tbuckley/cabot-search huggingface dataset:
Anti‐KIT monoclonal antibody CDX‐0159 induces profound and durable mast cell suppression in a healthy volunteer study
Authors: Diego Alvarado, Marcus Maurer, Richard Gedrich, Scott B. Seibel, Michael B. Murphy, Linda Crew, Joel Goldstein, Andrea Crocker, Laura A. Vitale, Pamela A. Morani, Lawrence J. Thomas, Thomas R. Hawthorne, Tibor Keler, Diane Young, Elizabeth Crowley, Martin Kankam, Margo Heath‐Chiozzi
Journal: Allergy (2022)

Abstract Background Mast cells (MC) are powerful inflammatory immune sentinel cells that drive numerous allergic, inflammatory, and pruritic disorders when activated. MC‐targeted therapies are approved in several disorders, yet many patients have limited benefit suggesting the need for approaches that more broadly inhibit MC activity. MCs require the KIT receptor and its ligand stem cell factor (SCF) for differentiation, maturation, and survival. Here we describe CDX‐0159, an anti‐KIT monoclonal antibody that potently suppresses MCs in human healthy volunteers. Methods CDX‐0159‐mediated KIT inhibition was tested in vitro using KIT‐expressing immortalized cells and primary human mast cells. CDX‐0159 safety and pharmacokinetics were evaluated in a 13‐week good laboratory practice (GLP)‐compliant cynomolgus macaque study. A single ascending dose (0.3, 1, 3, and 9 mg/kg), double‐blinded placebo‐controlled phase 1a human healthy volunteer study ( n = 32) was conducted to evaluate the safety, pharmacokinetics, and pharmacodynamics of CDX‐0159. Results CDX‐0159 inhibits SCF‐dependent KIT activation in vitro . Fc modifications in CDX‐0159 led to elimination of effector function and reduced serum clearance. In cynomolgus macaques, multiple high doses were safely administered without a significant impact on hematology, a potential concern for KIT inhibitors. A single dose of CDX‐0159 in healthy human subjects was generally well tolerated and demonstrated long antibody exposure. Importantly, CDX‐0159 led to dose‐dependent, profound suppression of plasma tryptase, a MC‐specific protease associated with tissue MC burden, indicative of systemic MC suppression or ablation. Conclusion CDX‐0159 administration leads to systemic mast cell ablation and may represent a safe and novel approach to treat mast cell‐driven disorders.
Impaired lymphocyte reactivity against tumour cells in patients with Crohn's disease
Authors: B. P. Maclaurin, W. T. Cooke, N. R. Ling
Journal: Gut (1972)

Evidence is presented which indicates a possible reduction in recognition capacity for tumour cell antigens (EB<sub>2</sub> Burkitt lymphoma cell line) by lymphocytes from some patients with longstanding but inactive Crohn9s disease. Three out of seven patients tested also showed diminished or absent lymphocytotoxicity when their cells were grown in mixed culture with chromium-labelled lymphoma cells and absent response has never been observed in a large series of controls similarly tested. In both test systems impaired reactivity appeared to be partly caused by a factor present in Crohn9s disease serum. Increased tumour incidence in Crohn9s disease may in part be attributable to defective immune surveillance and the histology of Crohn9s disease could reflect an imbalance between the proliferative and the cytotoxic responses of lymphocytes to various antigens in the bowel lumen in this disease.
Survival outcomes and characterization of patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) undergoing intensified androgen deprivation therapy (ADT) who do not achieve an optimal PSA response (PSA ≤0.2 ng/mL).
Authors: Nicolas Sayegh, Nishita Tripathi, Beverly Chigarira, Yeonjung Jo, Taylor Ryan McFarland, Adam Kessel, Roberto Nussenzveig, Haoran Li, Clara Tandar, Divyam Goel, Kamal Kant Sahu, Benjamin Haaland, Benjamin L. Maughan, Umang Swami, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2022)

123 Background: In pts with mCSPC undergoing intensified ADT, achieving a PSA nadir ≤0.2 ng/mL “anytime” after the start of treatment was associated with a significantly improved overall survival (OS) versus those with a PSA &gt;0.2 ng/mL: HR 0.17 (95% CI, 0.13-0.23) (Chi AUA 2021, abstract 1281). Our objective was to validate these findings in a real-world population and characterize the clinical and tumor genomic landscape according to PSA response. Methods: In this IRB-approved study, patient-level data were collected retrospectively. Eligibility: presence of mCSPC undergoing intensified ADT with either docetaxel or novel hormonal therapy (NHT) started within 3 months of diagnosis, availability of PSA nadir, and availability of tumor comprehensive genomic profiling (CGP) prior to start of ADT. Variants of unknown significance and genomic aberrations present in &lt;5% pts were excluded. Optimal PSA response (OR): PSA≤0.2 ng/mL. Study endpoints: PFS was calculated per PCWG-2 defined PSA progression or radiographic progression or clinical progression whichever occurred first; OS was defined as start of therapy to date of death or censored after last follow-up. The relationship between PSA nadir and both PFS and OS was assessed in the context of Cox proportional hazards. Gene prevalence was compared using a chi square test. Results: 134 pts were eligible and included. Optimal responders (OR) (n=104) and non-OR (n=30): median age at diagnosis 63 vs 65 years; median PSA at ADT start 18.1 vs 74.5 ng/mL; high volume of disease 48% vs 77%. For OR and non-OR: median PFS, 60.6 vs 13.2 (P&lt;0.001); median OS, 94.9 vs 35.2 months (P&lt;0.001) respectively. Multivariate analysis is described in the table. Conclusions: Only a minority of pts with mCSPC do not achieve an optimal PSA response with intensified ADT. Those non-OR have worse outcomes on treatment with intensified ADT. Herein we externally validate that achieving a PSA nadir ≤0.2 ng/mL is correlated with superior OS. Detailed genomic landscape of these pts will be presented in the meeting.[Table: see text]
Epidemiological and virological assessment of influenza activity in Europe, during the 2006-2007 winter
Authors: J MS Arkema, A Meijer, T J Meerhoff, J Van Der Velden, W  J Paget, Collective European Influenza Surveillance Scheme (EISS)
Journal: Eurosurveillance (2008)

Influenza surveillance in Europe is based on influenza surveillance networks that cooperate and share information through the European Influenza Surveillance Scheme (EISS). EISS collected clinical and virological data on influenza in 33 countries during the 2006-2007 winter. Influenza activity started around 1 January and first occurred in Greece, Scotland and Spain. It then moved gradually across Europe from south to north and lasted until the end of March. In 29 out of 33 countries, the consultation rates for influenza-like-illness or acute respiratory infections in the winter of 2006-2007 were similar or somewhat higher than in the 2005-2006 winter. The highest consultation rates for influenza-like-illness were generally observed among children aged 0-4 years and 5-14 years. The predominant virus strain was influenza A (97% of total detections) of the H3 subtype (93% of H-subtyped A viruses; 7% were A(H1)). The influenza A(H3) and A(H1) viruses were similar to the vaccine reference strains for the 2006-2007 season, A/Wisconsin/67/2005 (H3N2) and A/New Caledonia/20/99 (H1N1) respectively. The majority of the influenza B viruses were similar to the reference strain B/Malaysia/2506/2004, included in the 2006-2007 vaccine. In conclusion, the 2006-2007 influenza season in Europe was characterised by moderate clinical activity, a south to north spread pattern across Europe, and a dominance of influenza A(H3). Overall there was a good match between the vaccine virus strains and the reported virus strains.
A phase Ib, open-label study evaluating the safety and efficacy of ipatasertib + rucaparib in patients with metastatic castration-resistant prostate cancer (mCRPC).
Authors: David William Pook, Daniel M. Geynisman, Joan Carles, Filippo G. De Braud, Anthony M. Joshua, Jose Luis Perez-Gracia, Casilda Llácer Pérez, Sang Joon Shin, Bruno Fang, Minal A. Barve, Marco Maruzzo, Sergio Bracarda, Miso Kim, Yannick Kerloeguen, Jorge Daniel Gallo, Sophia Maund, Adam Harris, Kuan-Chieh Huang, Dhruvitkumar S. Sutaria, Howard Gurney
Journal: Journal of Clinical Oncology (2022)

95 Background: mCRPC remains an incurable disease with unmet need for improved therapies. PARP inhibition has demonstrated antitumor activity, and preclinical studies suggest synergy between PARP and AKT inhibition. This phase Ib trial (NCT03840200) sought to determine the maximum tolerated dose of PARP inhibitor rucaparib (ruca) with AKT inhibitor ipatasertib (ipat) and explore early safety and efficacy in patients (pts) with mCRPC. Methods: The study had 2 parts: a part 1 dose-escalation phase (cohort [C]1: ipat 300 mg QD + ruca 400 mg BID; C2a: ipat 300 mg QD + ruca 600 mg BID; C2b ipat 400 mg QD + ruca 400 mg BID; C3: ipat 400 mg QD + ruca 600 mg BID) in unselected pts with mCRPC or advanced breast or ovarian cancer, and a Part 2 dose-expansion phase in pts with mCRPC whose previous androgen deprivation therapy failed. The primary safety endpoints were AEs and dose-limiting toxicities, with the goal of identifying a recommended phase II dose (RP2D). The primary efficacy endpoint was prostate-specific antigen (PSA) response (PSA reduction of ≥ 50%) in pts with mCRPC. Secondary efficacy endpoints included ORR per RECIST 1.1, radiographic PFS (rPFS) per Prostate Cancer Working Group 3 and OS in pts with mCRPC. We assessed homologous recombination deficiency (HRD), PIK3CA/ AKT1/ PTEN status and other alterations by next-generation sequencing. Results: Part 1 enrolled 21 pts: 17 with mCRPC, 3 with ovarian cancer and 1 with breast cancer (C1 [n=8], C2a [n=6] and C2b [n=7], C3 [not opened]). Ipat 400 mg QD + ruca 400 mg BID was the selected RP2D. 30 pts enrolled in Part 2, so 37 pts with mCRPC (C2b + Part 2) received the RP2D (median follow-up 93 days). All grade AEs occurred in 37 pts (100%), serious AEs in 8 pts (22%) and AEs leading to treatment modification in 26 pts (70%). The most frequent AEs (all grade and grade 3, respectively) were diarrhea (35 [95%] and 2 [5%]); asthenia (24 [65%] and 4 [11%]); and nausea (24 [65%] and 2 [5%]). There was 1 grade 4 AE (anemia) and no grade 5 AEs. See the table for efficacy data. In biomarker subgroups, the PSA response rate was 50% (3/6) in pts with HRD tumors vs 25% (4/16) in pts with HR-proficient tumors, and 14% (1/7) vs 40% (6/15) in pts with PIK3CA/ AKT1/ PTEN–altered or intact tumors, respectively. Conclusions: The combination of ipat and ruca was well tolerated but did not show clinically relevant antitumor activity in pts with mCRPC, including in predefined biomarker subpopulations. Clinical trial information: NCT03840200. [Table: see text]
Correction to: Evaluating Quality of Care for Patients With Heart Failure
Authors: Harlan Krumholz, David Baker, Carol Ashton, Sandra Dunbar, ; Gottlieb, C Friesinger, Edward Havranek, Mark Hlatky, Marvin Konstam, Diana Ordin, Ileana Pina, Bertram Pitt
Journal: Circulation (2000)
Grants for Scientific Research
Authors: F. Fowke
Journal: BMJ (1901)

With reference to the sale of scheduled poisons, your petitioners would remait that during the twenty-five years succeeding the passing of the Pharmacy Acts, under the observation of framers thereof, no distinction was drawn between the owner of the shop and the seller of the poison.Recently, however, it has been made to appear by legal decisions that the assistant is the " actual seller in fact."Since the courts of law de- cided in this manner, medical practitioners have expressly forbidden their unqualified drug assistants to sell scheduled poisons.Your petitioners now contend that as no breach of any law is committed by them they are entitled to respeetfully ask you to refrain from any line of action which would seriously hamper the work of medical practitioners in this district.In conclusion, your petitioners would respectfully submit that they have no right nor desire to enterinto the merits of the particular case of Dr. Thomson.But while they recogni6e their position in this respect they feel it incumbent upon them to protest against an indictment, the terms of which have led to many derogatory and invidious remarks regarding general medical practice in Glasgow and the West of Scotland.
Tracheostomy.
Authors: F. Pigott
Journal: BMJ (1969)

BRsITIH 383midline.This included one case seen two hours after attendance at hospital where the patient was given ampicillin and paracetamol.Detorsion relieves the pain immediately and dramatically and the testis descends in the scrotum with immediate relief to the patient.Analgesics may not be needed to do this.This does not of course reduce the need for operation on both sides, 'since recurrence is likely, but it does make operation less urgent, and may be a useful practical pro- cedure while awaiting anaesthesia or make the operation an elective one.-Iam, etc.,
Editorial Board
Authors: Clarence Loeb, Arthur Proetz, William Wherry, William Benedict, W Morrison, Stanley Truhlsen, Paul Henkind, Paul Lichter, Donald Minckler, Andrew Schachat, George Bartley, Stephen Mcleod, Russell Van Gelder, Seattle Wa, Daniel Albert, Creig Hoyt, San Francisco
Journal: Ophthalmology (2022)
Enfortumab Vedotin Checks Urothelial Cancer
Journal: Cancer Discovery (2019)

Treatment with enfortumab vedotin generated robust responses in patients with locally advanced or metastatic urothelial carcinoma. In a phase II trial of 125 patients who had previously received platinum-based chemotherapy and a PD-1 or PD-L1 checkpoint inhibitor, the overall response rate was 44%. Although nearly all patients experienced a treatment-related adverse event, most side effects were mild to moderate.
MOTOR NOTES FOR MEDICAL MEN
Authors: H. M. Buist
Journal: BMJ (1923)

Trade Association, which was opened by the Duke York at Kelvin Hall, Glasgow, on January 26thl, not so representative as those in London because the only building available is quite serve thle purpose.The Englishi and French chiefly manufacturers' exlhibitions promoted op-portunity of meeting agents and motor traders quarters of the globe.By contrast the Scottislh slhow primarily a display for the purpose of enabling thleir clients.Hence relatively few miianufacturerslhave stands, thouglh the exceptions include Arrol-Jolhnston, Bean, Beardmore, Clement-Talbot, Citroen, Humber, Lanchester, and Vulcan.There London coachbuilders, eacll of whlom lhas taken namely, Barker and Co. and Windover; botlh cars, such as Rolls-Royce and Daimiiler typev withi their special town carriage coacliwork.the rest, the well known manufactureis prefer to the stands of their various Scottislh agents.
Endocardial Fibroelastosis
Authors: J. O. Forfar, R. A. Miller, A. D. Bain, W. Macleod
Journal: BMJ (1964)

there is still much doubt about the nature, the incidence, and the course of this disease.Different diagnostic criteria adopted by various authors make comparisons difficult, and most of the published reports are based on selected groups of cases.During the 15- year period from 1946 to 1962 72 cases of endocardial fibro- elastosis have been recognized after death in the South-Eastern Region of Scotland, and these are analysed here against the background of all cases of congenital heart disease seen at necropsy over the same period.Throughout this period the majority of post-mortem examinations on children under 12 years of age, including newborn and stillborn infants, have been carried out by the regional paediatric pathology service.The necropsy rate has been high, of the order of 85 to 95 %.This regionalization of paediatric pathology services and high necropsy rate permit a fairly comprehensive appreciation both of the particular problem of endocardial fibroelastosis and of the wider one of all forms of congenital heart disease. IncidenceIn the period under review 8,595 consecutive post-mortem examinations were carried out, including stillbirths.The inci- TABLE I.-Necropsies, 1948-62, With Incidence of Congenital Heart Disease and Endocardial Fibroelastosis Necropsies Remarks Total necropsies .8,595Live-born 4,759 (55%) Stillborn .3,836(45%) Total cases of congenital heart disease 433 50/ of all necropsies Live-born .383(88-5%) 8 0 of all live-born necropsies Stillborn .50(11-5%) 1-3% of all stillbirth necropsies Total cases of endocardial fibroelastosis 72 17% of all C.H.D. necropsies Live-born .72 19% of all live-born C.H.D. necropsies Stillborn .0... ... Uncomplicated endocardial fibroelastosis 16 (22%) 4% of all live-born necropsies Complicated endocardial fibroelabtosis 56 (78%) 15% of all live-born C.H.D. necropsies dence of congenital heart disease and of endocardial fibroelasto- sis among these is shown in Table I.Keith et al. (1958) found the overall incidence of endocardial fibroelastosis in congenital heart disease to be 4%, considerably
Ethical dilemmas for house staff physicians
Authors: William Winkenwerder
Journal: JAMA (1986)

<h3>In Reply.—</h3> I agree strongly with the comments of Drs Forrow, Arnold, and Cassel and Ms Blank. There are major deficiencies in graduate medical training programs regarding ethical dimensions of clinical care, and the residency training period would be the best time to have an impact on physicians' behavior. However, there are obstacles in addressing this problem. Many attending physicians are not prepared to discuss, much less teach, ethical problems in patient care. Such activities are not rewarded. There is little consensus about how to teach approaches for dealing with complex ethical dilemmas. Residents already feel over-whelmed with their current load of educational demands. Nonetheless, efforts must be made, and I am gratified by the obvious interest of the American Board of Internal Medicine and others in seeking better ways to prepare physicians for ethical dimensions of clinical care. It can be done. I share Dr Light's belief that time
When I use a word . . . . Medical patronymics, metronymics, and papponymics
Authors: Jeffrey K Aronson
Journal: BMJ (2022)

Many family names are patronymics, surnames derived from fathers' first names, or more generally from those of some forebears. Metronymics, or matronymics, are similarly derived, but from the first name of a mother, and papponymics from the name of a grandfather. Different languages have different forms that denote patronymics. Typical patronymics are either derived directly from a given name (e.g. Andrews, Evans, Jones, Williams) or by adding a suffix, such as <i>–son</i> and variants or <i>–ovich</i> and variants, or a prefix, such as <i>Mac</i>, <i>Mc</i>, and <i>M'</i> (Scottish and Irish), <i>Ap</i> (Welsh), <i>Fitz</i> (English and Irish, from Norman French), and <i>Ben</i> or <i>Bar</i> (Jewish). <i>O9</i> denotes an Irish papponymic. There are many medical examples of all of these.
THE LEISURE CORNER
Journal: JAMA (1953)

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
Poliomyelitis
Authors: M. M. Hutchins
Journal: BMJ (1947)

MEDIBCAtUAH 431 population.He described an experiment on mice in which sulphetrone had been combined with streptomycin; the success- ful result was not due to cumulative but to synergic action.Finally, Dr. I. A. B. Cathie described the application of streptomycin in tuberculous meningitis and miliary tubercu- losis at the Hospital for Sick Children.The relapse rate was so high that a longer follow-up than had yet been possible was required, and therefore, he said, his remarks were in no sense a report on these cases.Twenty cases had been treated, all under the age of 7. Administration had been intramuscular and intrathecal, both attended by a certain amount of pain.He and his colleagues were leaning more to intramuscular administration alone, and reactions were fewer with the newer batches of streptomycin.The blood sedimentation rate nearly always fell in the initial stages of treatment with streptomycin, and rose again as the case failed to respond and death approached, in contrast to the usual course of events.No renal changes were observed and no alteration in the blood count.He believed that streptomycin provided something in the treat- ment of tuberculosis which had not existed before.If not a life-saver it was a life-prolonger.In meningitis the results had been disappointing; in miliary cases they had been encouraging, and so far there had been no deaths and the clinical and radiological improvement had been striking.How long adminis- tration should be continued was still not known, nor was it yet determined what was the best route and whether administration should be continuous or intermittent.A report on the later sessions of the conference will appear next week.
Geriatric risk factors for serious COVID-19 outcomes among older adults with cancer: a cohort study from the COVID-19 and Cancer Consortium
Authors: Arielle Elkrief, Cassandra Hennessy, Nicole M Kuderer, Samuel M Rubinstein, Elizabeth Wulff-Burchfield, Rachel P Rosovsky, Karen Vega-Luna, Michael A Thompson, Orestis A Panagiotou, Aakash Desai, Donna R Rivera, Ali Raza Khaki, Lisa Tachiki, Ryan C Lynch, Catherine Stratton, Rawad Elias, Gerald Batist, Anup Kasi, Dimpy P Shah, Ziad Bakouny, Angelo Cabal, Jessica Clement, Jennifer Crowell, Becky Dixon, Christopher R Friese, Stacy L Fry, Punita Grover, Shuchi Gulati, Shilpa Gupta, Clara Hwang, Hina Khan, Soo Jung Kim, Elizabeth J Klein, Chris Labaki, Rana R McKay, Amanda Nizam, Nathan A Pennell, Matthew Puc, Andrew L Schmidt, Armin Shahrokni, Justin A Shaya, Christopher T Su, Sarah Wall, Nicole Williams, Trisha M Wise-Draper, Sanjay Mishra, Petros Grivas, Benjamin French, Jeremy L Warner, Tanya M Wildes
Journal: The Lancet Healthy Longevity (2022)