tbuckley/cabot-search huggingface dataset:
Osteoporosis and skeletal fractures in chronic liver disease.
Authors: T Diamond, D Stiel, M Lunzer, M Wilkinson, J Roche, S Posen
Journal: Gut (1990)

In order to determine the prevalence and severity of hepatic osteodystrophy by non-invasive means we compared 115 consecutive ambulant patients with histologically proven chronic liver disease to 113 age and sex matched control subjects. Methods used included the assessment of fracture prevalence rates, spinal radiography, and measurements of bone mineral density in the spine and the forearm. Spinal and peripheral fractures were more prevalent in the patients than in the control subjects (p less than 0.03 and p less than 0.01 respectively). The type of the underlying liver disease did not significantly affect the fracture prevalence rates, but alcoholic patients sustained more peripheral fractures than patients with other hepatic disorders (p less than 0.05). The bone mineral densities of the spines and the forearms were significantly reduced in male patients of all age groups and in female patients aged 60 years or more (p less than 0.001 for men and p less than 0.01 for women for both measurements). The prevalence rates of spinal and forearm osteoporosis were twice as high among patients with liver disease than in control subjects regardless of the definitions used. The presence of cirrhosis and hypogonadism were major risk factors for development of both spinal (Beta coef = 0.190 and 0.176; SE = 0.079 and 0.086 respectively) and forearm osteoporosis (Beta coef = 0.20 and 0.29; SE = 0.073 and 0.80 respectively). Spinal bone density was the predominant determinant of spinal fractures (Beta coef = -0.007; SE = 0.001), while hypogonadism (Beta coef = 0.363; SE = 0.075) and cirrhosis (Beta coef = 0.185; SE = 0.068) were the major predictors of peripheral fractures. The concentrations of serum calcium and serum vitamin D metabolites and the use of corticosteroids were apparently without effect on the prevalence of skeletal fractures or bone density.
Hepatic, gut, and renal substrate flux rates in patients with hepatic cirrhosis.
Authors: O E Owen, F A Reichle, M A Mozzoli, T Kreulen, M S Patel, I B Elfenbein, M Golsorkhi, K H Chang, N S Rao, H S Sue, G Boden
Journal: Journal of Clinical Investigation (1981)

The roles of liver, kidney, and gut in maintaining fuel homeostasis were studied in 28 patients with severe hepatic cirrhosis, 25 of whom had alcohol-induced cirrhosis. Hepatic, portal, and renal blood flow rates were measured and combined with substrate concentration differences across liver, gut, and kidney to calculate the net flux of free fatty acids, ketone bodies, triglycerides, and glucose with selected glucose precursors, including glycerol, lactate, pyruvate, and amino acids. Data from the catheterization studies were related to hepatic histology, glycogen content, and activities of gluconeogenic enzymes and compared with data obtained from control patients. The effects of food deprivation on net flux of fuels across the liver, gut, and kidney were assessed after overnight and after 3d of fasting. Activities of gluconeogenic enzymes were normal, but hepatic glycogen content was diminished in cirrhotic livers, probably as a consequence of extensive hepatic fibrosis. Extrahepatic splanchnic tissues (gut) had only a small influence on total splanchnic flux rates of carbohydrates, lipids and, amino acids. In cirrhotic patients, there was no mean renal glucose contribution to the bloodstream after an overnight or after a 3-d fast. After an overnight fast hepatic glucose production in patients with cirrhosis was diminished as a result of low-rate glycogenolysis. Hepatic gluconeogenesis and ketogenesis were increased. This pattern of hepatic metabolism mimics that seen in "normal" patients after more advanced stages of starvation. After 3 d of starvation, patients with hepatic cirrhosis have hepatic gluconeogenic and ketogenic profiles comparable to those of normal patients undergoing starvation of similar duration. Nevertheless, the total number of caloric equivalents derived from ketone bodies plus glucose corrected for recycled lactate and pyruvate added to the bloodstream by the cirrhotic livers that could be terminally oxidized by peripheral tissues was less than the contributions made by the normal livers, both after and overnight and after a 3-d fast.
A Novel Automated Platform for Quantifying the Extent of Skeletal Tumour Involvement in Prostate Cancer Patients Using the Bone Scan Index
Authors: David Ulmert, Reza Kaboteh, Josef J Fox, Caroline Savage, Michael J Evans, Hans Lilja, Per-Anders Abrahamsson, Thomas Björk, Axel Gerdtsson, Anders Bjartell, Peter Gjertsson, Peter Höglund, Milan Lomsky, Mattias Ohlsson, Jens Richter, May Sadik, Michael J Morris, Howard I Scher, Karl Sjöstrand, Alice Yu, Madis Suurküla, Lars Edenbrandt, Steven M Larson
Journal: European Urology (2012)
Angiotensin Blockade Inhibits Activation of Mitogen-Activated Protein Kinases in Rat Balloon-Injured Artery
Authors: Shokei Kim, Yasukatsu Izumi, Masahiko Yano, Akinori Hamaguchi, Katsuyuki Miura, Shinya Yamanaka, Hitoshi Miyazaki, Hiroshi Iwao
Journal: Circulation (1998)

Background —The effect of balloon injury on the arterial signal transduction pathway has not been examined. In vitro studies show that extracellular signal-regulated kinases (ERKs) and c-Jun NH 2 -terminal kinases (JNKs), belonging to the mitogen-activated protein kinase (MAPK) family, play a critical role in the activation of transcription factor activator protein-1 (AP-1) and cell proliferation or apoptosis. However, the activation and role of MAPKs in vascular diseases in vivo remain to be determined. Therefore, we examined the effect of balloon injury on arterial MAPKs and the possible role of angiotensin II. Methods and Results —Arterial JNK and ERK activities were measured by in-gel kinase assay. AP-1 DNA binding activity was determined by gel mobility shift analysis. After balloon injury of rat carotid artery, JNK (p46JNK and p55JNK) and ERK (p44ERK and p42ERK) activities were increased as early as 2 minutes, reached their peak (6- to 18-fold) at 5 minutes, and thereafter rapidly declined to control levels. JNK and ERK activations were followed by a 3.9-fold increase in arterial AP-1 DNA binding activity, which contained c-Jun and c-Fos proteins. Arterial JNK activation at 2 or 5 minutes was remarkably suppressed by E4177 (an angiotensin AT1 receptor antagonist) and cilazapril (an ACE inhibitor). E4177 also prevented activation of ERKs by suppressing their tyrosine phosphorylation, whereas cilazapril failed to prevent such activation. The increased AP-1 DNA binding activity was significantly inhibited by both E4177 and cilazapril. Conclusions —Arterial JNKs and ERKs are dramatically activated by balloon injury associated with the activation of the AP-1 complex. These MAPK activations, followed by AP-1 activation, are mediated at least in part by the AT1 receptor. Thus, activation of JNKs and ERKs may be responsible for balloon injury–induced neointima formation.
Survival Following Recurrence in Stage II and III Colon Cancer: Findings From the ACCENT Data Set
Authors: Michael J. O'Connell, Megan E. Campbell, Richard M. Goldberg, Axel Grothey, Jean-François Seitz, Jacqueline K. Benedetti, Thierry André, Daniel G. Haller, Daniel J. Sargent
Journal: Journal of Clinical Oncology (2008)

Purpose This study was undertaken to examine five possible prognostic factors in patients with recurrent stage II and III colon cancer: time from randomization on an adjuvant therapy clinical trial to tumor recurrence (&lt; 1 year, 1 to 2 years, 2 to 3 years, 3 to 4 years, &gt; 4 years), initial stage (II v III), initial adjuvant treatment (fluorouracil [FU]-based v surgery alone), the era in which the patient entered an adjuvant therapy clinical trial (1978 to 1985, 1986 to 1992, 1993 to 1999), and patient age at recurrence. Methods The Adjuvant Colon Cancer End Points (ACCENT) data set was analyzed using univariate and multivariate Cox proportional hazards models, stratified by study. Results 5,722 (32.9%) of 17,381 patients experienced recurrence. Median survival following recurrence was 13.3 months. Time from randomization to recurrence was highly prognostic of survival following recurrence (P &lt; .0001). Longer survival following recurrence was seen in patients with initial stage II versus III disease (P &lt; .0001; 14.3% 6-year overall survival after recurrence in initial stage II patients), patients entered more recently onto trials (P &lt; .0001), and patients initially treated with surgery alone versus FU adjuvant treatment (P = .0005). All relationships were maintained in multivariate models. Conclusion Time from initial treatment to recurrence and initial stage are important prognostic factors in patients with recurrent colon cancer. Survival following recurrence increased modestly from 1978 to 1999. Patients who had a recurrence following adjuvant therapy had poorer prognosis than those who progressed after surgery alone. These prognostic factors may be useful for clinical trial design and treatment decisions in patients with recurrent colon cancer.
Is the multidrug resistance an ATP channel?
Authors: Jorge J. Gumucio, Irwin M. Arias
Journal: Hepatology (1993)

The multidrug resistance ( mdr1 ) gene product, P-glycoprotein, is responsible for the ATP-dependent extrusion of a variety of compounds, including chemotherapeutic drugs, from cells. The data presented here show that cells with increaed levels of the P-glycoprotein release ATP to the medium in proportion to the concentration of the protein in their plasma membrane. Furthermore, measurements of whole-cell and single-channel currents with patch-clamp electrodes indicate that the P-glycoprotein serves as an ATP-conducting channel in the plasma membrane. These findings suggest an unusual role for the P-glycoprotein.
Clinical Evaluation of Computer-Assisted Self-Monitoring of Blood Glucose System
Authors: David G Marrero, Kathleen K Kronz, Michael P Golden, James C Wright, Donald P Orr, Naomi S Fineberg
Journal: Diabetes Care (1989)

The Glucometer M Diabetes Management System includes a glucose-reflectance meter with memory that can interface with a microcomputer for data manipulation and analysis. We evaluated the system in a short-term randomized control trial to determine its impact on metabolic control, self-monitoring of blood glucose (SMBG) testing behaviors, regimen selfadjustment, understanding of insulin-dependent diabetes mellitus (IDDM) treatment, attitudes about SMBG, and perceived quality of patient-physician interaction. Twenty-nine adolescent subjects (experimental) with IDDM were randomly assigned the Glucometer M system for 4 mo. Twenty-eight control subjects used meters without memory. All subjects returned twice to the clinic at 2-mo intervals during the study. At clinic visits, both groups reviewed their SMBG data with their physician. Reviews on experimental subjects were conducted with computer-generated data formats. Control subject reviews used traditional logbooks. Both groups showed a significant drop in glycosylated hemoglobin during the study period (P &amp;lt; .001); however, there were no between-group differences. There were also no differences in SMBG testing behavior or self-reported regimen selfadjustment between groups or within groups compared with baseline. Compared with control subjects, experimental subjects indicated a significant increase in self-reported understanding of IDDM treatment (P = .002), perceived importance of testing (P = .006), and the quality of interaction with their physician (P &amp;lt; .001). These data suggest that use of computer-assisted SMBG systems in the outpatient setting does not improve metabolic control over 4 mo. It may, however, contribute to improving communication between the patient and health-care providers.
Addressing violence against women: a call to action
Authors: Claudia García-Moreno, Cathy Zimmerman, Alison Morris-Gehring, Lori Heise, Avni Amin, Naeemah Abrahams, Oswaldo Montoya, Padma Bhate-Deosthali, Nduku Kilonzo, Charlotte Watts
Journal: The Lancet (2014)
Vegetarian Dietary Patterns Are Associated With a Lower Risk of Metabolic Syndrome
Authors: Nico S. Rizzo, Joan Sabaté, Karen Jaceldo-Siegl, Gary E. Fraser
Journal: Diabetes Care (2011)

OBJECTIVE The study objective was to compare dietary patterns in their relationship with metabolic risk factors (MRFs) and the metabolic syndrome (MetS). RESEARCH DESIGN AND METHODS Cross-sectional analysis of 773 subjects (mean age 60 years) from the Adventist Health Study 2 was performed. Dietary pattern was derived from a food frequency questionnaire and classified as vegetarian (35%), semi-vegetarian (16%), and nonvegetarian (49%). ANCOVA was used to determine associations between dietary pattern and MRFs (HDL, triglycerides, glucose, blood pressure, and waist circumference) while controlling for relevant cofactors. Logistic regression was used in calculating odds ratios (ORs) for MetS. RESULTS A vegetarian dietary pattern was associated with significantly lower means for all MRFs except HDL (P for trend &amp;lt; 0.001 for those factors) and a lower risk of having MetS (OR 0.44, 95% CI 0.30–0.64, P &amp;lt; 0.001) when compared with a nonvegetarian dietary pattern. CONCLUSIONS A vegetarian dietary pattern is associated with a more favorable profile of MRFs and a lower risk of MetS. The relationship persists after adjusting for lifestyle and demographic factors.
Is patellofemoral osteoarthritis a common sequela of patellofemoral pain?
Authors: Kay M Crossley
Journal: British Journal of Sports Medicine (2014)

Patellofemoral pain (PFP) remains one of the most common conditions encountered in sports medicine. Characterised by anterior knee pain that is aggravated by activities such as running, squatting and stair ambulation; PFP generally reduces or restricts physical activity. While PFP may subside with activity reduction, the natural history of this common condition is not one of spontaneous recovery. Indeed, PFP is often recalcitrant and can persist for many years. In a prospective study of people with PFP, symptoms persisted in 25% of people up to 20 years.1 Despite considerable evidence for the efficacy of conservative interventions for PFP, such as multimodal physiotherapy,2 these interventions do not appear to have long-lasting effects.2 Compounding the management of PFP is that surgery for PFP is widely considered to have poor outcomes.

As mentioned in the 2014 consensus statement from the International Patellofemoral Pain Research Retreat3 there is speculation that PFP may be a prelude to degenerative joint changes and ultimately the development of patellofemoral osteoarthritis (PFOA).4 ,5 While no current studies have prospectively studied people with PFP through to the development of PFOA (and thus verify this relationship), a recent systematic review4 observed that individuals undergoing arthroplasty for PFOA were more than twice as likely (OR=2.31, 95% CI 1.37 to 3.88) to report having had PFP as an adolescent than patients undergoing an arthroplasty for isolated tibiofemoral OA.

In the absence of rigorous …
HLA and Killer Immunoglobulin-like Receptor Genes as Outcome Predictors of Hepatitis C Virus–Related Hepatocellular Carcinoma
Authors: Elisabetta Cariani, Massimo Pilli, Alessandro Zerbini, Cristina Rota, Andrea Olivani, Paola Zanelli, Adele Zanetti, Tommaso Trenti, Carlo Ferrari, Gabriele Missale
Journal: Clinical Cancer Research (2013)

We evaluated the impact of the killer immunoglobulin-like receptors (KIR) of natural killer (NK) cells and of their HLA ligands over the clinical outcome of hepatitis C virus (HCV)-related hepatocellular carcinoma after curative treatment by either surgical resection or radiofrequency thermal ablation (RTA).Sixty-one consecutive patients with HCV-related hepatocellular carcinoma underwent KIR genotyping and HLA typing. A phenotypic/functional characterization of NK cells was carried out in patients with different KIR/KIR-ligand genotype.Activating KIR2DS5 was associated with significantly longer time to recurrence (TTR) and overall survival (OS; P < 0.03 each). Homozygous HLA-C1 (P < 0.02) and HLA-Bw4I80 (P < 0.05) were expressed by patients with significantly better OS, whereas HLA-C2 (P < 0.02) and HLA-Bw4T80 (P < 0.01) were associated with a worse OS. Multivariate analysis identified as parameters independently related to TTR the type of treatment (surgical resection vs. RTA; P < 0.03) and HLA-C1 (P < 0.03), whereas only KIR2DS5 was an independent predictor of longer OS (P < 0.05). Compound KIR2DL2-C1 and KIR3DS1-Bw4T80 genotypes were associated with better TTR (P < 0.03) and worse OS (P = 0.02), respectively. A prevalent cytotoxic (CD56(dim)) NK phenotype was detected in patients with both longer TTR and OS. Cytotoxic capacity measured by upregulation of CD107a was significantly higher in subjects with HLA-C1 alone or combined with KIR2DL2/KIR2DL3.These results support a central role of NK cells in the immune response against hepatocellular carcinoma, providing a strong rationale for therapeutic strategies enhancing NK response and for individualized posttreatment monitoring schemes.
Twelve Group I Introns in the Same Pre-rRNA Transcript of the Myxomycete Fuligo septica: RNA Processing and Evolution
Authors: Eirik W. Lundblad, Christer Einvik, Sissel Rønning, Kari Haugli, Steinar Johansen
Journal: Molecular Biology and Evolution (2004)

The ribosomal DNA region of the myxomycete Fuligo septica was investigated and found to contain 12 group I introns (four in the small subunit and eight in the large subunit ribosomal RNAs). We have performed molecular and phylogenetic analyses to provide insight into intron structure and function, intron-host biology, and intron origin and evolution. The introns vary in size from 398 to 943 nt, all lacking detectable open reading frames. Secondary structure models revealed considerable structural diversity, but all, except one (subclass IB), represent the common group IC1 intron subclass. In vitro splicing analysis revealed that 10 of the 12 introns were able to self-splice as naked RNA, but all 12 introns were able to splice out from the precursor rRNA in vivo as evaluated by reverse transcription PCR analysis on total F. septica RNA. Furthermore, RNA processing analyses in vitro and in vivo showed that 10 of 12 introns perform hydrolytic cleavage at the 3' splice site, as well as intron circularization. Full-length intron RNA circles were detected in vivo. The order of splicing was analyzed by a reverse transcription PCR approach on cellular RNA, but no strict order of intron excision could be detected. Phylogenetic analysis indicated that most Fuligo introns were distantly related to each other and were independently gained in ribosomal DNA during evolution.
Place of Death and the Differences in Patient Quality of Death and Dying and Caregiver Burden
Authors: Hiroya Kinoshita, Isseki Maeda, Tatsuya Morita, Mitsunori Miyashita, Akemi Yamagishi, Yutaka Shirahige, Toru Takebayashi, Takuhiro Yamaguchi, Ayumi Igarashi, Kenji Eguchi
Journal: Journal of Clinical Oncology (2014)

Purpose To explore the associations between place of death and quality of death and dying and caregiver burden in terminally ill patients with cancer and their families. Methods Two bereavement surveys were conducted in October 2008 and October 2011. A total of 2,247 family caregivers of patients with cancer who were deceased responded to the mail surveys (response rate, 67%). Family members reported patient quality of death and dying and caregiver burden by using the Good Death Inventory and Caregiving Consequences Inventory. Results Patient quality of death and dying was significantly higher at home relative to other places of dying after adjustment for patient and/or family characteristics (adjusted means): 5.0 (95% CI, 4.9 to 5.2) for home, 4.6 (95% CI, 4.5 to 4.7) for palliative care units, and 4.3 (95% CI, 4.2 to 4.4) for hospitals. For all combinations, pairwise P &lt; .001; the size of the difference between home and hospital was moderate (Hedges' g, 0.45). Home was superior to palliative care units or hospitals with respect to “dying in a favorite place,” “good relationships with medical staff,” “good relationships with family,” and “maintaining hope and pleasure” (P &lt; .001 for all combinations of home v palliative care units and home v hospitals). Home death was significantly associated with a lower overall (P = .03) and financial caregiver burden (P = .004) relative to hospital death. Conclusion Dying at home may contribute to achieving good death in terminally ill patients with cancer without causing remarkably increased caregiver burden. Place of death should be regarded as an essential goal in end-of-life care.
T cell receptor-mediated signaling events in CD4+CD8+ thymocytes undergoing thymic selection: requirement of calcineurin activation for thymic positive selection but not negative selection.
Authors: C R Wang, K Hashimoto, S Kubo, T Yokochi, M Kubo, M Suzuki, K Suzuki, T Tada, T Nakayama
Journal: The Journal of Experimental Medicine (1995)

The goal of this study was to identify the differences of intracellular signals between the processes of thymic positive and negative selection. The activation of calcineurin, a calcium- and calmodulin-dependent phosphatase, is known to be an essential event in T cell activation via the T cell receptor (TCR). The effect of FK506, an inhibitor of calcineurin activation, on positive and negative selection in CD4+CD8+ double positive (DP) thymocytes was examined in normal mice and in a TCR transgenic mouse model. In vivo FK506 treatment blocked the generation of mature TCRhighCD4+CD8- and TCRhighCD4-CD8+ thymocytes, and the induction of CD69 expression on DP thymocytes. In addition, the shutdown of recombination activating gene 1 (RAG-1) transcription and the downregulation of CD4 and CD8 expression were inhibited by FK506 treatment suggesting that the activation of calcineurin is required for the first step (or the very early intracellular signaling events) of TCR-mediated positive selection of DP thymocytes. In contrast, FK506-sensitive calcineurin activation did not appear to be required for negative selection based on the observations that negative selection of TCR alpha beta T cells in the H-2b male thymus (a negative selecting environment) was not inhibited by in vivo treatment with FK506 and that there was no rescue of the endogenous superantigen-mediated clonal deletion of V beta 6 and V beta 11 thymocytes in FK506-treated CBA/J mice. DNA fragmentation induced by TCR activation of DP thymocytes in vitro was not affected by FK506. In addition, different effects of FK506 from Cyclosporin A on the T cell development in the thymus were demonstrated. The results of this study suggest that different signaling pathways work in positive and negative selection and that there is a differential dependence on calcineurin activation in the selection processes.
Bilateral pleural effusions associated with pravastatin sodium treatment
Authors: I. Kalomenidis, S. Papiris, S. Loukides
Journal: European Respiratory Journal (2007)

To the Editors: 

Pravastatin sodium is a 3-hydroxyl-3-methylglutaryl-CoA reductase blocker used in the treatment of hypercholesterolaemia. We report on a patient who developed bilateral pleural effusions while he was being treated with the drug. The patient was a 60-yr-old male, a nonsmoker who was under treatment with 40 mg·day−1 pravastatin since September 2005. He had no history of allergy or significant environmental or occupational exposure to agents that may harm the respiratory system.

He presented with persistent bilateral pleuritic chest pain and mild dyspnoea of several days’ duration in September 2006. He had neither constitutional symptoms nor extrathoracic abnormalities. A chest radiograph revealed small bilateral pleural effusions …