tbuckley/cabot-search huggingface dataset:
Abstract 19334: Responses to a Pre-PCI Screening Questionnaire Influence Stent Type Used During PCI
Authors: Matthew J Chung, Sunil V Rao, Thomas J Povsic, W S Jones, Ryan D Schulteis
Journal: Circulation (2014)

Introduction: The strong correlation between early termination of dual antiplatelet therapy and stent thrombosis in patients treated with drug-eluting stents (DES) warrants emphasis on appropriate selection of patients for DES. Using a simple questionnaire administered pre-procedurally, we aimed to determine which clinical factors might predict the use of DES during PCI. Hypothesis: A “yes” response to any item on the pre-PCI questionnaire (table 1) will decrease the odds of DES use during PCI. Methods: Using the Durham Veterans Affairs electronic health record, we identified 1202 patients who underwent PCI from July 2008 to January 2013. We excluded patients without a complete pre-PCI questionnaire within 14 days of PCI, repeat procedures and those who received both DES and BMS or no stent during PCI, leaving 864 patients. Using logistic regression we performed univariate analyses of age, sex, diabetes, PCI indication (stable angina, unstable angina/NSTEMI or STEMI) and target vessel type (vein graft or native). Only age and PCI indication were significant predictors of DES use (p &lt; 0.10). Adjusting for age and PCI indication with multivariate logistic regression, we then determined the association between “yes” responses to questionnaire items and DES use. Results: Of the 864 patients receiving stents, 661 received DES and 203 received BMS. Increasing age, presenting with STEMI, and a “yes” response to any item on the questionnaire decreased the odds of DES use, however, this was not significant for questions 2 and 6 (table 1). Presenting with unstable angina or NSTEMI, as compared with stable angina, significantly increased the odds of DES use. Conclusions: Age, PCI indication and responses to 4 of 6 items on a questionnaire administered pre-PCI were associated with stent type used during PCI. Future studies should investigate whether implementation of this questionnaire leads to lower rates of stent thrombosis through appropriate patient selection for DES.
Childhood Thyrotoxicosis: A Long-term Perspective
Authors: K. M. Saxena, J. D. Crawford, N. B. Talbot
Journal: BMJ (1964)

Thyrotoxicosis is a puzzling disorder, especially from the standpoint of aetiology and epidemiology.Basically it represents a disturbance in thyroidal homoeostasis so that there is un- restricted hormone secretion.Clinically this is manifested as hypermetabolism, goitre, and exophthalmos.The overall paediatric contribution to the incidence of thyrotoxicosis is small, the age-group 0-15 years contributing only about 5 % of the total cases.However, this has been one of the commonest thyroid disorders encountered at our Children's Endocrine and Metabolic Clinic, constituting about 45 % of all goitres.The present report summarizes experience with 70 juvenile thyrotoxic patients seen over the 20-year period 1941- 61.The prolonged follow-up in these patients has provided an opportunity to appraise many of them as adults and thus judge the end-products of our paediatric workmanship.Of the 70 patients, 55 (79%) were female.The ratio of females to males, roughly 4: 1, compares with the overall ratio of 6: 1 reported in the childhood age-group (Hayles, 1962) and 7: 1 in adults with Graves's disease. Onset of DiseaseOnset of hyperthyroidism in both boys and girls was most commonly in the early adolescent group aged 10 to 13 years (29 patients).The age of onset was from birth to 5 years in 9 children, 6 to 10 years in 19, and 11 to 16 years in 42.One patient with neonatal thyrotoxicosis, born of a thyrotoxic mother, constituted the only subject under 3 years of age in this series.In about one-third of the patients the opset of thyrotoxic symptoms so closely followed physical or psychic stress as to arouse suspicion that the stress was directly involved in precipi- tating the condition.Thus in six instances the child has been in an automobile accident within a few weeks of the onset of the disease.In seven children convalescence from an infectious disease merged imperceptibly into thyrotoxicosis.In seven others serious psychic trauma, including attempted rape, death of a parent, or separation of parents, immediately preceded the thyroid disorder.The onset was usually insidious, and for this reason many children had advanced disease before coming to medical atten- tion.In retrospect, mild symptoms were present for four to six months or even longer before beingnoted by parents, teacher, or physician.In eight patients the onset was more acute in nature.It was interesting to note that even well- marked symptoms were passed off as " nervousness," " school phobia,'" " chorea," etc., thyrotoxicosis being omitted from consideration because of its presumed rarity.Looking back
Registration trials for specific immunotherapy in Europe: advanced guidance from the new European Medical Agency guideline
Authors: V. Gödicke, F. Hundt
Journal: Allergy (2010)

Marketing authorization of medicinal products is granted based on results of registration trials. The European Medical Agency (EMA) has issued general and disease state-specific guidelines for the conduct of such trials. In the area of allergic diseases, there are basically two general therapeutic approaches: Drugs that mitigate the symptoms and an approach that is targeted to the root cause of the disease, the allergen-specific immunotherapy (SIT). While the 'Guideline on the Clinical Development of Medicinal Products for the Treatment of Allergic Rhino-Conjunctivitis' (CHMP/EWP/2455/02) and the 'Note for Guidance on the Clinical Investigation of Medicinal Products in the Treatment of Asthma' (CPMP/EWP/2922/01) focuses exclusively on the development of medicinal products to treat allergic symptoms, there was no guideline for SIT in the past. In consequence, the conduct of clinical trials for SIT was widely lacking a standardized approach. This created difficulties when comparing drugs and outcomes and also uncertainty to predict marketing authorization. In 2009, the EMA has issued a new guideline on the clinical development of products for SIT. Despite some white spots in some areas, the new guideline constitutes a breakthrough with regard to guidance, harmonization and transparency in the conduct of clinical trials in SIT.
Food Chain of Evidence Points to Brain Toxin
Authors: Tracy Hampton
Journal: JAMA (2003)

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
Investigation of Association Between Hip Osteoarthritis Susceptibility Loci and Radiographic Proximal Femur Shape
Authors: Claudia Lindner, Shankar Thiagarajah, J. Mark Wilkinson, Kalliope Panoutsopoulou, Aaron G. Day‐Williams, Timothy F. Cootes, Gillian A. Wallis
Journal: Arthritis & Rheumatology (2015)

Objective To test whether previously reported hip morphology or osteoarthritis (OA) susceptibility loci are associated with proximal femur shape as represented by statistical shape model (SSM) modes and as univariate or multivariate quantitative traits. Methods We used pelvic radiographs and genotype data from 929 subjects with unilateral hip OA who had been recruited previously for the Arthritis Research UK Osteoarthritis Genetics Consortium genome‐wide association study. We built 3 SSMs capturing the shape variation of the OA‐unaffected proximal femur in the entire mixed‐sex cohort and for male/female‐stratified cohorts. We selected 41 candidate single‐nucleotide polymorphisms (SNPs) previously reported as being associated with hip morphology (for replication analysis) or OA (for discovery analysis) and for which genotype data were available. We performed 2 types of analysis for genotype–phenotype associations between these SNPs and the modes of the SSMs: 1) a univariate analysis using individual SSM modes and 2) a multivariate analysis using combinations of SSM modes. Results The univariate analysis identified association between rs4836732 (within the ASTN2 gene) and mode 5 of the female SSM ( P = 0.0016) and between rs6976 (within the GLT8D1 gene) and mode 7 of the mixed‐sex SSM ( P = 0.0003). The multivariate analysis identified association between rs5009270 (near the IFRD1 gene) and a combination of modes 3, 4, and 9 of the mixed‐sex SSM ( P = 0.0004). Evidence of associations remained significant following adjustment for multiple testing. All 3 SNPs had previously been associated with hip OA. Conclusion These de novo findings suggest that rs4836732, rs6976, and rs5009270 may contribute to hip OA susceptibility by altering proximal femur shape.
Abstract MP88: Fetuin-A, a Vascular Biomarker of Cognitive Decline in Older Adults
Authors: Gail A Laughlin, Linda K McEvoy, Elizabeth Barrett-Connor, Lori B Daniels, Joachim H Ix
Journal: Circulation (2014)

Objectives: The contribution of vascular disease to neurocognitive decline is now widely recognized. Fetuin-A is an abundant plasma protein known to predict vascular disease. Prior studies have shown that fetuin-A levels are lower in patients with Alzheimer’s disease in direct proportion to the severity of cognitive impairment; however, their association with normal cognitive aging is unknown. We evaluated the association of serum fetuin-A levels with cognitive function in relatively high-functioning, community-dwelling older adults from the Rancho Bernardo Study. Methods: This is a population-based study of 1382 older adults (median age 75) who had plasma fetuin-A levels and cognitive function evaluated in 1992-96; 855 had repeat cognitive function assessment a median of 4 years later. Results: Adjusting for age, sex, education, and depression, higher levels of fetuin-A were associated with better baseline performance on the Mini-Mental Status Exam (MMSE) (P=0.012) and a tendency for better Trails Making B scores (P=0.066). In longitudinal analyses, the likelihood of a major decline (highest decile of change) in Trails B was 29% lower (P=0.010) for each SD higher baseline fetuin-A level; odds of major decline in MMSE was 42% lower (P=0.005) per SD higher fetuin-A for individuals with no known CVD, but were not related to fetuin-A in those with CVD (P=0.33). Fetuin-A was not related to Category Fluency performance. Results did not vary by sex and were not explained by numerous vascular risk factors and comorbidities. Conclusions: Higher plasma fetuin-A concentrations are associated with better performance on tests of global cognitive function and executive function and with reduced likelihood of major decline in these cognitive abilities over a 4-year period. These observations are consistent with the hypothesis that higher fetuin-A protects against cognitive decline in relatively high functioning older adults, although this may be less apparent in those with established vascular disease. Fetuin-A may serve as a biological link between vascular disease and normal age-related cognitive decline.
Murine IgE and IgG antibody responses to allergenic and non-allergenic foods*1Potential model for allergenicity assessment of foods in man
Authors: P.A. Gaudry, J. Fernandes, R. Reish, K.H. Roux, S.K. Sathe, S.S. Teuber, G. Reese, S.B. Lehrer
Journal: Journal of Allergy and Clinical Immunology (2004)
Randomized trial with or without granulocyte colony-stimulating factor as adjunct to induction VNCOP-B treatment of elderly high-grade non-Hodgkin's lymphoma.
Authors: Pier Luigi Zinzani, Enzo Pavone, Sergio Storti, Luciano Moretti, Pier Paolo Fattori, Luciano Guardigni, Brunangelo Falini, Marco Gobbi, Patrizia Gentilini, Vito Michele Lauta, Maurizio Bendandi, Filippo Gherlinzoni, Massimo Magagnoli, Stefamia Venturi, Enrico Aitini, Maurizio Tabanelli, Giuseppe Leone, Vincenzo Liso, Sante Tura
Journal: Blood (1997)
A conversation with Robert Schrier
Authors: Ushma S. Neill
Journal: Journal of Clinical Investigation (2015)

A prolific expert in the renal field, Dr. Robert Schrier is professor of medicine at the University of Colorado Denver School of Medicine, where he was chairman of the Department of Medicine for 26 years. Schrier (Figure 1) is an expert in patient-oriented research in acute kidney injury, autosomal dominant polycystic kidney disease, hypertension, and diabetic nephropathy; he is behind most of what we know about fluid balance in the body.
Abstract 3616: Hypoxia determines the fate of myeloid cell differentiation by controlling STAT3 activation in tumor site
Authors: Vinit Kumar
Journal: Cancer Research (2014)

Abstract The abnormal differentiation of myeloid cells is the key element of altered immune response in cancer. Myeloid derived suppressor cells (MDSC) are a major component of immune suppressive network. MDSC accumulate in large numbers in peripheral lymphoid organs and inside tumors. Recent data indicated that the fate of MDSC depends on the localization of these cells. In contrast to peripheral lymphoid organs, inside tumors, MDSC rapidly differentiate to tumor associated macrophages with potent immune suppressive activity. Hypoxia is intricate part of tumor microenvironment. We have found that hypoxia plays a major role in regulation of MDSC differentiation to macrophages in tumor site. Hypoxia caused dramatic reduction in phosphorylated STAT3 in MDSC. These results were unexpected, since high level of STAT3 activity is a hallmark of MDSC present in blood and lymphoid organs. In our experiments spleen MDSC in tumor-bearing mice had much higher level of STAT3 phosphorylation than their counterparts in tumor site from the same mice. In cancer patients MDSC in tumor site also had substantially lower level of pSTAT3 than MDSC in peripheral blood. In vitro culture of spleen MDSC in hypoxia led to the suppression of STAT3 activation. Furthermore, mice with constitutively active STAT3 had shown the dramatic expansion of MDSC and down-regulation of macrophage population in tumor microenvironment, suggesting that STAT3 is a downstream target for hypoxia driven myeloid cells differentiation in cancer. We found that CD45 protein tyrosine phosphatase was a molecule that regulated STAT3 activation in hypoxia. The activity but not expression of CD45 phosphatase was up-regulated in tumor MDSC as compared to MDSC in spleens. The exposure of spleen MDSC to hypoxia led to the significant increase in CD45 activity. The siRNA mediated silencing of CD45 abrogated the effect of hypoxia on the down-regulation of STAT3 activity in MDSC. This suggests that hypoxia driven up-regulation of CD45 phosphatase activity suppresses STAT3 activation, which in turn plays a key role in differentiation of myeloid cells in tumor site. These unexpected findings may provide rationale for re-evaluation of therapeutic strategies targeting myeloid cells in cancer. Citation Format: Vinit Kumar. Hypoxia determines the fate of myeloid cell differentiation by controlling STAT3 activation in tumor site. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3616. doi:10.1158/1538-7445.AM2014-3616
p73 is required for the apoptotic activity of an engineered nuclear BCR-ABL tyrosine kinase
Authors: Paolo Vigneri, Maria Stella Pennisi, Alessandra Aloisi, Jean Wang, Angelo Messina
Journal: Cancer Research (2008)

2782  The BCR-ABL oncoprotein of Chronic Myelogenous Leukemia (CML) localizes to the cell cytoplasm because its nuclear localization signals (NLS) are inactivated. In the cytoplasm, BCR-ABL activates several proliferative and anti-apoptotic signaling pathways leading to the development of CML.  We have previously reported that the NLS of BCR-ABL can be re-activated and that the nuclear BCR-ABL can trigger cell death. To clarify the molecular mechanisms responsible for the apoptosis induced by nuclear BCR-ABL, we investigated its possible interactions with the p53 family of proteins.  We engineered a BCR-ABLNuk construct that is capable of nuclear import while maintaining its constitutive tyrosine kinase activity. Immunofluorescence analysis and cell fractionation experiments confirmed that BCR-ABLNuk and its kinase defective counterpart BCR-ABLKDNuk both migrate to the cell nucleus. Furthermore, IP-Western experiments demonstrated that these constructs physically interact with p73 but not with p53 and p63. This interaction requires the SH3 domain of BCR-ABLNuk, since a BCR-ABLNuk construct devoid of the SH3 domain can no longer bind p73.  Following its association with BCR-ABLNuk, p73 is phosphorylated on tyrosines 99 and 121. This post-translational modification stabilizes the p73 protein and leads to the induction of cell death. These results were further confirmed in fibroblasts derived from p73-null mice. In this cellular context, BCR-ABLNuk was unable to elicit cell death. However, the reconstitution of these cells with wild-type p73 promptly reestablished an apoptotic response.  Our results identify p73 as a molecular target of nuclear BCR-ABL, suggesting that, in order to induce cell death, the oncoprotein requires binding and phosphorylation of p73.
Abstract 3759: Identification of novel carboplatin resistance gene in ovarian cancer
Authors: Han Wei, Yun She, Tao Lu
Journal: Cancer Research (2014)

Abstract Ovarian cancer (OC) is the most lethal gynecology cancer in the world. Although carboplatin is one of the major drugs used to treat OC, resistance to carboplatin remains a major barrier to successful treatment. To date, the mechanisms of carboplatin resistance are still poorly understood. The purpose of this study is to use the novel validation-based insertional mutagenesis (VBIM) technique to identify carboplatin resistance gene in A2780 OC cells. A2780 cells were infected with VBIM virus to cause the overexpression of drug resistance genes, then were further selected under carboplatin treatment. Targeted gene was then identified by using VBIM specific primers. In a preliminary screen, we identified the novel carboplatin resistance gene 1 (NCR1). Overexpression of NCR1 increased carboplatin resistance in A2780 OC cells, while knocking it down with shRNA had the opposite effect. In an attempt to investigate the molecular mechanism that underlying NCR1-mediated carboplatin resistance, we found that NCR1 is a potential NF-κB activator. In summary, we conclude that using a novel VBIM technique, we discovered a previously unknown carboplatin resistance gene NCR1, which may mediate drug resistance via NF-κB signaling pathway. This study is of extreme importance by identifying a potential novel therapeutic target NCR1 in carboplatin resistance. Development of small chemical inhibitors targeting NCR1 could ultimately lead to novel therapeutic approach for ovarian cancer treatment. Citation Format: Han Wei, Yun She, Tao Lu. Identification of novel carboplatin resistance gene in ovarian cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3759. doi:10.1158/1538-7445.AM2014-3759
A Short Practice of Midwifery, Embodying the Treatment Adopted in the Rotunda Hospital, Dublin
Authors: Henry Jellett
Journal: JAMA (1897)

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
810. Ex-Vivo Activation and Genetic Manipulation of Human T Cells Results in Consistent In-Vivo Expansion and Lethal GvHD in a Novel Murine Xenotransplant Model
Authors: Bruno Nervi, Michael P. Rettig, Julie K. Ritchey, Gerhard Bauer, Jon Walker, Phillip E. Herrbrich, Todd E. Meyerrose, Mark Bonyhadi, Jan A. Nolta, John F. DiPersio
Journal: Molecular Therapy (2005)

Our group has previously reported the development of novel CD34-TK chimeric suicide genes for optimal T cell engraftment, graft versus leukemia effect and minimal graft versus host disease (GvHD) in murine BMT models (Rettig et al., Mol. Ther. 2003; Rettig et al., J. Immunol. 2004). These studies have demonstrated critical functional impairment of murine T cells after selected methods of activation, transduction and selection. Unfortunately no in-vivo models exist to consistently examine the impact of ex-vivo manipulation of human T cells (HuT) on T cell function in-vivo. NOD SCID2M null mice (2 mice) were conditioned with 250cGy TBI on day -1 (n=31), or 300cGy on day 0 (n=22). 107 naive HuT or CD3/28 bead activated (XcyteTMDynabeads®) with 50 U/ml IL-2 for 4 days (Act 4d) or 8 days (Act 8d) HuT were injected retroorbitaly (ro), intravenous tail vein injection (iv) or lower HuT doses resulted in no expansion or GvHD. Engraftment of HuT in peripheral blood (PB) of recipient mice was evaluated weekly by FACS and euthanasia was performed if mice lost > 20% body weight. (See Table 1)