tbuckley/cabot-search huggingface dataset:
AB1371 Severity of incident vertebral fracture and future fracture risk: A 3-year prospective study
Authors: O. Bruyere, C. Roux, D. Nicolet, J. Fechtenbaum, R. Deroisy, J.-Y. Reginster
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To examine whether the severity of an incident vertebral fracture can predict subsequent fracture. <h3>Methods</h3> Analysis from the placebo group of two 3-year randomized controlled trials investigating the clinical effect of an anti-osteoporotic drug. Vertebral and major non-vertebral fractures (i.e. ribs sternum, wrist region, pelvic sacrum, collarbone, humerus, proximal femur) were assessed during 3 years. At the end of the first year, each vertebra received a severity grade corresponding to either no fracture either a mild, moderate or severe fracture based on a semi-quantitative visual assessment on standard radiographs. All women received calcium and vitamin D during the 3 years of the study. <h3>Results</h3> 2550 women aged mean (SD) 74.4 (6.1) years were included in the present analysis. After one year of follow-up, 6.9% of the women (n=271) experienced a new vertebral fracture. Among these new fractures, 47.8% were mild, 30.9% were moderate and 21% were severe. During the following two years of follow-up (i.e. years 2 and 3), 410 patients experienced a new vertebral fracture. Among women with an incident vertebral fracture at year 1, 28.0% experienced a new vertebral fracture during years 2 and 3. However, this rate of new fracture was only 15.4% among women without incident vertebral fracture during the first year of follow-up. Compared to women without new vertebral fracture after one year of follow-up, women who experienced a severe fracture during year 1 have an increased risk of new vertebral fractures during the following two years (OR 2.39 [1.56-3.67]). When considering major non-vertebral fracture, 149 subjects experienced such fractures during year 2 and 3. Women who experienced a severe vertebral fracture during the first year have an increased risk of major non-vertebral fractures during the following two years compared to women without incident vertebral fracture after one year of follow-up (OR 2.31 [1.01-5.32]). <h3>Conclusions</h3> New severe incident vertebral fracture is an independent predictor of new vertebral and non-vertebral fractures that could be taken into account in fracture risk management. <h3>Disclosure of Interest</h3> None Declared
The splendid century: life in the France of Louis XIV
Authors: Lester S. King
Journal: JAMA (1963)

The curtain of the past covers over the glories and heartaches, the achievements and disappointments, the casual social moments and weighty political events of other days. Only the unusual author can take us behind that curtain and make the past live again with all its vivid intensity. W. H. Lewis, not a professional historian but a retired army officer, has achieved this goal for the glorious age of Louis XIV. And in so doing he has incidentally brought into vivid focus the medical as well as social and political life of the era. Obviously a picture of times past must be selective. Lewis has covered only certain aspects of 17th century life in France, but his selection of topics and his manner of presentation are most admirable. The entire period centered on the King, the "Grand Monarque." Or, to change the figure of speech, the King was the apex of
Irs1 and Irs2 signaling is essential for hepatic glucose homeostasis and systemic growth
Authors: Xiaocheng Dong, Sunmin Park, Xueying Lin, Kyle Copps, Xianjin Yi, Morris F. White
Journal: Journal of Clinical Investigation (2005)

Insulin receptor substrates, including Irs1 and Irs2, integrate insulin and IGF receptor signals with heterologous pathways to coordinate growth and metabolism. Since Irs2 is thought to be especially important in hepatic nutrient homeostasis, we deleted Irs2 [corrected] from hepatocytes of WT mice (called LKO) or genetically insulin-resistant Irs1-/- mice (called LKO::Irs1-/-). Viable LKO::Irs1-/- mice were 70% smaller than WT or LKO mice, and 40% smaller than Irs1-/- mice. Hepatic insulin receptors were functional in all the mice, but insulin signaling via the Akt-FoxO1 pathway was reduced in Irs1-/- and LKO liver, and undetected in LKO::Irs1-/- liver; however, Gsk3beta phosphorylation (Ser9) and hepatic glycogen stores were nearly normal in all of the mice. LKO and Irs1-/- mice developed insulin resistance and glucose intolerance that never progressed to diabetes, whereas LKO::Irs1-/- mice developed hyperglycemia and hyperinsulinemia immediately after birth. Regardless, few hepatic genes changed expression significantly in Irs1-/- or LKO mice, whereas hundreds of genes changed in LKO::Irs1-/- mice--including elevated levels of Pck1, G6pc, Ppargc1, Pparg, and Igfbp1. Thus, signals delivered by Irs1 or Irs2 regulate hepatic gene expression that coordinates glucose homeostasis and systemic growth.
A STUDY OF PNEUMOCOCCI: A COMPARISON BETWEEN THE PNEUMOCOCCI FOUND IN THE THROAT SECRETIONS OF HEALTHY PERSONS LIVING IN BOTH CITY AND COUNTRY AND THOSE OBTAINED FROM PNEUMONIC EXUDATES AND DISEASED MUCOUS MEMBRANES
Authors: William H. Park, A. W. Williams
Journal: The Journal of Experimental Medicine (1905)

1. Typical pneumococci were present dunng the winter months in the throat secretions of a large percentage of healthy individuals in city and country. 2. A higher percentage of atypical strains of pneumococci have been obtained from healthy persons than from those suffering from pneumonia. In the latter cases the atypical strains may have been overlooked, because of the larger number of typical pneumococci present. Many of the atypical strains seem to be closely related to the streptococci. 3. The so-called Streptococcus mucosus Schottmuller, which has hitherto been classed with the distinct streptococci, is placed as a definite variety among the pneumococci, and it is recommended that the name be changed to Streptococcus lanceolatus, var. mucosus. 4. A lower percentage of strains of pneumococci virulent for rabbits in the doses used has been obtained from normal cases by rabbit inoculations of mass cultures than from cases of pneumonia by the same method. 5. Since the virulence of pneumococci may be rapidly increased for a susceptible species of experimental animal by successive passage, and since pneumococci obtained from most pneumonias are more virulent for experimental animals than are those obtained from healthy individuals, therefore the virulence of pneumococci from cases of human infection is probably increased for human beings; hence cases of pneumonia should be considered to a certain degree as contagious and, since the virulence of the pneumococcus may be quickly increased and since the organism is very prevalent in normal sputum, all possible measures should be taken to restrict public expectoration. 6. By repeated inoculations into sheep of a pneumococcus strain, a specific protective power of this serum for mice is developed against the homologous strain and against certain other strains, one morphological variety (Streptococcus lanceolatus, var.mucosus) being thus clearly differentiated from other strains. 7. Coincident with this production of protective power, a slight specific increase of the sheep serum in phagocytic power in vitro has been observed with some strains of pneumococci, all strains of Streptococcus lanceolatus, var. mucosus, acting similarly with the serum produced by the inoculation of one strain; the strains of some other varieties, however, have shown no definite relationship between the phagocytic power and the protective power of the serum.
Abstract 3251: Characterization of a novel Rac inhibitor as an anti cancer metastasis compound
Authors: Brendaliz Montalvo Ortiz, Eliud Hernandez Ofarrill, Jonibeth Hernandez, Cornelis Vlaar, Surangani Dharmawardhane Flanagan
Journal: Cancer Research (2011)

Abstract The objective of this project is to design novel therapeutics targeting cancer metastasis, the most deadly aspect of epithelial cancers. Our previous studies have shown that Rac, a key signaling intermediate that regulates actin cytoskeletal changes during cell migration/invasion and cancer metastasis, is associated with high cancer metastatic efficiency. Since Rac proteins are activated by GDP/GTP exchange, inhibition of the interaction of Rac with its guanine nucleotide exchange factors (GEF) is expected to inhibit Rac activity. Since the known Rac inhibitor NSC-23766 is not effective at therapeutically useful concentrations, we synthesized novel NSC-23766 derivatives. Results show that the new inhibitor EHop-016 is 100-fold more efficient than the parent compound at inhibiting Rac activity of metastatic cancer cells without affecting the activity of the related GTPase, Rho. EHop-016 inhibited Rac activity of metastatic cancer cells with an IC50 of 0.78 microM. Cell viability assays, performed to test for the toxicity of this compound, demonstrated that at concentrations below 5 microM, EHop-016 did not affect mammary epithelial cell (MCF-10A) viability and decreased proliferation of metastatic cancer cells (MDA-MB-435) by only 20%. We conclude that EHop-16 is a potent Rac inhibitor with promise of further development as a small molecule inhibitor of cancer cell invasion, and thus, metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3251. doi:10.1158/1538-7445.AM2011-3251
Caspase activation correlates with the degree of inflammatory liver injury in chronic hepatitis C virus infection
Authors: Heike Bantel, Andreas Lügering, Christopher Poremba, Norbert Lügering, Jürgen Held, Wolfram Domschke, Klaus Schulze-Osthoff
Journal: Hepatology (2001)

Hepatitis C virus (HCV) infection is a major cause of liver disease characterized by inflammation, cell damage, and fibrotic reactions of hepatocytes. Apoptosis has been implicated in the pathogenesis, although it is unclear whether proteases of the caspase family as the central executioners of apoptosis are involved and how caspase activation contributes to liver injury. In the present study, we measured the activation of effector caspases in liver biopsy specimens of patients with chronic HCV infection. The activation of caspase-3, caspase-7, and cleavage of poly(ADP-ribose)polymerase (PARP), a specific caspase substrate, were measured by immunohistochemistry and Western blot analysis by using antibodies that selectively detect the active truncated, but not the inactive precursor forms of the caspases and PARP. We found that caspase activation was considerably elevated in liver lobules of HCV patients in comparison to normal controls. Interestingly, the immunoreactive cells did yet not reveal an overt apoptotic morphology. The extent of caspase activation correlated significantly with the disease grade, i.e., necroinflammatory activity. In contrast, no correlation was observed with other surrogate markers such as serum transaminases and viral load. In biopsy specimens with low activity (grade 0) 7.7% of the hepatocytes revealed caspase-3 activation, whereas 20.9% of the cells stained positively in grade 3. Thus, our results suggest that caspase activation is involved in HCV-associated liver injury. Moreover, measurement of caspase activity may represent a reliable marker for the early detection of liver damage, which may open up new diagnostic and therapeutic strategies in HCV infection.
The Evolution of the Cognitive Model of Depression and Its Neurobiological Correlates
Authors: Aaron T. Beck
Journal: American Journal of Psychiatry (2008)

Although the cognitive model of depression has evolved appreciably since its first formulation over 40 years ago, the potential interaction of genetic, neurochemical, and cognitive factors has only recently been demonstrated. Combining findings from behavioral genetics and cognitive neuroscience with the accumulated research on the cognitive model opens new opportunities for integrated research. Drawing on advances in cognitive, personality, and social psychology as well as clinical observations, expansions of the original cognitive model have incorporated in successive stages automatic thoughts, cognitive distortions, dysfunctional beliefs, and information-processing biases. The developmental model identified early traumatic experiences and the formation of dysfunctional beliefs as predisposing events and congruent stressors in later life as precipitating factors. It is now possible to sketch out possible genetic and neurochemical pathways that interact with or are parallel to cognitive variables. A hypersensitive amygdala is associated with both a genetic polymorphism and a pattern of negative cognitive biases and dysfunctional beliefs, all of which constitute risk factors for depression. Further, the combination of a hyperactive amygdala and hypoactive prefrontal regions is associated with diminished cognitive appraisal and the occurrence of depression. Genetic polymorphisms also are involved in the overreaction to the stress and the hypercortisolemia in the development of depression—probably mediated by cognitive distortions. I suggest that comprehensive study of the psychological as well as biological correlates of depression can provide a new understanding of this debilitating disorder.
Continuing Medical Education
Authors: David G. Ashbaugh
Journal: JAMA (1976)

In 55 audits of 37 topics totaling 5,499 patient records, 94% of deficiencies were in the area of performance, while only 6% occurred in the area of lack of knowledge. In addition to defining problems, audit serves as an educational experience and a stimulus to improve practice. (<i>JAMA</i>236:1485-1488, 1976)
Statistics on Uremic Pericarditis
Authors: DAVID W. FRASER
Journal: Annals of Internal Medicine (1971)

Letters, Comments, and Corrections1 December 1971Statistics on Uremic PericarditisDAVID W. FRASER, M.D.DAVID W. FRASER, M.D.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-75-6-976_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: I wish to point out the statistical errors in the paper by Drs. Comty, Cohen, and Shapiro on uremic pericarditis in the August issue (Ann Intern Med 75:173-183, 1971).The authors point out that their chi-square manipulations "cannot be taken at face value." In fact, the chi-square test is inappropriate for data with such small observed and expected values; the Fisher's exact test is suitable.None of the individual entries nor subtotals recorded in their Table 8 as "expected" is correct. In addition, the subtotals of "expected" add up to 22, not 25.I am made uncomfortable... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: 1175 Church St. Decatur, Ga. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 December 1971Volume 75, Issue 6Page: 976-976 Issue Published: 1 December 1971 PDF downloadLoading ...
Mucus in chronic airway diseases: sorting out the sticky details
Authors: L. Cohn
Journal: Journal of Clinical Investigation (2006)

Mucous hypersecretion is a major cause of airway obstruction in asthma, chronic obstructive pulmonary disease, and cystic fibrosis. EGFR ligands and IL-13 are known to stimulate mucous induction, but the detailed mechanisms of epithelial mucous regulation have not been well defined. In this issue of the JCI, Tyner et al. show, in a mouse model of chronic mucous hypersecretion, that ciliated epithelial cell apoptosis is inhibited by EGFR activation, allowing IL-13 to stimulate the differentiation of these cells into goblet cells, which secrete mucus. In defining this coordinated, 2-step process, we can consider the therapeutic effects of blocking mucous production. This begs the question, Is it possible to reduce airway obstruction in chronic lung disease by inhibiting EGFR activation and/or by inhibiting IL-13?
Reporting to NCEPOD.
Authors: B. Jennett, H. Burton
Journal: BMJ (1992)

Mixed sex wards EDITOR,-Mixed sex wards exist in many hos- pitals,' but there are few studies of their acceptability to patients.We carried out a simple survey to determine patients' opinions before and after relocating the accident and emergency observation ward of this hospital from a ward with single sex six bed bays to a mixed sex Nightingale ward.The ward with single sex bays had separate toilets and washrooms for men and women; the mixed sex ward had shared toilets and washrooms, although the nurses tried to ensure that only men or women used these at any one time.Patients were aged over 13 and required observation or investigation for various acute problems.Most were discharged within 24 hours.
Surface morphology of the gastroduodenal mucosa in duodenal ulceration.
Authors: H W Steer
Journal: Gut (1984)

Endoscopic biopsies from the duodenal cap and prepyloric areas of 25 patients have been examined with the scanning electron microscope. Eleven patients had duodenal ulceration. Bacteria are related only to the surface of gastric type epithelial cells whether these cells are located at areas of gastric metaplasia in the duodenal bulb or in the pre-pyloric region of the stomach. The bacteria are not associated with the surface of intestinal type epithelial cells. The bacteria are absent from the biopsies of those patients with a normal stomach and duodenum. Of those patients with duodenal ulceration, 73% have bacteria related to the epithelial surface. The bacteria are of two morphological types - a kidney shaped bacillus and an S-shaped bacillus.
The Computer and Its Potential for Medicine
Authors: JOHN G. MAYNE
Journal: Annals of Internal Medicine (1969)

Special Article1 January 1969The Computer and Its Potential for MedicineJOHN G. MAYNE, M.D.JOHN G. MAYNE, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-70-1-207 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAt the Fiftieth Annual Session of the American College of Physicians, to be held in Chicago this April, one of the main subjects to be discussed will be that of the role of the computer in medicine. At the request of the College, Dr. John Mayne prepared a primer on computers for that program. This primer is published below as a special article in the ANNALSin order that as many members of the College and readers may prepare themselves ahead of time for this interesting educational venture. Reprints of this article will be made available to the participants of...Bibliography1. TAYLOR TR: The Principles of Medical Computing, Blackwell Scientific Publications, Ltd., Oxford, 1967, 154 pp. Google Scholar2. HALACY DS: Computers—The Machines We Think With, Hoeber Medical Division, Harper & Row, Publishers, Inc., New York, 1962, 279 pp. Google Scholar3. LAURIE EJ: Computers and How They Work, South-Western Publishing Co., Cincinnati, 1963, 441 pp. Google Scholar4. Information: Sci. Amer. 215: 1, 1966. (The entire September issue was devoted to the use of computers in the handling of information.) Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Rochester, MinnesotaFrom the Mayo Clinic, Rochester, Minn.Requests for reprints should be addressed to John G. Mayne, M.D., Section of Internal Medicine and Rheumatology, Mayo Clinic, Rochester, Minn. 55901 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byA comprehensive surveillance system of infections and antimicrobials use at Presbyterian-St. Luke's Hospital, Chicago. 1 January 1969Volume 70, Issue 1Page: 207-214KeywordsComputersSoftware tools Issue Published: 1 January 1969 PDF downloadLoading ...
General practice observed
Authors: M Drury
Journal: BMJ (1989)

Two unrelated neonates were born with a large purplish congenital mass of the thigh and forearm. Both showed signs of heart dysfunction, and one of them had anaemia and thrombocytopenia. The imaging assessment of the lesions showed well-defined subcutaneous solid masses with an exuberant vascular component. Both were kept under surveillance and maintenance therapy. A progressive dimensional reduction of the lesions supported the diagnosis of rapidly involuting congenital haemangioma (RICH). RICH is a rare vascular tumour that presents as a congenital purplish bulky mass. The diagnosis depends on the clinical evaluation of the lesion and the imaging characterisation of its solid components and vascular network. RICH may be complicated by high-output heart failure, anaemia and thrombocytopenia. Despite its exuberant presentation, it undergoes involution in the first year of life; therefore, early invasive therapies should be avoided. It is essential to detect any dimensional increase, suggesting more aggressive diagnoses, such as kaposiform haemangioendothelioma.
Histopathologic findings in amyloid heart disease: Comparison between AL and ATTR amyloidosis and genotype-phenotype correlations
Authors: Ornella Leone, Enrica Perugini, Claudio Rapezzi, Carlo Magelli, Fabrizio Salvi, Michela Santi, Francesco Grigioni, Fabio Coccolo, Angelo Branzi
Journal: Journal of the American College of Cardiology (2003)
Bcl-xL anti-apoptotic network is dispensable for development and maintenance of CML but is required for disease progression where it represents a new therapeutic target
Authors: J G Harb, P Neviani, B J Chyla, J J Ellis, G J Ferenchak, J J Oaks, C J Walker, P Hokland, D C Roy, M A Caligiuri, G Marcucci, C S Huettner, D Perrotti
Journal: Leukemia (2013)
Characterization of angiotensin II receptors in cultured adult rat cardiac fibroblasts. Coupling to signaling systems and gene expression.
Authors: M Crabos, M Roth, A W Hahn, P Erne
Journal: Journal of Clinical Investigation (1994)

Cardiac hypertrophy is largely due to cardiac fibroblast growth and increased synthesis of extracellular matrix. This study has investigated the contribution of the vasoactive hormone, angiotensin II, toward this hypertrophic process. We have demonstrated that cultures of adult rat cardiac fibroblasts express AT1 but not AT2 receptors for angiotensin II. The ability of angiotensin II to stimulate phosphoinositide catabolism and to elevate intracellular calcium concentrations in these cells was blocked by losartan, a specific AT1 receptor antagonist, but not by the AT2 receptor antagonist CGP 42112. Exposure of adult cardiac fibroblasts to angiotensin II resulted in the induction of several growth-related metabolic events including c-fos protooncogene expression and increased synthesis of DNA, RNA, and protein. Angiotensin II was also found to induce collagen type I, alpha 1 chain transcript expression in cardiac fibroblasts as well as the synthesis and secretion of collagen by these cells. The data demonstrate that angiotensin II, via AT1 receptors, can stimulate cardiac fibroblast growth and increase collagen synthesis in cardiac tissue. Thus, angiotensin II may contribute toward the development of cardiac hypertrophy in conditions of hypertension that are associated with elevated concentrations of angiotensin II.