tbuckley/cabot-search huggingface dataset:
The Case Against Identifying Carotid Stenosis in Asymptomatic Patients
Authors: Allan S. Brett, Joshua D. Levine
Journal: JAMA Internal Medicine (2014)

Carotid ultrasonography is performed frequently to identify carotid stenosis in patients with no history of carotid-territory cerebrovascular ischemia. The premises of such testing are that the potential benefit of endarterectomy or stenting exceeds the potential harm in patients with asymptomatic stenosis and that discovery of asymptomatic stenosis may trigger beneficial changes in lifestyle or medical management that otherwise would not have occurred. However, given low contemporary rates of stroke in medically managed patients with asymptomatic carotid stenosis, invasive carotid procedures cannot be justified in this population. Moreover, among patients at increased cardiovascular risk, there is no evidence that carotid imaging motivates behavioral change or improves risk stratification beyond consideration of conventional risk factors. In this focused review, we address topics that should help health care professionals advise patients who inquire about carotid screening and patients in whom asymptomatic carotid stenosis has already been identified. We conclude that there is currently no role for carotid imaging in patients without a history of carotid-territory stroke or transient ischemic attack.
A novel addition to the T cell repertory. Cell surface expression of tumor necrosis factor/cachectin by activated normal human T cells.
Authors: M Kinkhabwala, P Sehajpal, E Skolnik, D Smith, V K Sharma, H Vlassara, A Cerami, M Suthanthiran
Journal: The Journal of Experimental Medicine (1990)

Expression of the pluripotent molecule TNF in a focused and antigen-restricted fashion might provide an advantage to the host organism. Given the central role of T cells in antigen-specific immunity, we examined whether activated T cells express TNF on their cell surface. FACS analysis of highly purified normal human T cells labeled with an anti-TNF mAb revealed that T cells express cell surface TNF when signaled with the synergistic combination of a calcium ionophore, ionomycin, and a protein kinase C activator, 12-o-tetradecanoyl phorbol acetate. Cell surface radioiodination studies of stimulated T cells demonstrated the presence of 26-kD transmembrane protein, a size predicted by TNF cDNA and different from that of the 17-kD secreted TNF molecule. The induced cell surface expression of TNF could be blocked with cyclosporine and/or methylprednisolone, and Northern analysis for TNF-specific transcripts revealed that this inhibitory effect occurs pretranslationally. Our demonstration for the first time that stimulated normal human T cells display cell surface TNF provides a mechanistic basis for the realization of effects of TNF in an antigen-specific fashion.
Theatre: A Number
Authors: A. J. Klotzko
Journal: BMJ (2002)

By Caryl Churchill Rating ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> Royal Court Theatre, London, until 16 November 2002 www.royalcourttheatre.com/ How would it feel to find out that one is a clone? What would this knowledge do to one's sense of self and relationship to others, especially the other clone? This is this play's principal subject and it is handled in a creative and mostly fascinating manner. Cloning as a subject is both a benefit and a burden. It's hot. And many of those who chose to treat it in dramatic form have got burned in the process. Eva Hoffman's novel The Secret is but one disappointing example of works that sink beneath the weight of contorted scientific exposition, moral conceits, and characters who exist merely … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
Multimarker Approach to Risk Stratification in Non-ST Elevation Acute Coronary Syndromes
Authors: Marc S. Sabatine, David A. Morrow, James A. de Lemos, C. Michael Gibson, Sabina A. Murphy, Nader Rifai, Carolyn McCabe, Elliott M. Antman, Christopher P. Cannon, Eugene Braunwald
Journal: Circulation (2002)

Background — In patients with acute coronary syndromes (ACS), troponin I (TnI), C-reactive protein (CRP), and B-type natriuretic peptide (BNP) each predict adverse cardiac events. Little is known, however, about the utility of these biomarkers in combination. Methods and Results — Baseline measurements of TnI, CRP, and BNP were performed in 450 patients in OPUS-TIMI 16. Elevations in TnI, CRP, and BNP each were independent predictors of the composite of death, myocardial infarction (MI), or congestive heart failure (CHF). When patients were categorized on the basis of the number of elevated biomarkers at presentation, there was a near doubling of the mortality risk for each additional biomarker that was elevated ( P =0.01). Similar relationships existed for the endpoints of MI, CHF, and the composite, both at 30 days and through 10 months. In a validation cohort of 1635 patients in TACTICS-TIMI 18, the number of elevated biomarkers remained a significant predictor of the composite endpoint after adjustment for known clinical predictors: patients with one, two, and three elevated biomarkers had a 2.1- ( P =0.006), 3.1- ( P &lt;0.001), and 3.7- ( P =0.001) fold increase in the risk of death, MI, or CHF by 6 months. Conclusions — Troponin, CRP, and BNP each provide unique prognostic information in patients with ACS. A simple multimarker strategy that categorizes patients based on the number of elevated biomarkers at presentation allows risk stratification over a broad range of short- and long-term major cardiac events.
The Chemistry of the Immunoglobulins
Authors: Henry Metzger
Journal: JAMA (1967)

The immunoglobulins are the most complex system of proteins known. They have no peers with respect to the structural diversity which they exhibit or with respect to the sophisticated mechanisms which must regulate their synthesis. On the other hand, there are few proteins which have been as thoroughly studied and about which there exists such a large body of information regarding structure, synthesis, catabolism, and function. Several detailed reviews of immunoglobulin chemistry have recently appeared<sup>1,2</sup>and several are in press.<sup>3,4</sup>In this paper, I will try to outline present concepts in a more general way. I have tried to organize the material in a logical framework so that the various levels of organization of the immunoglobulin system are highlighted. <h3>The Structure of Immunoglobulins</h3> There are three aspects of immunoglobulin structure which must be understood: All immunoglobulins have a common fundamental structure. Superimposed on this common subunit
Chronic Hepatitis: Therapy
Authors: PATRICK J. ROONEY
Journal: Annals of Internal Medicine (1976)

Comments and Correction1 January 1976Chronic Hepatitis: TherapyPATRICK J. ROONEYPATRICK J. ROONEYSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-84-1-101 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: A recent editorial in the "Annals" on chronic hepatitis (1) and subsequent correspondence (2, 3), raise a fundamental ethical problem facing the medical profession today that involves deciding whether or not to treat asymptomatic disease when the natural history of such disease is unknown.No one would deny patients with symptoms referable to chronic active hepatitis the proper therapy. However, what is to be done with the asymptomatic subject discovered during unrelated investigation? This problem has obviously troubled Dr. DeFord (2), and the statement by Drs. Henley and Appelman (3) that therapy for all such patients is...References1. HENLEYAPPELMAN KH: The fading menace of chronic hepatitis. Ann Intern Med 82:840-841, 1975 LinkGoogle Scholar2. DEFORD J: Chronic hepatitis. Ann Intern Med 83:581-582, 1975 LinkGoogle Scholar3. HENLEYAPPELMAN KH: Chronic hepatitis. Ann Intern Med 83:582, 1975 MedlineGoogle Scholar4. PLOTZ P: Asymptomatic chronic hepatitis. Gastroenterology 68:1629-1630, 1975 CrossrefMedlineGoogle Scholar1. SOLOWAYSUMMERSKILLBAGGENSTOSS RWA: Clinical, biochemical and histological remission of severe chronic active liver disease: a controlled study of treatment and early prognosis. Gastroenterology 63:820-833, 1972 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByBor und spezielle Borverbindungen 1 January 1976Volume 84, Issue 1Page: 101-101KeywordsChronic hepatitisNatural history of disease Issue Published: 1 January 1976 PDF DownloadLoading ...
Abstract LB-119: Therapeutic sensitivity and predictive markers for CDK4/6 inhibition defined by ex vivo analyses of human tumors
Authors: Agnieszka Witkiewicz, Jeffry Dean, Amy McClendon, Erik S. Knudsen
Journal: Cancer Research (2012)

Abstract To model the heterogeneity of breast cancer as observed in the clinic, we employed an ex vivo model of breast tumor tissue. This methodology maintained the histological integrity of the tumor tissue in unselected breast cancers, and importantly, the explants retained key molecular markers that are currently used to guide breast cancer treatment (e.g. ER and Her2 status). The primary tumors displayed the expected wide range of positivity for the proliferation marker Ki67, and a strong positive correlation between the Ki67 indices of the primary and corresponding explanted tumor tissues was observed. Collectively, these findings indicate that multiple facets of tumor pathophysiology are recapitulated in this ex vivo model. To interrogate the potential of this preclinical model to inform determinants of therapeutic response, we investigated the cytostatic response to the CDK4/6 inhibitor, PD-0332991. This inhibitor was highly effective at suppressing proliferation in approximately 85% of cases, irrespective of ER or HER2 status. However, 15% of cases were completely resistant to PD-0332991. Marker analyses in both the primary tumor tissue and the corresponding explant revealed that cases resistant to CDK4/6 inhibition lacked the RB-tumor suppressor. These studies provide important insights into the spectrum of breast tumors that could be treated with CDK4/6 inhibitors, and defines functional determinants of response analogous to those identified through neoadjuvant studies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-119. doi:1538-7445.AM2012-LB-119
Re: Prospective Randomized Phase II Trial of a Single Early Intravesical Instillation of Pirarubicin (THP) in the Prevention of Bladder Recurrence After Nephroureterectomy for Upper Urinary Tract Urothelial Carcinoma: The THP Monotherapy Study Group Trial
Authors: Evanguelos Xylinas, Shahrokh F. Shariat
Journal: European Urology (2013)
THU0416 Attrition Bias in Rheumatoid Arthritis Randomised Trials with Different Modified Intention-To-Treat Approaches: A Meta-Epidemiological Study: Table 1
Authors: A. Dossing, S. Tarp, D.E. Furst, C. Gluud, J. Beyene, B.B. Hansen, H. Bliddal, R. Christensen
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The intention-to-treat (ITT) principle preserves randomisation and prevents attrition bias [1]. Frequently data are missing [2] and the ITT analysis is executed by means of non-responder imputation (NRI) [3]. Deviations from ITT, referred to as modified ITT (mITT), excludes a restricted patient-group post-randomisation and is commonly used [4]. <h3>Objectives</h3> 1) To examine if mITT is associated with a different effect size compared to ITT as evaluated by the composite index ACR20. 2) To examine how imputation and different ITT deviations affect effect size. <h3>Methods</h3> A systematic search in MEDLINE, EMBASE, and CENTRAL was performed. Inclusion criteria: Blinded RCTs investigating approved biological treatments for RA; reporting ACR20 as an outcome. Exclusion criteria: Open-label RCTs. A meta-epidemiological random-effects analysis was used to calculate the OR of pre-specified trial characteristics. Formal tests of interaction were performed between intervention groups (active or control) and study characteristics. Statistical analyses were based on GLIMMIX procedure in SAS. Study protocol [5]. <h3>Results</h3> Among 5,237 references, 87 RCTs were included and analysed (36,924 randomised patients and 36,256 analysed patients), with 185 active intervention groups and 87 control groups. As illustrated in Table 1, empirical evidence suggests that the choice of the analysis population affects the net benefit of an intervention (p=0.0024); although the OR for the mITT and ITT populations were comparable. The net benefit is further significantly affected by the withdrawal population considered to be non-responders (p=0.0029). The significant differences reflects an over- or underestimation of treatment, with higher OR favouring the intervention. <h3>Conclusions</h3> The size of treatment effect may be biased based on the population analysed, and the population to which NRI is applied. Our results suggest, however, that the recommended statistical ITT approach is comparable to mITT. <h3>References</h3> Higgins J. P., et al. BMJ 343 (2011):d5928. Boers M. Arthritis Rheum. 59.1 (2008): 2. EMA. Guideline on Missing Data in Confirmatory Clinical Trials. London: European Medicines Agency (EMA), 2010. Montedori A., et al. Trials 12 (2011): 58. Dossing A, et al. PROSPERO CRD42013006702, 2013. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2210
Monarthritis: an unusual presentation of renal cell carcinoma.
Authors: K K Chakravarty, M Webley
Journal: Annals of the Rheumatic Diseases (1992)

<h3>Summary</h3> Ubiquitylation regulates all aspects of development, and components are frequently mutated in developmental disorders. Tonne-Kalscheuer Syndrome (TOKAS) is a X-linked multiple congenital anomaly disorder caused by mutations in the E3 ubiquitin ligase RNF12/RLIM and characterized by intellectual disability and urogenital abnormalities. However, the molecular underpinnings of TOKAS remain largely unknown. Here, we show that RNF12 catalytic activity relieves gene repression to drive a transcriptional program required for germ cell development and priming of pluripotent cells towards the germline. A major feature of the RNF12-dependent gametogenesis gene program is a transcriptional feed-forward loop featuring the deubiquitylase <i>Usp26</i>/USP26. <i>Usp26</i>/USP26 induction stabilises RNF12 to amplify transcriptional responses, which is disrupted by RNF12 TOKAS mutations and USP26 variants identified in patients with fertility defects. In summary, we uncover remarkable synergy within a ubiquitylation cycle that controls expression of key genes required for germ cell development and is disrupted in patients with urogenital abnormalities.
Intracellular processing of human vs. rat immunoglobulin A in the rat liver
Authors: Albert L. Jones, Gary T. Hradek, Douglas L. Schmucker
Journal: Hepatology (1985)

It is well established that in the rat, rat dimeric IgA is transported from blood to bile across rat liver parenchymal cells via a series of minute smooth membrane–limited vesicles. This pathway is unique from that taken by a number of other ligands, which are internalized for degradation, in that there appears to be little involvement of coated vesicles, multivesicular bodies and lysosomes. The transmembrane receptor for IgA, secretory component, is not recycled but is secreted in part with the ligand into bile and must be produced continuously within the liver cell. Several recent studies have suggested that the receptor for asialoglycoproteins, as well as the structures involved in its processing, may play an important role in IgA processing. It was noted, however, that in all of these studies human polymeric IgA 1 was used in the rat model. Using purified rat and human IgA preparations, we have demonstrated by light and quantitative electron microscopic autora–diography, as well as by certain biochemical procedures, that the two ligands are processed quite differently from one another in the rat. Human IgA disappears from the plasma at a slower rate and is much less efficiently transported into the bile. In addition, up to as much as 30% of the human IgA is diverted to the lysosomal pathway. This diversion of human polymeric IgA may be related to either the association of a serine–linked oligosaccharide at the hinge region of the human polymeric IgA 1 or that large polymers, often found in human IgA preparations may initiate secretory component receptor aggregation, which in turn, interferes with the normal physiological processing of the IgA molecule.
Doctor may face manslaughter charges after a confidential report is made public
Authors: T. Sheldon
Journal: BMJ (2002)

A Dutch paediatric cardiologist is waiting to hear if he is to be charged with manslaughter, after a confidential report into a heart operation was made public, under a law on the disclosure of government information.

The author of the report, Professor Hans Boller, professor of paediatric medicine at Rotterdam's Erasmus University Medical Centre, was angry that his report had been made public, saying: “If you do not allow committees to do fact finding in complete confidentiality you are in trouble.”

The paediatric cardiologist who carried out the procedure was detained in custody for 10 days for …
PTH-004 Prevention of Relapse following Clostridium Difficile Infection using Probiotics: A Retrospective Case-Control study
Authors: L Lee, R Golmohamad, G Macfaul
Journal: Gut (2013)

<h3>Introduction</h3> Clostridium difficile infection is an important hospital acquired infection causing significant healthcare burden. Once patients have had C diff diarrhoea, recurrence rates are high with 44.8% of patients having a relapse of their disease. Lactobacillus Casei is a probiotic that has been shown to reduce rates of antibiotic-associated diarrhoea in elderly patients. There have been no studies analysing the use of probiotics in patients who have had established C.diff infection. <h3>Methods</h3> The study was a single site, retrospective, case-control study of patients who have had C.diff infection and treated with either antibiotics and probiotics or antibiotics alone. Potential study participants were identified from the microbiology database. Criteria for inclusion in the study were adult patients (aged &gt; 18 at time of infection), presence of diarrhoea (defined as ≥ 3 non-formed stool in 24 hours), positive stool C. diff toxin A or B and positive C. Diff antigen. <h3>Results</h3> 66 patients were included for analysis in this study, 31 who had probiotics and 35 who had no-probiotics. The median age of the patients was 78 and 33.3% were male. The number of patients who had a further hospital admission for diarrhoea in the probiotic cohort was 6 (19.4%), compared to 13 in the non-probiotic cohort (35.1%) (p = 0.09). Rates of recurrent C.diff infection were significantly lower, 31.4% vs 6.5% (p = 0.024). <h3>Conclusion</h3> Patients who have had a c.diff infection often have early re-admissions to hospitals as a result of further episodes of diarrhoea or c.diff recurrence. These admissions are associated with significant morbidity and mortality and cost to the health service. This study suggests that the widely available probiotic strain lactobacillus casei appears able to reduce rates of c.diff recurrence rates though further prospective studies are required. <h3>Disclosure of Interest</h3> None Declared.
Mortality After Myocardial Infarction
Authors: Barnett Zumoff
Journal: JAMA (1983)

<h3>To the Editor.—</h3> A recent article by Weinblatt et al inThe Journal(1982; 247:1576) reported the somewhat discouraging conclusion that there was no significant change in mortality after myocardial infarction between the 1960s and 1970s in carefully watched groups, which implies that improvements in care may have little influence on this mortality. Commenting on this in an editorial (<i>JAMA</i>1982;247:1605), Havlik suggested that the authors did not look far enough into the future and that the results of the β-blocker trials with timolol maleate<sup>1</sup>and propranolol hydrochloride (<i>JAMA</i>1981;246:2073) indicated that a decline in postinfarction mortality is indeed to be expected in the 1980s, when these drugs come into wide use for postinfarction prophylaxis. Although this expectation seems reasonable, the mortality experience of the control group in the propranolol study, studied in the late 1970s, did not differ significantly from that of the group studied in the early
Myelodysplastic syndromes with nephrotic syndrome
Authors: Takayuki Saitoh, Hirokazu Murakami, Hideki Uchiumi, Kazuaki Moridaira, Tadashi Maehara, Takafumi Matsushima, Norifumi Tsukamoto, Jun'ichi Tamura, Masamitsu Karasawa, Takuji Naruse, Jun Tsuchiya
Journal: American Journal of Hematology (1999)

It is sometimes reported that the immunological abnormalities in myelodysplastic syndromes (MDS) induce autoimmune disease (i.e., acute systemic vasculitic syndrome, chronic cutaneous vasculitis, polyneuropathy, relapsing polychondritis, and steroid-responsive pulmonary disorders). We investigated the clinical features of patients with MDS accompanied by nephrotic syndrome. We enrolled 125 patients with MDS who were admitted between January 1979 and May 1996 in this study. The renal function was assessed based on the laboratory data and the findings at the physical examination. The diagnoses of nephrotic syndrome and glomerular disease were established when 24-hr urinary excretion was more than 3.5 g and serum total protein was less than 6.0 g/dl, and when the 24-hr protein excretion was more than 1.5 g. Five patients (4%) had glomerular disease, and three (2.4%) had nephrotic syndrome. Of the five patients with glomerular disease, two had refractory anemia (RA), and three had chronic myelomonocytic leukemia (CMMOL). Three of the total 11 patients with CMMOL were diagnosed as having nephrotic syndrome. Among the CMMOL patients, those with nephrotic syndrome showed higher absolute monocyte numbers than did those without nephrotic syndrome (8830 +/- 4677/microl vs. 3061 +/- 2887/microl, P = 0.03). One CMMOL patient was treated with VP-16 and hydroxyurea. As the white blood cell count in this patient decreased, the 24-hr urine protein excretion and the serum tumor necrosis factor alpha level decreased. The relationship between nephrotic syndrome and CMMOL was not clear. High monocyte count and the serum cytokines in MDS patients may play a partial role in the evolution of glomerulonephritis, and CMMOL may be closely related to nephrotic syndrome.
Mild Ulcerative Colitis
Authors: I. E. Gillespie
Journal: BMJ (1970)

Sterilization of Curettes R. J. Fallon, M.D.   690 Unheard Voices Helen M. F. Firth, F.F.A.R.C.S., and others .  690 Coagulation Failure in Pregnancy L. D. Courtney, M.R.C.O.G.   691 Postoperative Fibrinolysis E. T. O'Brien, L.R.C.P.I.   691 Diazepam and Muscle Relaxants S. A. Feldman, F.F.A.R.C.S., and B. E. Crawley, F.F.A.R.C.S   691 Corticosteroids and Pituitary-Adrenal Function J. R. Daly, M.R.C.PATH.   691 A Student's View R. D. Walker   692
A Testimonial to Prof. N. S. Davis.
Authors: S. Burden Overlock
Journal: JAMA (1896)

Pomfret, Conn., June 30, 1896. <h3>To the Editor:</h3> —D. L.'s letter in theJournalof June 20 in regard to a memorial to Dr. N. S. Davis reminds me that I have in my possession a medal struck in 1846, on its face a medallion and the words "N. S. Davis," and on the reverse the inscription "American Medical Association," and the date "1846." This medal was given to me by Mrs. Williams of this town, whose husband, the late Dr. Lewis Williams, was a delegate to the 1846 meeting, which I think met in Louisville, Ky. <h3>Note.</h3> —This convention met in New York in 1846.