tbuckley/cabot-search huggingface dataset:
Posttransplantation Relapse of FSGS Is Characterized by Glomerular Epithelial Cell Transdifferentiation
Authors: JEAN BARIÉTY, PATRICK BRUNEVAL, GARY HILL, THEANO IRINOPOULOU, CHANTAL MANDET, ALAIN MEYRIER
Journal: Journal of the American Society of Nephrology (2001)

This study examined six cases of idiopathic nephrotic syndrome with primary lesions of focal segmental glomerulosclerosis (FSGS) that relapsed after renal transplantation. The glomerular lesions comprised the cellular, the collapsing, and the scar variants of FSGS and showed shedding of large round cells into Bowman's space and within the tubular lumens. Immunohistochemistry and confocal laser microscopy carried out on kidneys with FSGS relapse disclosed several phenomena. (1) Some podocytes that expressed podocalyxin, synaptopodin, and glomerular epithelial protein-1 were detached from the tuft and were free in the urinary space. (2) In the cellular variant, most podocytes had lost podocyte-specific epitopes (podocalyxin, synaptopodin, glomerular epithelial protein-1, Wilm's tumor protein-1, complement receptor-1, and vimentin). In the scar variant, these podocyte markers were absent from cobblestone-like epithelial cells and from pseudotubules. (3) Podocytes had acquired expression of various cytokeratins (CK; identified by the AE1/AE3, C2562, CK22, and AEL-KS2 monoclonal antibodies) that were not found in the podocytes of control glomeruli. Parietal epithelial cells expressed AE1/AE3 CK that were faintly, if ever, found on the parietal epithelial cells of normal glomeruli. (4) Numerous cells located at the periphery of the tuft or free in Bowman's space and within tubular lumens expressed macrophagic epitopes (identified by PGM1 [CD68], HAM56, and 25F9 monoclonal antibodies). These macrophage-like cells expressed the activation epitopes HLA-DR and CD16. (5) A number of these cells coexpressed podocalyxin + AE1/AE3 CK, podocalyxin + CD68, and CD68 + AE1/AE3. These findings suggest that in primary FSGS relapsing on transplanted kidneys, some "dysregulated" podocytes, occasionally some parietal epithelial cells, and possibly some tubular epithelial cells undergo a process of transdifferentiation. This process of transdifferentiation was especially striking in podocytes that acquired macrophagic and CK epitopes that are absent from normal adult and fetal podocytes.
Colony growth and self renewal of plasma cell precursors in multiple myeloma.
Authors: T Takahashi, B Lim, N Jamal, D Tritchler, G Lockwood, S McKinney, D E Bergsagel, H A Messner
Journal: Journal of Clinical Oncology (1985)

Culture conditions that support the growth of multi-and single-lineage hemopoietic colonies are also able to give rise to large myeloma colonies from bone marrow and peripheral blood samples of some patients with multiple myeloma. The culture system was used to determine the frequency of hemopoietic precursors and clonogenic myeloma progenitors in 71 patients with multiple myeloma studied in various clinical phases of the disease. The frequency of normal hemopoietic precursors in patients with benign monoclonal gammopathy and smoldering myeloma were indistinguishable from normal controls. Myeloma colonies were not observed in these subgroups. In contrast, patients with active disease showed significantly reduced hemopoietic colony formation, even before the initiation of therapy. A further reduction was demonstrated for patients with acute phase disease. A correlation between the frequency of hemopoietic colonies and the concentration of plasma cells in the plated sample was not observed. Large myeloma colonies with recloning potential were identified in cultures of specimens derived from 14 of the studied patients. These colonies were most frequently (ten cases) obtained from patients who had entered the acute phase of the disease. These patients manifested marrow failure (pancytopenia) and their marrow had a limited capacity to generate normal hemopoietic colonies. Three of the patients that formed myeloma colonies were studied in chronic phase following chemotherapy and one patient was examined at diagnosis. The myeloma colonies were composed exclusively of cells characterized by the same M protein as the patient. Some of the cells within the colonies retained their ability to self renew extensively, as demonstrated by serial recloning studies. Colonies derived from six of the patients are now propagated in semisolid and liquid medium for as many as nine to 34 generations. Patients that form myeloma colonies under these culture conditions represent a high-risk group with significantly shorter survival than patients not able to give rise to myeloma colonies. A Cox proportional hazards model was fitted to the data to determine the prognostic role of myeloma colony growth in culture after accounting for the influence of other well established risk factors, such as concentration of plasma cells and disease status. The analysis indicated that myeloma colony growth in culture serves as a strong and independent predictive indicator of poor clinical prognosis.
Free-Text Notes as a Marker of Needed Improvements in Electronic Prescribing
Authors: Jeffrey L. Schnipper
Journal: JAMA Internal Medicine (2016)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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 Internal Medicine journal
Prevention of hip fractures in older men receiving androgen deprivation therapy for prostate cancer: A cost-effectiveness analysis
Authors: K. Ito, E. Elkin, M. Morris
Journal: Journal of Clinical Oncology (2009)

6530 Background: Androgen deprivation therapy (ADT) increases the risk of osteoporotic fractures. Our goal was to assess the cost-effectiveness of bone mineral density (BMD) screening followed by alendronate therapy at the onset of ADT in men with T2c-T4N0 prostate cancer. Methods: We developed a Markov model of prostate cancer progression and simulated the experience of 70-year-old men with T2c-T4N0 prostate cancer starting a 2-year course of ADT after radiation therapy. We compared four strategies: No BMD screening and no alendronate therapy; BMD screening with alendronate therapy for men with osteoporosis (a T-score ≤ -2.5); BMD screening with alendronate therapy for men with osteoporosis or osteopenia (a T-score ≤ -1.0); and universal alendronate therapy without BMD screening. The main outcome measure was cost per quality-adjusted life year (QALY) gained. Data sources were U.S. epidemiological studies and health care cost figures. A model-based estimate of median survival was 9.5 years. Proportions of men who had a T-score ≤ -2.5 and -1.0 were 10% and 45%, respectively. A model-based incidence of hip fractures with no therapy was 0.93 per 100 person-years. Alendronate reduced the risk of hip fractures by 10%. Results: Compared with no screening and no therapy, BMD screening with alendronate therapy for men with osteopenia or osteoporosis cost $66,100 per QALY gained. BMD screening with alendronate therapy only for those with osteoporosis was slightly more costly and more effective, but had a less favorable ICER. Universal alendronate therapy without screening cost $1,580,300 per QALY gained. These results were most sensitive to assumptions about the impact of alendronate on the rate of BMD loss during ADT and the price of alendronate. Conclusions: In men with T2c-T4N0 prostate cancer, BMD screening with alendronate therapy for men with osteoporosis or osteopenia is a cost-effective use of resources, compared with other medical interventions in oncology. [Table: see text] No significant financial relationships to disclose.
Creative consulting: more about placebos?
Authors: David Reilly
Journal: BMJ (2002)

In the fifth article in his series David Reilly is joined by Zelda Di Blasi to look at the placebo response If placebos are inactive, what is it that produces the remarkable changes? Do not ask what the placebo can do but, “What can the thing that responds to the placebo do?” You will end up thinking about self healing and self destructive processes. Just as you can work backwards from a successful recovery to study healing reactions,1 you can consider what placebo reactions say about healing responses and better care. If placebo can provoke a change indirectly perhaps we can learn to do so directly, because we are the only possible pathway for placebo action. The implications of this pathway, between our consciousness and our biology, can be missing in academic debate about placebo,234 but the discovery that people responding to placebo show definite brain scan changes can bring it back into focus.5 Universal cultural features in healing rituals24
Romidepsin for the treatment of relapsed/refractory peripheral T cell lymphoma: prolonged stable disease provides clinical benefits for patients in the pivotal trial
Authors: Francine Foss, Steven Horwitz, Barbara Pro, H. Miles Prince, Lubomir Sokol, Barbara Balser, Julie Wolfson, Bertrand Coiffier
Journal: Journal of Hematology & Oncology (2016)

Achievement of durable responses in patients with relapsed/refractory peripheral T cell lymphoma (PTCL) is challenging with current therapies, and there are few data regarding the potential benefits of continuing treatment in patients with the best response of stable disease (SD). Histone deacetylase inhibitors are a novel class of drugs with activity in T cell malignancies. Romidepsin was approved by the US Food and Drug Administration for the treatment of relapsed/refractory PTCL based on a pivotal trial demonstrating an objective response rate of 25 % (33/130), including 15 % with confirmed/unconfirmed complete response and a median duration of response of 28 months. Our objective was to further study the clinical benefits of romidepsin in patients that had the best response of SD. Patients with PTCL relapsed/refractory to ≥1 prior therapy were treated with the approved dose of 14 mg/m2 romidepsin on days 1, 8, and 15 of six 28-day cycles; patients with SD or response after cycle 6 were allowed to continue on study until progression. By protocol amendment, patients treated for ≥12 cycles could receive maintenance dosing twice per cycle; after cycle 24, dosing could be further reduced to once per cycle in those who had received maintenance dosing for ≥6 months. Of the 32 patients (25 %) with the best response of SD, 22 had SD for ≥90 days (SD90; cycle 4 response assessment). The longest SD was >3 years in a patient who received maintenance dosing of 14 mg/m2 on days 1 and 15 beginning in cycle 13. Patients with the best response of SD90 or partial response achieved similar overall and progression-free survival. Prolonged dosing of romidepsin was well tolerated. We concluded that patients who achieve SD may consider continuing treatment because the clinical benefits of romidepsin may extend beyond objective responses. NCT00426764
Five-year follow-up of radiographic sacroiliitis: progression as well as improvement?
Authors: Alexandre Sepriano, Martin Rudwaleit, Joachim Sieper, Rosaline van den Berg, Robert Landewé, Désirée van der Heijde
Journal: Annals of the Rheumatic Diseases (2016)

Determining the presence of radiographic sacroiliitis is a key feature in the diagnostic process of radiographic axial spondyloarthritis (r-axSpA), synonymous to ankylosing spondylitis according to the modified New York criteria (mNY).1 Its presence is considered prognostically relevant and paves the way for treatment with biological drugs.2 Multiread and multireader exercises have proven that radiographic sacroiliitis is an ambiguous finding, as reflected by large inter-reader and intrareader variability.3 ,4

Determining progression of radiographic sacroiliitis, which marks the arbitrary but irreversible change from non-radiographic axSpA (nr-axSpA) to r-axSpA, is even more ambiguous. The mNY lack sensitivity-to-change in this slowly progressing condition, and it is conceivable that regression of radiographic sacroiliitis is very rare if not impossible.5 Previous studies addressing progression from nr-axSpA to …
Modeling Future Cardiovascular Disease Mortality in the United States
Authors: Jonathan Pearson-Stuttard, Maria Guzman-Castillo, Jose L. Penalvo, Colin D. Rehm, Ashkan Afshin, Goodarz Danaei, Chris Kypridemos, Tom Gaziano, Dariush Mozaffarian, Simon Capewell, Martin O’Flaherty
Journal: Circulation (2016)

Accurate forecasting of cardiovascular disease mortality is crucial to guide policy and programming efforts. Prior forecasts often have not incorporated past trends in rates of reduction in cardiovascular disease mortality. This creates uncertainties about future trends in cardiovascular disease mortality and disparities.To forecast US cardiovascular disease mortality and disparities to 2030, we developed a hierarchical bayesian model to determine and incorporate prior age, period, and cohort effects from 1979 to 2012, stratified by age, sex, and race, which we combined with expected demographic shifts to 2030. Data sources included the National Vital Statistics System, Surveillance, Epidemiology, and End Results (SEER) single-year population estimates, and US Bureau of Statistics 2012 national population projections. We projected coronary disease and stroke deaths to 2030, first on the basis of constant age, period, and cohort effects at 2012 values, as is most commonly done (conventional), and then with the use of more rigorous projections incorporating expected trends in age, period, and cohort effects (trend based). We primarily evaluated absolute mortality. The conventional model projected total coronary and stroke deaths by 2030 to increase by ≈18% (67 000 additional coronary deaths per year) and 50% (64 000 additional stroke deaths per year). Conversely, the trend-based model projected that coronary mortality would decrease by 2030 by ≈27% (79 000 fewer deaths per year) and stroke mortality would remain unchanged (200 fewer deaths per year). Health disparities will be improved in stroke deaths but not coronary deaths.After prior mortality trends and expected demographic shifts are accounted for, total US coronary deaths are expected to decline, whereas stroke mortality will remain relatively constant. Health disparities in stroke but not coronary deaths will be improved but not eliminated. These age, period, and cohort approaches offer more plausible predictions than conventional estimates.
Epstein-Barr Virus in an American Patient With Burkitt's Lymphoma: Detection of Viral Genome in Tumor Tissue and Establishment of a Tumor-Derived Cell Line (NAB)2
Authors: M. Gravell, P. H. Levine, R. F. McIntyre, V. J. Land, J. S. Pagano
Journal: JNCI Journal of the National Cancer Institute (1976)

Journal Article Epstein-Barr Virus in an American Patient With Burkitt's Lymphoma: Detection of Viral Genome in Tumor Tissue and Establishment of a Tumor-Derived Cell Line (NAB) Get access M. Gravell, M. Gravell Search for other works by this author on: Oxford Academic PubMed Google Scholar P. H. Levine, P. H. Levine Search for other works by this author on: Oxford Academic PubMed Google Scholar R. F. McIntyre, R. F. McIntyre Search for other works by this author on: Oxford Academic PubMed Google Scholar V. J. Land, V. J. Land Search for other works by this author on: Oxford Academic PubMed Google Scholar J. S. Pagano J. S. Pagano Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 56, Issue 4, April 1976, Pages 701–704, https://doi.org/10.1093/jnci/56.4.701 Published: 01 April 1976 Article history Received: 09 June 1975 Accepted: 05 November 1975 Published: 01 April 1976
Inability of Serum to Completely Reverse Density-Dependent Inhibition of Cell Growth in Culture2
Authors: B. K. Nair
Journal: JNCI Journal of the National Cancer Institute (1974)

Secondary cultures of mouse embryo cells showed density-dependent inhibition of growth when the medium contained 10% serum. After change of medium or addition of fresh serum, denslty-lnhlblted cells started synthesizing DNA and dividing. Synthesis of DNA began after a lag of about 12 hours, reached a maximum between 18 and 24 hours, and then declined gradually. The capacity of fresh serum to stimulate growth depended on the nutritional status of the medium to which it was added. Increase in the amount of serum in the culture medium increased the rate of DNA synthesis. However, DNA synth esis declined drastically as the medium became depleted, though it contained higher concentrations of serum. This indicated that nutrients and regulating micromolecules in the chemically defined medium are important in controlling the growth stimulated by serum and that serum does not have a nutritional function in monolayer cell culture.
Isocitrate dehydrogenase 1 mutations prime the all-trans retinoic acid myeloid differentiation pathway in acute myeloid leukemia
Authors: Héléna Boutzen, Estelle Saland, Clément Larrue, Fabienne de Toni, Lara Gales, Florence A. Castelli, Mathilde Cathebas, Sonia Zaghdoudi, Lucille Stuani, Tony Kaoma, Romain Riscal, Guangli Yang, Pierre Hirsch, Marion David, Véronique De Mas-Mansat, Eric Delabesse, Laurent Vallar, François Delhommeau, Isabelle Jouanin, Ouathek Ouerfelli, Laurent Le Cam, Laetitia K. Linares, Christophe Junot, Jean-Charles Portais, François Vergez, Christian Récher, Jean-Emmanuel Sarry
Journal: The Journal of Experimental Medicine (2016)

Acute myeloid leukemia (AML) is characterized by the accumulation of malignant blasts with impaired differentiation programs caused by recurrent mutations, such as the isocitrate dehydrogenase (IDH) mutations found in 15% of AML patients. These mutations result in the production of the oncometabolite (R)-2-hydroxyglutarate (2-HG), leading to a hypermethylation phenotype that dysregulates hematopoietic differentiation. In this study, we identified mutant R132H IDH1-specific gene signatures regulated by key transcription factors, particularly CEBPα, involved in myeloid differentiation and retinoid responsiveness. We show that treatment with all-trans retinoic acid (ATRA) at clinically achievable doses markedly enhanced terminal granulocytic differentiation in AML cell lines, primary patient samples, and a xenograft mouse model carrying mutant IDH1. Moreover, treatment with a cell-permeable form of 2-HG sensitized wild-type IDH1 AML cells to ATRA-induced myeloid differentiation, whereas inhibition of 2-HG production significantly reduced ATRA effects in mutant IDH1 cells. ATRA treatment specifically decreased cell viability and induced apoptosis of mutant IDH1 blasts in vitro. ATRA also reduced tumor burden of mutant IDH1 AML cells xenografted in NOD–Scid–IL2rγnull mice and markedly increased overall survival, revealing a potent antileukemic effect of ATRA in the presence of IDH1 mutation. This therapeutic strategy holds promise for this AML patient subgroup in future clinical studies.
Abstract 18395: Safety of Continuing Ivabradine Treatment During Hospitalization for Worsening of Heart Failure in the SHIFT Study
Authors: Jeffrey Borer, Karl Swedberg, Michel Komajda, Ian Ford, Luigi Tavazzi, Michael Böhm, Fabienne Dominjon, Yuna Wu, Christophe Depre, Juan Maya
Journal: Circulation (2015)

Background: Chronic medical treatment is usually adapted during hospitalizations for worsening heart failure (HWHF). Ivabradine, a heart rate (HR)-slowing agent that inhibits the funny current (If) in the sinus node, when added to standard of care reduced the relative risk of HWHF by 26% in the Systolic Heart failure treatment with the If inhibitor ivabradine Trial (SHIFT). Upon HWHF in SHIFT, ivabradine could be maintained even though patients were in acute/unstable HF. This post hoc exploratory analysis assessed the safety of continuing administration of ivabradine during HWHF in SHIFT. Methods: The safety of ivabradine within the 30 days following the first HWHF admission was assessed in patients receiving either ivabradine or placebo presenting with at least 1 adjudicated HWHF during the trial. The safety of ivabradine within the 30 days following the first HWHF admission in patients who continued study drug (CSD) versus those that discontinued study drug (DSD) during hospitalization within each treatment arm were compared. Results: Baseline characteristics of patients who were at least once HWHF were comparable between the ivabradine (n = 447) and placebo (n = 619) arms. During HWHF, study drug was continued in 70% of ivabradine- and 73% of placebo-treated patients. Within the 30 days following the first HWHF admission, serious adverse events were reported in 10.1% of ivabradine- (CSD: 11.1%, DSD: 7.6%) and 12.6% placebo-treated patients (CSD: 14.2%, DSD: 8.4%). Cardiovascular death was reported in 0.7% of ivabradine- (CSD: 0.6%, DSD: 0.8%) and 0.6% of placebo-treated patients (CSD: 0.9%, DSD: 0%). Conclusions: The safety profile of ivabradine in patients within 30 days following admission for HWHF was comparable to placebo, regardless of whether patients continued or discontinued study drug.