tbuckley/cabot-search huggingface dataset:
A Review of Seafood Safety after the <i>Deepwater Horizon</i> Blowout
Authors: Julia M Gohlke, Dzigbodi Doke, Meghan Tipre, Mark Leader, Timothy Fitzgerald
Journal: Environmental Health Perspectives (2011)

The Deepwater Horizon (DH) blowout resulted in fisheries closings across the Gulf of Mexico. Federal agencies, in collaboration with impacted Gulf states, developed a protocol to determine when it is safe to reopen fisheries based on sensory and chemical analyses of seafood. All federal waters have been reopened, yet concerns have been raised regarding the robustness of the protocol to identify all potential harmful exposures and protect the most sensitive populations.We aimed to assess this protocol based on comparisons with previous oil spills, published testing results, and current knowledge regarding chemicals released during the DH oil spill.We performed a comprehensive review of relevant scientific journal articles and government documents concerning seafood contamination and oil spills and consulted with academic and government experts.Protocols to evaluate seafood safety before reopening fisheries have relied on risk assessment of health impacts from polycyclic aromatic hydrocarbon (PAH) exposures, but metal contamination may also be a concern. Assumptions used to determine levels of concern (LOCs) after oil spills have not been consistent across risk assessments performed after oil spills. Chemical testing results after the DH oil spill suggest PAH levels are at or below levels reported after previous oil spills, and well below LOCs, even when more conservative parameters are used to estimate risk.We recommend use of a range of plausible risk parameters to set bounds around LOCs, comparisons of post-spill measurements with baseline levels, and the development and implementation of long-term monitoring strategies for metals as well as PAHs and dispersant components. In addition, the methods, results, and uncertainties associated with estimating seafood safety after oil spills should be communicated in a transparent and timely manner, and stakeholders should be actively involved in developing a long-term monitoring strategy.
GPs in Hackney win bid to run out of hours service
Authors: Z. Kmietowicz
Journal: BMJ (2013)

GPs in the London borough of Hackney have won their bid to run the out of hours service in the area for the next four years, taking over from private company Harmoni.

Clare Highton, a GP and chair of NHS City and Hackney Clinical Commissioning Group, said that while she was not involved in the decision about the £6.4m (€7.6m; $10.3) contract, to avoid a conflict of interest, she was delighted with the outcome of the tender. 

“Local people deserve the best quality out of hours GP …
Mortality in under 5s dropped by 35% between 1990 and 2010, says UN report
Authors: J. Zarocostas
Journal: BMJ (2011)

The number of children under 5 years old who die each year fell by a third between 1990 and 2010, from more than 12 million deaths to 7.6 million, new data from Unicef, the World Health Organization, and other agencies show.

Overall about 12 000 fewer children died every day in 2010 than in 1990, the baseline year for measuring progress, the agencies said in their report.

The global under 5 death rate fell from 88 deaths per 1000 live births in 1990 to 57 in 2010, but the report concludes …
NATURE AND TREATMENT OF WOUND SHOCK AND ALLIED CONDITIONS
Authors: F B Gurd
Journal: JAMA (1918)

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
Abstract 1482: Role of TGF-beta signaling and mechanism of osteoblastic tumorigenesis in prostate cancer
Authors: Sweta Mishra, Yuping Tang, Sherry L Werner, LuZhe Sun
Journal: Cancer Research (2011)

Abstract Prostate cancer is the second leading cause of cancer death in men with 80% of deaths occurring due to bone metastasis. Transforming growth factor-beta (TGFβ) signaling is important for the regulation of bone mass and matrix properties. The role of TGFβ signaling in prostate cancer-induced bone metastasis is unclear due in part to a lack of prostate cancer cell lines that can efficiently induce bone metastasis and osteoblastic lesions in animal models. We have previously shown that a newly established human prostate cancer cell line, PacMetUT1, produces a large amount of active TGFβ1 and induces extensive bone metastases in calvaria, rib, femur, and tibia when inoculated in the left cardiac ventricle of male nude mice. Experimental data from our lab demonstrated that stable knockdown of TGFβ1 using a short hairpin-RNA resulted in a decreased tumor incidence and bone formation when the cells were directly injected into the right tibias of male nude mice. Systemic administration of either a small inhibitor of TGFβ type I receptor kinase or a pan-TGFβ binding protein also decreased osteoblastic intratibial tumor lesions. However, the mechanism by which prostate cancer cells metastasize to bone and how they induce formation of osteoblastic lesions remains to be intensively investigated. We hypothesize that TGFβ and other growth factors released from tumor cells can induce aromatase gene expression and activity in bone cells leading to an enhanced estradiol synthesis which would lead to an increase in bone formation as estrogen is a known osteogenic factor. We examined the effect of TGFβ1 and BMP-4/7 treatment on aromatase expression in pre-osteoblastic cells in vitro. In vitro treatment with 5ng/ml of TGFβ1 and 25ng/ml of BMP-4/7 resulted in an increase in aromatase expression in 2T3, a mouse mesenchymal stem cell and in 63 year old male mesenchymal stem cells (MSC) at the protein level. Furthermore, TGFβ resulted in an induction of Smad-1/5 signaling pathway in these pre-osteoblastic cells. Transient knockdown of Smad-1/5 expression in male MSC by siRNA, resulted in a decreased aromatase expression. Our results demonstrate TGFβ to be a major driver of osteoblastic tumorigenesis in PacMetUT1 cells, and Smad-1/5-dependent aromatase upregulation by TGFβ superfamily ligands in pre-osteoblastic cells. Future studies will delineate whether the induction of aromatase mediates osteoblastic bone metastasis in vivo, and if combination treatment of TGFβ and aromatase inhibitors can be used as a novel therapeutic strategy for bone metastatic prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1482. doi:10.1158/1538-7445.AM2011-1482
Abstract P6-15-03: Phase Ib Trial of the Gamma Secretase Inhibitor (GSI), MK-0752 Followed by Docetaxel in Locally Advanced or Metastatic Breast Cancer
Authors: AF Schott, JC Chang, IE Krop, KA Griffith, RM Layman, DF Hayes, MS. Wicha
Journal: Cancer Research (2010)

Abstract Background: The cancer stem cell hypothesis asserts that there is a small population of cells within a tumor that has the ability to self renew and differentiate, and that these cells drive tumor growth and metastasis but are resistant to conventional cytotoxic chemotherapy. Pathways involved in stem cell growth and differentiation are viable targets for new anticancer therapies. One such pathway, Notch, is inhibited by GSIs which prevent translocation of Notch intracellular domain to the nucleus. Inhibition of GS concurrent with chemotherapy might improve disease control by targeting both stem cells and differentiated cells within the tumor. This Phase Ib clinical trial was designed to determine the MTD of the GSI, MK-0752, in combination with docetaxel, and to evaluate an effect on stem cell markers in serial tumor biopsies. Methods: Eligible subjects had metastatic breast cancer or locally advanced breast cancer that did not respond to anthracycline therapy. Patients with disease that progressed on a taxane, or who had received a taxane within 6 months were excluded. MK-0752 was administered orally on days 1-3 of each 21-day cycle of therapy, in escalating doses. Dose levels (mg/day) 1=300; 2=450; 3=600; and 4=800. Docetaxel 80 mg/m2 IV was administered day 8, with pegfilgrastim day 9 each cycle. Treatment was continued until disease progression, unacceptable toxicity, or symptomatic deterioration. The trial was monitored using the Time to Event Continual Reassessment Method, targeting a 20% toxicity rate. Tumor biopsies were performed at baseline, after 1 cycle, and at treatment completion in a subset of patients. Results: 30 patients were enrolled between Mar 2008 and Jan 2010. Dose limiting toxicities of the combination included diarrhea, hand-foot syndrome, and LFT elevation. 20/30 patients experienced Grade 1 or 2 fatigue. The final estimates and confidence intervals for the probability of dose limiting toxicity at each dose level are summarized in the table: Probability = probability of dose-limiting toxicity 20 enrolled patients had measurable disease by RECIST criteria. Of these, 9 had PR, 8 SD, and 3 PD, for an estimated RR of 45% to the combination. 2 patients have been maintained on therapy in excess of 22 cycles. Conclusions: Dose level 3 was identified for further study in a Phase II randomized trial. Efficacy of docetaxel was not inhibited by MK-0752, as a 45% RR in patients with measurable disease was observed. There is intriguing long term disease stabilization in 2 patients. Evidence of an effect of the combination on the stem cell population was apparent on serial biopsies as presented at SABCS Dec 2009 (Abstract # 48); additional biopsy data will be presented. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-15-03.
MODELLING HIGH MYC MEDULLOBLASTOMA AND OTHER BRAIN TUMORS USING HUMAN NEURAL STEM CELLS
Authors: C. Eberhart, E. Raabe, A. Hanaford, S. Pomeroy
Journal: Neuro-Oncology (2014)

BACKGROUND: We used human fetal neural stem cells dissected from the cerebral cortex, thalamus, cerebellum and brainstem, then propagated as neurospheres, to model a range of brain tumors. Various combinations of oncogenic elements characteristic of medulloblastoma and glioblastoma were introduced into stem cells derived from these different sites. Transformation of cells was characterized in vitro and in vivo, and MYC driven medulloblastoma were used for preclinical testing of glutaminase inhibitors. METHODS: We transduced cerebellar derived human neural stem cells with lentivirus coding for MYC, dominant negative R248W p53, constitutively active AKT, and hTERT in several combinations. Growth of transformed cells and their response to therapy was analyzed in vitro and in vivo using standard techniques. RESULTS: MYC alone was sufficient to transform cerebellar progenitor cells into embryonal tumors with a predominantly neuronal phenotype, but with a long latency period and decreased penetrance suggesting secondary genetic changes were required. The R248Wp53/MYC/AKT/hTERT combination transformed cerebellar stem cells into more aggressive orthotopic xenografts with large cell/anaplastic histology and spinal metastases. Microarray expression analysis suggested that these tumors represent a model of high MYC group 3 medulloblastoma. MYC expression positively correlated with increased expression of glutaminase, and the glutaminase inhibitor Acivicin decreased cell proliferation more strongly in MYC-containing neurospheres compared to those without MYC. Acivicin treatment of MYC expressing cells also led to a much greater increase in apoptosis compared to MYC-negative cells. Introduction of other packages of oncogenic elements into cortical and thalamic neurospheres resulted in PNET-like tumors, including variants resembling medulloepithelioma, as well as glioblastoma. CONCLUSIONS: Human cerebellar stem cells can be transformed by c-MYC and cooperating oncogenes, resulting in a models that recapitulates group 3 medulloblastoma histologically and clinically. These cells and classical high-MYC medulloblastoma cell lines are sensitive to glutamine anti-metabolites, while non-MYC driven medulloblastoma and SV40 immortalized human cerebellar stem cells are resistant. Our group 3 human neural stem cell medulloblastoma model data suggest that glutamine metabolism may be a therapeutic target in MYC-driven medulloblastoma, and that glutamine anti-metabolites may be useful clinical agents. Neurospheres from other CNS sites can be transformed with other oncogenes into models of PNET and glioblastoma. SECONDARY CATEGORY: Tumor Biology.
Abstract 4596: Missense mutations in the p53 DNA-binding motifs (DBMs) are associated with shorter time to progression (TTP) in erlotinib-treated, EGFR-mutated patients
Authors: Miguel Angel Molina, Jordi Bertran-Alamillo, Clara Mayo, Bartomeu Massuti, Carlos Camps, Enric Carcereny, Santiago Viteri, Susana Benlloch, Miquel Taron, Rafael Rosell
Journal: Cancer Research (2012)

Abstract Background: Advanced non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations has an average time to progression (TTP) of 14 months (mo) and overall survival of 27 mo when treated with erlotinib. However, EGFR mutations can only imperfectly predict outcome. In NSCLC cell lines, tyrosine kinase inhibitors (TKIs) induce p53 translocation from the cytoplasm to the nucleus and subsequent up-regulation of Fas and caspase activation leading to apoptosis. This mechanism was defective in p53-null cells. We tested whether mutations in the TP53 gene influence outcome to erlotinib in EGFR-mutated patients (p). Expression levels of the p53 repressor MDM2 were also examined. Methods: We assesed p53 status in pretreatment paraffin-embedded tumor samples from 93 erlotinib-treated, EGFR mutated advanced NSCLC p. Mutations in exons 5, 6, 7 and 8 were screened by High Resolution Melting analysis (HRM) followed by sequencing of the amplified products with non-wild type melt curves. All mutant samples were re-confirmed by standard PCR and sequencing. Expression levels of MDM2 mRNA were determined by quantitative RT-PCR. Results: Mutations in exons 5-8 of the TP53 gene were detected in 26 of 93 p (28%). We found an unusually high frequency of in-frame and frameshift deletions (23% of mutations), indicating that the spectrum of p53 mutations might be different in EGFR-mutated NSCLC. Mutations in the TP53 gene were not associated with sex, age, smoking status, histology, exon 19 vs. 21 mutation, or response, but, within the study population, were significantly less frequent in p with ECOG 2 or above. The mutations were also associated with the presence of the pretreatment T790M mutation. 14 p had mutations in one of the p53 DNA binding motifs (DBMs), and showed TTP to erlotinib of only 9 mo, compared to 19 months for wt p and 27 mo for those carrying a non-DBM mutation. Survival was 24 mo vs. 31 mo, and not-reached, respectively. Finally, MDM2 mRNA levels were significantly lower in tumors with p53 mutations, especially when these affected DBMs. In the case of wt p, high MDM2 expression correlated with a better TTP and survival. Conclusions: TP53 mutations co-exist with EGFR mutations in a significant number of p; and those in the DBMs are associated with poorer response to erlotinib. This finding paves the way for the possibility of combining erlotinib with a drug restoring p53 function in those p harboring DBM mutations in the TP53 gene. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4596. doi:1538-7445.AM2012-4596
Abstract P6-10-04: Outcome of Triple Negative Breast Cancer in Patients with or without Deleterious BRCA Mutations
Authors: BK Arun, AM Gutierrez-Barrera, U Akar, JK Litton, C Albarracin, AM Gonzalez-Angulo, GN. Hortobagyi
Journal: Cancer Research (2010)

Abstract Background: Triple-negative breast cancer (TNBC) affects 10-17% of all breast cancers and is associated with a poor prognosis. The biology of TNBC is poorly understood; however, it has been shown that up to 60% of BRCA1 mutation carriers develop TNBC. The aim of this study was to determine if there were differences in the progression-free survival (PFS) and overall survival (OS) rates of BRCA mutation-associated TNBC and Non-BRCA mutation-associated TNBC. Methods: Patients with TNBC who were referred between 1997 and 2010 for genetic counseling were included in the analysis. Data was collected from a prospectively maintained IRB-approved research database. All patients with one primary breast cancer and negative expression of ER, PR, and Her2 were included in this study. A Kaplan-Meier survival analysis was performed to determine survival outcomes. Results: Out of 98 TNBC patients, 48 (48 %) were BRCA negative, and 47 (49%) were found to have a deleterious BRCA mutation (42 BRCA1 and 5 BRCA 2); 3 (3%) patients had a variant of uncertain significance in BRCA2 and were removed from study. The median age of diagnosis for BRCA positive TNBC was 42 years (range, 21-71) and for BRCA negative TNBC was 40.5 years (range, 21-64). There were no significant differences between age at diagnosis, nuclear grade, stage (I-III), or tumor histology of BRCA positive and BRCA negative TNBCs. The PFS for BRCA positive patients was 230.7 (range, 2-271) months and for BRCA negative was 203.1 (range, 2-258) months (p = 0.19). The overall survival (OS) for BRCA positive patients was 263.4 (range, 2-292) months and for BRCA negative 236.2 (2-279) months (p = 0.39). Conclusion: Outcome of triple-negative breast cancer is not different in BRCA mutation carriers versus non carriers. Further studies need to evaluate whether different therapies will change the outcome in these subgroups of TNBC. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-10-04.
508 IDENTIFICATION OF HBV AND HCV INFECTIONS IN THE PRIMARY CARE SETTING: PRE-DEFINED RISK SCENARIOS ARE A BETTER SCREENING STRATEGY THAN ELEVATED ALT VALUES
Authors: J. Wiegand, O. Bätz, I. Wolffram, J. Kramer, K. Jedrysiak, H. Tenckhoff, T. Berg
Journal: Journal of Hepatology (2013)
O5.10 * 5-ALA FLUORESCENCE GUIDED RESECTION OF HEMANGIOBLASTOMAS - IS IT USEFUL WITH CONVENTIONAL SURGICAL TOOLS?
Authors: J. M. De Campos, L. Sainz, A. L. Presti, M. Ramirez, D. Aguirre, C. Ordonez, L. Daoud
Journal: Neuro-Oncology (2014)

BACKGROUND: The use of 5-aminolevulinic acid (5-ALA) for fluorescent guided malignant glioma surgery has proved to be useful to ensure a complete resection and thus, a best survival result. One report has described its usefulness for the detection of hemangioblastoma fragments at the cyst wall after apparently complete tumor resection. Von Hippel-Lindau disease patients suffer from many CNS hemangioblastomas, requiring multiple surgical procedures for resection of tumors, many times obscured because distorted structures and dense gliotic scars. MATERIAL AND METHODS: In order to test the eventual utility of 5-ALA fluorescent guided surgery in multiple hemangioblastomas, we have performed surgical procedures in two VHL patients for resection of multiple hemangioblastomas. After patient consent and approval by the Ethical Committee, 5-ALA was administered as oral dose 20 mg/kg 3 hours before anesthesia induction. A surgical microscope modified for Protoporphyrin IX (PpIX)fluorescence guidance, and frameless neuronavigation were used for the surgical procedure. After neuronavigated location and microsurgical dissection of tumors, some involved in dense scars, surgical field visualization was performed alternating standard light illumination and violet-blue light mode, to excite PpIX and collect fluorescence by visualization in surgical oculars and registration on a color camera. RESULTS: Both VHL patients had been previously subjected to surgical procedures for resection of previous posterior fossa tumors. In one case, resection of 7 cerebellar and brainstem tumors was planned on neuronavegator after MRI images, and performed; postsurgical MRI showed a one residual tumor, unnoticed during the surgical procedure because dense scarring tissue. In the second patient, 4 tumors were planned for resection, 3 in cerebellum and 1 in brainstem, and all of them were found and resected. In no case red remitted fluorescence was observed during the location, dissection or resection of tumors. Histopathology analysis proved that all 11 tumors were typical hemangioblastomas. One small area with pink remitted fluorescence in the surgical bed of a tumor proved to be just gliosis without tumor cells. CONCLUSIONS: In the present cases, 5-ALA fluorescent guided surgery for multiple hemangioblastoma resections has not been of utility with the regular surgical armamentarium, instead of the above mentioned experience from one author. The different system for fluorescence evaluation (adapted surgical microscope visualization versus spectroscopy adapted probe system and digitized evaluation) could explain the different results. Other studies are necessary to confirm the results with regular surgical armamentarium, and to explore ancillary tools for detection of localization and extension of CNS tumors under fluorescent conditions during surgical procedures.
Renal and Extrarenal Hemodynamic Effects of Furosemide in Congestive Heart Failure after Acute Myocardial Infarction
Authors: Krishna Dikshit, John K. Vyden, James S. Forrester, Kanu Chatterjee, Ravi Prakash, H.J.C. Swan
Journal: New England Journal of Medicine (1973)

Abstract Furosemide, 0.5 to 1.0 mg per kilogram intravenously, was given to 20 patients with left ventricular failure after acute myocardial infarction. Within five to 15 minutes, average left ventricular filling pressure fell from 20.4 to 14.8 mm Hg, accompanied by a 52 per cent increase in mean calf venous capacitance. During the same period there was no physiologically important change in either urine output or heart rate, blood pressure and cardiac output. Peak increase in urine flow (from mean of 0.82 to 4.0 ml per minute) occurred at 30 minutes, and peak natriuretic effect at 60 minutes. Thus, the action of furosemide in the treatment of pulmonary congestion is immediate and is not related to its diuretic properties. Rather, the prompt fall in left ventricular filling pressure probably is primarily vascular in origin, since marked changes in venous capacitance accompany this phenomenon, which is only later supplemented by the increase in urine output and electrolyte excretion. (N Engl J Med 288:1087...