tbuckley/cabot-search huggingface dataset:
Health effects of climate change highlighted in Paris Agreement
Authors: John Vidal
Journal: BMJ (2015)

The United Nations’ Paris agreement on climate change has put health at the centre of the effort to control global warming and has sent a message to all countries saying that a reduction in fossil fuel burning will reduce illness.

The agreement, which binds countries to hold temperature rises to “well below” 2°C, was welcomed by the World Health Organization and thousands of health professionals.

Health is mentioned three times in the core text of the agreement, which refers to the “co-benefits” of tackling health and climate change at the same time.

Margaret Chan, director general of the WHO, said, “Many of the same inefficient and …
Amino Acid Utilization by 929-L Fibroblasts in Chemically Defined Media&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Joyce Mohberg, Marvin J. Johnson
Journal: JNCI Journal of the National Cancer Institute (1963)

A quantitative study of amino acid utilization by L cells, growing in Way-mouth's medium, MB 752/1, has been made. Glutamine, leucine, and isoleucine were exhausted when cell growth ceased. Most other amino acids were largely unused, and only about one third of the total nitrogen of the medium was incorporated into cell nitrogen. A comparison of amino acid utilization and amino acid composition of cell protein indicated that most amino acids were used in 1.5 to 2.5 times the quantities needed for protein synthesis. However, much more glutamine, more methionine and valine, and much less aspartic acid and glycine disappeared from medium than were needed for protein synthesis. The amounts of essential amino acids used by cells did not vary noticeably with amino acid composition of the medium. However, the nonessential amino acids were utilized if provided by medium, but otherwise were synthesized by cells. A modification of medium MB 752/1, which provided amino acids in the quantities consumed by cells, gave the same cell yield per volume of medium as did MB 752/1. The modified medium gave a 40 percent conversion of medium nitrogen to cell nitrogen. A medium, containing all the amino acids (except glutamine) in twice the amounts consumed by cells in MB 752/1, gave a cell yield twice that of MB 752/1, and 64 percent of the total nitrogen in the medium was incorporated into cells.
Direct-to-consumer genetic testing
Authors: Rachel Horton, Gillian Crawford, Lindsey Freeman, Angela Fenwick, Caroline F Wright, Anneke Lucassen
Journal: BMJ (2019)

What you need to know• Finding a "health risk" via direct-to-consumer (DTC) genetic testing often does not mean that a patient will go on to develop the health problem in question• DTC genetic tests might report false positives (artefacts)• "Reassuring" results from DTC genetic tests might be false negatives• Make sure you are confident in the provenance and interpretation of a genetic result before you base any clinical decisions on it• If your patient meets criteria for referral to clinical genetics, refer regardless of the results of their DTC genetic test Direct-to-consumer (DTC) genetic tests are sold online and in shops as a way to "find out what your DNA says." 1 2 Testing kits typically contain instructions and equipment for collecting a saliva sample, which customers post to the DTC company for analysis.Some DTC genetic tests promise insights into ancestry or disease risks; others claim to provide information on personality, athletic ability, and child talent.However, interpretation of genetic data is complex and context dependent, and DTC genetic tests may produce false positive and false negative results.Anyone concerned about a result from a DTC genetic test might turn to their general practitioner (GP) or other primary healthcare provider for advice.This practice pointer aims to help clinicians in this scenario and explains what sort of health information is provided by these tests, their limitations, and how clinicians can respond to common questions about them.
A cell-based screening strategy predicts Bcr-Abl mutations that cause resistance toward the second-generation Abl kinase inhibitor AMN107
Authors: Nikolas Von Bubnoff, Paul Manley, Doriano Fabbro, Jana Sanger, Christian Peschel, Justus Duyster
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

5986 

In chronic myeloid leukaemia (CML), the Abl kinase inhibitor imatinib mesylate (STI571, Gleevec) induces impressive responses. However, in advanced phase CML and Ph+ ALL resistance can occur, primarily as a consequence of point mutations within the Bcr-Abl kinase domain which hinder or prevent the binding of imatinib. Second-generation Abl kinase inhibitors such as AMN107 have been developed, which might be superior to imatinib in terms of response rates and the development of resistance. However, strategies to identify and evaluate resistance mechanisms towards such second-generation kinase inhibitors are necessary, and it will be critical to determine the resistance profile to a specific kinase inhibitor prior to its therapeutic application. We recently developed a cell-based screening strategy that allows to predict the frequency and pattern of Bcr-Abl resistance mutations emerging in the presence of imatinib. When applied to AMN107, we observed a frequency of resistant clones that was similar to imatinib at concentrations that correspond to 2.5 times the cellular IC50 value of each inhibitor. However, at 5 times the IC50, the frequency decreased by 50 per cent. The number of resistant clones dramatically decreased when the concentration of AMN107 was increased to 20 times the IC50. We next analysed AMN107 resistant clones for mutations within Bcr-Abl. AMN107 produced a distinct pattern of Bcr-Abl kinase domain mutations with some overlap to the pattern observed with imatinib. At 20 times the IC50, mutations observed with AMN107 narrowed to the exchange at position T315 to isoleucine. This was in contrast to high imatinib concentrations, where mutations were still widely distributed over the kinase domain. Thus, in this cell-based screening system, the selection of resistant clones can be prevented by 400 nM AMN107. However, plasma concentrations of at least 20 times the IC50 will be critical, and clinical resistance to AMN107 is predicted to be associated with the predominant emergence of T315I.
Abstract 19219: Distinct Cardiac Microvascular Endothelium-specific Gene Signatures in Experimental Pressure-overload Heart Failure
Authors: Sander Trenson, Ann Sophie Walravens, Ellen Caluwé, Sara Vandenwijngaert, Giulia Coppiello, Melissa Swinnen, Jozef Bartunek, Aernout Luttun, Stefan Janssens
Journal: Circulation (2014)

Introduction:  Pressure overload-induced heart failure is associated with a distinct molecular phenotype at the level of cardiac myocytes or fibroblasts. The role and phenotypic changes of microvascular endothelial cells (MiVEC) in the presence of sustained pressure overload are not known.   Methods:  Accordingly, we randomized 10 male Tie2-GFP transgenic heterozygote mice (FVB, age 10±2.5 weeks) to transverse aortic constriction (TAC) for 10 weeks or to sham surgery. At 10 weeks, TAC animals displayed cardiac hypertrophy (heart/body weight: 5.3±0.2 vs. 3.0±0.8 mg/g, P   Results:  After FACS, 99% of the extracted GFP+ cells showed surface expression of the MiVEC lineage markers CD31, CD34, and CD36, and were uniformly negative for CD45. RNA expression analysis revealed more than three-fold upregulation of 16 genes after TAC compared to sham. Among these genes, 11 encoded secreted proteins. They are involved in the regulation of the hypertrophic growth response (Thrombospondin 4, Microfibrillar associated protein 5), collagen content (MMP-2, Collagen XVα1) and angiogenic signaling (Endothelial cell specific molecule 1, Ectonucleoside triphosphate diphosphohydrolase 2) or endocrine function (Natriuretic peptide type A). Ingenuity Pathway Analysis revealed upstream targets involved mainly in the signal transduction of the transforming growth factor (TGF) β pathway. Only one gene with unknown function (6720456H20Rik) showed a significant down-regulation in TAC vs. sham.   Conclusions:  In summary, experimental pressure overload-induced heart failure is associated with a distinct molecular signature of MiVEC with upregulation of mainly secretory proteins. This suggests the potential paracrine interaction of MiVEC with surrounding cardiac myocytes and fibroblasts in the pathophysiology of hypertrophic remodeling and progression to heart failure.
Phase II trial of FOLFOX plus bevacizumab in advanced, progressive neuroendocrine tumors
Authors: A. P. Venook, A. H. Ko, M. A. Tempero, J. Uy, T. Weber, M. Korn, E. K. Bergsland
Journal: Journal of Clinical Oncology (2008)

15545 Background: Inhibitors of the VEGF pathway have been shown to have activity in neuroendocrine tumors (NET). Oxaliplatin- based chemotherapy also shows limited activity in this disease. We performed a prospective, phase II study to assess the safety and efficacy of mFOLFOX-6 plus bevacizumab (BV) in patients (pts) with advanced, progressive NET. Methods: Pts with carcinoid tumors (CARC), pancreatic NET (PNET), or platinum-refractory poorly differentiated (anaplastic, small- or large-cell) NET (PDNET) were enrolled using a Simon 2- stage design (3 groups). Eligibility criteria included clinical or radiologic evidence of progression, no prior anti-VEGF therapy, and no varices secondary to splenic vein thrombosis. Treatment consisted of mFOLFOX-6 plus BV (5 mg/kg IV) every 14 days (1 cycle = 2 weeks). Pts were followed for toxicity and response. Results: 13 pts with progressive NET have been enrolled: M/F=9/4; median age=60 (range 43–73); ECOG PS 0/1= 7/6; CARC/PNET/PDNET= 6/6/1. Pts on octreotide remained on the drug. Pts have received treatment for a median of 11 cycles (range 3–26). Grade 3–4 toxicities included: abdominal pain (15.4%), anemia (15.3%), neutropenia (30.8%), febrile neutropenia (7.6%), fatigue (38.4%), ascites (7.6%), gastrointestinal hemorrhage (7.6%), hypertension (23%), thrombocytopenia (7.6%), diarrhea (7.6%) and peripheral sensory neuropathy (15.3%). There was 1 arterial thromboembolic event (penetrating ulcer-thoracic aorta) and 1 treatment- related death from sepsis (in setting of neutropenia, diarrhea, and probable GI perforation). Of 9 pts with an elevated chromogranin at baseline; 4 pts demonstrated >50% decline (1 CARC, 3 PNET). One pt with metastatic insulinoma requiring home dextrose infusions experienced a >50% reduction in insulin levels and marked clinical improvement. 12 pts are evaluable for best radiologic response (by RECIST, confirmed): CARC 1/5 PR (20%), 4/5 SD (80%); PNET 2/6 PR (33%), 4/6 SD (67%); PDNET 1/1 SD. Conclusions: The combination of FOLFOX plus BV shows promising activity in pts with advanced, progressive NET. However, the toxicity profile suggests that careful pt selection may be important. Enrollment to this study continues. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech™ BioOncology, sanofi-aventis Genentech™ BioOncology, sanofi-aventis
Use of Clinical Prediction Rules for Guiding Use of Computed Tomography in Adults With Head Trauma
Authors: Frederick P. Rivara, Nathan Kuppermann, Richard G. Ellenbogen
Journal: JAMA (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA 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
血尿-黑便-关节腔出血
Authors: 黄晓明, 李剑, 陈嘉林, 曾学军
Journal: BMJ (2007)

@@ 男性,50岁,东北农民,因血尿、黑便、关节肿痛40 d于2005年3月9日入院. 患者于40 d前因右下肢肌肉疼痛自服小活络丹及止痛片,2 d后出现血尿,呈洗肉水样,伴尿频、尿急,尿量增多,并有黑便、牙龈出血,无皮肤淤斑、关节肿痛.停用上述药物,外院给予止血芳酸及输注血浆后,症状缓解.1个月前患者发现右髋关节肿痛,伴乏力、头晕.次日关节肿胀处皮下大片淤斑,并迅速蔓延到踝部,多次输注新鲜冰冻血浆及止血芳酸等药物治疗后,右下肢淤斑有所消退.1周来患者左髋关节再次出现类似症状.
Bony metastatic disease responses to sorafenib (BAY 43–9006) independent of PSA in patients with metastatic androgen independent prostate cancer
Authors: W. L. Dahut, C. D. Scripture, E. M. Posadas, S. Wu, P. M. Arlen, J. L. Gulley, J. Wright, C. C. Chen, E. Jones, W. D. Figg
Journal: Journal of Clinical Oncology (2006)

4506 Background: Sorafenib is a novel bis-aryl urea, multi-kinase inhibitor, approved for the treatment of advanced renal cell carcinoma. It inhibits b- and c-Raf kinase, PDGFR, c-kit, VEGFR, Flt-3 and p38 and demonstrates anti-proliferative and anti-angiogenic activity. Studies have shown a role for anti-angiogenic therapy for androgen-independent prostate cancer (AIPC). Evidence suggests that the Ras-Raf-MAPK-ERK signaling pathway is dysregulated in AIPC and might be targeted by sorafenib. Methods: 22 patients (pts) with progressive metastatic AIPC enrolled in an open-label, single arm phase II study. The primary objective was to determine if sorafenib is associated with a 50% 4 month probability of progression free survival as determined by clinical, radiographic, and PSA criteria. Sorafenib was given continuously at a dose of 400 mg orally twice daily in 28-day cycles. Clinical assessment and PSA measurement occurred every cycle with radiographic measurements every 2 cycles. Results: Baseline patient characteristics included a median (range) age of 64 (51–78), Gleason 8 (6–9), PSA 226.4 ug/l (2–1905), Alk Phos 108 u/l (48–259), Hb 12.7 g/dl (10.2–15.1). 60% of patients had received one prior chemotherapy regimen. Of the 19 pts with progressive disease, 10 progressed only by PSA criteria in the absence of evidence of clinical and radiographic progression. Two pts were found to have dramatic disappearance of bone metastatic lesions as demonstrated by bone scan, even though they met PSA progression criteria at the time the scans were obtained. Toxicities likely related to treatment include: one grade 3 hypertension and hand-foot syndrome; grade 1/2 toxicities: fatigue, anorexia, hypertension, skin rash, nausea, and diarrhea. Conclusion: Sorafenib in AIPC is relatively well tolerated with 2 patients demonstrating evidence of improved bony metastatic lesions. Interpretation of this study is complicated by discordant radiographic and PSA responses. PSA may not be an adequate biomarker for monitoring sorafenib activity. Further study of sorafenib in metastatic AIPC using clinical and radiographic endpoints is warranted. No significant financial relationships to disclose.
Problems with preference and place of death for children too
Authors: M. Bluebond-Langner, E. Beecham, B. Candy, R. Langner, L. Jones
Journal: BMJ (2015)

The problems raised by Pollock about preference and place of death also apply to seriously ill children, even though choices about care are made with or by a person other than the patient and children typically have one or more devoted carer.1 Our systematic …
Bronchodilating effect of intravenous magnesium sulfate in bronchial asthma
Authors: H. Okayama
Journal: JAMA (1987)

The bronchodilating effect of magnesium sulfate (MgSO<sub>4</sub>) was studied in ten asthmatic patients with mild attacks. In five patients, 0.5 mmol/min of MgSO<sub>4</sub>was administered intravenously for 20 minutes, and the time courses of respiratory resistance, forced vital capacity, and forced expiratory volume at 1 s were studied. In another five patients, MgSO<sub>4</sub>dose-response curves were obtained. Soon after administration began, MgSO<sub>4</sub>relieved bronchoconstriction in a dose-dependent manner. Maximum responses (mean ± SE) of respiratory resistance, forced vital capacity, and forced expiratory volume were 71% ±3%, 117% ±5%, and 118%±1% of initial values, respectively, and were similar to the effects of additional albuterol inhalation. The infusion of MgSO<sub>4</sub>also improved dyspnea and piping rales in three other asthmatic patients with a severe attack. We conclude that intravenous infusion of MgSO<sub>4</sub>produces a rapid and marked bronchodilation in both mild and severe asthma and may be a unique bronchodilating agent. (<i>JAMA</i>1987;257:1076-1078)
Targeted therapy for lung cancer
Authors: Anne-Pascale Meert, Jacques Cadranel
Journal: European Respiratory Journal (2015)

Thoracic malignancies are a menacing worldwide health problem. To treat lung cancer optimally, care must be prompt, multidisciplinary, and patient-centred. In the entire process, pulmonologists have a key role. Pulmonologists and their professional societies should also enhance lung cancer research and education to provide better treatment options and patient care [1]. Targeted therapy for lung cancer: ERS promotes exchange of knowledge <http://ow.ly/RV285>
Correlation of clinical activity of lumiliximab in combination with FCR and ZAP 70 expression on B-cell chronic lymphocytic leukemia cells
Authors: N. Pathan, A. Estrellado, J. Ranuio, S. O' Brien, T. J. Kipps, A. Cesano, H. Mu, S. Harris, S. Tangri
Journal: Journal of Clinical Oncology (2008)

7073 Background: Lumiliximab is an anti-CD23 monoclonal antibody under investigation for the treatment of patients with relapsed B-cell chronic lymphocytic leukemia (BCLL). Lumiliximab binds specifically to human CD23, a glycoprotein expressed on the majority of BCLL cells. As ZAP70 is a poor prognostic factor of CLL, expression of the ZAP70 antigen by malignant B cells was analyzed on samples taken pre-treatment and day 2 post-treatment in a subset of patients with relapsed BCLL enrolled in a clinical study evaluating lumiliximab as monotherapy. The ability of lumiliximab to induce ex-vivo apoptosis was also evaluated in BCLL samples collected in this subset. Subsequently, pre-treatment ZAP70 expression was analyzed in patients treated lumiliximab in combination with fludarabine, cyclophosphamide, and rituximab (L + FCR). Methods: In the lumiliximab monotherapy study, ZAP70 expression was quantified by Western blot assay using lysates from purified BCLL cells and apoptosis was evaluated by flow cytometric assessment of Caspase-3 activation on pre- treatment and day 2 treated samples (ex-vivo). In the L + FCR study, frequencies of BCLL cells and ZAP70 positive cells were estimated by four color flow cytometry using standard commercially available antibodies. BCLL cells were identified by first gating on viable CD45+ cells and subselecting with antibodies to CD5 and CD19 receptors (CD5+CD19+ phenotype). ZAP70 expression was reported as % BCLL cells. Results: Analysis of data from the monotherapy study suggested induction of apoptosis and decrease in CD5+CD19+ cells in patients expressing high levels of ZAP70 on purified B cells. Moreover, apoptosis was also observed in a patient that expressed activated ZAP70. Results from the L + FCR study demonstrated that clinical activity in this combination trial is observed in patients having high or low levels of ZAP70 expression. Conclusions: Lumiliximab potentially provides clinical benefit in BCLL patients with both low and high levels of ZAP70, whose expression is associated with aggressive disease and poor prognosis. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Biogen Idec Biogen Idec Biogen Idec
Randomized comparison of early versus late hyperfractionated thoracic irradiation concurrently with chemotherapy in limited disease small-cell lung cancer: A randomized phase II study of the Hellenic Cooperative Oncology Group (HeCOG)
Authors: D V Skarlos, E Samantas, E Briassoulis, E Panoussaki, N Pavlidis, H P Kalofonos, D Kardamakis, E Tsiakopoulos, P Kosmidis, D Tsavdaridis, J Tzitzikas, P Tsekeris, G Kouvatseas, N Zamboglou, G Fountzilas
Journal: Annals of Oncology (2001)
Cisplatin as first-line therapy for metastatic breast cancer.
Authors: G W Sledge, P J Loehrer, B J Roth, L H Einhorn
Journal: Journal of Clinical Oncology (1988)

Cisplatin has had only minimal activity when used as second- and third-line chemotherapy for metastatic breast cancer (MBC). There have been no phase II studies in the United States evaluating cisplatin in patients with MBC with no prior chemotherapy. We therefore treated 20 consecutive patients with cisplatin 30 mg/m2/d for four days every 3 weeks for a maximum of six courses. We obtained partial responses in nine of 19 evaluable patients (47%), with responses in liver, lung, and soft tissue indicator lesions. Our data suggest that cisplatin has substantial single-agent activity as front-line therapy in MBC, and should be considered for inclusion in first-line combination chemotherapy regimens.
Ibuprofen versus fosfomycin for uncomplicated urinary tract infection in women: randomised controlled trial
Authors: Ildikó Gágyor, Jutta Bleidorn, Michael M Kochen, Guido Schmiemann, Karl Wegscheider, Eva Hummers-Pradier
Journal: BMJ (2015)

<b>Study question</b>&nbsp;Can treatment of the symptoms of uncomplicated urinary tract infection (UTI) with ibuprofen reduce the rate of antibiotic prescriptions without a significant increase in symptoms, recurrences, or complications? <b>Methods</b>&nbsp;Women aged 18-65 with typical symptoms of UTI and without risk factors or complications were recruited in 42 German general practices and randomly assigned to treatment with a single dose of fosfomycin 3 g (n=246; 243 analysed) or ibuprofen 3×400 mg (n=248; 241 analysed) for three days (and the respective placebo dummies in both groups). In both groups additional antibiotic treatment was subsequently prescribed as necessary for persistent, worsening, or recurrent symptoms. The primary endpoints were the number of all courses of antibiotic treatment on days 0-28 (for UTI or other conditions) and burden of symptoms on days 0-7. The symptom score included dysuria, frequency/urgency, and low abdominal pain. <b>Study answer and limitations</b>&nbsp;The 248 women in the ibuprofen group received significantly fewer course of antibiotics, had a significantly higher total burden of symptoms, and more had pyelonephritis. Four serious adverse events occurred that lead to hospital referrals; one of these was potentially related to the trial drug. Results have to be interpreted carefully as they might apply to women with mild to moderate symptoms rather than to all those with an uncomplicated UTI. <b>What this paper adds</b>&nbsp;Two thirds of women with uncomplicated UTI treated symptomatically with ibuprofen recovered without any antibiotics. Initial symptomatic treatment is a possible approach to be discussed with women willing to avoid immediate antibiotics and to accept a somewhat higher burden of symptoms. <b>Funding, competing interests, data sharing</b>&nbsp;German Federal Ministry of Education and Research (BMBF) No 01KG1105. Patient level data are available from the corresponding author. Patient consent was not obtained but the data are anonymised and risk of identification is low. <b>Trial registration No</b>&nbsp;ClinicalTrialGov Identifier NCT01488955.