tbuckley/cabot-search huggingface dataset:
Outcome Predictors for the Cognitive Behavior Treatment of Bulimia Nervosa: Data From a Multisite Study
Authors: W S Agras, S J Crow, K A Halmi, J E Mitchell, G T Wilson, H C Kraemer
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: The aim of this study was to discover clinically useful predictors of attrition and outcome in the treatment of bulimia nervosa with cognitive behavior therapy. METHOD: Pretreatment, course of treatment, and outcome data were gathered on 194 women meeting the DSM-III-R criteria for bulimia nervosa who were treated with 18 sessions of manual-based cognitive behavior therapy in a three-site study. Differences between dropouts and nondropouts and between recovered and nonrecovered participants were first examined descriptively, and signal detection analyses were then used to determine clinically significant cutoff points predicting attrition and abstinence. RESULTS: The dropouts were characterized by more severe bulimic cognitions and greater impulsivity, but it was not possible to identify clinically useful predictors. The participants with treatment failures were characterized by poor social adjustment and a lower body mass index, presumably indicating greater dietary restriction. However, early progress in therapy best predicted outcome. Signal detection analyses revealed that poor outcome was predicted by a reduction in purging of less than 70% by treatment session 6, allowing identification of a substantial proportion of prospective failures. CONCLUSIONS: A cutoff point based on reduction of purging by session 6 usefully differentiates patients who will and will not respond to cognitive behavior therapy for bulimia nervosa, potentially allowing early use of a second therapy.
Synergistic Inhibition of Vascular Smooth Muscle Cell Migration by Phosphodiesterase 3 and Phosphodiesterase 4 Inhibitors
Authors: Daniel Palmer, Keith Tsoi, Donald H. Maurice
Journal: Circulation Research (1998)

Abstract —Cyclic nucleotide phosphodiesterases (PDEs) hydrolyze cAMP or cGMP and terminate their signaling. Two important families of PDEs that regulate cAMP signaling in cardiovascular tissues are the cGMP-inhibited PDEs (PDE3) and the cAMP-specific PDEs (PDE4). In this study, we have used a combination of an in vitro motility assay and a sensitive method for the measurement of cAMP in order to determine the relative roles of PDE3 and of PDE4 in the regulation of cAMP-mediated inhibition of VSMC migration. Our data demonstrate that forskolin, an activator of adenylyl cyclases, causes concentration-dependent inhibition of platelet-derived growth factor–induced VSMC migration. Incubation of cultured VSMCs with a PDE4-selective inhibitor, Ro 20-1724, markedly potentiated both the antimigratory effect and the increase in cAMP caused by forskolin. Cilostamide, a PDE3-selective compound, did not affect either the antimigratory activity of forskolin or its ability to increase cAMP. Cilostamide and Ro 20-1724 interacted synergistically to potentiate the inhibition of VSMC migration by forskolin and caused a supra-additive increase in cAMP. These data are consistent with an important role for both PDE3 and PDE4 in the regulation of cAMP-mediated inhibition of VSMC migration.
Tyrosine kinase dependent expression of TGF-β induced by stretch in mesangial cells
Authors: Masao Hirakata, Shinya Kaname, Un-Gil Chung, Nobuhiko Joki, Yuichi Hori, Masakuni Noda, Yoh Takuwa, Tomoki Okazaki, Toshiro Fujita, Tetsuo Katoh, Kiyoshi Kurokawa
Journal: Kidney International (1997)
Relationship Between Urinary Sodium Excretion Over Time and Mortality in Type 2 Diabetes
Authors: Elif I. Ekinci, John L. Moran, Merlin C. Thomas, Karey Cheong, Sophie Clarke, Angela Chen, Matt Dobson, Amanda Leong, Richard J. MacIsaac, George Jerums
Journal: Diabetes Care (2014)

It remains unclear whether dietary salt intake over years (not just at baseline) influences hard outcomes. We have previously demonstrated an increased risk of mortality in patients with type 2 diabetes (T2D) and low baseline 24-h urinary sodium excretion (24hUNa) (1). Based on the same cohort of patients, the aim of the current study was to examine the relationship among serial measurements of 24hUNa, estimated glomerular filtration rate (eGFR), and all-cause mortality, adjusting for covariates associated with 24hUNa and eGFR.

This was a prospective cohort study of patients with T2D attending a single tertiary hospital diabetes clinic, initiated in mid-2000 with follow-up completed in 2010 (1). Serial 24hUNa (mmol/24 h) and eGFR (mL/min/1.73 m2) measurements were performed at regular intervals. The impact of 24hUNa and eGFR over time on all-cause mortality was determined by a joint model of longitudinal (linear-mixed model) and time-to-event (Weibull parametric survival model) data.

Follow-up 24hUNa and eGFR data from 588 patients were used in the current analysis. There were 152 deaths …
Plasma Osteopontin, Hypoxia, and Response to Radiotherapy in Nasopharyngeal Cancer
Authors: Edwin P. Hui, Fion L. Sung, Brian K.H. Yu, Cesar S.C. Wong, Brigette B.Y. Ma, Xiaorong Lin, Andrew Chan, Wai-lap Wong, Anthony T.C. Chan
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Recent studies have suggested that osteopontin is induced by hypoxia in head and neck cancer cell lines and its plasma level may serve as a surrogate marker for tumor hypoxia and treatment outcome in head and neck cancer. We investigated the response of osteopontin to in vitro hypoxia in nasopharyngeal carcinoma cell lines, and determined plasma osteopontin levels in nasopharyngeal carcinoma patients, nonnasopharyngeal carcinoma head and neck cancer patients, and healthy controls. We explored the relationship of plasma osteopontin and response to radiotherapy in nasopharyngeal carcinoma. Experimental Design: Nasopharyngeal carcinoma cell lines HK1, HONE-1, C666-1, and CNE-2 were treated with 0 to 48 hours of hypoxia or normoxia, +/− reoxygenation. Osteopontin secretion in the supernatant was measured by ELISA assay. Cellular osteopontin protein and mRNA were detected by Western blotting and reverse transcription-PCR, respectively. Plasma osteopontin levels in patients (n = 66; 44 nasopharyngeal carcinoma, 22 head and neck cancer) and controls (n = 29) were measured by ELISA. Results: Hypoxia has no effect on osteopontin protein and mRNA level in nasopharyngeal carcinoma cells. Only CNE-2 secreted osteopontin, and there was no significant induction by hypoxia. Plasma osteopontin levels in patients of metastatic nasopharyngeal carcinoma and head and neck cancer, but not in locoregional nasopharyngeal carcinoma, were significantly higher than in controls. In patients with locoregional nasopharyngeal carcinoma receiving curative radiotherapy (n = 31), a high (&amp;gt;median) pretreatment plasma osteopontin level was a significant predictor of poor response to radiotherapy (complete response rate, 40% versus 88%; P = 0.009), which remained significant in multivariate analysis. Conclusion: Our results suggested that the pretreatment plasma osteopontin level may be a useful biomarker of response to radiotherapy in nasopharyngeal carcinoma.
Circadian Rhythms and Episodic Hormone Secretion in Man
Authors: E D Weitzman
Journal: Annual Review of Medicine (1976)

The temporal ordering of physiological and pathological processes has always been of considerable interest to the biological scientist as well as to the clinician. How­ ever, the historical dominance of the concept of constancy of the milieu interior and biological homeostasis as formulated by Claude Bernard in France and Walter B. Cannon in the United States has directed most past research efforts in the direction of studying stimulus-response and steady-state mechanisms. During the past 25 years, however, the field of biological rhythms has made great strides and has emphasized that all singleand multicell organisms and a wide variety of biological functions within these organisms demonstrate endogenous oscillatory behavior. The disciplines of endocrinology and neuroendocrinology have been at the forefront of these issues because of the critical interface relationsips of the central and peripheral nervous system, endocrine secretory systems, and the blood circulat­ ing communicative pathway. During the past ten years there has been a major conceptual change emphasizing the rhythmic oscillatory and episodic temporal ordering of neuroendocrine events in relation to the 24-hr sleep-waking rhythm. The cross-fertilization of the disciplines of biological rhythms, sleep physiology, and neuroendocrinology has led to a series of important observations which have chal­ lenged 24-hr homeostatic and steady-state concepts. The use of the techniques of frequent serial blood sampling, sophisticated microchemical assay techniques, and polygraphic sleep stage analysis have allowed studies to be carried out in man correlating large numbers of sequential multiple hormone measurements with sleep­ waking functional states. The results of these studies have demonstrated that hor-
Platelet Transfusion for Patients With Cancer: Clinical Practice Guidelines of the American Society of Clinical Oncology*
Authors: Charles A. Schiffer, Kenneth C. Anderson, Charles L. Bennett, Steven Bernstein, Linda S. Elting, Miriam Goldsmith, Michael Goldstein, Heather Hume, Jeffery J. McCullough, Rosemary E. McIntyre, Bayard L. Powell, John M. Rainey, Scott D. Rowley, Paolo Rebulla, Michael B. Troner, Alton H. Wagnon
Journal: Journal of Clinical Oncology (2001)

OBJECTIVE: To determine the most effective, evidence-based approach to the use of platelet transfusions in patients with cancer. OUTCOMES: Outcomes of interest included prevention of morbidity and mortality from hemorrhage, effects on survival, quality of life, toxicity reduction, and cost-effectiveness. EVIDENCE: A complete MedLine search was performed of the past 20 years of the medical literature. Keywords included platelet transfusion, alloimmunization, hemorrhage, threshold and thrombocytopenia. The search was broadened by articles from the bibliographies of selected articles. VALUES: Levels of evidence and guideline grades were rated by a standard process. More weight was given to studies that tested a hypothesis directly related to one of the primary outcomes in a randomized design. BENEFITS/HARMS/COST: The possible consequences of different approaches to the use of platelet transfusion were considered in evaluating a preference for one or another technique producing similar outcomes. Cost alone was not a determining factor. RECOMMENDATIONS: Appendix A summarizes the recommendations concerning the choice of particular platelet preparations, the use of prophylactic platelet transfusions, indications for transfusion in selected clinical situations, and the diagnosis, prevention, and management of refractoriness to platelet transfusion. VALIDATION: Five outside reviewers, the ASCO Health Services Research Committee, and the ASCO Board reviewed this document. SPONSOR: American Society of Clinical Oncology
Antisense oligonucleotide treatment ameliorates alpha-1 antitrypsin–related liver disease in mice
Authors: Shuling Guo, Sheri L. Booten, Mariam Aghajan, Gene Hung, Chenguang Zhao, Keith Blomenkamp, Danielle Gattis, Andrew Watt, Susan M. Freier, Jeffery H. Teckman, Michael L. McCaleb, Brett P. Monia
Journal: Journal of Clinical Investigation (2013)

Alpha-1 antitrypsin deficiency (AATD) is a rare genetic disease that results from mutations in the alpha-1 antitrypsin (AAT) gene. The mutant AAT protein aggregates and accumulates in the liver leading to AATD liver disease, which is only treatable by liver transplant. The PiZ transgenic mouse strain expresses a human AAT (hAAT) transgene that contains the AATD-associated Glu342Lys mutation. PiZ mice exhibit many AATD symptoms, including AAT protein aggregates, increased hepatocyte death, and liver fibrosis. In the present study, we systemically treated PiZ mice with an antisense oligonucleotide targeted against hAAT (AAT-ASO) and found reductions in circulating levels of AAT and both soluble and aggregated AAT protein in the liver. Furthermore, AAT-ASO administration in these animals stopped liver disease progression after short-term treatment, reversed liver disease after long-term treatment, and prevented liver disease in young animals. Additionally, antisense oligonucleotide treatment markedly decreased liver fibrosis in this mouse model. Administration of AAT-ASO in nonhuman primates led to an approximately 80% reduction in levels of circulating normal AAT, demonstrating potential for this approach in higher species. Antisense oligonucleotides thus represent a promising therapy for AATD liver disease.
Tpl2 Is a Key Mediator of Arsenite-Induced Signal Transduction
Authors: Kyung Mi Lee, Ki Won Lee, Ann M. Bode, Hyong Joo Lee, Zigang Dong
Journal: Cancer Research (2009)

Arsenite is a well-known human carcinogen that especially targets skin. The tumor progression locus 2 (Tpl2) gene encodes a serine/threonine protein kinase that is overexpressed in various cancer cells. However, the relevance of Tpl2 in arsenite-induced carcinogenesis and the underlying mechanisms remain to be explored. We show that arsenite increased Tpl2 kinase activity and its phosphorylation in mouse epidermal JB6 P+ cells in a dose- and time-dependent manner. Exposure to arsenite resulted in a marked induction of cyclooxygenase-2 (COX-2) and prostaglandin E(2) (PGE(2)), important mediators of inflammation and tumor promotion. Treatment with a Tpl2 kinase inhibitor or Tpl2 short hairpin RNA suppressed COX-2 expression and PGE(2) production induced by arsenite treatment, suggesting that Tpl2 is critical in arsenite-induced carcinogenesis. We also found that arsenite-induced phosphorylation of extracellular signal-regulated kinases (ERK) or c-Jun NH(2)-terminal kinases (JNK) was markedly suppressed by Tpl2 kinase inhibitor or Tpl2 short hairpin RNA. Inhibition of arsenite-induced ERK or JNK signaling using a pharmacologic inhibitor of ERK or JNK substantially blocked COX-2 expression. Furthermore, inhibition of Tpl2 reduced the arsenite-induced promoter activity of NF-kappaB and activator protein-1 (AP-1), indicating that NF-kappaB and AP-1 are downstream transducers of arsenite-triggered Tpl2. Our results show that Tpl2 plays a key role in arsenite-induced COX-2 expression and PGE(2) production and further elucidate the role of Tpl2 in arsenite signals that activate ERK/JNK and NF-kappaB/AP-1 in JB6 P+ cells.
A population-based, multifaceted strategy to implement antenatal corticosteroid treatment versus standard care for the reduction of neonatal mortality due to preterm birth in low-income and middle-income countries: the ACT cluster-randomised trial
Authors: Fernando Althabe, José M Belizán, Elizabeth M McClure, Jennifer Hemingway-Foday, Mabel Berrueta, Agustina Mazzoni, Alvaro Ciganda, Shivaprasad S Goudar, Bhalachandra S Kodkany, Niranjana S Mahantshetti, Sangappa M Dhaded, Geetanjali M Katageri, Mrityunjay C Metgud, Anjali M Joshi, Mrutyunjaya B Bellad, Narayan V Honnungar, Richard J Derman, Sarah Saleem, Omrana Pasha, Sumera Ali, Farid Hasnain, Robert L Goldenberg, Fabian Esamai, Paul Nyongesa, Silas Ayunga, Edward A Liechty, Ana L Garces, Lester Figueroa, K Michael Hambidge, Nancy F Krebs, Archana Patel, Anjali Bhandarkar, Manjushri Waikar, Patricia L Hibberd, Elwyn Chomba, Waldemar A Carlo, Angel Mwiche, Melody Chiwila, Albert Manasyan, Sayury Pineda, Sreelatha Meleth, Vanessa Thorsten, Kristen Stolka, Dennis D Wallace, Marion Koso-Thomas, Alan H Jobe, Pierre M Buekens
Journal: The Lancet (2014)
835-5 Candesartan improves functional class across a broad spectrum of patients with chronic heart failure: Results of the candesartan in heart failure-assessment of reduction in mortality and morbidity programme (CHARM)
Authors: John J McMurray, Jan Östergren, Bertil Olofsson, Christopher B Granger, Eric Michelson, James B Young, Mark Dunlap, Salim Yusuf, Karl Swedberg, Marc A Pfeffer
Journal: Journal of the American College of Cardiology (2004)
A dramatic finding at colonoscopy: cause for concern?
Authors: Benjamin Crooks, Fotios Sampaziotis, Emma Purkis, Sarah Cerys, Susan Catnach
Journal: Gut (2012)

A 66-year-old woman with a background of diverticular disease, hypertension, chronic kidney disease and amaurosis fugax was referred to our unit for colonoscopy as part of the bowel cancer screening programme following a positive faecal occult blood result.

The colonoscopy was performed following bowel preparation with Moviprep and under sedation with Midazolam 1.5 mg and Pethidine 25 mg. The procedure was straightforward using carbon dioxide for insufflation. Upon examination of the ascending colon several bright red linear lesions with some extravasation of fresh blood were noted (figure 1). These lesions were visualised in …
Painful Diabetic Neuropathy Is Associated With Greater Autonomic Dysfunction Than Painless Diabetic Neuropathy
Authors: Rajiv A. Gandhi, Jefferson L.B. Marques, Dinesh Selvarajah, Celia J. Emery, Solomon Tesfaye
Journal: Diabetes Care (2010)

Although a clear link between diabetic peripheral neuropathy (DPN) and autonomic neuropathy is recognized, the relationship of autonomic neuropathy with subtypes of DPN is less clear. This study aimed to investigate the relationship of autonomic neuropathy with painless and painful DPN.Eighty subjects (20 healthy volunteers, 20 with no DPN, 20 with painful DPN, 20 with painless DPN) underwent detailed neurophysiological investigations (including conventional autonomic function tests [AFTs]) and spectral analysis of short-term heart rate variability (HRV), which assesses sympathovagal modulation of the heart rate. Various frequency-domain (including low frequency [LF], high frequency [HF], and total power [TP]) and time-domain (standard deviation of all normal-to-normal R-R intervals [SDNN] and root mean square of successive differences [RMSSD]) parameters were assessed.HRV analysis revealed significant differences across the groups in LF, HF, TP, SDNN, and RMSSD (ANOVA P < 0.001). Subgroup analysis showed that compared with painless DPN, painful DPN had significantly lower HF (3.59 +/- 1.08 [means +/- SD] vs. 2.67 +/- 1.56), TP (5.73 +/- 1.28 vs. 4.79 +/- 1.51), and SDNN (2.91 +/- 0.65 vs. 1.62 +/- 3.5), P < 0.05. No significant differences were seen between painless DPN and painful DPN using an AFT.This study shows that painful DPN is associated with significantly greater autonomic dysfunction than painless DPN. These changes are only detected using spectral analysis of HRV (a simple test based on a 5-min electrocardiogram recording), suggesting that it is a more sensitive tool to detect autonomic dysfunction, which is still under-detected in people with diabetes. The greater autonomic dysfunction seen in painful DPN may reflect more predominant small fiber involvement and adds to the growing evidence of its role in the pathophysiology of painful DPN.
MPs back scientists' plea to be able to create hybrid embryos
Authors: Adrian O'Dowd
Journal: BMJ (2007)

Government proposals to prevent the creation of part human, part animal embryos for research purposes have been condemned by an influential group of MPs.

MPs on the House of Commons Select Committee on Science and Technology said that the Department of Health's stance was out of line with scientists, funders of research, the regulator, patients' groups, other government departments, and even the prime minister.

The committee this week published the findings of its inquiry into government proposals for the regulation of human-animal chimeras or hybrid embryos.

The issue arose after two teams of scientists at Newcastle University and King's College London submitted applications …
Regional myocardial blood flow during acute myocardial infarction in the conscious dog.
Authors: S P Bishop, F C White, C M Bloor
Journal: Circulation Research (1976)

Regional myocardial blood flow was studied in the conscious dog at periods of 5 minutes to 4 days after occlusion of a major branch of the left coronary artery. Dogs were instrumented with aortic electromagnetic flow probes, occlusive cuffs on either the anterior descending or circumflex branch of the left coronary artery, and a left atrial Silastic catheter for injection of microspheres (15 +/- 5 mum) labeled with either 85Sr, 141Ce, or 51Cr. Microspheres were injected into 25 fully conscious dogs during three of the following time periods: control preocclusion and 0.1, 2, 6, 24, or 96 hours postocclusion. In the conscious dog, before occlusion, the endocardial half of the left ventricular myocardium received 28% more blood flow than the epicardial half. After sudden occlusion of a coronary artery branch, there was a marked reduction in blood flow as well as an alteration in distribution of blood flow within the ischemic tissue; blood flow was most severly reduced in the subendocardial center of the ischemic region, less so in the epicardial ischemic region, and least reduced in the marginal region of the infarct. Blood flow was increased to the nonischemic tissue. There was no change in this pattern of reduced blood flow by 6 hours postocclusion, but by 24 hours, flow was moderately increased to all areas except the central subendocardial core, and was further increased at 96 hours. Blood flow to the endocardial half of the left ventricular myocardium averaged 63 ml/100 g per min during the control period, was reduced to 12-18 ml/100 g per min at 0.1-6 hours in the ischemic region, increased to 29 ml/100 g per min at 24 hours, and to 48 ml/100 g per min by 96 hours. These findings indicate that there is a reversal of the flow ratio within ischemic myocardium with relative under-perfusion of the endocardial half of the wall, which is not corrected by 4 days. There is a modest increase of collateral blood flow to ischemic tissue by 24 hours and this increase is considerably augmented by 96 hours, apparently as a result of the growth and enlargement of collateral vessels.