms of their optimal management. This article reviews the literature and evaluates the role of surgery in the treatment of advanced RCC. Surgery is the optimal treatment for locally advanced RCC and minimal, resectable, metastatic disease. Patients with metastatic disease, and some forms of locally advanced disease, may also benefit from multimodal management with local surgical therapy and systemic treatment using either immunotherapy or targeted therapy. Regardless of the disease stage, patients with locally advanced or metastatic RCC represent heterogenous patient populations with different disease characteristics and risk factors. Individualization of care in the setting of a sound oncologic framework may optimize the risk/benefit ratio within individual patient cohorts.
A self-taught artificial agent for multi-physics computational model personalization
Authors: Dominik Neumann, Tommaso Mansi, Lucian Itu, Bogdan Georgescu, Elham Kayvanpour, Farbod Sedaghat-Hamedani, Ali Amr, Jan Haas, Hugo Katus, Benjamin Meder, Stefan Steidl, Joachim Hornegger, Dorin Comaniciu
Journal: Medical Image Analysis (2016)
PTPS-22DUAL mTOR KINASE INHIBITOR (MLN0128) MARKEDLY INDUCES GROWTH SUPPRESSION AND APOPTOSIS IN DIFFUSE INTRINSIC PONTINE GLIOMA CELL LINES
Authors: Hiroaki Miyahara, Manabu Natsumeda, Isabella Taylor, Jeffrey Rubens, Harpreet Kaur, Charles Eberhart, Eric Raabe
Journal: Neuro-Oncology (2015)

BACKGROUND: Diffuse intrinsic pontine glioma (DIPG) is an invasive and treatment-refractory pediatric brain tumor. The Target of Rapamycin Complex 1 and 2 (mTORC1/2) regulate protein translation, cell growth, survival, invasion and metabolism. Primary DIPG tumors harbor mutations in PTEN, AKT, and PI3K. Inhibition of TORC1 with rapalogs is minimally effective in DIPG, however, the efficacy of dual mTOR kinase inhibitors has not been examined in this tumor type. METHODS: Three DIPG cell lines (JHHDIPG1, SF7761, and SUDIPG XIII), maintained in medium with EGF and FGF, were treated for 4-72 hours with DMSO or 1-50 nM levels of the TORC1/2 kinase inhibitor MLN0128. Cell growth analysis was performed using MTS reagent and measured in 490-nm absorbance. Protein was extracted from cell lysates and Western blotting was performed using primary antibodies specific for pAKT, AKT, pS6, S6, and cleaved PARP, as well as β-actin. Immunofluorescence staining against cleaved caspase 3 (CC3) and BrdU were done to evaluate apoptosis and proliferation, respectively. RESULTS: Both pAKT and pS6 were highly expressed in these DIPGs cell lines. pAKT and pS6 were inhibited after 25nM and 10-25nM levels of MLN0128, respectively. Cell growth of DIPGs (MTS assay) was markedly inhibited by 25-50 nM MLN0128 (SF7761: 10 nM p = 0.0002, 25/50 nM p < 0.0001; SUDIPG XIII: 25 nM p = 0.0065, 50 nM p = 0.0003, all vs vehicle). Decreased proliferation (%BrdU: JHHDIPG1 p = 0.0001, SF7761 p < 0.0001, SUDIPG XIII p < 0.0003, all vehicle vs 25 nM) and increased apoptosis (%CC3: JHHDIPG1 p = 0.0004, SF7761 p = 0.0005, SUDIPG XIII p = 0.0032, all vehicle vs 25 nM; increased cleaved PARP) were seen after treatment. CONCLUSIONS: In these DIPG cell lines, the mTOR pathway is active, and inhibition of the pathway suppresses growth and induces apoptosis. These effects may be induced as a consequence of inhibition of both mTORC1 and mTORC2. Dual mTOR inhibition is a promising candidate for DIPG treatment.
Relationship of Bone Marrow Blast (BMBL) Response to Overall Survival (OS) in Patients with Higher-Risk Myelodysplastic Syndrome (HR-MDS) Treated with Rigosertib after Failure of Hypomethylating Agents (HMAs)
Authors: Lewis R. Silverman, Pierre Fenaux, Aref Al-Kali, Maria R. Baer, Mikkael A. Sekeres, Gail J. Roboz, Gianluca Gaidano, Bart L. Scott, Peter L. Greenberg, Uwe Platzbecker, David P. Steensma, Suman Kambhampati, Karl-Anton Kreuzer, Lucy A Godley, Robert Collins, Ehab Atallah, Shyamala C. Navada, Francois Wilhelm, Nozar Azarnia, Guillermo Garcia-Manero
Journal: Blood (2014)
End-Tidal Carbon Dioxide Concentration during Cardiopulmonary Resuscitation
Authors: Jay L. Falk, Eric C. Rackow, Max Harry Weil
Journal: New England Journal of Medicine (1988)

We prospectively measured the end-tidal carbon dioxide concentration during 13 episodes of cardiac arrest in 10 critically ill patients receiving mechanical ventilation, to evaluate its usefulness as an indicator of circulatory status during cardiac arrest and resuscitation. The end-tidal carbon dioxide concentration decreased from a mean (+/- SD) of 1.4 +/- 0.9 to 0.4 +/- 0.4 percent after the onset of cardiac arrest. During precordial compression, it increased to 1.0 +/- 0.5 percent. The decreases in the end-tidal carbon dioxide concentration were associated with increases in systemic oxygen extraction (r = 0.79). Spontaneous circulation was restored on seven occasions. This was heralded by a rapid increase in the end-tidal carbon dioxide concentration, from 1.3 +/- 0.5 percent to an overshoot value of 3.7 +/- 2.1 percent, within approximately 30 seconds. The concentration then declined to a stable value of 2.4 +/- 1.8 percent four minutes after resuscitation. However, it remained 0.7 +/- 0.4 percent in six patients in whom resuscitative efforts failed to restore spontaneous circulation. These observations are consistent with experimental studies of cardiopulmonary resuscitation in pigs, in which the end-tidal carbon dioxide concentration varied directly with the cardiac output produced by precordial compression. We therefore propose that measurement of the end-tidal carbon dioxide concentration may be a practical, non-invasive method for monitoring blood flow generated by precordial compression during cardiopulmonary resuscitation and an almost immediate indicator of successful resuscitation.
Case 10-1998
Authors: Gus J. Vlahakes, George J. Hanna, Eugene J. Mark
Journal: New England Journal of Medicine (1998)

Presentation of CaseA 46-year-old man was admitted to the hospital because of unstable angina pectoris.The patient had been well until three weeks earlier, when he began to have episodes of anterior and posterior chest pain that radiated to the right arm. They occurred only on exertion, were relieved by rest, and lasted for a few minutes to over a half hour. During the several days before admission, the chest pain increased in frequency and severity. On the day before admission, the patient entered another hospital, where no evidence of acute myocardial infarction was found. Cardiac catheterization revealed that . . .
Cobra Venom in the Treatment of Angina Pectoris
Authors: A. Stone Freedberg, Joseph E. F. Riseman
Journal: New England Journal of Medicine (1945)

THE usefulness of cobra venom for the control of pain was first suggested in 1929 by Monaelesser.1 In 1936, Bullrich2 reported favorable results in the treatment of angina pectoris. Seven patients — 5 with syphilitic aortitis and 2 with coronary arteriosclerosis — received 1.25 to 5.0 mouse units§ of cobra venom intravenously; the succeeding doses and frequency of administration varied in each case. The physiologic and pharmacodynamic effects of cobra venom have been investigated by Macht,3 , 4 who demonstrated that its effects were those of a sedative acting on the thalamus. He5 reported relief of various types of pain in approximately . . .
Case 21-2010
Authors: David M. Greer, Aaron K. Styer, Thomas L. Toth, Charles P. Kindregan, Javier M. Romero
Journal: New England Journal of Medicine (2010)

A 36-year-old woman had severe anoxic brain damage due to a pulmonary embolus during a long airplane flight. She was admitted to the neurology intensive care unit but remained in a coma despite maximal medical therapy. On the ninth day, the family decided to institute comfort measures only. Later, they requested that maximal therapy be resumed, to permit consideration of oocyte retrieval for the purpose of posthumous conception of future offspring. A management decision was made.