tbuckley/cabot-search huggingface dataset:
Multiplicity of Benign Breast Lesions Is a Risk Factor for Progression to Breast Cancer
Authors: Maria J. Worsham, Usha Raju, Mei Lu, Alissa Kapke, Jingfang Cheng, Sandra R. Wolman
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Benign breast disease (BBD) in women encompasses a broad spectrum of histopathologic lesions. Studies on BBD have focused on the risks for subsequent breast cancer associated with three broad categories of lesions, classified as nonproliferative, proliferative, or proliferative with atypia, without addressing the issue of the contribution of concurrent multiple BBD lesions. There is very limited information with regard to the issue of BBD lesion multiplicity and breast cancer risk. Experimental Design: We evaluated a detailed microscopic spectrum of 18 BBD lesions from fibrosis to atypical hyperplasia in a BBD cohort of 4,544 subjects, within which 4.5% (n = 201) developed breast cancer during an average follow-up period of 10.3 years. Lesions were defined as nonproliferative (8 diagnoses; risk level 1 = no risk or low risk), proliferative without atypical hyperplasia (8 diagnoses; risk level 2 = intermediate risk), and proliferative with atypical hyperplasia (2 diagnoses; risk level 3 = highest risk level). Twenty variables including age (≥50 or &amp;lt;50 years) at the time of BBD diagnosis and race (African American or non–African American) were assessed. A categorical variable, surrogate for lesion type and number, was represented initially by four levels: 1, nonproliferative = 1 (reference); 2, nonproliferative &amp;gt; 1; 3, proliferative = 1; and 4, proliferative &amp;gt; 1. Results: The majority of BBD subjects in our cohort (almost 70%) had more than one BBD lesion. Concurrent multiple nonproliferative or proliferative BBD lesions with or without atypia in a BBD biopsy and age are significant predictors of risk for progression of BBD to breast cancer. The presence of atypical hyperplasia in a BBD biopsy alone or in conjunction with other lesions without atypia conferred higher risks. Women with fibrosis had a reduced risk for progression to breast cancer. Race was not a significant predictor of progression to breast cancer. The effect of age, fibrosis, and multiple lesions (whether nonproliferative, proliferative, or atypia) on breast cancer progression was not influenced by race. Conclusion: BBD lesion multiplicity is frequent, and teasing out the heterogeneity of multiple concurrent BBD lesions is warranted to refine and improve risk estimates for progression of breast cancer from BBD.
Hyperinsulinemia Inhibits Myocardial Protein Degradation in Patients With Cardiovascular Disease and Insulin Resistance
Authors: Patrick H. McNulty, Rita J. Louard, Lawrence I. Deckelbaum, Barry L. Zaret, Lawrence H. Young
Journal: Circulation (1995)

Background Insulin resistance, hyperinsulinemia, and myocardial hypertrophy frequently coexist in patients. Whether hyperinsulinemia directly affects myocardial protein metabolism in humans has not been examined, however. To test the hypothesis that hyperinsulinemia is anabolic for human heart protein, we examined the effects of insulin infusion on myocardial protein synthesis, degradation, and net balance in patients with ischemic heart disease. Methods and Results Eleven men (aged 57±3 years) with coronary artery disease who had fasted for 12 to 16 hours received a constant infusion of insulin (50 mU · m −2 · min −1 ) while plasma concentrations of glucose and amino acids were kept constant. Rates of myocardial protein synthesis, degradation, and net balance were estimated from steady state extraction and isotopic dilution of L-[ ring -2,6- 3 H]phenylalanine across the heart basally and 90 minutes into infusion. Subjects had elevated fasting plasma insulin concentrations (173±21 pmol/L) and used little exogenous glucose during insulin infusion, suggesting resistance to the effects of insulin on whole-body carbohydrate metabolism. Basally, myocardial protein degradation, as estimated by phenylalanine release (133±28 nmol/min), exceeded protein synthesis, estimated by phenylalanine uptake (31±15 nmol/min), resulting in net negative phenylalanine balance (−102±17 nmol/min). Insulin infusion reduced myocardial protein degradation by 80% but did not affect protein synthesis, returning net phenylalanine balance to neutral. Conclusions Acute hyperinsulinemia markedly suppresses myocardial protein degradation in patients with cardiovascular disease who are resistant to its effects on whole-body glucose metabolism. This antiproteolytic action represents a potential mechanism by which hyperinsulinemia could contribute to the development of myocardial hypertrophy in patients with cardiovascular disease.
A Group of Genome-Based Biomarkers That Add to a Kattan Nomogram for Predicting Progression in Men with High-Risk Prostate Cancer
Authors: Pamela L. Paris, Vivian Weinberg, Giancarlo Albo, Ritu Roy, Catherine Burke, Jeffry Simko, Peter Carroll, Colin Collins
Journal: Clinical Cancer Research (2009)

Abstract Purpose: The three main treatment options for primary prostate cancer are surgery, radiation, and active surveillance. Surgical and radiation intervention for prostate cancer can be associated with significant morbidity. Therefore, accurate stratification predictive of outcome for prostate cancer patients is essential for appropriate treatment decisions. Nomograms that use clinical and pathologic variables are often used for risk prediction. Favorable outcomes exist even among men classified by nomograms as being at high risk of recurrence. Experimental Design: Previously, we identified a set of DNA-based biomarkers termed Genomic Evaluators of Metastatic Prostate Cancer (GEMCaP) and have shown that they can predict risk of recurrence with 80% accuracy. Here, we examined the risk prediction ability of GEMCaP in a high-risk cohort and compared it to a Kattan nomogram. Results: We determined that the GEMCaP genotype alone is comparable with the nomogram, and that for a subset of cases with negative lymph nodes improves upon it. Conclusion: Thus, GEMCaP shows promise for predicting unfavorable outcomes for negative lymph node high-risk cases, where the nomogram falls short, and suggests that addition of GEMCaP to nomograms may be warranted. Clin Cancer Res; 16(1); 195–202
Minimal T-cell requirements for triggering haemophagocytosis associated with Epstein-Barr virus-driven B-cell proliferation: a clinical case study
Authors: T. Daikeler, A. Tzankov, G. Hoenger, O. Gasser, A. Tyndall, A. Gratwohl, C. Hess
Journal: Annals of the Rheumatic Diseases (2011)

The pathophysiology of Epstein–Barr virus (EBV)-associated haemophagocytosis remains poorly understood.1 In EBV-related haemophagocytic lymphohistiocytosis, EBV-infected CD8 T cells and natural killer cells are thought to trigger haemophagocytosis and the associated ‘cytokine-storm’/systemic inflammatory response syndrome (SIRS) directly.2,–,4

By contrast, in the context of uncontrolled proliferation of EBV-infected B cells, hyperactively responding EBV-specific T cells are assumed to mediate haemophagocytosis/SIRS.5 Both the quantity and quality of such deregulated EBV-specific T-cell reactivity remain undefined. Unique insight into basic aspects of the postulated T-cell requirements necessary to trigger haemophagocytosis was provided by the case of a 37-year-old woman with mixed connective tissue disease (ribonucleoprotein-Ab positive, severe pulmonary arterial hypertension, polyarthritis, pericarditis and oesophageal sclerosis). Immunosuppression with azathioprine and ciclosporin, as well as a 3-month trial of oral cyclophosphamide due to progressing pulmonary arterial hypertension was ineffective, yet worsened pre-existing lymphopenia. Based on the severe and cyclophosphamide-resistant course of the disease the indication for haematopoietic stem cell transplantation (HSCT) was established. …
Ankylosing spondylitis in West Africans---evidence for a non-HLA-B27 protective effect
Authors: M A Brown, A Jepson, A Young, H C Whittle, B M Greenwood, B P Wordsworth
Journal: Annals of the Rheumatic Diseases (1997)

<h3>OBJECTIVE</h3> To determine the prevalence of ankylosing spondylitis in the Fula ethnic group in The Gambia, and relate the disease prevalence to the B27 frequency and subtype distribution of that population. <h3>METHODS</h3> 215 first degree relatives of 48 B27 positive Fula twin pairs, and 900 adult Fula males were screened for ankylosing spondylitis by clinical and, where appropriate, radiographic means. The B27 prevalence was determined by PCR/sequence specific oligonucleotides on finger prick samples from 100 unrelated Fula, and B27 subtype distribution by SSCP on unrelated B27 positive individuals. This data were then compared with the prevalence of ankylosing spondylitis among B27 positive Caucasians. <h3>RESULTS</h3> No case of ankylosing spondylitis was seen. Six per cent of Fula are B27 positive, of which 32% are B*2703 and 68% B*2705. Assuming the penetrance of ankylosing spondylitis in B27 positive Fula is the same as in B27 positive Caucasians, the probability of not observing any cases of ankylosing spondylitis among the Fula examined is remote (P = 6.7 × 10<sup>-6</sup>). Similarly, the chance of not seeing any cases among those expected to be either B*2705 or B*2703 was small (P = 3.2 × 10<sup>-4</sup> for B*2705, and P = 0.02 for B*2703). <h3>CONCLUSIONS</h3> The risk of developing ankylosing spondylitis in B27 positive Fula is lower than in B27 positive Caucasians. This is not explained by the B27 subtype distribution among Fula, and suggests the presence of some non-B27 protective factor reducing the prevalence of ankylosing spondylitis in this population.
Evaluation of Food Effect on Pharmacokinetics of Vismodegib in Advanced Solid Tumor Patients
Authors: Manish R. Sharma, Theodore G. Karrison, Bethany Kell, Kehua Wu, Michelle Turcich, David Geary, Soonmo P. Kang, Naoko Takebe, Richard A. Graham, Michael L. Maitland, Richard L. Schilsky, Mark J. Ratain, Ezra E.W. Cohen
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Vismodegib, an orally bioavailable small-molecule Smoothened inhibitor, is approved for treatment of advanced basal cell carcinoma (BCC). We conducted a pharmacokinetic study of vismodegib in patients with advanced solid tumors to explore the effects of food on drug exposure. Experimental Design: In part I, patients were randomized to fasting overnight (FO), a high fat meal (HF), or a low fat meal (LF) before a single dose of vismodegib 150 mg. Plasma concentrations of vismodegib were determined by a validated liquid chromatography-tandem mass spectrometry assay. Primary endpoints were Cmax and area under the curve (AUC0–168). In part II, patients randomized to FO or HF in part I took vismodegib 150 mg daily after fasting; those randomized to LF took it after a meal. Primary endpoints after two weeks were Cmax and AUC0–24. Results: Sixty (22 FO, 20 HF, 18 LF) and 52 (25 fasting, 27 fed) patients were evaluable for primary endpoints in parts I and II, respectively. Mean Cmax and AUC0–168 after a single dose were higher in HF than FO patients [ratios of geometric means (90% CI) = 1.75 (1.30, 2.34) and 1.74 (1.25, 2.42), respectively]. There were no significant differences in Cmax or AUC0–24 between fasting and fed groups after daily dosing. The frequencies of drug-related toxicities were similar in both groups. Conclusions: A HF meal increases plasma exposure to a single dose of vismodegib, but there are no pharmacokinetic or safety differences between fasting and fed groups at steady-state. Vismodegib may be taken with or without food for daily dosing. Clin Cancer Res; 19(11); 3059–67. ©2013 AACR.
Induction of delayed-type hypersensitivity to azobenzenearsonate by a monoclonal anti-idiotype antibody.
Authors: W R Thomas, G Morahan, I D Walker, J F Miller
Journal: The Journal of Experimental Medicine (1981)

Azobenzenearsonate (ABA)-specific sensitivity was induced in A/J mice by injecting a monoclonal anti-idiotype reagent, 14A, directed against a determinant present on a minor subpopulation of immunoglobulin molecules within the anti-ABA antibodies of A/J mice. Sensitivity was transferrable by purified T cells and this was abrogated by treating the cells with 14A, rabbit anti-mouse immunoglobulin and complement, not by treatment with only the last two reagents. The transfer was restricted by the K-end of the major histocompatibility complex.
Is Dual-Chamber Programming Inferior to Single-Chamber Programming in an Implantable Cardioverter-Defibrillator?
Authors: Brian Olshansky, John D. Day, Stephen Moore, Lawrence Gering, Murray Rosenbaum, Maureen McGuire, Scott Brown, Darin R. Lerew
Journal: Circulation (2006)

The INTRINSIC RV (Inhibition of Unnecessary RV Pacing with AVSH in ICDs) study tested the hypothesis that dual-chamber rate-responsive (DDDR) with atrioventricular search hysteresis (AVSH) 60-130 programming is not inferior to single-chamber (VVI)-40 programming in an implantable cardioverter defibrillator with respect to all-cause mortality and heart failure hospitalizations using an equivalence margin of 5%.At 108 centers, 1530 patients with an implantable cardioverter defibrillator indication received a VITALITY AVT (Guidant Corporation, St. Paul, Minn) implantable cardioverter defibrillator programmed consistently to DDDR AVSH 60-130 for the first week. Of those, 988 patients with <20% right ventricular pacing at 1 week were randomized to DDDR AVSH 60-130 or to VVI-40 programming. Among those randomized, 502 were assigned to DDDR AVSH and 486 to VVI. Groups were similar with regard to coronary disease (68%), gender (21% female), and New York Heart Association functional class >I (79%). A total of 32 patients (6.4%) in the DDDR AVSH arm and 46 patients (9.5%) in the VVI arm died or were hospitalized for heart failure during a mean follow-up of 10.4 months (relative risk=0.67, P=0.072 in favor of DDDR AVSH). DDDR AVSH was not inferior to VVI programming (P<0.001). All-cause mortality was not significantly different between the DDDR AVSH arm (3.6%) and the VVI arm (5.1%; P=0.23). The mean percent right ventricular pacing in the DDDR AVSH arm was 10% (median 4%) versus 3% (median 0%) in the VVI arm.In the INTRINSIC RV trial, among those randomized, DDDR AVSH was associated with similar outcomes as with VVI backup pacing.
IPRONIAZID (MARSILID): ITS USE IN OFFICE TREATMENT OF DEPRESSION
Authors: WILSON G. SCANLON, WILLIAM M. WHITE
Journal: American Journal of Psychiatry (1958)

1. Judicious management of the iproniazid dosage and of the patient's activities so as to prevent syncope, makes usage of the drug safer, avoids the majority of reported adverse side-effects, and still provides the blood stream and spinal fluid with a sufficient titer to produce a salutary effect on mood. 2. It is our impression that iproniazid is most effective and produces fewer side-effects in cases of uncomplicated depression. 3. The rapid and sustained response of the patients who required ECT suggests that ECT and iproniazid are synergistic.
Prospective Study of Wide Excision Alone for Ductal Carcinoma in Situ of the Breast
Authors: Julia S. Wong, Carolyn M. Kaelin, Susan L. Troyan, Michele A. Gadd, Rebecca Gelman, Susan C. Lester, Stuart J. Schnitt, Dennis C. Sgroi, Barbara J. Silver, Jay R. Harris, Barbara L. Smith
Journal: Journal of Clinical Oncology (2006)

Purpose It has been hypothesized that wide excision alone with margins ≥ 1 cm may be adequate treatment for small, grade 1 or 2 ductal carcinoma in situ (DCIS). To test this hypothesis, we conducted a prospective, single-arm trial. Methods Entry criteria included DCIS of predominant grade 1 or 2 with a mammographic extent of ≤ 2.5 cm treated with wide excision with final margins of ≥ 1 cm or a re-excision without residual DCIS. Tamoxifen was not permitted. The accrual goal was 200 patients. Results In July 2002, the study closed to accrual at 158 patients because the number of local recurrences met the predetermined stopping rules. The median age was 51 and the median follow-up time was 40 months. Thirteen patients developed local recurrence as the first site of treatment failure 7 to 63 months after study entry. The rate of ipsilateral local recurrence as first site of treatment failure was 2.4% per patient-year, corresponding to a 5-year rate of 12%. Nine patients (69%) experienced recurrence of DCIS and four (31%) experienced recurrence with invasive disease. Twelve recurrences were detected mammographically and one was palpable. Ten were in the same quadrant as the initial DCIS and three were elsewhere within the ipsilateral breast. No patient had positive axillary nodes at recurrence or subsequent metastatic disease. Conclusion Despite margins of ≥ 1 cm, the local recurrence rate is substantial when patients with small, grade 1 or 2 DCIS are treated with wide excision alone. This risk should be considered in assessing the possible use of radiation therapy with or without tamoxifen in these patients.
Major Vascular Anomalies in Turner Syndrome
Authors: Vincent B. Ho, Vladimir K. Bakalov, Margaret Cooley, Phillip L. Van, Maureen N. Hood, Thomas R. Burklow, Carolyn A. Bondy
Journal: Circulation (2004)

Turner syndrome (TS) is associated with aortic coarctation and dissection; hence, echocardiographic evaluation of all patients is currently recommended. X-ray angiography in clinically symptomatic patients has suggested a range of other vascular anomalies, but the true prevalence of such lesions in TS is unknown. To better understand the prevalence and pathogenesis of cardiovascular defects in TS, we prospectively evaluated a group of asymptomatic adult volunteers with TS using magnetic resonance (MR) angiography.A total of 85 adults with TS and 27 normal female adult volunteers underwent gadolinium-enhanced 3D MR angiography. A high prevalence of aortic anomalies was seen in women with TS, including elongation of the transverse arch (49%), aortic coarctation (12%), and aberrant right subclavian artery (8%). Venous anomalies were also prominent, including persistent left superior vena cava (13%) and partial anomalous pulmonary venous return (13%). None of these anomalies were found in healthy female controls. The constellation of elongation of the transverse arch, aortic coarctation, and persistent left superior vena cava was significantly associated with women with TS. Neck webbing and increased thoracic anterior-to-posterior dimension diameters were strong predictors for arterial and venous anomalies.Thoracic vascular anomalies are common in TS, occurring in approximately 50% of a group not preselected for cardiovascular disease. The highly significant association between neck webbing, increased chest diameter, and these vascular anomalies suggests that in utero, centrally localized lymphatic obstruction may contribute to these cardiovascular deformities in TS. Improved recognition of these often-undetected vascular lesions may be important for identification of patients in need of closer cardiovascular monitoring.
The relationship between changes in interstitial creatine kinase and game-related impacts in rugby union
Authors: D J Smart, N D Gill, C M Beaven, C J Cook, A J Blazevich
Journal: British Journal of Sports Medicine (2007)

The primary purpose of this study was to investigate the relationship between the pre-game to post-game changes in creatine kinase concentration (Delta[CK]) and impact-related game statistics in elite rugby union players.Twenty-three elite male rugby union players each provided interstitial fluid samples obtained via electrosonophoresis (ESoP) 210 min before and within a maximum time of 30 min after up to five rugby union games. Specific game statistics that were deemed to be important in determining the relationship between impact and [CK] were obtained from AnalyRugby software for each individual player. Regression equations to predict Delta[CK] from game statistics were created using a backwards random-effects maximum likelihood regression.The Delta[CK] (mean (SD)) from pre-game to post-game was 926.8 (204.2) IU. Game time and time defending were significantly correlated to Delta[CK] in both the forwards and backs. The predicted Delta[CK] (mean (95% confidence limit)) was 1439.8 (204.9) IU for the forwards and 545.3 (78.0) IU for the backs and was significantly correlated with the actual Delta[CK] (r = 0.69 and r = 0.74).CK increased from pre-game to post-game in a position-specific manner. A large proportion of the Delta[CK] can be explained by physical impact and thus can be predicted using a prescribed number of game statistics. As the Delta[CK] is an indicator of muscle damage, the prediction of Delta[CK] provides a theoretical basis for recovery strategies and adjustment of subsequent training sessions after rugby union games.
How to rehabilitate an athlete with low back pain
Authors: Rusu Ligia
Journal: British Journal of Sports Medicine (2011)

Lecture 12 Low back pain is one of the most common cause of loss playing time at athletes. The best rehabilitation in low back pain can be considered the early prevention. In the case of injury is important to know and to understanding the phases of rehabilitation and needed. At the level of low back during its motions is important to know the kinetic and kinematics aspects. The kinematics of spinal flexion and extension are associated with a shifting instantaneous axis of rotation. Spinal kinetics at athletes includes intrinsic and extrinsic forces that can affect the spine. The sources of low back pain include the intervertebral disc, nerve roots, sacroiliac joints, ligamentous, muscular tissue. Assessment begins with history of pain and relation with sport activity, location of the pain in relation with body position, walking, effort, daily moment and also progressivity. In assessment we include clinical examination of the entire kinetic chain of the spine, by assess the posture, mobility and also using some specific tests like: Gielett, Faber, Thomas, Gaenslen completed by imaging evaluation (MRI, plain radiographs, bone scan, CT scan). Most common causes of low back pain to athletes are: fractures, acute disc herniations, muscular contusions and strain or degenerative disc diseases, spondylolysis, spondylolisthesis, facet syndrome, lordotic posture, sacroiliac inflammation. Rehabilitation depends of how we understanding the involved sports and according to the injury. Are three phases: acute and subacute, rehabilitative phase and sport specific rehabilitation. Medication includes non-steroidal anti-inflammatory drugs (NSAIDs) and also brace, manipulation. Acute and subacute phase: propose few days of rest, icing, ultrasounds, iontophoresis, laser therapy and brace. In subacute phase is possible aerobic activity in the pool. For entire period we recommend isometric contraction for abdominal and extensors muscle. Rehabilitative phase: in this phase we prefer core stabilisation and depend of pathology mechanism, we shall promote flexion or extension programme, for obtain neutral zone that involves comfortable spinal motion. We begin the closed chain strengthening and co-activated muscular coordination for improvement muscle balance. In second part of rehabilitation phase, the programme depends of sports activity, because the core have to transfer the forces from lowers limbs to uppers limbs or to generate forces and recoil forces. For this the athletes must to make these motions. Sport specific rehabilitation is the third phase and prepare the returning to sport activity. So, are specific programmes for dancers, gymnasts, golf and racquet sports, football, throwing, weightlifters. The programmes must to involve decrease of stress forces at the back, to maintain the static of spine and decrease the disc injuries. All of these programmes have to be included in the training programmes for minimising recurrence and improve sport performance.