tbuckley/cabot-search huggingface dataset:
Users' Guides to the Medical Literature
Authors: Andrew D. Oxman
Journal: JAMA (1994)

<h3>CLINICAL SCENARIO</h3> A 55-year-old man had his serum cholesterol level measured at a shopping mall 2 months ago. His cholesterol level was elevated and he comes to you, his primary care physician, for advice. He does not smoke, is not obese, and does not have hypertension, diabetes mellitus, or any first-order relatives with premature coronary heart disease (CHD). You repeat his cholesterol test and schedule a follow-up appointment. The test confirms an elevated cholesterol level (7.9 mmol/L [305 mg/dL]), but before deciding on a treatment recommendation, you elect to find out just how big a reduction in the risk of CHD this patient could expect from a cholesterollowering diet or drug therapy. <h3>THE SEARCH</h3> There are a number of cholesterol-lowering trials, and instead of trying to find and review all of the original studies yourself, you use Grateful Med to find a recent overview. On the first subject line you
Psychologic Intervention and Survival: Wishing Does Not Make It So – Letter
Authors: Steven C. Palmer, Michael E. Stefanek, Brett D. Thombs, James C. Coyne
Journal: Clinical Cancer Research (2010)

Andersen et al. ([1][1]) claimed that breast cancer patients experiencing a recurrence survived longer when they had been exposed to a brief psychologic intervention an average of 11 years earlier. We are concerned that breast cancer patients, clinicians, and researchers might accept these claims at
A 66-Year-Old Man With Sexual Dysfunction
Authors: Abraham Morgentaler
Journal: JAMA (2004)

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
A uniform activated B-cell–like immunophenotype might explain the poor prognosis of primary central nervous system lymphomas: analysis of 83 cases
Authors: Sophie Camilleri-Broët, Emmanuelle Crinière, Philippe Broët, Vincent Delwail, Karima Mokhtari, Anne Moreau, Michèle Kujas, Martine Raphaël, Wafae Iraqi, Catherine Sautès-Fridman, Philippe Colombat, Khê Hoang-Xuan, Antoine Martin
Journal: Blood (2005)
Prospects for Immunotoxin Therapy in Cancer
Authors: A E Frankel, L L Houston, B F Issell, G Fathman
Journal: Annual Review of Medicine (1986)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Phase I Study of Rigosertib, an Inhibitor of the Phosphatidylinositol 3-Kinase and Polo-like Kinase 1 Pathways, Combined with Gemcitabine in Patients with Solid Tumors and Pancreatic Cancer
Authors: Wen Wee Ma, Wells A. Messersmith, Grace K. Dy, Colin D. Weekes, Amy Whitworth, Chen Ren, Manoj Maniar, Francois Wilhelm, S. Gail Eckhardt, Alex A. Adjei, Antonio Jimeno
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Rigosertib, a dual non-ATP inhibitor of polo-like kinase 1 (Plk1) and phosphoinositide 3-kinase pathways (PI3K), and gemcitabine have synergistic antitumor activity when combined in preclinical studies. This phase I study aimed to determine the recommended phase II dose (RPTD) of the combination of rigosertib and gemcitabine in patients with cancer. Experimental Design: Patients with solid tumors who failed standard therapy or were candidates for gemcitabine-based therapy were eligible. Gemcitabine was administered on days 1, 8, and 15 on a 28-day cycle and rigosertib on days 1, 4, 8, 11, 15, and 18. Pharmacokinetic studies were conducted during an expansion cohort of patients with advanced pancreatic ductal adenocarcinoma (PDA). Results: Forty patients were treated, 19 in the dose-escalation phase and 21 in the expansion cohort. Dose levels evaluated were (gemcitabine/rigosertib mg/m2): 750/600 (n = 4), 750/1,200 (n = 3), 1,000/600 (n = 3), 1,000/1,200 (n = 3), and 1,000/1,800 (n = 6 + 21). One dose-limiting toxicity (death) occurred at the highest dose level (1,000/1,800) tested. Non–dose-limiting ≥grade II/III toxicities included neutropenia, lymphopenia, thrombocytopenia, fatigue, and nausea. Grade III/IV neutropenia, thrombocytopenia, and fatigue were seen in two, one, and two patients in the expansion cohort. Partial responses were observed in PDA, thymic cancer, and Hodgkin lymphoma, including gemcitabine-pretreated PDA. The pharmacokinetic profile of rigosertib was not affected by gemcitabine. Conclusion: The RPTD established in this study is rigosertib 1,800 mg/m2 and gemcitabine 1,000 mg/m2. This regimen is well tolerated with a toxicity profile of the combination similar to the profile of gemcitabine alone. Antitumor efficacy was observed in patients who previously progressed on gemcitabine-based therapy. Clin Cancer Res; 18(7); 2048–55. ©2012 AACR.
Non-specific interstitial pneumonia: findings on sequential CT scans of nine patients
Authors: M. Akira
Journal: Thorax (2000)

The purpose of this study was to describe findings on sequential high resolution computed tomographic (CT) scans of nine patients with non-specific interstitial pneumonia.Thin section CT scans of nine patients with pathologically proven non-specific interstitial pneumonia were evaluated retrospectively. All patients underwent sequential CT scanning (mean follow up 3.1 years (range 1-8)).The predominant finding on the initial CT scans in seven patients was patchy areas of ground glass opacity in both the central and peripheral lung, with (n = 5) or without (n = 2) irregular areas of consolidation. In another two patients areas of consolidation in both the central and peripheral lung were seen as the predominant abnormality. The initial parenchymal abnormalities had resolved completely in four patients with predominant ground glass opacity without bronchiolectasis. Some of the bronchiectasis and bronchiolectasis resolved. In two patients bronchiectasis and bronchiolectasis occurred at one year and two years of follow up, respectively. In two patients with predominant consolidation the consolidation decreased but persisted, and in one patient the consolidation evolved into honeycombing. In the other patient bronchiectasis progressed over the course of seven years, forming varicoid bronchiectasis.Patients with non-specific interstitial pneumonia may recover completely after treatment with corticosteroids, but as many as half of these patients will have persistent pulmonary abnormalities on CT scans including bronchiectasis and honeycomb lung.
Surgical and medical treatment of adenomyosis
Authors: C Wood
Journal: Human Reproduction Update (1998)

The treatment of adenomyosis has been limited by the difficulty and delay associated with the diagnosis, often not until after hysterectomy. Magnetic resonance imaging, high resolution vaginal ultrasound and uterine biopsy have improved early detection of adenomyosis. Drug therapy may be effective in controlling symptoms but the frequent coexistence of endometriosis and the lack of controlled studies make their efficacy difficult to quantify. Conservative surgery involving endomyometrial ablation, laparoscopic myometrial electrocoagulation or excision has proven to be effective in >50% of patients, although follow-up has been restricted to 3 years. Hysterectomy will still be necessary in severe cases of adenomyosis. Early diagnosis may improve treatment. Investigations are indicated in women with menstrual pain or menorrhagia not responding to drug therapy. Key words: adenomyosis/conservative surgery/drug treatment
Bufalin Is a Potent Small-Molecule Inhibitor of the Steroid Receptor Coactivators SRC-3 and SRC-1
Authors: Ying Wang, David M. Lonard, Yang Yu, Dar-Chone Chow, Timothy G. Palzkill, Jin Wang, Ruogu Qi, Alexander J. Matzuk, Xianzhou Song, Franck Madoux, Peter Hodder, Peter Chase, Patrick R. Griffin, Suoling Zhou, Lan Liao, Jianming Xu, Bert W. O'Malley
Journal: Cancer Research (2014)

Virtually all transcription factors partner with coactivators that recruit chromatin remodeling factors and interact with the basal transcription machinery. Coactivators have been implicated in cancer cell proliferation, invasion, and metastasis, including the p160 steroid receptor coactivator (SRC) family composed of SRC-1 (NCOA1), SRC-2 (TIF2/GRIP1/NCOA2), and SRC-3 (AIB1/ACTR/NCOA3). Given their broad involvement in many cancers, they represent candidate molecular targets for new chemotherapeutics. Here, we report on the results of a high-throughput screening effort that identified the cardiac glycoside bufalin as a potent small-molecule inhibitor for SRC-3 and SRC-1. Bufalin strongly promoted SRC-3 protein degradation and was able to block cancer cell growth at nanomolar concentrations. When incorporated into a nanoparticle delivery system, bufalin was able to reduce tumor growth in a mouse xenograft model of breast cancer. Our work identifies bufalin as a potentially broad-spectrum small-molecule inhibitor for cancer.
Role of capsaicin-sensitive afferent nerves in initiation and maintenance of pathological pain
Authors: Gábor Jancsó, Mária Dux, Péter Sántha
Journal: Behavioral and Brain Sciences (1997)

This commentary provides experimental data in support of the critical role of capsaicin-sensitive primary afferent fibers in the initiation and maintenance of pathological pain. The demonstration of capsaicin-induced, centrally-evoked cutaneous hyperalgesia, and of neuroplastic changes elicited by the degeneration of C-fiber primary afferent terminals following peripheral nerve damage, indicates a significant contribution of capsaicin-sensitive sensory ganglion neurons in the development of pathological pain conditions. [coderre &amp; katz]
131I–anti-CD45 antibody plus busulfan and cyclophosphamide before allogeneic hematopoietic cell transplantation for treatment of acute myeloid leukemia in first remission
Authors: John M. Pagel, Frederick R. Appelbaum, Janet F. Eary, Joseph Rajendran, Darrell R. Fisher, Ted Gooley, Katherine Ruffner, Eneida Nemecek, Eileen Sickle, Larry Durack, Jeanette Carreras, Mary M. Horowitz, Oliver W. Press, Ajay K. Gopal, Paul J. Martin, Irwin D. Bernstein, Dana C. Matthews
Journal: Blood (2005)
Phase II Trial of Irinotecan in Children With Relapsed or Refractory Rhabdomyosarcoma: A Joint Study of the French Society of Pediatric Oncology and the United Kingdom Children's Cancer Study Group
Authors: Gilles Vassal, Dominique Couanet, Elizabeth Stockdale, Anne Geoffray, Birgit Geoerger, Daniel Orbach, Fabienne Pichon, Jean Claude Gentet, Susan Picton, Christophe Bergeron, Laura Cisar, Sylvie Assadourian, Bruce Morland
Journal: Journal of Clinical Oncology (2007)

Purpose This phase II study was designed to evaluate the efficacy of irinotecan administered intravenously once every 3 weeks in pediatric patients with recurrent or refractory rhabdomyosarcoma. Patients and Methods A total of 35 patients younger than age 20 years, with refractory or relapsed rhabdomyosarcoma for which standard treatments have failed, received irinotecan at 600 mg/m 2 administered as a 60-minute infusion every 3 weeks. Concomitant treatments included atropine for cholinergic symptoms, loperamide for diarrhea at the first liquid stool, and preventive antiemetic treatment. Tumor response was assessed every two cycles until progression according to WHO criteria. Results The best overall response rate to irinotecan was 11.4% (95% CI, 3.2 to 26.7%; 2.9% complete responses, 8.5% partial responses) from all patients recruited. The median times to progression and survival were 1.4 and 5.8 months, respectively. A total of 112 cycles were administered, with a median number of two cycles per patient (range, 1 to 16). The most common grade 3/4 toxicities were neutropenia (46%), abdominal pain or cramping (17%), cholinergic syndrome (14%), nausea/vomiting (11%), anemia (11%), thrombocytopenia (9%), and diarrhea (6%). Conclusion In heavily pretreated children with a high tumor burden who have been treated with multiagent chemotherapy, irinotecan administered intravenously as a single agent, at 600 mg/m 2 every 3 weeks, showed an interesting objective response rate and a good tolerance profile in rhabdomyosarcoma.
Radiologist Characteristics Associated With Interpretive Performance of Diagnostic Mammography
Authors: Diana L. Miglioretti, Rebecca Smith-Bindman, Linn Abraham, R. James Brenner, Patricia A. Carney, Erin J. Aiello Bowles, Diana S. M. Buist, Joann G. Elmore
Journal: JNCI Journal of the National Cancer Institute (2007)

BackgroundExtensive variability has been noted in the interpretive performance of screening mammography; however, less is known about variability in diagnostic mammography performance.
Spatial reorganization of telomeres in long-lived quiescent cells
Authors: Micol Guidi, Myriam Ruault, Martial Marbouty, Isabelle Loïodice, Axel Cournac, Cyrille Billaudeau, Antoine Hocher, Julien Mozziconacci, Romain Koszul, Angela Taddei
Journal: Genome biology (2015)

The spatiotemporal behavior of chromatin is an important control mechanism of genomic function. Studies in Saccharomyces cerevisiae have broadly contributed to demonstrate the functional importance of nuclear organization. Although in the wild yeast survival depends on their ability to withstand adverse conditions, most of these studies were conducted on cells undergoing exponential growth. In these conditions, as in most eukaryotic cells, silent chromatin that is mainly found at the 32 telomeres accumulates at the nuclear envelope, forming three to five foci. Here, combining live microscopy, DNA FISH and chromosome conformation capture (HiC) techniques, we report that chromosomes adopt distinct organizations according to the metabolic status of the cell. In particular, following carbon source exhaustion the genome of long-lived quiescent cells undergoes a major spatial re-organization driven by the grouping of telomeres into a unique focus or hypercluster localized in the center of the nucleus. This change in genome conformation is specific to quiescent cells able to sustain long-term viability. We further show that reactive oxygen species produced by mitochondrial activity during respiration commit the cell to form a hypercluster upon starvation. Importantly, deleting the gene encoding telomere associated silencing factor SIR3 abolishes telomere grouping and decreases longevity, a defect that is rescued by expressing a silencing defective SIR3 allele competent for hypercluster formation. Our data show that mitochondrial activity primes cells to group their telomeres into a hypercluster upon starvation, reshaping the genome architecture into a conformation that may contribute to maintain longevity of quiescent cells.
Recurrence and Survival Outcomes After Anatomic Segmentectomy Versus Lobectomy for Clinical Stage I Non–Small-Cell Lung Cancer: A Propensity-Matched Analysis
Authors: Rodney J. Landreneau, Daniel P. Normolle, Neil A. Christie, Omar Awais, Joseph J. Wizorek, Ghulam Abbas, Arjun Pennathur, Manisha Shende, Benny Weksler, James D. Luketich, Matthew J. Schuchert
Journal: Journal of Clinical Oncology (2014)

Purpose Although anatomic segmentectomy has been considered a compromised procedure by many surgeons, recent retrospective, single-institution series have demonstrated tumor recurrence and patient survival rates that approximate those achieved by lobectomy. The primary objective of this study was to use propensity score matching to compare outcomes after these anatomic resection approaches for stage I non–small-cell lung cancer. Patients and Methods A retrospective data set including 392 segmentectomy patients and 800 lobectomy patients was used to identify matched segmentectomy and lobectomy cohorts (n = 312 patients per group) using a propensity score matching algorithm that accounted for confounding effects of preoperative patient variables. Primary outcome variables included freedom from recurrence and overall survival. Factors affecting survival were assessed by Cox regression analysis and Kaplan-Meier estimates. Results Perioperative mortality was 1.2% in the segmentectomy group and 2.5% in the lobectomy group (P = .38). At a mean follow-up of 5.4 years, comparing segmentectomy with lobectomy, no differences were noted in locoregional (5.5% v 5.1%, respectively; P = 1.00), distant (14.8% v 11.6%, respectively; P = .29), or overall recurrence rates (20.2% v 16.7%, respectively; P = .30). Furthermore, when comparing segmentectomy with lobectomy, no significant differences were noted in 5-year freedom from recurrence (70% v 71%, respectively; P = .467) or 5-year survival (54% v 60%, respectively; P = .258). Segmentectomy was not found to be an independent predictor of recurrence (hazard ratio, 1.11; 95% CI, 0.87 to 1.40) or overall survival (hazard ratio, 1.17; 95% CI, 0.89 to 1.52). Conclusion In this large propensity-matched comparison, lobectomy was associated with modestly increased freedom from recurrence and overall survival, but the differences were not statistically significant. These results will need further validation by prospective, randomized trials (eg, Cancer and Leukemia Group B 140503 trial).
Antibiotic treatment in patients with low-back pain associated with Modic changes Type 1 (bone oedema): a pilot study
Authors: H B Albert, C Manniche, J S Sorensen, B W Deleuran
Journal: British Journal of Sports Medicine (2008)

Objective: The aim of this study was to assess the clinical effect of antibiotic treatment in a cohort of patients with low-back pain (LBP) and Modic changes Type 1 (bone oedema) following a lumbar herniated disc. Design: This was a prospective uncontrolled trial of 32 LBP patients who had Modic changes and were treated with Amoxicillin-clavulanate (500 mg/125 mg) 3 × day for 90 days. All patients had previously participated in a randomised controlled trial (RCT) that investigated active conservative treatment for a lumbar herniated disc (n = 166). All patients in that RCT who had Modic changes and LBP at 14 months follow-up (n = 37) were invited to participate in this subsequent antibiotic trial but five did not meet the inclusion criteria. Results: 29 patients completed the treatment, as three patients dropped out due to severe diarrhoea. At the end of treatment and at long-term follow-up (mean 10.8 months) there was both clinically important and statistically significant (p⩽0.001) improvement in all outcome measures: LBP intensity, number of days with pain, disease-specific and patient-specific function, and global perceived effect. Conclusions: In this uncontrolled trial, the clinical effect of antibiotic treatment was large in a group of patients with Modic changes suffering from persistent LBP following a disc herniation. These results provide tentative support for a hypothesis that bacterial infection may play a role in LBP with Modic changes and indicate the need for randomised controlled trials to test this hypothesis.
Nuclear Plakoglobin Is Essential for Differentiation of Cardiac Progenitor Cells to Adipocytes in Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Raffaella Lombardi, Maria da Graca Cabreira-Hansen, Achim Bell, Richard R. Fromm, James T. Willerson, A.J. Marian
Journal: Circulation Research (2011)

Rationale: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disease of desmosome proteins characterized by fibroadipogenesis in the myocardium. We have implicated signaling properties of junction protein plakoglobin (PG) in the pathogenesis of ARVC. Objective: To delineate the pathogenic role of PG in adipogenesis in ARVC. Methods and Results: We generated mice overexpressing PG, either a wildtype (PG WT ) or a truncated (PG TR ), known to cause ARVC, in the heart; and PG null (PG −/− ) embryos. PG WT and PG TR mice exhibited fibro-adiposis, cardiac dysfunction, and premature death. Subcellular protein fractionation and immunofluorescence showed nuclear localization of PG WT and PG TR and reduced membrane localization of PG TR . Coimmunoprecipitation showed reduced binding of PG TR but not PG WT to desmosome proteins DSP and DSG2. Transgene PG WT and PG TR were expressed in c-Kit + :Sca1 + cardiac progenitor cells (CPCs) isolated from the hearts of PG WT and PG TR by fluorescence activated cell sorting. CPCs isolated from the transgenic hearts showed enhanced adipogenesis, increased levels of adipogenic factors KLF15, C/EBP-α and noncanonical Wnt5b, and reduced level of CTGF, an inhibitor of adipogenesis. Treatment with BIO activated the canonical Wnt signaling, reversed the proadipogenic transcriptional switch and prevented adipogenesis in a dose-dependent manner. Moreover, c-Kit + CPCs, isolated from PG −/− embryos, were resistant to adipogenesis, expressed high mRNA levels of CTGF and other canonical Wnt signaling targets. Conclusions: Nuclear PG provokes adipogenesis in c-Kit + CPCs by repressing the canonical Wnt signaling and inducing a proadipogenic gene expression. The findings suggest that adipocytes in ARVC, at least in part, originate from c-Kit + CPCs.
Airways inflammation among workers in a paper industry
Authors: R. Rylander, J. Thorn, R Attefors
Journal: European Respiratory Journal (1999)

Exposure to organic dusts may cause airways inflammation in a large proportion of exposed persons. Most studies have relied on questionnaires and spirometry for diagnosis. To assess the possibility of determining the presence of inflammation using clinical diagnostic procedures, a study was undertaken among workers in a paper industry. Participants were 83 workers and 44 controls. Airborne endotoxin and (1--&gt;3)-beta-D-glucan levels at the worksites were determined. The effects of this exposure were evaluated using a questionnaire, spirometry and measurements of airway responsiveness (methacholine) and levels of eosinophil cationic protein (ECP), myeloperoxidase (MPO), and C-reactive protein (CRP) in serum. The workers had a decreased baseline forced expiratory volume in one second (FEV1) and an increased airway responsiveness compared with controls. The concentrations of ECP and MPO were elevated compared with controls. There was a relation between exposure to endotoxin and (1--&gt;3)-beta-D-glucan and airway responsiveness as well as ECP levels, when controlling for age, sex, smoking habits, atopy and asthma. The results suggest an increased prevalence of subjective respiratory symptoms, and an increased airway responsiveness among exposed workers. There was also a relationship between the serum concentration of eosinophil cationic protein and airway responsiveness. Taken together, the results suggest the presence of airways inflammation in the workers.