tbuckley/cabot-search huggingface dataset:
Outcome after invasive local recurrence in patients with ductal carcinoma in situ of the breast.
Authors: M J Silverstein, M D Lagios, S Martino, B S Lewinsky, P H Craig, P J Beron, P Gamagami, J R Waisman
Journal: Journal of Clinical Oncology (1998)

To detail the outcome, in terms of local recurrence, local invasive recurrence, distant recurrence, and breast cancer mortality for patients previously treated for ductal carcinoma in situ (DCIS).Clinical, pathologic, and outcome data were collected prospectively for 707 patients with DCIS accrued from 1972 through June 1997.There were 74 local recurrences; 39 were noninvasive (DCIS) and 35 were invasive. Fifty-one percent of patients with invasive recurrences presented with stage 1 disease; the remainder presented with more advanced disease. Invasive local recurrence after mastectomy was a rare event that occurred in 0.8% of patients. Invasive recurrence after breast preservation was more common and occurred in 7.4% of patients. The 8-year probability of breast cancer mortality after breast preservation was 2.1%, a number that is likely to increase with longer follow-up. The 8-year breast cancer-specific mortality and distant-disease probability for the subgroup of 74 patients with locally recurrent disease was 8.8% and 20.8%, respectively. If only the 35 invasive recurrences are considered as events, the 8-year breast cancer-specific mortality and distant-disease probability was 14.4% and 27.1%, respectively.Invasive local recurrence after breast-preservation treatment for patients with DCIS is a serious event that converts patients with previous stage 0 disease to patients with disease that ranges from stage I to stage IV. These results, however, indicate that most DCIS patients with local recurrence can be salvaged.
Pneumococcal Prevention Gets Older and Wiser
Authors: Anne Schuchat
Journal: JAMA Internal Medicine (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA 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
Phenotyping of Staphylococcus aureus reveals a new virulent ST398 lineage
Authors: T. Schmidt, J. Zündorf, T. Grüger, K. Brandenburg, A.-L. Reiners, J. Zinserling, W. Witte, N. Schnitzler
Journal: Clinical Microbiology and Infection (2012)

Staphylococcus aureus sequence type (ST)398, which is commonly found as a colonization strain in pig farming, is emerging more frequently as the cause of human infections. In this study, we analysed ST398 of porcine and human origin at the genetic, protein and immunogenic levels. Although genetic analysis of the genes encoding the major virulence factors revealed the presence of the same genes in all strains studied, the results demonstrated spa type crossing alterations in adhesion abilities in addition to a strongly enhanced lysis activity directly linked to impaired clearance attributable to polymorphonuclear leukocytes (PMNs). This change in virulence pattern indicates high heterogenicity in the ST398 pool that is not based on a different genetic make-up, but probably on variations in the genetic regulation systems. These modifications, which are tightly connected to pathogenicity, cannot be detected by conventional diagnostic methods.
Work of inflation is the best correlate to lung fibrosis induced by bleomycin in mice
Authors: Jonathan E. Phillips, Ruoqi Peng, Gaurav Tyagi, Rosario Garrido, Lisa Burns, Paul Harris, Jay S. Fine, Christopher S. Stevenson
Journal: European Respiratory Journal (2011)

Introduction:  Bleomycin (BLM) induces a transient lung fibrosis that has been used to investigate mechanisms related to idiopathic pulmonary fibrosis. Our aim was to determine the method for assessing lung function that provided the strongest correlation to the lung fibrosis.   Methods:  BLM (2U/kg) or saline was intratracheally microsprayed to male, C57BL/6 mice under isofluorane. Lung function was assessed using the flexivent system and after euthanasia, lungs were inflated in situ under a constant pressure of 25 cm H2O starting 1–35d after BLM administration (n=8). Right and left lung sections, stained with Masson9s trichrome, were graded for fibrosis (0-4, i.e. no fibrosis to severe) and the scores were combined (0-8).   Results:  Lung fibrosis scores were progressive 1-14d after BLM challenge. From 14-35d, the fibrosis scores did not significantly change. Lung function changes were more subtle and no significant changes in resistance or elastance were observed at 21d post-BLM. The only significant change occurred in work of inflation (WoI).  Compared to other indicators of lung function, WoI showed the most significant correlation to fibrotic score with the highest Pearson correlation coefficient = 0.74 (P    Conclusion:  Scores for lung fibrosis are the robust indicator of BLM-induced changes to the lung. Although changes in lung function were less obvious, WoI provided a greatest level of precision to detect significant changes.
Spontaneous Maturation and Differentiation of B16 Melanoma Cells in Culture2
Authors: John W. Kreider, Mary E. Schmoyer
Journal: JNCI Journal of the National Cancer Institute (1975)

B16 melanoma tumors and cultures are composed of cells with different melanin contents and replicative activities. The hypothesis was tested in vitro that these various cells constituted a population in the process of differentiation and maturation. Early cultures were predominantly composed of small, amelanotic cells with high replicative activity. Older cultures contained mostly larger and heavily melanotic cells with little or no replicative activity. Replicative activity, as measured by the uptake of tritiated thymidine, was inversely proportional to cell size and melanin content. Colony-forming ability was impaired if the original cells were melanotic. Tumorigenicity was unaffected except in very old (9-day) cultures. Our results support the concept that malignant melanocytes undergo a sequence of developmental changes which eventuates in the production of mature cells characterized by enlargement, elevated melanin content, and reduced replicative and colony-forming capacity.
Adherence to a dietary fat intake reduction program in postmenopausal women receiving therapy for early breast cancer. The Women's Intervention Nutrition Study.
Authors: R T Chlebowski, G L Blackburn, I M Buzzard, D P Rose, S Martino, J D Khandekar, R M York, R W Jeffery, R M Elashoff, E L Wynder
Journal: Journal of Clinical Oncology (1993)

PURPOSE To evaluate the feasibility of integrating a program based on dietary fat intake reduction into adjuvant treatment strategies for postmenopausal women receiving therapy for early breast cancer. PATIENTS AND METHODS Two hundred ninety postmenopausal women with localized (stage I to IIIa) breast cancer receiving conventional systemic therapy provided informed consent and were randomized in a multicenter trial to either a dietary intervention group receiving a program of individualized instruction for reducing total fat intake or a dietary control group with minimal dietary counseling. RESULTS Significantly reduced (P &lt; .001) fat intake (in terms of percent calories derived from fat) was observed in the intervention group versus the control group at 3 months (20.3% +/- 2.4% v 31.5% +/- 2.6%, mean +/- SD, respectively) and maintained throughout 24 months of observation. The 50% reduction in daily fat-gram intake (from 66 +/- 23 to 33 +/- 14 g, P &lt; .001) seen at 6 months was associated with reduced saturated fat, monounsaturated fat, polyunsaturated fat, and linoleic acid (P &lt; .001). Significantly lower body weight was also seen in intervention compared with control patients at all observation periods, resulting in a 3.3-kg weight difference 18 months after randomization (P &lt; .001). CONCLUSION Substantial and sustained dietary fat reduction with associated weight change can be achieved at relatively low cost within the context of conventional multimodality clinical management of postmenopausal women with localized breast cancer. This result supports the feasibility of conducting a full-scale evaluation of the influence of dietary fat intake reduction on the clinical outcome of breast cancer patients.
Optimal duration of dual antiplatelet therapy after drug eluting stent remains unclear
Authors: S. Mayor
Journal: BMJ (2015)

Longer duration of dual antiplatelet therapy after implantation of a drug eluting stent is associated with fewer myocardial infarctions but more major bleeding than a shorter duration, a systematic review has found.

Current guidelines recommend six or 12 months of treatment with aspirin plus a P2Y12 inhibitor (clopidogrel, ticagrelor, or prasugrel) to reduce the risk of stent thrombosis. But the optimal duration of therapy …
Serum microRNAs explain discordance of non-alcoholic fatty liver disease in monozygotic and dizygotic twins: a prospective study
Authors: Amir Zarrinpar, Shakti Gupta, Mano R Maurya, Shankar Subramaniam, Rohit Loomba
Journal: Gut (2015)

<h3>Objective</h3> In the setting where two individuals are genetically similar, epigenetic mechanisms could account for discordance in the presence or absence of non-alcoholic fatty liver disease (NAFLD). This study investigated if serum microRNAs (miRs) could explain discordance in NAFLD. <h3>Design</h3> This is a cross-sectional analysis of a prospective cohort study of 40 (n=80) twin-pairs residing in Southern California. All participants underwent a standardised research visit, liver MRI using proton-density fat fraction to quantify fat content and miR profiling of their serum. <h3>Results</h3> Among the 40 twin-pairs, there were 6 concordant for NAFLD, 28 were concordant for non-NAFLD and 6 were discordant for NAFLD. The prevalence of NAFLD was 22.5% (18/80). Within the six discordant twins, a panel of 10 miRs differentiated the twin with NAFLD from the one without. Two of these miRs, miR-331-3p and miR-30c, were also among the 21 miRs that were different between NAFLD and non-NAFLD groups (for miR-331-3p: 7.644±0.091 vs 8.057±0.071, respectively, p=0.004; for miR-30c: 10.013±0.126 vs 10.418±0.086, respectively, p=0.008). Both miRs were highly heritable (35.9% and 10.7%, respectively) and highly correlated with each other (R=0.90, p=2.2×10<sup>−16</sup>) suggesting involvement in a common mechanistic pathway. An interactome analysis of these two miRs showed seven common target genes. <h3>Conclusions</h3> Using a novel human twin-study design, we demonstrate that discordancy in liver fat content between the twins can be explained by miRs, and that they are heritable.
Interobserver variability on the histopathologic diagnosis of cutaneous melanoma and other pigmented skin lesions.
Authors: R Corona, A Mele, M Amini, G De Rosa, G Coppola, P Piccardi, M Fucci, P Pasquini, T Faraggiana
Journal: Journal of Clinical Oncology (1996)

PURPOSE To assess the interobserver agreement on the diagnosis and classification of cutaneous melanoma. MATERIALS AND METHODS A set of 140 slides of cutaneous melanoma, including a small subset of benign pigmented skin lesions, were circulated to four experienced histopathologists. The kappa statistic for multiple ratings per subject was calculated using the method described by Fleiss. RESULTS The kappa value on the diagnosis of cutaneous melanoma versus benign lesions was 0.61. There was some discordance on the diagnosis in 37 of 140 cases (26%). For the histopathologic classification of cutaneous melanoma, the highest kappa values were attained for Breslow thickness (kappa = 0.76) and presence of ulceration (kappa = 0.87). The agreement was generally poor for other histologic features, such as level of dermal invasion (kappa = 0.38), presence of regression (kappa = 0.27), and lymphocytic infiltration (kappa = 0.27). CONCLUSION Our study suggests considerable disagreement among pathologists on the diagnosis of melanoma versus other pigmented lesions. Tumor thickness and presence of ulceration are the most reproducible histologic features of cutaneous melanoma.
A phase I study of temsirolimus in combination with metformin in advanced solid tumors
Authors: Mary Jean Mackenzie, Eric Winquist, Scott Ernst, Craig Johnson, Paul O'Brien
Journal: Clinical Cancer Research (2008)

AACR Centennial Conference: Translational Cancer Medicine-- July 20-23, 2008; Monterey, CA

B1 

Background: Temsirolimus is an intravenous inhibitor of mammalian target of rapamycin (mTOR). Metformin has been recently observed to have anti-tumor activity in in vitro and in vivo studies, likely through activation of adenosine monophosphate kinase (AMPK). The molecular pathways targeted by these two agents both affect cellular glucose metabolism and cell proliferation. Dual inhibition of the AMPK-TSC protein-mTOR pathway by both metformin and temsirolimus would be a novel strategy to enhance the antitumour activity of temsirolimus. The additional downregulation of the involved pathways may overcome the resistance to temsirolimus that is seen in most clinical cancers. Initial in vitro evidence in support of the combination of mTOR inhibition and AMPK activation has been published by other authours.    We have undertaken a phase I, open label dose-escalation trial to establish the maximum tolerated dose and recommended phase II dose of the combination of intravenous temsirolimus and oral metformin in patients with advanced solid cancers.    Methods: Eligible patients include those with histologically confirmed advanced solid tumors who are either not eligible for, or have declined, further standard therapy. Patients must have adequate hematologic and biochemical parameters and measurable disease by RECIST criteria. Patients must be non-diabetic, with normal creatinine clearance and no unstable central nervous system metastases.    Treatment: This is a standard dose-escalation phase I trial with planned dose escalation as noted below    Patients will be monitored for clinical, hematologic and biochemical toxicity according to NCI CTCAE criteria. Radiologic response to treatment will be assessed by RECIST criteria. Dose escalation cohorts will be accrued in a standard Fibonnaci sequence until maximum tolerated dose is achieved.    Results: Thus far, the first cohort of three patients has been enrolled on study, and one patient has actually received treatment. This one patient has experienced a grade 3 mucositis, diarrhea, and skin toxicity, without significant hematologic toxicity. Updated toxicity data will be presented.
Influence Of Concomitant NSAID Or ASA On The Efficacy and Safety Of Dabigatran Versus Warfarin For The Treatment Of Acute Venous Thromboembolism: A Pooled Analysis From RE-Cover and RE-Cover II
Authors: Sam Schulman, Henry Eriksson, Samuel Z Goldhaber, Ajay Kakkar, Clive Kearon, Sebastian M Schellong, Martin Feuring, Nuala Peter, Jeffrey Friedman
Journal: Blood (2013)
C-reactive protein in pulmonary tuberculosis-correlation with extent and severity of the disease
Authors: Nelson Teixeira, Hans Dabó, Isabel Gomes, Agostinho Marques
Journal: European Respiratory Journal (2012)

Background: Pulmonary tuberculosis (PT) presents a broad clinical spectrum. C-reactive protein (CRP) has been identified as a possible marker of severity in this disease.  Aims: To assess the role of CRP in patients admitted for PT and its relation with radiological extent, bacterial load, hospital stay and mortality.  Methods: We retrospectively evaluated 201 adult patients admitted in a tertiary hospital for PT without HIV infection (2007-2011). Demographic, clinical, analytical and radiological data as well as hospital evolution were studied. Patients were categorized according to radiological extent (National Tuberculosis Association classification) and initial bacterial sputum load (ATS criteria). For statistical analysis, Spearman correlation coefficient, analysis of variance ANOVA and Bonferroni test were used, with SPSS18 support.  Results: Most were male (74,3%), mean age 53,5 yrs. Sputum smear on admission was negative in 39,8%; in these, CRP was significantly lower (mean: 82.1 mg/L) than in smear-positive patients (mean: 114.5 mg/L), p=0.003. However, CRP did not increase with higher bacterial load (p=0.113). CRP values increased significantly with more extensive disease on chest X-ray (Est.I: 61.7mg/L; Est.II: 109,9mg/L; Est.III: 170.8mg/L), p=0.000. A positive correlation between CRP value and hospital mortality was found (r=0.141, p=0.027) but not with duration of hospitalization (p=0.065).  Conclusions: CRP may play an important role as an indicator of the extent and severity of PT and showed prognostic value for short term mortality of the disease. Studies including ambulatory patients may help defining its role in identifying those who need to escalate health care.
Murine Leukemia Virus-Associated Cell Surface Antigens in Rats Neonatally Infected With Gross Murine Leukemia Virus&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: R S Basch, D Grausz, N Harris, N A Mitchison
Journal: JNCI Journal of the National Cancer Institute (1979)

The inoculation of newborn W/F, Lew, AS and DA rats with Gross murine leukemia virus (G-MuLV) resulted in the prompt appearance of cells with viral protein antigens (VPA) on their surfaces. These were first found in the bone marrow and spleen and later in the thymus gland. As the animals developed, the VPA-positive population expanded and the intensity of the fluorescence increased. In the spleen, the cells with the strongest fluorescence had the properties of T-cells, but in both spleen and bone marrow low levels of VPA were found on non-T-cells. The VPA-positive population expanded long before malignant cells could be detected and, in most animals, the entire T-cell compartment became antigen-positive. These animals were unable to respond to G-MuLV antigens and many eventually developed leukemia. However, some animals apparently broke the tolerance that followed neonatal infection and eliminated VPA-positive cells from their tissues
Abstract 17942: A Novel Transgenic Pig Model Overexpressing Ectonucleoside Triphosphate Diphosphohydrolase 1 (entpd-1/cd39) Demonstrates Reduced Myocardial Injury
Authors: Shouvik Mahamud, Debra G Wheeler, Matthew Jospeh, Karen M Dwyer, Mark B Nottle, Sharon J Harrison, Simon C Robson, Peter J Cowan, Anthony J d'Apice, Richard J Gumina
Journal: Circulation (2011)

Background: Ectonucleoside Triphosphate Diphosphohydrolase-1 (ENTPD-1/CD39) rapidly converts ATP and ADP to AMP which is further degraded by ecto-5’-nucleotidase (CD73) to adenosine, an anti-thrombotic, vasodilatory and cardiovascular protective mediator. The objective was to determine whether overexpression of ENTPD1 reduces myocardial ischemia-reperfusion injury in a large animal model of myocardial injury. Methods: Transgenic pigs expressing human ENTPD-1 under the control of the H-2Kb promoter were generated via somatic cell nuclear transfer. Myocardial ischemia-reperfusion (I/R) injury was evaluated in transgenic pigs overexpressing human ENTPD1 (CD39). I/R injury was induced by intracoronary balloon inflation in the left anterior descending (LAD) artery for 60 min followed by 3 hours of reperfusion. Myocardial infarct size was determined by staining with triphenyl tetrazolium chloride (TTC) and the area-at-risk was delineated by perfusion with 5% Phthalo Blue. For all assessments the operator was blinded to animal genotype. Results: Expression of ENTPD1 in the cardiac tissue was confirmed by Western analysis and immunohistochemistry. In response to 60 minutes of left anterior artery ischemia followed by 3 hours of reperfusion, ENTPD1 animals displayed a marked reduction in infarct size compared to wild-type littermate controls (WT: 44.7±5.2% vs ENTPD1: 17.2±4.3%; Figure). Conclusions: Overexpression of human ENTPD1 significantly attenuates myocardial infarction in a novel large animal transgenic model of myocardial ischemia-reperfusion injury.
Co-dispensing of inhaled corticosteroids and antibiotics
Authors: Helen Reddel, Leanne Poulos, Rosario Ampon, Guy Marks
Journal: European Respiratory Journal (2012)

Background:   Regular use of inhaled corticosteroids (ICS) is recommended for management of asthma and moderate/severe COPD. However, in Australia, most people who receive any ICS-containing medication have it dispensed only once in a year. We tested the hypothesis that ICS are commonly prescribed for respiratory infections in patients without chronic airways disease.    Methods:   Data for concessional patients dispensed any respiratory medications during 2008 were obtained from the national Pharmaceutical Benefits Scheme. Individuals dispensed ICS only once in a year, and no other respiratory medications (defined as  ICS), were assumed to be unlikely to have asthma or COPD, and co-dispensing with oral antibiotics suggested the ICS were prescribed for symptoms of a respiratory infection. We calculated the proportion of people prescribed one-off ICS who were co-dispensed oral antibiotics.    Results:   In 2008, 43.6% of the 115,763 patients who were dispensed one-off ICS were co-dispensed oral antibiotics. Co-dispensing was seasonal, peaking in winter. In adults, the co-dispensing phenomenon was most commonly observed for moderate/high dose ICS/LABA, while lower doses of ICS alone were co-dispensed among children. In this cohort, the cost to government of one-off ICS, when co-dispensed with oral antibiotics, was $2.7 million/year.    Conclusions:   Many people who receive one-off ICS prescriptions do not appear to have airways disease. As indicated by co-prescribing of antibiotics, many people may be inappropriately prescribed ICS for management of respiratory infections. Interventions are required to improve the quality of prescribing of ICS and management of respiratory infections in clinical practice.