tbuckley/cabot-search huggingface dataset:
The patient perspective on remission in rheumatoid arthritis: ‘You've got limits, but you're back to being you again’
Authors: Lilian H D van Tuyl, Sarah Hewlett, Martina Sadlonova, Bev Davis, Caroline Flurey, Wijnanda Hoogland, John Kirwan, Tessa Sanderson, Dirkjan van Schaardenburg, Marieke Scholte-Voshaar, Josef Smolen, Tanja Stamm, Maarten Boers
Journal: Annals of the Rheumatic Diseases (2014)

Objectives The aim of rheumatoid arthritis (RA) treatment is remission. As treatment should be targeted at outcomes relevant to patients, it is important to understand how patients perceive remission, and to assess whether the current definition of remission adequately reflects these perceptions. The objective of this study is to explore the patient perspective on remission in RA. Methods Nine focus-group discussions in Austria, The Netherlands and UK were conducted, including patients in American College of Rheumatology (ACR)/ European League of Rheumatology (EULAR) remission, self-declared remission and in moderate/high disease activity. Moderators employed a prespecified interview guide helped to engage patients in a discussion on their experience with remission. Inductive thematic analysis was performed within each country, and identified themes were discussed across countries. Results 47 RA patients (66% women, disease duration 9 years) participated. Three major themes of patient-perceived remission emerged: (1) symptoms would either be absent or strongly reduced, (2) impact of the disease on daily life would diminish by increased independence, ability to do valued activities, improved mood and ability to cope; (3) leading to a return to normality, including work, family role and perception of others. Patients felt the concept of remission was influenced by ageing, side effects of medication, comorbidities, accrued damage to joints and disease duration. Opinions on duration of state, the role of medication and measurement instruments varied widely. Conclusions Patients characterise remission by the absence or reduction of symptoms, but more directly by decreased daily impact of their condition and the feeling of a return to normality. The next step is to study whether an additional patient-perceived measure of remission may add value to the ACR/EULAR definition of remission.
Elaboration of Type-1 Plasminogen Activator Inhibitor From Adipocytes
Authors: Craig H. Lundgren, Steven L. Brown, Thomas K. Nordt, Burton E. Sobel, Satoshi Fujii
Journal: Circulation (1996)

Background Obesity is known to predispose to attenuated fibrinolysis attributable to increased concentrations in plasma of type-1 plasminogen activator inhibitor (PAI-1), the primary physiological inhibitor of endogenous fibrinolysis. PAI-1 is present in neointimal vascular smooth muscle cells and lipid-laden macrophages. Methods and Results The present study was designed to determine whether PAI-1 expression occurs in adipose tissue as well, thereby potentially contributing to increased cardiovascular risk associated with obesity. 3T3-L1 preadipocytes were differentiated into adipocytes by exposing them to isobutylxanthine (0.5 mmol/L) and dexamethasone (0.25 μmol/L) over 7 days and incubated for 24 hours with transforming growth factor-β (TGF-β), known to augment PAI-1 synthesis in several cell types and to be released from platelets when they are activated. TGF-β increased PAI-1 activity in the conditioned media of the 3T3-L1–derived cells in a concentration-dependent fashion without significantly affecting cell proliferation. Western blotting and immunoprecipitation of 35 S-labeled PAI-1 showed that the increased PAI-1 activity paralleled increased PAI-1 protein. Northern blotting showed that increased PAI-1 mRNA preceded increased accumulation of PAI-1 activity and protein in the conditioned media. Furthermore, TGF-β (10 ng/g body wt) administered in vivo increased PAI-1 activity in mouse plasma and PAI-1 mRNA expression in mouse adipose tissue. Conclusions Increased plasma PAI-1 activity in obese human subjects may result from PAI-1 release from an increased mass of adipose tissue, particularly in association with thrombosis and elaboration of TGF-β from platelet α-granules into the circulation. The increased PAI-1 may exacerbate vascular disease by shifting the balance between thrombosis and thrombolysis toward thrombosis and consequently exposing luminal surfaces of vessels to mitogens associated with microthrombi over protracted intervals.
Aberrant cytokine production from tenosynovium in dialysis associated amyloidosis.
Authors: N Miyasaka, K Sato, Y Kitano, M Higaki, K Nishioka, K Ohta
Journal: Annals of the Rheumatic Diseases (1992)

Culture supernatants of tenosynovial tissues from patients with carpal tunnel syndrome undergoing chronic haemodialysis contained interleukin (IL) 1-like and IL6-like activity. These culture supernatants also induced active proliferation of rheumatoid synovial cells. Immunohistochemical analysis of teno-synovial tissues showed the accumulation of mononuclear cells bearing CD14 and HLA-DR antigens adjacent to the deposition of amyloid protein (beta 2 microglobulin). These cells also reacted with antibodies to IL1 and IL6 respectively. These data suggest that multiple cytokines, including IL1 and IL6, produced from tenosynovial tissues in patients with dialysis associated amyloidosis might induce the proliferation of synovial cells that, together with deposition of amyloid protein, might cause carpal tunnel syndrome.
Genioglossal But Not Palatal Muscle Activity Relates Closely to Pharyngeal Pressure
Authors: ATUL MALHOTRA, GIORU PILLAR, ROBERT B. FOGEL, JOSIE BEAUREGARD, JILL K. EDWARDS, DAVID I. SLAMOWITZ, STEVEN A. SHEA, DAVID P. WHITE
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

The stimuli controlling pharyngeal dilator muscles are poorly defined. Local mechanoreceptors are a leading possibility. To address this, we assessed the relationship between two dilator muscle electromyograms (EMGs, i.e., genioglossus [GG-an inspiratory phasic muscle], tensor palatini [TP-a tonically active muscle]) and potential stimuli (i.e., epiglottic pressure [Pepi], airflow [V], and pharyngeal resistance [Rpha]). Fifteen normal subjects were studied, during wakefulness and stable non-rapid eye movement (NREM) sleep. The GGEMG and TPEMG were assessed during basal breathing and during inspiratory resistive loading (four loads, done in triplicate), while quantifying Pepi and choanal pressures (Pcho, Millar catheters) plus V. There was a strong correlation between Pepi and GGEMG during wakefulness in most subjects (9 of 15 had absolute R > 0.7 [p < 0.05], group mean R = -0.62, p < 0.05). These correlations were less robust during NREM sleep (8 of 15 absolute R > 0.6 [p < 0.05], group mean R = -0.39, ns). The slope of the Pepi versus GGEMG relationship was greater during wakefulness than sleep (-0.67 versus -0.39% max/ cm H(2)O, p < 0.05). No significant correlations were observed between TPEMG and any of the measured potential stimuli. We conclude that intrapharyngeal pressure may modulate genioglossus activity during wakefulness, with a fall in muscle responsiveness during sleep. The activity of the TP was not clearly influenced by any measured local stimulus either awake or asleep.
Presence of Intraplaque Hemorrhage Stimulates Progression of Carotid Atherosclerotic Plaques
Authors: Norihide Takaya, Chun Yuan, Baocheng Chu, Tobias Saam, Nayak L. Polissar, Gail P. Jarvik, Carol Isaac, Judith McDonough, Cynthia Natiello, Randy Small, Marina S. Ferguson, Thomas S. Hatsukami
Journal: Circulation (2005)

Previous studies suggest that erythrocyte membranes from intraplaque hemorrhage into the necrotic core are a source of free cholesterol and may become a driving force in the progression of atherosclerosis. We have shown that MRI can accurately identify carotid intraplaque hemorrhage and precisely measure plaque volume. We tested the hypothesis that hemorrhage into carotid atheroma stimulates plaque progression.Twenty-nine subjects (14 cases with intraplaque hemorrhage and 15 controls with comparably sized plaques without intraplaque hemorrhage at baseline) underwent serial carotid MRI examination with a multicontrast weighted protocol (T1, T2, proton density, and 3D time of flight) over a period of 18 months. The volumes of wall, lumen, lipid-rich necrotic core, calcification, and intraplaque hemorrhage were measured with a custom-designed image analysis tool. The percent change in wall volume (6.8% versus -0.15%; P=0.009) and lipid-rich necrotic core volume (28.4% versus -5.2%; P=0.001) was significantly higher in the hemorrhage group than in controls over the course of the study. Furthermore, those with intraplaque hemorrhage at baseline were much more likely to have new plaque hemorrhages at 18 months compared with controls (43% versus 0%; P=0.006).Hemorrhage into the carotid atherosclerotic plaque accelerated plaque progression in an 18-month period. Repeated bleeding into the plaque may produce a stimulus for the progression of atherosclerosis by increasing lipid core and plaque volume and creating new destabilizing factors.
Immunizations, Immunoprophylaxis, and Chemoprophylaxis to Prevent Selected Infections
Authors: F. Marc LaForce
Journal: JAMA (1987)

VACCINES have played a vital role in improving health care in the United States. One need only remember that from 1951 to 1955 the United States averaged more than 35 000 cases of paralytic poliomyelitis annually, whereas in 1984 there were only eight reported cases. Nonetheless, there continue to be difficulties with immunization programs. Complacency is a major one; there are times when the glamour of modern curative medicine has overshadowed the steady, undramatic activities involved in immunization programs. This is particularly true when adult immunizations are considered. The emphasis on disease prevention, so dominant in the training of pediatricians, has not been as strong in the training received by US internists or general practitioners. The low 20% figure of yearly influenza immunizations given to high-risk patients is eloquent but sad testimony to this problem. Table 1 summarizes commonly used vaccines and immunoprophylactic agents. This review briefly describes the efficacy
Phase I study of rubitecan and gemcitabine in patients with advanced malignancies
Authors: P.M. Fracasso, J.S. Rader, R. Govindan, T.J. Herzog, M.A. Arquette, A. Denes, D.G. Mutch, J. Picus, B.R. Tan, C.L. Fears, S.A. Goodner, S.L. Sun
Journal: Annals of Oncology (2002)
Prophylactic Intravenous Immunoglobulin in HIV-Infected Children With CD4+ Counts of 0.20×109/L or More
Authors: Lynne M. Mofenson
Journal: JAMA (1992)

<h3>Objective.</h3> —To evaluate the efficacy of intravenous immunoglobulin (IVIG) for prevention of viral, opportunistic, and minor bacterial infections in children infected with human immunodeficiency virus (HIV). <h3>Design.</h3> —Randomized, double-blind, placebo-controlled, outpatient clinical trial comparing subjects treated with 400 mg of IVIG per kilogram of body weight every 28 days with those given albumin placebo. <h3>Setting.</h3> —Twenty-eight clinical centers in mainland United States and Puerto Rico. <h3>Patients.</h3> —Three hundred seventy-six children infected with human immunodeficiency virus with clinical or immunologic evidence of HIV disease, 313 of whom had entry CD4<sup>+</sup>counts of at least 0.20×10<sup>9</sup>/L (≥200/mm<sup>3</sup>). <h3>Main Outcome Measures.</h3> —The incidence of laboratory-proven and clinically diagnosed viral, opportunistic, and bacterial infections. <h3>Main Results.</h3> —Viral infections and minor bacterial infections contributed more frequently to morbidity in children with entry CD4<sup>+</sup>counts of at least 0.20×10<sup>9</sup>/L (together over five times as frequent) than did serious bacterial infection, the primary outcome measure of the trial. Opportunistic infections occurred at a similar rate as laboratory-proven serious bacterial infections. In this group of children, IVIG was significantly associated with a decrease in the rate of viral infections and minor bacterial infections per 100 patient-years (36.0 vs 54.0 episodes of viral infection per 100 patient-years, IVIG vs placebo,<sup>P</sup>=.01; and 115.1 vs 159.7 episodes of minor bacterial infection per 100 patient-years, IVIG vs placebo,<sup>P</sup>-.02), as well as a decrease in the rate of serious bacterial infections per 100 patient-years (26.4 vs 48.2 episodes per 100 patient-years;<sup>P</sup>=.002). There was no apparent difference in the rate of opportunistic infections between treatment arms. <h3>Conclusions.</h3> —Beneficial effect of IVIG was seen across multiple infectious outcome measures, with reductions in serious and minor viral and bacterial infections observed in children with entry CD4<sup>+</sup>counts of at least 0.20×10<sup>9</sup>/L. (<i>JAMA</i>. 1992;268:483-488)
Anomalous drainage of inferior vena cava to left atrium in association with total anomalous pulmonary venous drainage.
Authors: R K Lamb, S A Qureshi, R G Patel, D I Hamilton
Journal: Thorax (1987)

Drainage of the inferior vena cava directly into the left atrium is a rare but well recognised anomaly of systemic venous drainage. It has been reported in isolation and in association with other cardiac defects. We report a case of anomalous drainage of the inferior vena cava into the left atrium in association with total anomalous pulmonary venous drainage of the supracardiac type, a hitherto unreported combination.
Long-Term Prognostic Value of Dobutamine Stress Echocardiography in Diabetic Patients With Limited Exercise Capability
Authors: Jors N. van der Sijde, Henk J. Boiten, Fabiola B. Sozzi, Abdou Elhendy, Ron T. van Domburg, Arend F.L. Schinkel
Journal: Diabetes Care (2012)

To determine the incremental prognostic value of dobutamine stress echocardiography (DSE) at 13-year follow-up (SD 3.2 years) for predicting mortality and cardiac events in diabetic patients.A total of 396 diabetic patients (mean age 61 ± 11 years; 252 men [64%]) with limited exercise capacity who underwent DSE for evaluation of ischemia were studied. End points were all causes of mortality, cardiac death, and hard cardiac events (cardiac death and nonfatal myocardial infarction).During a mean follow-up of 13 years, 230 patients (58%) died (121 cardiac deaths), and 30 patients had nonfatal myocardial infarction. Cumulative survival in patients with an abnormal DSE at 5, 10, and 15 years was 68, 49, and 41%, respectively. In patients with a normal DSE, these respective numbers were 74, 57, and 44%. Multivariate analyses showed that DSE provided incremental value over clinical characteristics and stress test parameters for prediction of mortality and cardiac events. Survival analysis showed that DSE provided optimal risk stratification up to 7 years after initial testing; after that period, the risk of adverse outcome increased comparably in both normal and abnormal DSE patients.DSE provided restricted predictive value of adverse outcome in patients with diabetes who were unable to perform an adequate exercise stress test. DSE provided optimal risk stratification up to 7 years after initial testing. Repeated DSE at that time might add to its prognostic value.
Prognostic factors for 60-day mortality in first-line treatment of metastatic colorectal cancer (mCRC): individual patient analysis of four randomised, controlled trials by the AIO colorectal cancer study group
Authors: C. Giessen, U. Graeven, R.P. Laubender, D.P. Modest, C. Schulz, R. Porschen, W. Schmiegel, A. Reinacher-Schick, S. Hegewisch-Becker, S. Stintzing, V. Heinemann
Journal: Annals of Oncology (2013)
Endogenous opioids modify dyspnoea during treadmill exercise in patients with COPD
Authors: D. A. Mahler, J. A. Murray, L. A. Waterman, J. Ward, W. J. Kraemer, X. Zhang, J. C. Baird
Journal: European Respiratory Journal (2009)

Exogenous opioid drugs, such as morphine, relieve breathlessness. The present study hypothesis was that endogenous opioids, released during the stress of exercise, modify dyspnoea in patients with chronic obstructive pulmonary disease. After familiarisation, patients performed an incremental treadmill exercise test followed by constant work on the treadmill for 10 min. At subsequent visits (2 to 3 days apart), patients received two puffs of albuterol, had a catheter placed in an arm vein for removal of blood to measure β-endorphin immunoreactivity, received normal saline or 10 mg of naloxone intravenously in randomised order, and then performed high-intensity constant work rate exercise on the treadmill. The mean± sd age of the 17 patients (eight females and nine males) was 63±7 yrs, and post-bronchodilator forced expiratory volume in one second was 50±17% predicted. In both conditions, β-endorphin levels increased three-fold from rest to end-exercise. The regression slope of breathlessness as a function of oxygen consumption (primary outcome), mean ratings of breathlessness throughout exercise and peak ratings of breathlessness were significantly higher with naloxone than normal saline. There were no differences in physiological responses throughout exercise between conditions. In conclusion, endogenous opioids modify dyspnoea during treadmill exercise in patients with chronic obstructive pulmonary disease by apparent alteration of central perception.
Updated Prognostic Model for Predicting Overall Survival in First-Line Chemotherapy for Patients With Metastatic Castration-Resistant Prostate Cancer
Authors: Susan Halabi, Chen-Yen Lin, W. Kevin Kelly, Karim S. Fizazi, Judd W. Moul, Ellen B. Kaplan, Michael J. Morris, Eric J. Small
Journal: Journal of Clinical Oncology (2014)

Prognostic models for overall survival (OS) for patients with metastatic castration-resistant prostate cancer (mCRPC) are dated and do not reflect significant advances in treatment options available for these patients. This work developed and validated an updated prognostic model to predict OS in patients receiving first-line chemotherapy.Data from a phase III trial of 1,050 patients with mCRPC were used (Cancer and Leukemia Group B CALGB-90401 [Alliance]). The data were randomly split into training and testing sets. A separate phase III trial served as an independent validation set. Adaptive least absolute shrinkage and selection operator selected eight factors prognostic for OS. A predictive score was computed from the regression coefficients and used to classify patients into low- and high-risk groups. The model was assessed for its predictive accuracy using the time-dependent area under the curve (tAUC).The model included Eastern Cooperative Oncology Group performance status, disease site, lactate dehydrogenase, opioid analgesic use, albumin, hemoglobin, prostate-specific antigen, and alkaline phosphatase. Median OS values in the high- and low-risk groups, respectively, in the testing set were 17 and 30 months (hazard ratio [HR], 2.2; P < .001); in the validation set they were 14 and 26 months (HR, 2.9; P < .001). The tAUCs were 0.73 (95% CI, 0.70 to 0.73) and 0.76 (95% CI, 0.72 to 0.76) in the testing and validation sets, respectively.An updated prognostic model for OS in patients with mCRPC receiving first-line chemotherapy was developed and validated on an external set. This model can be used to predict OS, as well as to better select patients to participate in trials on the basis of their prognosis.
Margaret McCartney: Is Jeremy Hunt our colleague?
Authors: Margaret McCartney
Journal: BMJ (2015)

When the health secretary, Jeremy Hunt, emailed all junior doctors with his contract proposals, he began, “Dear colleague.” So let’s consider Hunt as a colleague, a team mate, a coworker, an ally—a doctor.

The NHS’s “duty of candour” policy requires doctors to apologise for and reflect on errors that they make. A photograph that Hunt tweeted of himself in a hospital contained identifiable patient information. It was subsequently altered, but there has been no public apology or statement of reflection from the Department of Health.

The General Medical Council takes a dim view of misleading claims. Hunt has promised a “truly seven day NHS.” But we already have a seven day NHS. Rather, Hunt seems to be promising an NHS with the same …
Mechanism for the Suppression of the Mammalian Stress Response by Genistein, an Anticancer Phytoestrogen From Soy
Authors: Yanhong Zhou, Amy S. Lee
Journal: JNCI Journal of the National Cancer Institute (1998)

Soy products contain high levels of genistein, a phytoestrogen that is a potent inhibitor of cell proliferation and angiogenesis. Genistein has been found to inhibit the growth of carcinogen-induced cancers in rats and human leukemia cells transplanted into mice. The induction of stress proteins (e.g., glucose-related proteins and heat shock proteins) in tumor cells has been shown to protect them against programmed cell death; this stress response is inhibited by genistein. The mechanism(s) by which genistein affects certain stress response genes was explored in this study.Mammalian cell cultures were treated with azetidine, a proline analog, which elicits a stress response that includes the induction of the expression of glucose-regulated protein GRP78 and heat shock protein HSP70. The effects of azetidine and/or genistein treatment on cellular levels of grp78 and hsp70 messenger RNAs and proteins were measured by northern blot hybridization and western blot analyses, respectively, and the binding of nuclear factors to sequence motifs in the upstream (promoter) regions of these two genes were examined by electrophoretic mobility shift assays.Genistein antagonized the binding of a specific transcription factor, nuclear factor-Y/CCAAT binding factor (NF-Y/CBF), to the CCAAT sequence element most proximal to the transcription start sites in the hsp70 and grp78 promoters; this CCAAT element was previously shown to be necessary for full-stress inducibility of both genes. Treatment of cells with genistein converted NF-Y/CBF into a nonbinding, transcriptionally inactive form.The anticancer effects of genistein may be related to its ability to reduce the expression of stress response-related genes.
Occupational scleroderma. A 17-year follow-up study
Authors: O. ISHIKAWA, S. WARITA, A. TAMURA, Y. MIYACHI
Journal: British Journal of Dermatology (2006)

Two patients with a scleroderma‐like disorder induced by epoxy resins were reported from the Department of Dermatology, Gunma University School of Medicine, Japan in 1980. Here, we describe the clinical and laboratory characteristics of these patients after 17 years' follow‐up from 1976 to 1993. Their systemic manifestations and indurated sclerotic skin changes disappeared within 5 years. No internal organ involvement has developed during the period of follow‐up. On routine laboratory tests, no abnormalities have been found in the peripheral blood or in the blood chemistry or serology. Histological examination revealed atrophy of the dermis and restoration of the normal pattern of fine collagen bundles, when compared ulth the previous skin biopsy specimens. This scleroderma‐like disorder induced by epoxy resins is considered to be different from systemic sclerosis: it has an acute onset and a fairly good prognosis, and does not show involvement of the internal organs.