tbuckley/cabot-search huggingface dataset:
Use of Statins and Risk of Fractures
Authors: Tjeerd-Pieter van Staa
Journal: JAMA (2001)

Previous studies have reported lower fracture risks in patients taking 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins).To investigate risk of fracture among statin users.Case-control study of data from the General Practice Research Database (GPRD).A total of 683 general clinical practices in the United Kingdom.Cases were 81 880 patients aged 50 years or older who had a fracture of the vertebrae, clavicle, humerus, radius/ulna, carpus, hip, ankle, or foot occurring between the enrollment date of their practice into the GPRD and July 1999, paired with 81 880 age-, sex-, and practice-matched controls.Risk of fracture in current users vs nonusers of statins. Odds ratios were estimated from conditional logistic regression and adjusted for smoking, medications and illnesses associated with fracture risk, and body mass index when known.The adjusted odds ratio (OR) for current use of statins compared with nonuse was 1.01 (95% confidence interval [CI], 0.88-1.16). For forearm, hip, and vertebral fractures, the ORs were 1.01 (95% CI, 0.80-1.27), 0.59 (95% CI, 0.31-1.13), and 1.15 (95% CI, 0.62-2.14), respectively. Relative to nonuse, a statin dosage of less than 20 mg/d (standardized to simvastatin) was associated with an adjusted OR of fracture of 1.13 (95% CI, 0.96-1.33); this OR was 1.07 (95% CI, 0.82-1.38) at dosages of 20 to 39.9 mg/d and 0.85 (95% CI, 0.47-1.53) at dosages of 40 mg/d or more. The adjusted OR was 0.71 (95% CI, 0.50-1.01) for statin use durations of 0 to 3 months, 1.31 (95% CI, 0.87-1.95) for durations of 3 to 6 months, 1.14 (95% CI, 0.82-1.58) for durations of 6 to 12 months, and 1.17 (95% CI, 0.99-1.40) for durations of more than 12 months.In this study, use of statins at dosages prescribed in clinical practice was not associated with a reduction in risk of fracture.
Analysis of the functional effects of a mutation in SOD1 associated with familial amyotrophic lateral sclerosis
Authors: T. Tsuda, S. Munthasser, P.E. Fraser, M.E. Percy, I. Rainero, G. Vaula, L. Pinessi, L. Bergamini, G. Vignocchi, D.R. Crapper McLachlan, W.G. Tatton, P. St George-Hyslop
Journal: Neuron (1994)
Managing Preexisting Diabetes for Pregnancy
Authors: John L. Kitzmiller, Jennifer M. Block, Florence M. Brown, Patrick M. Catalano, Deborah L. Conway, Donald R. Coustan, Erica P. Gunderson, William H. Herman, Lisa D. Hoffman, Maribeth Inturrisi, Lois B. Jovanovic, Siri I. Kjos, Robert H. Knopp, Martin N. Montoro, Edward S. Ogata, Pathmaja Paramsothy, Diane M. Reader, Barak M. Rosenn, Alyce M. Thomas, M. Sue Kirkman
Journal: Diabetes Care (2008)

his document presents consensus panel recommendations for the medical care of pregnant women with preexisting diabetes, including type 1 and type 2 diabetes.The intent is to help clinicians deal with the broad spectrum of problems that arise in management of diabetes before and during pregnancy, and to prepare diabetic women for treatment that may reduce complications in the years after pregnancy.A thorough discussion of the evidence supporting the recommendations is presented in the book, Management of Preexisting Diabetes andPregnancy, authored by the consensus panel and published by the American Diabetes Association (ADA) in 2008 (1).A consensus statement on obstetrical and postpartum management will appear separately.The recommendations are diagnostic and therapeutic actions that are known or believed to favorably affect maternal and perinatal outcomes in pregnancies complicated by diabetes.The grading system adapted by the ADA was used to clarify and codify the evidence that forms the basis for the recommendations (2).Unfortunately there is a paucity of randomized controlled trials (RCTs) of the different aspects of management of diabetes and pregnancy.Therefore our recommendations are often based on trials conducted in nonpregnant diabetic women or nondiabetic pregnant women, as well as on peer-reviewed experience before and during pregnancy in women with preexisting diabetes (3-4).We also reviewed and adapted existing diabetes and pregnancy guidelines (5-10) and guidelines on diabetes complications and comorbidities (2,3,(11)(12)(13)(14). I. MANAGING PREEXISTING DIABETES FOR PREGNANCYA. Organization of preconception and pregnancy care Recommendations • Women with diabetes and childbearing potential should be educated about the need for good glucose control before pregnancy and should participate in effective family planning.(E) • Whenever possible, organize multidiscipline patient-centered team care for women with preexisting diabetes in preparation for pregnancy.(B) • Women with diabetes who are contemplating pregnancy should be evaluated and, if indicated, treated for diabetic nephropathy, neuropathy, and retinopathy, as well as cardiovascular disease (CVD), hypertension, dyslipidemia, depression, and thyroid disease.(E) • Medication use should be evaluated before conception, since drugs commonly used to treat diabetes and its complications may be contraindicated or not recommended in pregnancy, including statins, ACE inhibitors, angiotensin II receptor blockers (ARBs), and most noninsulin therapies.(E) • Continue multidiscipline patientcentered team care throughout pregnancy and postpartum.(E) • Regular follow-up visits are important•
Bone marrow stem cells contribute to repair of the ischemically injured renal tubule
Authors: Sujata Kale, Anil Karihaloo, Paul R. Clark, Michael Kashgarian, Diane S. Krause, Lloyd G. Cantley
Journal: Journal of Clinical Investigation (2003)

The paradigm for recovery of the renal tubule from acute tubular necrosis is that surviving cells from the areas bordering the injury must migrate into the regions of tubular denudation and proliferate to re-establish the normal tubular epithelium. However, therapies aimed at stimulating these events have failed to alter the course of acute renal failure in human trials. In the present study, we demonstrate that Lin–Sca-1+ cells from the adult mouse bone marrow are mobilized into the circulation by transient renal ischemia and home specifically to injured regions of the renal tubule. There they differentiate into renal tubular epithelial cells and appear to constitute the majority of the cells present in the previously necrotic tubules. Loss of stem cells following bone marrow ablation results in a greater rise in blood urea nitrogen after renal ischemia, while stem cell infusion after bone marrow ablation reverses this effect. Thus, therapies aimed at enhancing the mobilization, propagation, and/or delivery of bone marrow stem cells to the kidney hold potential as entirely new approaches for the treatment of acute tubular necrosis.
Preoperative prediction of postoperative delirium
Authors: D. A. O'Hara
Journal: JAMA (1994)

To the Editor.  —We have read with interest the article by Marcantonio et al. 1 It was surprising not to see any contribution by anesthesiologists to the protocol, as the anesthetic and postoperative pain regimens should significantly affect the incidence of delirium.  Although this study attempted to find a preoperative predictive scale, failure to control for the anesthetic technique and intraoperative events admits a bias that might affect, if not negate, the results. Different anesthesiologists may administer drugs that produce frank delirium under some circumstances. Drugs such as droperidol or benzodiazepines, especially in the elderly, can cause confusion. Whether or not a regional anesthetic with or without sedation was administered would also be important. For example, it has been demonstrated that the incidence of thromboembolic events (including stroke) decreases with epidural anesthesia for vascular surgery. 2   These data should have been collected, and possibly controlled for, in this prospective study.
The hepatic sympathetic nerve plays a critical role in preventing Fas induced liver injury in mice
Authors: Y Chida
Journal: Gut (2005)

<b>Background:</b> Although previous studies have shown that the hepatic sympathetic nerve controls various physiological functions in the liver, the role of this nerve in liver injury has yet to be clarified. <b>Aims:</b> The purpose of this study was to elucidate the role of this nerve, based on our newly developed technique for selectively removing the activities of the hepatic sympathetic nerve. <b>Subjects and methods:</b> Male C57BL/6 mice were operated on for hepatic sympathetic denervation. Thereafter, mice were intravenously administered 0.25 or 0.35 μg/g weight of the Fas agonist antibody, Jo-2, after which mortality by fulminant hepatitis was evaluated. Apoptosis in the liver was also examined by both terminal deoxynucleotidyl transferase mediated dUTP nick end labelling and caspase-3 assay. <b>Results:</b> Mortality in sympathectomised mice was significantly higher than that in sham operated mice following administration of Jo-2. This result was also supported by apoptosis data in which sympathectomised livers exhibited a significant elevation in the number of apoptotic hepatocytes and caspase-3 activity after Jo-2 treatment compared with sham operated livers. Moreover, pretreatment with norepinephrine dose dependently inhibited the hepatic sympathectomy induced increase in mortality after Jo-2 injection. Antiapoptotic protein levels of FLICE inhibitory protein, Bcl-xL, and Bcl-2 in the liver were significantly lower in sympathectomised mice at one and two hours following Jo-2 treatment than in sham operated animals. In addition, interleukin 6 supplementation dose dependently suppressed the hepatic sympathectomy induced increase in mortality after Jo-2 treatment. <b>Conclusions:</b> These results suggest that norepinephrine released from the hepatic sympathetic nerve plays a critical role in protecting the liver from Fas mediated fulminant hepatitis, possibly via mechanisms including antiapoptotic proteins and interleukin 6.
Metformin Use Reduction in Mild to Moderate Renal Impairment
Authors: James H. Flory, Sean Hennessy
Journal: JAMA Internal Medicine (2015)

score.We conclude that the combined use of PAR and MEWS is more accurate than MEWS alone.A generalizable way to incorporate clinical judgment into aggregated weighted scoring systems on the wards may improve detection of clinical deterioration and assist with timely mobilization of resources to address the etiology of clinical deterioration.
The sequence of the mu transmembrane segment determines the tissue specificity of the transport of immunoglobulin M to the cell surface.
Authors: G T Williams, A R Venkitaraman, D J Gilmore, M S Neuberger
Journal: The Journal of Experimental Medicine (1990)

Membrane IgM is expressed on the surface of B lymphocytes. It is not transported to the surface of transfected plasmacytoma or COS cells. Here, we show that mutation of four hydrophilic amino acids in the microm transmembrane is sufficient to overcome the intracellular retention of membrane IgM in non-B cells. This suggests that the B cell-specific IgM-associated proteins that have been postulated to assist the transport of membrane IgM to the cell surface (3) act either by forming a hydrophobic sheath that surrounds the microm transmembrane segment or by displacing an interaction with this segment that would otherwise cause retention. Experiments with a CD8/mu hybrid H chain indicate that the proteins that assist the transport of membrane IgM to the B cell surface at most need the mu CH4 and transmembrane/cytoplasmic portion for interaction.
864-2 One-year follow-up of transendocardial injection of autologous bone marrow mononuclear cells for ischemic cardiomyopathy
Authors: Emerson C Perin, Hans F Dohmann, Radovan Borojevic, Suzana A Silva, Andre L Sousa, Guilherme V Silva, Joao A Assad, Claudio T Mesquita, Luciano Belem, Roberto Esporcatte, Fernando O Rangel, Antonio C Carvalho, Isabel Rossi, William K Vaughn, Hans J Dohmann, James T Willerson
Journal: Journal of the American College of Cardiology (2004)
Modification of apolipoprotein(a) lysine binding site reduces atherosclerosis in transgenic mice.
Authors: N W Boonmark, X J Lou, Z J Yang, K Schwartz, J L Zhang, E M Rubin, R M Lawn
Journal: Journal of Clinical Investigation (1997)

Lipoprotein(a) contributes to the development of atherosclerosis through the binding of its plasminogen-like apolipoprotein(a) component to fibrin and other plasminogen substrates. Apolipoprotein(a) contains a major lysine binding site in one of its kringle domains. Destruction of this site by mutagenesis greatly reduces the binding of apolipoprotein(a) to lysine and fibrin. Transgenic mice expressing this mutant form of apolipoprotein(a) as well as mice expressing wild-type apolipoprotein(a) have been created in an inbred mouse strain. The wild-type apolipoprotein(a) transgenic mice have a fivefold increase in the development of lipid lesions, as well as a large increase in the focal deposition of apolipoprotein(a) in the aorta, compared with the lysine binding site mutant strain and to nontransgenic littermates. The results demonstrate the key role of this lysine binding site in the pathogenic activity of apolipoprotein(a) in a murine model system.
Intratumoral CD14+ Cells and Circulating CD14+HLA-DRlo/neg Monocytes Correlate with Decreased Survival in Patients with Clear Cell Renal Cell Carcinoma
Authors: Michael P. Gustafson, Yi Lin, Jonathan S. Bleeker, Deepti Warad, Matthew K. Tollefson, Paul L. Crispen, Peggy A. Bulur, Susan M. Harrington, Rebecca R. Laborde, Dennis A. Gastineau, Bradley C. Leibovich, John C. Cheville, Eugene D. Kwon, Allan B. Dietz
Journal: Clinical Cancer Research (2015)

Immunotherapeutic strategies to treat patients with renal cell carcinoma (RCC) offer new opportunities for disease management. Further improvements to immunotherapy will require additional understanding of the host response to RCC development.Using a novel approach to understanding the immune status of cancer patients, we previously showed that patients with a certain immune profile had decreased overall survival. Here, we examine in more detail the phenotypic changes in peripheral blood and the potential consequences of these changes in RCC patients.We found that CD14(+)HLA-DR(lo/neg) monocytes were the most predominant phenotypic change in peripheral blood of RCC patients, elevated nearly 5-fold above the average levels measured in healthy volunteers. Intratumoral and peritumoral presence of CD14 cells was an independent prognostic factor for decreased survival in a cohort of 375 RCC patients. The amount of peripheral blood CD14(+)HLA-DR(lo/neg) monocytes was found to correlate with the intensity of CD14 staining in tumors, suggesting that the measurement of these cells in blood may be a suitable surrogate for monitoring patient prognosis. The interaction of monocytes and tumor cells triggers changes in both cell types with a loss of HLA-DR expression in monocytes, increases of monocyte survival factors such as GM-CSF in tumors, and increased production of angiogenic factors, including FGF2.Our results suggest a model of mutually beneficial interactions between tumor cells and monocytes that adversely affect patient outcome.
Insulin Therapy and Glycemic Control in Hospitalized Patients With Diabetes During Enteral Nutrition Therapy
Authors: Mary T. Korytkowski, Rose J. Salata, Glory L. Koerbel, Faith Selzer, Esra Karslioglu, Almoatazbellah M. Idriss, Kenneth K.W. Lee, A. James Moser, Frederico G.S. Toledo
Journal: Diabetes Care (2009)

To compare two subcutaneous insulin strategies for glycemic management of hyperglycemia in non-critically ill hospitalized patients with diabetes during enteral nutrition therapy (ENT).Fifty inpatients were prospectively randomized to receive sliding-scale regular insulin (SSRI) alone (n = 25) or in combination with insulin glargine (n = 25). NPH insulin was added for persistent hyperglycemia in the SSRI group (glucose >10 mmol/l).Glycemic control was similar in the SSRI and glargine groups (mean +/- SD study glucose 8.9 +/- 1.6 vs. 9.2 +/- 1.6 mmol/l, respectively; P = 0.71). NPH insulin was added in 48% of the SSRI group subjects. There were no group differences in frequency of hypoglycemia (1.3 +/- 4.1 vs. 1.1 +/- 1.8%; P = 0.35), total adverse events, or length of stay.Both insulin strategies (SSRI with the addition of NPH for persistent hyperglycemia and glargine) demonstrated similar efficacy and safety in non-critically ill hospitalized patients with type 2 diabetes during ENT.
Matrilysin-dependent Elastolysis by Human Macrophages
Authors: Sergey Filippov, Ingrid Caras, Richard Murray, Lynn M. Matrisian, Harold A. Chapman, Steven Shapiro, Stephen J. Weiss
Journal: The Journal of Experimental Medicine (2003)

Human macrophages found in juxtaposition to fragmented elastin in vivo express the elastolytic matrix metalloproteinases (MMPs) progelatinase B, prometalloelastase, and promatrilysin. Though MMPs can degrade a range of extracellular matrix components, increasing evidence suggests that preferred targets in vivo include nonmatrix substrates such as chemokines and growth factors. Hence, the means by which MMPs participate in elastin turnover remain undefined as does the identity of the elastolysins. Herein, human macrophage cultures have been established that express a complement of elastolytic proteinases similar, if not identical, to that found in vivo. Under plasminogen-free conditions, macrophages preferentially use metalloelastase to mediate elastolysis via a process that deposits active enzyme on elastin surfaces. By contrast, in the presence of plasminogen, human macrophages up-regulate proteolysis 10-fold by processing promatrilysin to an active elastolysin via a urokinase-type plasminogen activator-dependent pathway. Matrilysin-deficient human macrophages fail to mediate an elastolytic response despite the continued expression of gelatinase B and metalloelastase. Thus, acting in concert with cosecreted cysteine proteinases whose activities are constrained to sites of macrophage-elastin contact (Punturieri, A., S. Filippov, E. Allen, I. Caras, R. Murray, V. Reddy, and S.J. Weiss. 2000. J. Exp. Med. 192:789–799), matrilysin confers macrophages with their most potent MMP-dependent elastolytic system.
The Evolution of Self-Reported Urinary and Sexual Dysfunction over the Last Two Decades: Implications for Comparative Effectiveness Research
Authors: Matthew J. Resnick, Daniel A. Barocas, Alicia K. Morgans, Sharon E. Phillips, Tatsuki Koyama, Peter C. Albertsen, Matthew R. Cooperberg, Michael Goodman, Sheldon Greenfield, Ann S. Hamilton, Karen E. Hoffman, Richard M. Hoffman, Sherrie H. Kaplan, Dan McCollum, Lisa E. Paddock, Janet L. Stanford, Antoinette M. Stroup, Xiao-Cheng Wu, David F. Penson
Journal: European Urology (2014)
Underestimation of acute pancreatitis: patients with only a small increase in amylase/lipase levels can also have or develop severe acute pancreatitis
Authors: P G Lankisch, S Burchard-Reckert, D Lehnick
Journal: Gut (1999)

In most treatment studies on acute pancreatitis, pancreatologists base their diagnosis on amylase/lipase levels more than three times above the upper limit of normal (>3n) and thus exclude patients with smaller enzyme level increases. The recommendations derived from the results of treatment studies do not take into account such patients. Non-pancreatologists frequently believe that only patients with high enzyme levels have a serious prognosis.To question the assumption that high enzyme levels indicate severe, and conversely low enzyme levels indicate mild, acute pancreatitis.This retrospective study includes 284 consecutive patients with a first attack of acute pancreatitis. The cause was biliary in 114 (40%) patients, alcoholism in 83 (29%), other in 21 (7%), and unknown in 66 (23%). Patients were divided into two groups according to their serum enzyme levels (amylase: </=3n, n = 88; >3n, n = 196; lipase: </=3n, n = 51; >3n, n = 233). Renal impairment, indication for dialysis and artificial ventilation, development of pseudocysts, necessity for surgery, and mortality were taken as parameters of severity.The incidence of severity was the same for both the </=3n and >3n groups.The severity of acute pancreatitis is independent of the elevation in serum amylase/lipase level (</=3n or >3n) on admission. Patients with only a slight increase can also have or develop severe acute pancreatitis. Patients with </=3n elevated enzyme levels on admission represent a substantial group that treatment studies have frequently overlooked. This is especially true for patients with alcohol induced acute pancreatitis whose amylase levels are lower than in other aetiological groups.
Association between increased arterial-wall thickness and impairment in ABCA1-driven cholesterol efflux: an observational study
Authors: Marjel J van Dam, Eric de Groot, Susanne M Clee, G Kees Hovingh, Roosje Roelants, Angie Brooks-Wilson, Aeilko H Zwinderman, Andries J Smit, August HM Smelt, Albert K Groen, Michael R Hayden, John JP Kastelein
Journal: The Lancet (2002)
<i>TNFAIP3</i> (A20) is a tumor suppressor gene in Hodgkin lymphoma and primary mediastinal B cell lymphoma
Authors: Roland Schmitz, Martin-Leo Hansmann, Verena Bohle, Jose Ignacio Martin-Subero, Sylvia Hartmann, Gunhild Mechtersheimer, Wolfram Klapper, Inga Vater, Maciej Giefing, Stefan Gesk, Jens Stanelle, Reiner Siebert, Ralf Küppers
Journal: The Journal of Experimental Medicine (2009)

Proliferation and survival of Hodgkin and Reed/Sternberg (HRS) cells, the malignant cells of classical Hodgkin lymphoma (cHL), are dependent on constitutive activation of nuclear factor kappaB (NF-kappaB). NF-kappaB activation through various stimuli is negatively regulated by the zinc finger protein A20. To determine whether A20 contributes to the pathogenesis of cHL, we sequenced TNFAIP3, encoding A20, in HL cell lines and laser-microdissected HRS cells from cHL biopsies. We detected somatic mutations in 16 out of 36 cHLs (44%), including missense mutations in 2 out of 16 Epstein-Barr virus-positive (EBV(+)) cHLs and a missense mutation, nonsense mutations, and frameshift-causing insertions or deletions in 14 out of 20 EBV(-) cHLs. In most mutated cases, both TNFAIP3 alleles were inactivated, including frequent chromosomal deletions of TNFAIP3. Reconstitution of wild-type TNFAIP3 in A20-deficient cHL cell lines revealed a significant decrease in transcripts of selected NF-kappaB target genes and caused cytotoxicity. Extending the mutation analysis to primary mediastinal B cell lymphoma (PMBL), another lymphoma with constitutive NF-kappaB activity, revealed destructive mutations in 5 out of 14 PMBLs (36%). This report identifies TNFAIP3 (A20), a key regulator of NF-kappaB activity, as a novel tumor suppressor gene in cHL and PMBL. The significantly higher frequency of TNFAIP3 mutations in EBV(-) than EBV(+) cHL suggests complementing functions of TNFAIP3 inactivation and EBV infection in cHL pathogenesis.