tbuckley/cabot-search huggingface dataset:
Abstract P151: Differential Effects of Concurrent and Sequential Combined Lapatinib and Doxorubicin Treatment on Cardiac Function in Mice
Authors: David Goukassian, Sharath Sasi, Juyong Lee, James R Stone, Daniela Budiu, Christopher Lawson, Michael Maysky, Lynn Hlatky, Joseph Carrozza, James P Morgan, Giannoula Klement, Xinhua Yan
Journal: Circulation Research (2011)

Background: Clinical studies showed that Trastuzumab, a monoclonal antibody that blocks the HER2 receptor, exacerbated chemotherapy drug doxorubicin (DOX)-induced heart failure. Lapatinib, a small molecule inhibitor of HER2 and EGF receptor (EGFR), is currently studied in clinical trials for cancer therapy, in combination with DOX, concurrently and sequentially. Therefore, it is important to assess the cardiac effect of the combination treatment using lapatinib and DOX. Methods: Two mouse models were used. In the first model, mice were treated with a single dose of DOX (20 mg/kg, i.p.), concurrently with lapatinib (100 mg/kg, oral gavage, daily). In the second model, mice were treated with DOX (2 mg/kg, i.p. twice a week) for seven weeks, followed by lapatinib (100 mg/kg, oral gavage, daily) for three weeks. Survival was analyzed by the Kaplan-Meier method. Cardiac function was monitored by hemodynamic measurements. Results: When mice were treated concurrently with lapatinib and DOX, ten-day survival was significantly lower in DOX+lapatinib vs. DOX mice (13 vs. 0 %, n=7–8/group, P &lt;0.001). Five to seven days after the treatment, cardiac contractile function was significantly lower in DOX+lapatinib vs. control mice [left ventricular systolic pressure (LVSP): 83 ± 2 vs. 93 ± 2 mmHg, P &lt;0.05; dP/dtmin: 4020 ± 360 vs. 7112 ± 580 mmHg/sec, P &lt;0.05; cardiac output (CO): 1236 ± 266 vs. 2734 ± 209 unit/min, P &lt;0.05, n=5/group]; however, these indices were maintained in DOX mice (LVSP: 99 ±4 mmHg; dP/dtmin: 7787 ± 965 mmHg/sec; CO: 2315 ± 366 unit/min, P =NS vs. control, n=5–6/ group). On the other hand, when mice were treated sequentially with DOX and lapatinib, seventy-day survival was higher in DOX+lapatinib vs. DOX mice (63 vs. 43 %, n=7–8/ group). Cardiac output was decreased in DOX vs. control mice (1733±135 vs. 3438±268 unit/min, P &lt;0.05, n=4–5/group). However, cardiac output was less depressed in DOX+lapatinib mice (2817±559 unit/min, P =NS vs. control, n=4/group). Conclusions: These results showed that concurrent and sequential combined lapatinib and DOX treatment produced opposite effects on survival and cardiac function in mice. This study suggests that the cardiac safety of lapatinib and DOX combination therapy depends on the specific treatment regimen.
Targeting CD74 with Novel Antibody Drug Conjugates (ADCs) for the Treatment of B-Cell Non-Hodgkin's Lymphoma (NHL)
Authors: Xiaofan Li, Cristina Abrahams, Millicent Embry, Abigail Yu, Jason Kahana, Michael Brown, Rama Krishna Narla, Leo Barnes, Eric Schwartz, John Boylan, James Zawada, Heather Stephenson, Maureen Bruhns, Stuart Bussell, Alexander Steiner, Adam Galan, Toni Kline, Alice Yam, Ryan Stafford, Heidi Hoffmann, Shannon Matheny, Venita DeAlmeida, Nicki Vasquez, Henry Heinsohn, Aaron Sato, Arturo Molina, Trevor Hallam, Mark Lupher
Journal: Blood (2016)
Integrated Mechanism for Functional Mitral Regurgitation
Authors: Shengqiu He, Arnold A. Fontaine, Ehud Schwammenthal, Ajit P. Yoganathan, Robert A. Levine
Journal: Circulation (1997)

Background Functional mitral regurgitation in patients with ischemic or dilated ventricles has been related to competing factors: altered tension on the leaflets due to displacement of their papillary muscle and annular attachments, which restricts leaflet closure, versus global ventricular dysfunction with reduced transmitral pressure to close the leaflets. In vivo, however, geometric changes accompany dysfunction, making it difficult to study these factors independently. Functional mitral regurgitation also paradoxically decreases in midsystole, despite peak transmitral driving pressure, suggesting a change in the force balance acting to create a regurgitant orifice, with rising transmitral pressure counteracting forces that restrict leaflet closure. In vivo, this mechanism cannot be tested independently of annular contraction that could also reduce midsystolic regurgitation. Methods and Results An in vitro model was developed that allows independent variation of papillary muscle position, annular size, and transmitral pressure, with direct regurgitant flow rate measurement, to test the hypothesis that functional mitral regurgitation reflects an altered balance of forces acting on the leaflets. Hemodynamic and echocardiographic measurements of excised porcine valves were made under physiological pressures and flows. Apical and posterolateral papillary muscle displacement caused decreased leaflet mobility and apical leaflet tethering or tenting with regurgitation, as seen clinically. It reproduced the clinically observed midsystolic decrease in regurgitant flow and orifice area as transmitral pressure increased. Tethering delayed valve closure, increased the early systolic regurgitant volume before complete coaptation, and decreased the duration of coaptation. Annular dilatation increased regurgitation for any papillary muscle position, creating clinically important regurgitation; conversely, increased transmitral pressure decreased regurgitant orifice area for any geometric configuration. Conclusions The clinically observed tented-leaflet configuration and dynamic regurgitant orifice area variation can be reproduced in vitro by altering the three-dimensional relationship of the annular and papillary muscle attachments of the valve so as to increase leaflet tension. Increased transmitral pressure acting to close the leaflets decreases the regurgitant orifice area. These results are consistent with a mechanism in which an altered balance of tethering versus coapting forces acting on the leaflets creates the regurgitant orifice.
Transracial studies of corneodesmosin (S) gene association with psoriasis.
Authors: M Ameen, M H Allen, C Veal, Sheila Fisher, Cathryn Lewis, G Rowley, E Kondeatis, T Murakami, Christopher Mathew, R W Vaughan, H Nakagawa, Richard Trembath, Jonathan Barker
Journal: British Journal of Dermatology (2001)
A game theory appraisal of the insurance hypothesis: Specific polymorphisms in the energy homeostasis network as imprints of a successful minimax strategy
Authors: Tobias A Mattei
Journal: Behavioral and Brain Sciences (2017)

Abstract The existence of specific polymorphisms in genes of key hormones of the energy homeostasis network that have been shown to predispose to obesity and the so-called metabolic syndrome provides further biological support for the proposed insurance hypothesis. In a broader sense, such polymorphisms can be understood as biological imprints of an evolutionarily successful minimax strategy employed by ancient Homo sapiens subpopulations in a one-player game against nature.
STING Activation Reverses Lymphoma-Mediated Resistance to Antibody Immunotherapy
Authors: Lekh N. Dahal, Lang Dou, Khiyam Hussain, Rena Liu, Alexander Earley, Kerry L. Cox, Salome Murinello, Ian Tracy, Francesco Forconi, Andrew J. Steele, Patrick J. Duriez, Diego Gomez-Nicola, Jessica L. Teeling, Martin J. Glennie, Mark S. Cragg, Stephen A. Beers
Journal: Cancer Research (2017)

Abstract Tumors routinely attract and co-opt macrophages to promote their growth, angiogenesis, and metastasis. Macrophages are also the key effector cell for mAb therapies. Here we report that the tumor microenvironment creates an immunosuppressive signature on tumor-associated macrophages (TAM), which favors expression of inhibitory rather than activating Fcγ receptors (FcγR), thereby limiting the efficacy of mAb immunotherapy. We assessed a panel of TLR and STING agonists (a) for their ability to reprogram macrophages to a state optimal for mAb immunotherapy. Both STINGa and TLRa induced cytokine release, modulated FcγR expression, and augmented mAb-mediated tumor cell phagocytosis in vitro. However, only STINGa reversed the suppressive FcγR profile in vivo, providing strong adjuvant effects to anti-CD20 mAb in murine models of lymphoma. Potent adjuvants like STINGa, which can improve FcγR activatory:inhibitory (A:I) ratios on TAM, are appealing candidates to reprogram TAM and curb tumor-mediated immunosuppression, thereby empowering mAb efficacy. Cancer Res; 77(13); 3619–31. ©2017 AACR.
Rapid Diagnosis of Intravascular Catheter-Associated Infection by Direct Gram Staining of Catheter Segments
Authors: Glenn L. Cooper, Cyrus C. Hopkins
Journal: New England Journal of Medicine (1985)

We conducted a study to determine the usefulness of the Gram stain in the detection of intravascular catheter-associated infection. A total of 330 intravascular catheters were prospectively collected from adults and children suspected of having such an infection. Semiquantitative solid-agar cultures of the distal catheter tip were correlated with blood cultures. Catheter-associated bacteremia occurred in 34 per cent of cases in which catheter tips were colonized (≥15 colonies per agar plate). There were no cases of catheter-associated bacteremia in patients with uncolonized catheters. Immediately after culture, whole catheter segments were stained by the Gram technique. Gram-negative and gram-positive bacteria and yeast were easily identifiable under oil immersion (X1000), located predominantly on external catheter surfaces. Any catheter with at least one organism per 20 oil-immersion fields was designated as positive by Gram stain, but the majority of the 41 positive catheters had much larger numbers of organisms. The Gram stain of the catheter tip was 100 per cent sensitive and 96.9 per cent specific for the detection of catheter-tip colonization, with positive and negative predictive values of 83.9 and 100 per cent, respectively. We conclude that a Gram stain of the distal catheter tip is a simple, inexpensive, and accurate test for the rapid diagnosis of intravascular catheter-associated infection. (N Engl J Med 1985; 312:1142–7.)
Treatment of pre-existing melanoma tumors using allogeneic vaccines expressing alpha(1,3)Gal epitopes. Efficacy and toxicology study
Authors: Gabriela R. Rossi, Mario R. Mautino, Henry Lejukole, Marie Koenigsfeld, Christy Loiacono, Nicholas Vahanian, Tatiana Seregina, Charles J. Link
Journal: Cancer Research (2006)

1423  The hyperacute immune response in humans is a potent mechanism of xenograft rejection mediated by complement-fixing natural antibodies that recognize alpha(1,3)Galactosyl epitopes (aGal) not present on human cells. In this study we exploited this immune mechanism to create an allogeneic whole cell cancer vaccine to treat murine melanoma. We used the alpha(1,3)Galactosyltransferase (aGT H-2bb) knockout mice, which do not express aGal epitopes on their cell surfaces and develop high titers of anti-aGal antibodies. Melanoma cell lines (B16 and S91M3) naturally lack the expression of aGal epitopes. These cells were retrovirally transduced using lentiviral vectors encoding the murine aGT enzime to produce the aGal(+) variants of these cell lines. Mice with pre-existing subcutaneous (sc) and pulmonary B16 (H-2bb) melanoma tumors were treated with allogeneic aGal(+)S91M3 (H-2dd) melanoma vaccines or with control aGal(-)S91M3 vaccines. Mice with sc tumors had significant prolonged survival (p 8 each group). Vaccination with aGal(+)S91M3 induced CD8+ T cells recognizing the “autologous” aGal(-)B16 tumors measured by intracellular TNF-alpha. These cells reduced the pulmonary burden of syngeneic recipients with pre-existing pulmonary melanoma in adoptive transfer experiments. Interestingly, mice vaccinated with allogeneic aGal(+).S91M3 or “autologous” aGal(+)B16 cells failed to induce DTH responses to B16, despite the induction of a strong T cell dependent mediated anti-tumor immunity. Since effective anti-tumor immunity is associated with autoimmunity in several immunotherapies, we tested whether vaccination with allogeneic aGal(+) vaccines induced autoimmunity or other detectable signs of toxicity in three murine models. Mice (aGT KO H-2bb) were vaccinated six times with irradiated aGal(+)EMT-6 (breast H-2dd) cells. The aGT KO H-2dd mice received six vaccine doses of aGal(+)LLC (lung H-2bb) or aGal(+)B16 melanoma cells. High titers (>1:200) of anti-aGal Ab titers (IgG and IgM) were demonstrated in all mice. Samples (blood and tissues) were collected at early time points and at 6 months after the last allogeneic vaccine. Analysis of the hematology, chemistry and histopathology of major perfused organs (kidneys, lungs, liver and spleen) data revealed no significant differences among mice receiving allogeneic vaccines and control groups. In addition mice were weighted weekly for a period of 6 months showing no differences in the growth patterns among the groups in three animal models. This study establishes the safety and efficacy data of allogeneic aGal(+) whole cell vaccines and constituted the basis for the initiation of human clinical trials to treat human cancers which are currently open.
Ethical and Social Consequences of Selling a Kidney
Authors: David J Rothman
Journal: JAMA (2002)

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
Multiple-System Atrophy
Authors: Alessandra Fanciulli, Gregor K. Wenning
Journal: New England Journal of Medicine (2015)

Multiple-system atrophy is a neurodegenerative disease characterized by progressive autonomic failure, parkinsonism, and cerebellar and pyramidal tract symptoms. Glial cytoplasmic inclusions of α-synuclein are a defining histologic feature. There is no curative treatment.
The Use of Streptomycin in Surgical Patients
Authors: H A ZINTEL, M WILEY
Journal: JAMA (1949)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Surgeon is struck off after three “never events”
Authors: Clare Dyer
Journal: BMJ (2017)

A senior surgeon has been struck off the UK medical register for his role in three surgical “never events” in a two year period.

“A never event is something that should never, ever happen,” Michael Zeigerman, an expert witness for the General Medical Council, told a medical practitioners’ tribunal in Manchester. “It’s so serious that [England’s health secretary] Jeremy Hunt himself has every single one of them written in his office—and we have three of them here.”

The three botched operations were the work of Lawal Haruna, 59, a specialty doctor in general surgery at Sheffield Teaching Hospitals NHS Trust. In September 2013, while doing an emergency laparoscopic appendicectomy, he failed to identify …
PTH-034 Blinded Comparison of Magnetically Assisted Gastric Capsule Endoscopy and Conventional Endoscopy in Recurrent and Refractory Iron Deficiency Anaemia: A Feasibility Study: Abstract PTH-034 Table 1
Authors: MF Hale, K Drew, M Kurien, R Sidhu, ME McAlindon
Journal: Gut (2016)

<h3>Introduction</h3> Magnetically assisted capsule endoscopy (MACE) of the stomach has been demonstrated to be safe and feasible.<sup>1</sup> The aim of this prospective feasibility study was to compare the ability of MACE to recognise gastric landmarks compared to conventional flexible endoscopy in patients with recurrent or refractory iron deficiency anaemia. <h3>Methods</h3> Twenty patients with recurrent/refractory iron deficiency anaemia were enrolled between Jan-Nov 2015. After conventional oesophagogastroduodenoscopy, MACE was performed using MiroCam Navi (Intromedic, Seoul, Korea). Visualisation of major upper gastrointestinal landmarks was graded on a 1–5 scale (1 = poor, 5 = excellent), abnormalities were recorded. Primary outcome measure: gastric landmark recognition. Secondary outcome measures: pathology detection, patient tolerance. <h3>Results</h3> MACE achieved satisfactory visualisation (grade 4 or 5) in 11% for the gastro-oesophageal junction, 21% for the cardia, 16% for the fundus, 79% for the anterior wall of the gastric body, 79% for the posterior wall, 79% for the greater curvature, 84% for the lesser curvature, 95% for the antrum and 89% for the pylorus. 38 pathological findings were identified (<i>Table 1</i>). Patients experienced less pain, discomfort and distress during MACE compared to flexible endoscopy (p = 0.0009, p = 0.001 and p = 0.006 respectively). <h3>Conclusion</h3> MACE can visualise gastric landmarks, detect a variety of gastric pathology and is better tolerated than conventional endoscopy. Capsule identification of hiatal hernias is difficult and may improve with experience.<sup>2</sup> Better oesophageal visualisation is possible with other models and it seems likely that Mirocam Navi could be developed to this end. Proximal gastric views may be more reliable using a double ended capsule, better depth of illumination, and perhaps with control of capsule movement, all of which need further study before MACE becomes a viable alternative to conventional endoscopy. <h3>References</h3> 1 Hale MF, Drew K, Sidhu R, McAlindon ME. Does magnetically assisted capsule endoscopy improve small bowel capsule endoscopy completion rate? A randomised controlled trial. <i>Endosc Int Open</i>. 2016 Feb; <b>4</b>(2):E215–21. 2 Marelli L, Jaboli FM, Jackson L, Palmer H, Erian G, Hamilton M, Epstein O. A pilot study comparing ESO-2 capsule endoscopy with conventional upper endoscopy for the assessment of uncomplicated heartburn and dyspepsia. <i>Frontline Gastroenterol</i><b>201</b>;4:96–101. <h3>Disclosure of Interest</h3> None Declared
Labour’s pledge to boost NHS funding by £30bn is “still not enough”
Authors: Matthew Limb
Journal: BMJ (2017)

The Labour Party’s “costed” election pledges on spending for health and social care will still not be enough to meet rising long term demand and service pressures, say analysts.

The Health Foundation said that Labour’s proposed £30bn (€35bn; $38.9bn)1 investment in the English NHS over the next parliament would provide an “immediate and significant” £7.4bn cash boost this year, including an extra £2bn a year for capital investment.

For the remainder of this decade Labour has committed to an average increase of 2.2% a year, accounting for inflation, that will leave a £7bn shortfall by 2020-21, the Health Foundation said.

Anita Charlesworth, the healthcare charity’s director of research and economics, said, “Under Labour’s manifesto plans, healthcare funding would not match the demand and cost pressures on the health service, which the independent Office for Budget Responsibility estimates at more than 4% a year …
Screening for the prevalence of EGFR and ALK mutations in lung adenocarcinoma patients in the Levant area: A prospective analysis.
Authors: Arafat H. Tfayli, Alain Mina, Hind Rafei, Najla Fakhreddine, Haifa Salah Dbouk, Maya Khalil, Rami Mahfouz, Fadi Sami Farhat, Haider N. Salh, Ziad Salem, Ghazi Zaatari
Journal: Journal of Clinical Oncology (2015)

e12648 Background: Recent evidence suggests that a significant percentage of lung adenocarcinomas have a driver mutation that is responsible for the development of the tumor and promotion of its growth and spread. Significant variation in the prevalence of these mutations has been documented with race and smoking status being two major factors (more common in Asians and/or non-smokers). To date, no data has prospectively assessed the prevalence of these mutations in a Middle Eastern population and that will be the aim of our study. Methods: Patients with lung adenocarcinoma were prospectively enrolled as part of a multicenter, multinational study. Tumors were tested for various EGFR mutations in exons 18-21 by PCR and for EML4-ALK translocation by FISH Break-Apart test. Study was open in 10 sites in Lebanon, Jordan and Iraq and was restricted to patients of Middle Eastern origin. Results: 190 patients have been recruited so far. 128 (67.4%) males and 62 females (32.6%) with a mean age of 62.8 years. EGFR testing was done in 178 (93.7%) patients and has been found to be Wild type in 154 (86.5%) patients, mutated in 24 (13.5%). Tissue has been insufficient in 12 (6.3%) of the samples. As for the EML4-ALK translocation, it has been tested in 125 patients (65.8%). Results were negative in 121 (96.8%) patients and positive in 4 (3.2%). 23 attempts at ALK testing failed (12.1%) while the remainder of results are either pending (4 (2.1%)), unattainable due to insufficient tissue (14(7.4%)) or undone because patients were either EGFR or KRAS mutation positive (24(12.6%)). Conclusions: Because of overwhelming evidence in favor of the survival benefits of targeted therapies, assessing the prevalence of clinically significant mutations has become a must. Although the frequencies of such mutations (KRAS, EGFR, ALK…) have been well established in Western populations, our study will be the first to establish their frequencies in the Levant area. Preliminary results have shown an EGFR mutation rate of 13.5% and an ALK translocation rate of 3.2% in our patient population as compared to a 15-20% and 5% in western literature respectively.
Homozygous transcription factor 3 gene (TCF3) mutation is associated with severe hypogammaglobulinemia and B-cell acute lymphoblastic leukemia
Authors: Meriem Ben-Ali, Jing Yang, Koon Wing Chan, Imen Ben-Mustapha, Najla Mekki, Chaouki Benabdesselem, Fethi Mellouli, Mohamed Bejaoui, Wanling Yang, Lamia Aissaoui, Yu Lung Lau, Mohamed-Ridha Barbouche
Journal: Journal of Allergy and Clinical Immunology (2017)