tbuckley/cabot-search huggingface dataset:
Summary of clinical trials in rheumatoid arthritis using infliximab, an anti-TNFalpha treatment
Authors: G. Harriman, L. K Harper, T. F Schaible
Journal: Annals of the Rheumatic Diseases (1999)

Cytokines play a central part in the human immune response and can generally be categorised as proinflammatory or anti-inflammatory cytokines in nature. Tumour necrosis factor α (TNFα) is a proinflammatory cytokine and is a key mediator of inflammation. It has been shown to be pivotal early in the inflammatory cascade. Its effect on upregulation of inflammatory events within the joints makes it an appropriate pharmacological target in rheumatoid arthritis (RA). Infliximab, an anti-TNF treatment, has been successful in clinical trials in reducing TNFα induced production of other inflammatory mediators, thereby reducing the signs and symptoms of RA.

Infliximab is a chimeric monoclonal antibody that is 75% human and 25% mouse protein.1 The mouse portion contains a variable region binding site while the human portion is responsible for effector function. Infliximab binds to soluble TNFα as well as membrane bound TNFα. It has also been shown to lyse TNFα producing cells in vitro, although this has not been studied in vivo.2 The antibody binds with high affinity, avidity and specificity to human TNFα. It does not bind to TNFβ, otherwise known as lymphotoxin-α. This high specificity decreases the potential for non-specific effects on other biological pathways. There is a dose proportional neutralisation of TNFα at doses ranging from 0.01 to 10 mg/kg in subjects with increased TNFα levels after endotoxin challenge. Because infliximab is a protein, it is not metabolised by cytochrome P-450 enzymes providing additional advantages. For example, the genetic polymorphisms of P-450 isoenzymes and the consequent variability in metabolism leading to different toxic or inactive metabolites are less of an issue. Also, the likelihood of complex drug interactions are decreased in comparison with small molecules.

Infliximab has also been studied in inflammatory bowel disease, specifically Crohn's disease. TNFα seems to play a central part in the inflammatory …
PMO-130 Altered acetyl-coa metabolism in hepatic mitochondrial impairment in in vitro models of hepatic cellular steatosis
Authors: K Lockman, K E Burgess, P Lee, A Pryde, P C Hayes, C Filippi, J N Plevris
Journal: Gut (2012)

<h3>Introduction</h3> Increased ketogenesis, in the presence of unaltered β-oxidation, is a feature of human steatohepatitis. This is thought to be attributable to decreased acetyl-coA entry to tricarboxylic acid cycle with mitochondrial impairment. In this study, we examined the diversion of acetyl-coA towards free fatty acid (FFA) biosynthesis and mevalonate pathways (including vitamin D3, steroids hormones and bile acids) in the presence of mitochondrial dysfunction and triglyceride accumulation. <h3>Methods</h3> Human hepatoblastoma C3A cells were treated with; oleate or various combinations of octanoate (O), lactate (L), pyruvate (P) and ammonia (N) for 72 h. Metabolites that correspond to the intermediates of FFA biosynthesis, mevalonate pathways were measured using metabolomics study. <h3>Results</h3> We have previously shown that LPON treatment, but not oleate, affected mitochondrial function as evidenced by decreased respiration and ROS formation with concomitant enhanced ketogenesis despite the similarities in triglyceride accumulation. Using metabolomics analysis, we identified three metabolites that correspond to FFA biosynthesis, three were bile acids and three were the derivatives of steroid hormones and vitamin D3 synthesis. We also identified mevalonate and 7-dehydrodemosterol, the intermediates of cholesterol biosynthesis. The concentrations of FFA biosynthesis intermediates were higher with LPON compared with oleate (3-oxo-tetradecanoate (p=0.005) and 3-oxo-hexadecanoate (p=0.02)). Although mevalonate (p=0.37) and 7-dehydrodesmosterol (p=0.46) levels were higher with oleate than that seen with LPON, these differences did not reach statistical significance. In contrast, bile acids were significantly elevated with oleate than LPON ((taurocholate (p=0.002), glycocholate (p=0.001), (6RS)-22-oxo-23,24,25,26,27-pentanorvitamin D3 6,19-sulphur dioxide adduct (p=0.04) and 1,25-dihydroxy-2,4-dinor-1,3-secovitamin D3 (p=0.0006). <h3>Conclusion</h3> These data suggest that, aside from enhanced ketogenesis, impaired mitochondrial function is also associated with acetyl-coA diversion towards FFA synthesis, but not mevalonate pathways. These differences are likely to reflect cellular demand in the presence of decreased ATP formation with mitochondrial dysfunction. <h3>Competing interests</h3> None declared.
Persistent Infecton Uptake in an Infected Prosthetic Knee
Authors: Bruce K. Adams, Inas Youssef, El-Fatih Ahmed El-Tom
Journal: Clinical Nuclear Medicine (2006)

A 62-year-old diabetic woman underwent a total knee replacement 2 months before presenting to the hospital with a swollen, red, painful left knee. Examination revealed cellulitis around the knee, tenderness, and limited range of movement. She ran a temperature, had a C-reactive protein of 60, white cell counts of 6 to 8 × 103/μL, an erythrocyte sedimentation rate of 120 mm/h, and a blood sugar of 157 mg/dL (normal range, 70–110 mg/dL). Bone scanning done to exclude bone involvement showed intense activity in the lateral condyle of the left femur, the tibial condyles, and patella. Infecton imaging of the left knee demonstrated increased periprosthetic uptake that persisted at 24 hours. The patient recovered after surgical debridement and intensive antibiotic treatment.
INTRAUTERINE EXPOSURE TO MATERNAL DIABETES IS ASSOCIATED WITH INCREASED AORTIC STIFFNESS IN EARLY AND LATE INFANCY
Authors: Halima Aadam Alhashemi, Timothy Colen, Akiko Hirose, Najla Alrajaa, Sandra Davidge, Winnie Savard, Michael Stickland, Venu Jain, Lisa Hornberger
Journal: Journal of the American College of Cardiology (2013)
Diagnostic Strategy for Obstructive Jaundice
Authors: CHARLES SAFRAN
Journal: Annals of Internal Medicine (1983)

Letters and Corrections1 October 1983Diagnostic Strategy for Obstructive JaundiceCHARLES SAFRAN, M.D., ROBERT A. GREENES, M.D., PH.D., TURNER E. BYNUM, M.D.CHARLES SAFRAN, M.D.Search for more papers by this author, ROBERT A. GREENES, M.D., PH.D.Search for more papers by this author, TURNER E. BYNUM, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-99-4-571_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The article by Richter and associates (1) on the analysis of diagnostic strategies in suspected obstructive jaundice is deficient in two major ways. First, this analysis ignores the significant published mortality of both transhepatic cholangiography (2, 3) and endoscopic retrograde cholangiopancreatography (2, 4, 5). What would be the average cost of these techniques to the patient if physicians valued the life of the patient in every 1000 who dies from the invasive imaging techniques?Secondly, the authors have confused diagnosis with outcome. Clearly the diagnosis of advance malignancy causing extrahepatic obstruction leads to a different outcome than...References1. RICHTERSILVERSTEINSCHAPIRO JMR. Suspected obstructive jaundice: a decision analysis of diagnostic strategies. Ann Intern Med. 1983;99:46-51. LinkGoogle Scholar2. SCHARSCHMIDTGOLDBERGSCHMID BHR. Current concepts in diagnosis: approach to the patient with cholestatic jaundice. N Engl J Med. 1983:308:25 1515-9. CrossrefGoogle Scholar3. MUELLERHARBINFERRUCCIWITTENBERGVANSONNENBERG PWJJE. Fine-needle transhepatic cholangiography: reflections after 450 cases. AJR. 1981;136:85-90. CrossrefMedlineGoogle Scholar4. IHREHELLERS TG. Complications and endoscopic retrograde cholangio-pancreatography: a review of the literature and presentation of a duodenal perforation. Acta Chir Scand. 1977;143:167-7. MedlineGoogle Scholar5. BILBAODOTTERLEE MCT. Complications of endoscopic retrograde cholangiopancreatography (ERCP), a study of 10,000 cases. Gastroenterology. 1976;70:314-20. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Beth Israel Hospital and Brighman and Women's Hospital Harvard Medical School Boston, MA 02215 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 October 1983Volume 99, Issue 4Page: 571-572KeywordsEndoscopic retrograde cholangiopancreatographyImaging techniquesMortality Issue Published: 1 October 1983 PDF downloadLoading ...
Chlamydial perihepatitis (Curtis-Fitz-Hugh syndrome) after hydrotubation
Authors: D Shanahan, C Wastell, J D Treharne
Journal: BMJ (1984)

likely that more subjects with unidentified hyper- tension would tend to be classified as normotensive than the reverse, tending to inflate the normotensive group at the expense of the untreated hypertension group.Given all these uncertainties little can be concluded-for reasons which Dr Black and others may well understand but to which little lip service is paid.They acknowledge uncertainty in the prospective categorisation of stroke by reserving an "unknown" category but apparently are confident that retrospectively they have been able to identify patients' blood pressure state (normo- tensive, treated, or untreated hypertensive) with accuracy and without bias.(Even prospectively, how much risk to assign to a known blood pressure measurement and how to measure the adequacy of treatment are difficult questions.)One further criticism is that having determined that there was an excess of cases of haemorrhage and a deficit of cases of infarction in the "untreated hypertension" group the finding of the converse in the "treated hypertension" group is not unexpected on the basis of chance alone given the limited number of degrees of freedom remaining-and as such carries no additional information.For these several reasons it is wrong to make any conjectures at all about the incidence of cerebral infarction in the treatment of hypertension.Such a question could only be settled prospectively-optimally by a rando- mised controlled trial including both normo- tensives and hypertensives.Modern methods of clinical examination such as computed tomography must be matched with modern design to answer the questions which the authors address to themselves.
A prescription for better prescribing: Summary of responses
Authors: Birte Twisselmann
Journal: BMJ (2006)

A prescription for better prescribing Medical education is a continuumEditor-The editorial by Aronson et al raises important concerns about the preparedness of newly qualified doctors to prescribe safely and effectively, but fails to provide evidence to support the claims that are made. 1 Importantly, the authors assume that the number of curricular hours equates to learning.The General Medical Council issues and regularly updates requirements for the content and outcomes of undergraduate medical education and the first foundation year.We deliberately do not tell medical schools how many hours must be spent on a particular subject: it is the acquisition of our learning objectives that is important.Medical education is a continuum.With respect to prescribing, as with so many other areas of medical education, we expect principles to be learnt and understood at medical school and then put into practice, under supervision, during the F1 year.Our requirements are laid out clearly in Tomorrow's Doctors and The New Doctor and include very clear expectations about the quality and extent of knowledge about the safe and effective use of drugs.Despite the strength of views expressed in the editorial, the authors have not presented robust and generally applicable evidence to show serious inadequacies in the learning of clinical pharmacology in the undergraduate medical curriculum.We look forward, however, to engaging with all interested parties to clarify the issues surrounding this very important subject.
Pernicious Anemia, 18q Deletion Syndrome, and IgA Deficiency
Authors: Raphael B. Stricker
Journal: JAMA (1982)

THE CHROMOSOME 18q deletion (18q—) syndrome is a well-described clinical entity characterized by mental retardation, short stature, and a variety of developmental abnormalities.<sup>1,2</sup>The syndrome often includes selective IgA deficiency.<sup>3</sup>Although IgA deficiency has been associated with a wide range of autoimmune disorders,<sup>4,5</sup>only a few patients with 18q— and IgA deficiency have exhibited autoimmune phenomena.<sup>6</sup> We report a case of 18q— syndrome with IgA deficiency complicated by a polyglandular autoimmune disorder composed of pernicious anemia, hypothyroidism, and hypoparathyroidism. <h3>Report of a Case</h3> A 21-year-old woman experienced the sudden onset of pallor and fatigue and was hospitalized because of severe anemia. She was the product of a normal gestation and delivery, but her growth and development were strikingly slowed. At the age of 9 years, the diagnosis of 18q— syndrome was made, with the additional finding of a ring 18p chromosome. The IgA level was 8
A proper range of the international normalized ratio for left atrial thrombi resolution among candidates for percutaneous transvenous mitral commissurotomy under oral anticoagulant therapy
Authors: Songkwan Silaruks, Bandit Thinkhamrop, Chaiyasith Wongvipaporn, Wirote Tantikosum, Pyatat Tatsanavivat, Virat Klungboonkrong
Journal: Journal of the American College of Cardiology (2002)
Partner in Crime
Authors: Louise Shewell
Journal: JAMA (1989)

As I stand in the doorway of your hospital room, arms full of admission assessment forms, light from the high window striates your face and shines on the metal side rails of your bed. Your face is sunken, all eyes; your chest heaves in spasmodic jerks. Heart disease, dementia, old age. I can't believe you're the same lady who used to cheat my grandmother at cards. I never understood why you cheated. Gran was so distracted by my failing grandfather, you could've beaten her fair and square. I remember the day the two of you were playing canasta on the back porch while Grandpa slouched in his wheelchair nearby. I was in the yard, squatting near the porch stairs, waiting for Gran to play her hand so I could crawl under the porch and drag out the garden hose to wet down my sandbox, a practice Gran forbade. The time
Diagnosis and management of acute myeloid leukemia in children and adolescents: recommendations from an international expert panel
Authors: Ursula Creutzig, Marry M. van den Heuvel-Eibrink, Brenda Gibson, Michael N. Dworzak, Souichi Adachi, Eveline de Bont, Jochen Harbott, Henrik Hasle, Donna Johnston, Akitoshi Kinoshita, Thomas Lehrnbecher, Guy Leverger, Ester Mejstrikova, Soheil Meshinchi, Andrea Pession, Susana C. Raimondi, Lillian Sung, Jan Stary, Christian M. Zwaan, Gertjan J. L. Kaspers, Dirk Reinhardt
Journal: Blood (2012)
Haemodynamic and electrocardiographic effects of practolol during upright exercise in coronary heart disease
Authors: M. F. ROUSSEAU, L. A. BRASSEUR, J.-M. R. DETRY
Journal: Cardiovascular Research (1973)

The effects of practolol (400 mg orally) on haemodynamic and electrocardiographic data have been studied at rest and during several levels of submaximal upright exercise in six patients with coronary heart disease. After practolol, the heart rate, aortic pressure, cardiac output, pressure-time index, and mean systolic ejection rate were reduced, while mean pulmonary arterial pressure was increased; stroke work was unchanged. Practolol appears to depress left ventricular function and to decrease myocardial contractility. At submaximal levels of exercise, the magnitude of the ST segment depression is decreased after practolol and its relationship to the pressure time index is modified. After beta blockade, angina pectoris occurs either at a lesser degree of myocardial ischaemia, as suggested by less depression of the ST segment, or the magnitude of the ST segment depression is no longer a reliable sign of myocardial ischaemia.
Pathogenesis of Bronchiectasis
Authors: F. P. L. Lander, M. Davidson
Journal: BMJ (1938)

ABORTION MTIIEBRITISH 1047 ninety-six it was associated with uterine sepsis.A further group of twenty-six patients developed a temperature after admission, with the presence of uterine sepsis.In twelve patients pyrexia was present but was due to other causes -for example, pneumonia causing abortion.In 188 cases there was no temperature, but thirty-three of these patients had a purulent uterine discharge.In one case pyrexia was present with uterine sepsis following abortion, apparently due to a bicycle accident some days previously.It is possible for a natural abortion to be accompanied by a temperature-for instance, a natural abortion which occurred in hospital in a patient suffering from heart disease.Course of Illness Normal course ...
AMERICAN BIRTH CONTROL LEAGUE
Authors: Robert L. Dickinson
Journal: JAMA (1925)

To the Editor:  —InThe Journal, September 19, p. 908, a resolution on birth control is reported from a recent meeting of the Rock Island County Medical Society condemning affiliation by any member with the American Birth Control League and labeling such affiliation unethical and unprofessional conduct. This action impels me to state briefly the experiences of the Committee on Maternal Health with the officials of this league.  When the committee's review appeared in the American Journal of Obstetrics and Gynecology , Mrs. Sanger sent their medical director to ask how the criticisms of the league contained in that report could be met. He was referred to the Public Health Committee of the Academy of Medicine and submitted to it a proposition from the league to carry out any alterations in method that would make its practice professionally ethical. It developed that 7,000 physicians had applied to the league for
Longitudinal Assessment of Genetic and Epigenetic Markers in Oligodendrogliomas
Authors: Iris Lavon, Daniel Zrihan, Bracha Zelikovitch, Yakov Fellig, Dana Fuchs, Dov Soffer, Tali Siegal
Journal: Clinical Cancer Research (2007)

Because little is known about the evolution of genetic and epigenetic changes that occur during tumor progression in oligodendrogliomas, we evaluated these changes in paired early and progressive oligodendrogliomas.1p36, 19q13, 10q22-26, and O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status were assessed in 46 paired early and progressive oligodendrogliomas from 23 patients.In early tumors, 60.8% were of low grade compared with only 17% low-grade tumors at recurrence. Of 17 early tumors described as pure oligodendrogliomas, 76.5% remained in this lineage, regardless of their grade, whereas others changed to astrocytic tumors. Oligoastrocytic tumors had a significantly higher tendency to transform to astrocytic tumors. All pure oligodendrogliomas with 1p/19q codeletions remained phenotypically unchanged, unlike mixed tumors with codeletions, of which 83% changed their cell lineage. Of tumors with early 1p deletion, 80% remained oligodendroglial at progression, whereas 75% of tumors with an intact 1p changed to astrocytic phenotype. 10q loss was uncommon in both early and progressive tumors. The proportional gain in methylation at progression was 31% for tumors with early 1p deletion, unlike tumors with an intact 1p, which had an 87.5% gain of methylation at progression.Pure oligodendrogliomas with 1p/19q deletion tend to retain their cell phenotype and genetic profile unlike tumors with no deletions or mixed histology. MGMT promoter methylation is more pronounced at tumor progression, particularly in tumors with an intact 1p. These observations suggest that MGMT promoter methylation is a late event in progressive oligodendrogliomas, and therefore, their chemosensitivity is not necessarily related to MGMT methylation status.
Abstract 466: LMO1 is a novel oncogene in neuroendocrine lung cancer
Authors: Zhenze Zhao, Xiuye Ma, Xiaojie Yu, Tzu-Hung Hsiao, Yidong Chen, Milind Suraokar, Ignacio Wistuba, John D. Minna, Alexander Pertsemlidis, Liqin Du
Journal: Cancer Research (2014)

Abstract Introduction. The aim of the study is to characterize the role of LMO1 in tumorigenesis of neuroendocrine lung cancer. LMO1 is a transcription factor that belongs to the LMO protein family containing the cysteine-rich LIM domains. LMO1 has been demonstrated to function as an important oncogene in the development of T-lineage leukemia and lymphoma. A recent study in neuroblastoma suggests that aberrant overexpression of LMO1 may play a critical role in the development of neuroendocrine cancers. The role of LMO1 in neuroendocrine lung cancer, however, was not investigated. Experimental Approaches. By analyzing a large panel of cell lines including lung cancer cell lines and normal lung epithelial cells, we compared the relative expression of LMO1 in different subtypes of lung cancers, and examined the correlation of LMO1 expression levels with neuroendocrine differentiation markers. Using in vitro approaches, we investigated the function of LMO1 in regulating lung cancer cell growth. To investigate the clinical significance of LMO1 dysregulation in lung cancer patients, we analyzed the correlation of LMO1 tumor levels with lung cancer patient survival. Results. We show that LMO1 is significantly overexpressed in small cell lung cancer (SCLC), an aggressive and major subtype of neuroendocrine lung cancers, relative to non-small cell lung cancer (NSCLC) and normal lung cells. In addition, in NSCLC cells, LMO1 mRNA levels are significantly correlated with expression of neuroendocrine differentiation markers. Functional in vitro investigations indicate that LMO1 overexpression significantly promotes growth of cultured lung cancer cells, suggesting its oncogenic function in lung cancer. More strikingly, our investigations of two independent lung cancer patient populations indicate that high tumor LMO1 mRNA level is an independent predictor of poor patient survival. Conclusions. Altogether, our findings strongly suggest that LMO1 is a neuroendocrine-specific oncogene in lung cancer that plays an important role in determining the cancer aggressiveness. Further studies are certainly warranted to define the mechanisms underlying the oncogenic function of LMO1 in neuroendocrine lung cancer and to further evaluate the clinical significance of LMO1 as a diagnostic and prognostic marker for neuroendocrine lung cancers in prospective studies. Citation Format: Zhenze Zhao, Xiuye Ma, Xiaojie Yu, Tzu-Hung Hsiao, Yidong Chen, Milind Suraokar, Ignacio Wistuba, John D. Minna, Alexander Pertsemlidis, Liqin Du. LMO1 is a novel oncogene in neuroendocrine lung cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 466. doi:10.1158/1538-7445.AM2014-466
PREVENTION OF EMESIS IN PATIENTS RECEIVING CYTOTOXIC DRUGS BY GR38032F, A SELECTIVE 5-HT3 RECEPTOR ANTAGONIST
Authors: D. Cunningham, A. Pople, H.T. Ford, J. Hawthorn, J.-C. Gazet, T. Challoner, R.C. Coombes
Journal: The Lancet (1987)
IMPACT OF AN EMERGENCY STEMI NETWORK IN OCTOGENARIAN PATIENTS
Authors: Roberta Montisci, Massimo Ruscazio, Marina Taccori, Michela Congia, Maria Francesca Marchetti, Cristina Cacace, Roberto Floris, Raimondo Pirisi, Gianfranco Decandia, Luigi Meloni
Journal: Journal of the American College of Cardiology (2015)