tbuckley/cabot-search huggingface dataset:
SOME OBSERVATIONS ON SIX CASES OF RUPTURED SPLEEN
Authors: R. Jamison
Journal: BMJ (1918)

RUPTURED SPLEEN. [LMTl tmmN 285 decreases.If the spring is set primarily at 20 lb.(with 1-1 in.leeway) a stretclhling of 1 in.will leave the spring with I in.leeway and a pull of 7 lb.The spring may have a dial inside its coils reading in pounds and inchles.Lately we have been using an extension applied with a cold glue composed of two parts mastisol and one part Canada balsam.Thle extension proper consists of a lengtll of cotton stockinette, such as is ordinarily used by American orthopaedic surgeons in applying plaster casts.It comes in 25 yard rolls, and is circular, witlh a breadtl of 4 in.The required lengtlh is cut off from tlle roll and rolled on itself, so as to make a garter-like circle.This is slipped over the foot, tlle leg is then painted in sections witlh the glue, and the stockinette is unrolled on to it, all the stretch being taken out during the unrolling.A roller bandage is then temporarily bound around it.The strip overlhauging the foot, which is purposely left, is then split front and back and tied to the bars of the footpiece, from whiclh the pull is taken at once.The foot is supported
The length of lipids bound to human CD1d molecules modulates the affinity of NKT cell TCR and the threshold of NKT cell activation
Authors: Corinna McCarthy, Dawn Shepherd, Sebastian Fleire, Victoria S. Stronge, Michael Koch, Petr A. Illarionov, Giovanna Bossi, Mariolina Salio, Galit Denkberg, Faye Reddington, Andrea Tarlton, B. Gopal Reddy, Richard R. Schmidt, Yoram Reiter, Gillian M. Griffiths, P. Anton van der Merwe, Gurdyal S. Besra, E. Yvonne Jones, Facundo D. Batista, Vincenzo Cerundolo
Journal: The Journal of Experimental Medicine (2007)

CD1d-restricted lymphocytes recognize a broad lipid range. However, how CD1d-restricted lymphocytes translate T cell receptor (TCR) recognition of lipids with similar group heads into distinct biological responses remains unclear. Using a soluble invariant NKT (iNKT) TCR and a newly engineered antibody specific for α-galactosylceramide (α-GalCer)–human CD1d (hCD1d) complexes, we measured the affinity of binding of iNKT TCR to hCD1d molecules loaded with a panel of α-GalCer analogues and assessed the rate of dissociation of α-GalCer and α-GalCer analogues from hCD1d molecules. We extended this analysis by studying iNKT cell synapse formation and iNKT cell activation by the same panel of α-GalCer analogues. Our results indicate the unique role of the lipid chain occupying the hCD1d F′ channel in modulating TCR binding affinity to hCD1d–lipid complexes, the formation of stable immunological synapse, and cell activation. These data are consistent with previously described conformational changes between empty and loaded hCD1d molecules (Koch, M., V.S. Stronge, D. Shepherd, S.D. Gadola, B. Mathew, G. Ritter, A.R. Fersht, G.S. Besra, R.R. Schmidt, E.Y. Jones, and V. Cerundolo. 2005. Nat. Immunol 6:819–826), suggesting that incomplete occupation of the hCD1d F′ channel results in conformational differences at the TCR recognition surface. This indirect effect provides a general mechanism by which lipid-specific lymphocytes are capable of recognizing both the group head and the length of lipid antigens, ensuring greater specificity of antigen recognition.
Performance of the aspartate aminotransferase-to-platelet ratio index for the staging of hepatitis C-related fibrosis: An updated meta-analysis
Authors: Zhong-Hua Lin, Yong-Ning Xin, Quan-Jiang Dong, Qing Wang, Xiang-Jun Jiang, Shu-Hui Zhan, Ying Sun, Shi-Ying Xuan
Journal: Hepatology (2010)

The aspartate aminotransferase-to-platelet ratio index (APRI), a tool with limited expense and widespread availability, is a promising noninvasive alternative to liver biopsy for detecting hepatic fibrosis. The objective of this study was to update the 2007 meta-analysis to systematically assess the accuracy of APRI in predicting significant fibrosis, severe fibrosis, and cirrhosis stage in hepatitis C virus (HCV) monoinfected and HCV / human immunodeficiency virus (HIV) coinfected individuals. Studies comparing APRI versus biopsy in HCV patients were identified via a thorough literature search. Areas under summary receiver operating characteristic curves (AUROC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were used to examine the APRI accuracy for the diagnosis of significant fibrosis, severe fibrosis, and cirrhosis. Heterogeneity was explored using meta-regression. Twenty-one additional studies were eligible for the update and, in total, 40 studies were included in this review (n = 8,739). The summary AUROC of the APRI for the diagnosis of significant fibrosis, severe fibrosis, and cirrhosis were 0.77, 0.80, and 0.83, respectively. For significant fibrosis, an APRI threshold of 0.7 was 77% sensitive and 72% specific. For severe fibrosis, a threshold of 1.0 was 61% sensitive and 64% specific. For cirrhosis, a threshold of 1.0 was 76% sensitive and 72% specific. Moreover, we found that the APRI was less accurate for the identification of significant fibrosis, severe fibrosis, and cirrhosis in HIV/HCV coinfected patients.Our large meta-analysis suggests that APRI can identify hepatitis C-related fibrosis with a moderate degree of accuracy. Application of this index may decrease the need for staging liver biopsy specimens among chronic hepatitis C patients.
BIG 1-98: A randomized double-blind phase III study evaluating letrozole and tamoxifen given in sequence as adjuvant endocrine therapy for postmenopausal women with receptor-positive breast cancer.
Authors: HT Mouridsen, A Giobbie-Hurder, L Mauriac, R Paridaens, M Colleoni, B Thuerlimann, JF Forbes, RD Gelber, A Wardley, I Smith, KN Price, A Coates, A Goldhirsch
Journal: Cancer Research (2009)

Abstract Abstract #13 Background: BIG 1-98 compares letrozole (Let), tamoxifen (Tam) and sequences of Let and Tam as adjuvant endocrine therapy for postmenopausal women with receptor-positive breast cancer. Initial results (published in 2005) demonstrated the superiority of Let over Tam in significantly prolonging disease-free survival (DFS) and reducing the risk of relapse in distant sites. Following these results, investigators were informed of the treatment allocation for patients randomized to Tam alone, and about one third of these patients opted to receive Let. The three Let-containing treatments remained blinded. We now evaluate Let and Tam given in sequence compared with Let alone and update the comparison of Let alone and Tam alone.&amp;#x2028; Methods: 6182 patients were randomized to the 4-arm option (entry Sep99-May03) [Tam x 5 years (Tam), Let x 5 (Let), Tam x 2→Let x 3 (Tam→Let), or Let x 2→Tam x 3 (Let→Tam)]. Another 1828 patients were randomized to the 2-arm option (Tam vs. Let; entry Mar98-Mar00). The primary endpoint was DFS (time from randomization to first occurrence of invasive breast cancer recurrence, invasive contralateral breast cancer, second non-breast malignancy, or death from any cause). The presentation will focus on the clinically-relevant comparisons evaluating Tam→Let vs. Let and Let→Tam vs. Let, assessed from the time of randomization. Acknowledging multiple comparisons, the hazard ratios are presented with 99% confidence intervals (CIs).&amp;#x2028; Results: The median follow-up time is 71 months. Hazard ratios comparing treatments from time of initial randomization in terms of DFS, overall survival, and time to distant recurrence are displayed below.&amp;#x2028; &amp;#x2028; With this long term follow-up, adverse events for Let and Tam are consistent with the known safety profile of both agents.&amp;#x2028; A protocol-specified update of the previously-reported comparison of Let x 5 vs. Tam x 5 (i.e., the monotherapy arms, including patients in both the 2-arm and 4-arm options; N=4922) suggests improved survival for patients treated with Let (HR=0.87, 95% CI=0.75-1.02, p=0.08, 76 months median follow-up). In this comparison, about a quarter of the patients in the Tam arm crossed over to Let after 3-5 years of Tam.&amp;#x2028; Conclusion: The sequential treatments did not improve DFS compared with Let alone. Trends support initial use of Let in patients at higher risk of relapse. Patients commenced on Let can be switched to Tam if required. Updated results of the monotherapy comparison suggest superior overall survival with Let compared with Tam. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 13.
Cholecystectomy, Serum Cholesterol, and Colon Cancer
Authors: A. M. Y. Nomura, G. N. Stemmermann, L. K. Heilbrun, A. Kagan
Journal: JAMA (1982)

<h3>To the Editor.—</h3> Of 9,354 men examined in a prospective study, we were able to identify 270 who had a cholecystectomy a year or longer before examination, as confirmed by a subsequent hospital record review. The 270 men with cholecystectomy had a significantly lower age-adjusted mean serum cholesterol level of 208.2 mg/dL, compared with 216.4 mg/dL for the rest of the study population (<i>P</i>&lt;.001). This observation is relevant in view of two recent findings: first, cholecystectomy subjects had an increased risk for right-sided colon cancer<sup>1,2</sup>; second, we found in a prospective study that a low serum cholesterol level in men increased their risk for colon cancer, especially on the right side, excluding the hepatic flexure.<sup>3</sup>Consequently, there is a suggestion that a low serum cholesterol level in cholecystectomy subjects may be related to an increased risk for right-sided colon cancer. A subsample of the examined menalso
Comparative study on the proarrhythmic effects of some antiarrhythmic agents.
Authors: S Dhein, A Müller, R Gerwin, W Klaus
Journal: Circulation (1993)

BACKGROUND A main side effect of antiarrhythmic drug therapy is the tendency of these drugs to promote arrhythmia within the therapeutic concentration range, i.e., the proarrhythmic activity of these drugs. However, a model for in vitro assessment, quantification, and comparison of proarrhythmic drug activities was still lacking, and only sparse data were available. METHODS AND RESULTS To analyze the arrhythmogenic risk of common antiarrhythmic drugs in a quantitative and comparative manner, isolated perfused rabbit hearts were treated with increasing concentrations of antiarrhythmic drugs corresponding to low, medium, and high therapeutic concentrations. For analysis of the epicardial activation process, an epicardial mapping (256 unipolar leads) was performed. For each electrode, the activation time was determined. From these data, the origins of epicardial activation ("breakthrough points" [BTP]) were determined. At each electrode, an activation vector (VEC) was calculated giving direction and velocity of the local excitation wave. The beat similarity of various heartbeats (under treatment) compared with control was evaluated by determination of the percentage of identical BTPs (deviation &lt; or = 1 mm) and of similar VECs (deviation &lt; or = 5 degrees). BTP and VEC were reduced by all antiarrhythmic agents tested (propafenone = flecainide &gt; quinidine &gt; ajmaline &gt; procainamide &gt; disopyramide &gt; mexiletine = lidocaine &gt; sotalol), indicating a more or less pronounced disturbance of the epicardial activation process. Treatment with propafenone, quinidine, and disopyramide and to a lesser extent sotalol prolonged the activation-recovery interval (ARI). ARI dispersion was greatly enhanced by flecainide and was reduced by sotalol. In addition, it could be shown that propranolol is able to reduce the proarrhythmic action of flecainide. This effect seemed to be due to a reduction of the flecainide-induced increase in ARI dispersion. CONCLUSIONS From the results of our study, we propose the following rank order of the arrhythmogenic risk: flecainide &gt; propafenone &gt; quinidine &gt; ajmaline &gt; disopyramide &gt; procainamide &gt; mexiletine, lidocaine &gt; sotalol. Moreover, we conclude that propranolol given additionally may be helpful in reducing the proarrhythmic risk of flecainide.
Discharge of Foetal Bones by the Rectum
Authors: V. H. Barnett
Journal: BMJ (1951)

The patient has been followed up for four years.There have been no further attacks, and she has been in good health.Investigation of the alimentary, renal, and biliary tracts revealed no possible source of origin of the enteroliths.Biochemical analysis indicated that they were composed mainly of organic debris, with some fat and lipoid matter, and a moderate amount of calcium and magnesium phosphates.
C1 Esterase Inhibitor (C1-INH) Concentrate in the Treatment of Acute Attacks in Hereditary Angioedema: Interim Results of the Treatment of 975 Attacks in an Ongoing, Prospective, Open-Label Study in North America (I.M.P.A.C.T.2)
Authors: S. Goodman, R. Levy, R. Wasserman, A. Bewtra, D. Hurewitz, J. Moy, W. Yang, L. Schneider, F. Packer, S. Bahna, K. Jacobson, J. Offenberger, F. Eidelman, G. Janss, P. Kiessling, C. Peters, T. Craig
Journal: Journal of Allergy and Clinical Immunology (2010)
Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trials
Authors: Ebenezer Daniel, Cynthia A. Toth, Juan E. Grunwald, Glenn J. Jaffe, Daniel F. Martin, Stuart L. Fine, Jiayan Huang, Gui-shuang Ying, Stephanie A. Hagstrom, Katrina Winter, Maureen G. Maguire
Journal: Ophthalmology (2013)
Altered Ligands Reveal Limited Plasticity in the T Cell Response to a Pathogenic Epitope
Authors: Sabine Pingel, Pascal Launois, Deborah J. Fowell, Christoph W. Turck, Scott Southwood, Alessandro Sette, Nicolas Glaichenhaus, Jacques A. Louis, Richard M. Locksley
Journal: The Journal of Experimental Medicine (1999)

Experimental leishmaniasis offers a well characterized model of T helper type 1 cell (Th1)-mediated control of infection by an intracellular organism. Susceptible BALB/c mice aberrantly develop Th2 cells in response to infection and are unable to control parasite dissemination. The early CD4(+) T cell response in these mice is oligoclonal and reflects the expansion of Vbeta4/ Valpha8-bearing T cells in response to a single epitope from the parasite Leishmania homologue of mammalian RACK1 (LACK) antigen. Interleukin 4 (IL-4) generated by these cells is believed to direct the subsequent Th2 response. We used T cells from T cell receptor-transgenic mice expressing such a Vbeta4/Valpha8 receptor to characterize altered peptide ligands with similar affinity for I-Ad. Such altered ligands failed to activate IL-4 production from transgenic LACK-specific T cells or following injection into BALB/c mice. Pretreatment of susceptible mice with altered peptide ligands substantially altered the course of subsequent infection. The ability to confer a healer phenotype on otherwise susceptible mice using altered peptides that differed by a single amino acid suggests limited diversity in the endogenous T cell repertoire recognizing this antigen.
Clinical characteristics and electrophysiologic properties of atrioventricular accessory pathways: Importance of the accessory pathway location
Authors: Christian de Chillou, Luz Maria Rodriguez, Jürg Schläpfer, Kostas G. Kappos, Apostolos Katsivas, Xie Baiyan, Joep L.R.M. Smeets, Hein J.J. Wellens
Journal: Journal of the American College of Cardiology (1992)
Fuel-Mediated Teratogenesis and Breastfeeding
Authors: Andreas Plagemann, Thomas Harder
Journal: Diabetes Care (2011)

About 30 years ago, Norbert Freinkel and Boyd Metzger introduced a seminal hypothesis into developmental medicine and diabetes research. The fuel-mediated teratogenesis concept says that prenatal exposure to increased levels of “mixed nutrients,” especially increased glucose, and the corresponding increase in fetal insulin have immediate as well as long-lasting deleterious consequences for the offspring of diabetic mothers (1,2). In fact, this paradigm became a kind of forerunner of today's rapidly expanding fields of “perinatal programming” and “developmental origins of health and disease.” It has variously been proven to be valid and has even been extended to the case of maternal overweight during pregnancy (3). Accordingly, exposure to maternal gestational diabetes mellitus (GDM) and overweight is meanwhile one of the best proven paradigms concerning the long-term impact of perinatal programming (4,5).

It is crucial for the concept of fuel-mediated teratogenesis that altered food supply during critical periods of early development gives rise to lasting deleterious consequences. Differentiation and maturation, however, of affected organs and systems, such as pancreas, adipose tissue, and brain, are not finished at birth (2). The question therefore arises whether a prolongation of these critical exposures into the neonatal period might have similar effects.

Colostrum is already produced during the last trimester of gestation. The composition of early breast milk reflects metabolic changes that occur in GDM (6). Moreover, in a considerable number of women with GDM, glucose metabolism does not completely normalize after pregnancy (7). Studies suggest that breast milk from women with diabetes contains, for example, increased levels of glucose and insulin as compared with breast milk from healthy mothers (6,8,9). Moreover, it has been shown that not only glucose but even hormones like insulin and leptin are absorbed from milk in the immature gut of an …
The Diagnosis of Whipple's Disease
Authors: William O. Dobbins
Journal: New England Journal of Medicine (1995)

Whipple's disease is both rare and enigmatic. It usually presents in middle-aged men, but in the 80 or so years since it was first described, fewer than 10 cases per year have been reported in the world's literature.1 The most common clinical presentation is a malabsorption syndrome, although patients may have severe arthralgias for years before diarrhea develops. Cardiac and central nervous system involvement is also common. Patients may present with fever of undetermined cause, a sarcoidosis-like illness, or a wasting syndrome. Because the illness is insidious in its onset, has a varied clinical presentation, and is rare, it is . . .
The channelopathies: novel insights into molecular and genetic mechanisms of human disease
Authors: R. S. Kass
Journal: Journal of Clinical Investigation (2005)

Ion channels are pore-forming proteins that provide pathways for the controlled movement of ions into or out of cells. Ionic movement across cell membranes is critical for essential and physiological processes ranging from control of the strength and duration of the heartbeat to the regulation of insulin secretion in pancreatic beta cells. Diseases caused by mutations in genes that encode ion channel subunits or regulatory proteins are referred to as channelopathies. As might be expected based on the diverse roles of ion channels, channelopathies range from inherited cardiac arrhythmias, to muscle disorders, to forms of diabetes. This series of reviews examines the roles of ion channels in health and disease.
Predicting treatment response in psoriasis using serum levels of adalimumab and etanercept: a single-centre, cohort study
Authors: S.K. Mahil, Z. Arkir, G. Richards, C.M. Lewis, J.N. Barker, C.H. Smith
Journal: British Journal of Dermatology (2013)

A substantial proportion of patients with psoriasis do not respond, or lose initial response to tumour necrosis factor‐α antagonists. One possible mechanism relates to subtherapeutic drug levels due to an immunogenic antibody response. To investigate the association between serum adalimumab and etanercept levels, antidrug antibody levels and clinical response in a cohort of patients with psoriasis using a commercially available enzyme‐linked immunoassay. In a single‐centre cohort of 56 adults with chronic plaque psoriasis initiated on adalimumab or etanercept monotherapy between 2009 and 2011, drug and antidrug antibody levels were measured at the patients' routine clinic reviews (4, 12 and 24 weeks of treatment and the last available observation). Patients' responses at 6 months were stratified into responders [75% reduction in Psoriasis Area and Severity Index from baseline (PASI 75) or Physician's Global Assessment score of 'clear' or 'nearly clear'] and nonresponders (failure to achieve PASI 50). After 4 weeks, adalimumab levels were significantly higher in responders compared with nonresponders (P =0·003) and these higher levels were sustained at 12 and 24 weeks. Anti adalimumab antibodies were detected in 25% of nonresponders (two of eight patients, average 22·5 weeks' follow‐up) and none of the responders (n =23, average 26·1 weeks' follow‐up). There was no significant association between etanercept levels and clinical response at 4 weeks (P =0·317) and no antietanercept antibodies were detected. Lack of serum trough levels may have resulted in underestimation of the prevalence of antidrug antibodies. Early adalimumab drug level monitoring at 4 weeks may be useful in predicting treatment response and potentially reduce drug exposure (and associated cost) with earlier review of treatment in those with low levels. No conclusions about the value of etanercept drug monitoring can be made due to the paucity of data. Larger studies are now required to assess the clinical utility and cost‐effectiveness of these assays in personalizing therapy in psoriasis.
Endoscopic Findings in a Case of Kaposi's Sarcoma with Involvement of the Large and Small Bowel
Authors: Ch. Ell, W. Matek, M. Gramatzki, B. Kaduk, L. Demling
Journal: Endoscopy (1985)

A case of Kaposi's sarcoma in underlying acquired immunodeficiency syndrome (AIDS) with involvement of the colon and the terminal ileum is presented. The endoscopic and histological findings are described and the technical and clinical aspects of the results discussed.
Planned splenectomy in treatment of idiopathic thrombocytopenic purpura.
Authors: A I Macpherson, J Richmond
Journal: BMJ (1975)

The results of a policy of treatment in idiopathic thrombocytopenic purpura based on previous observations on the natural history of the disease and its response to corticosteroids are described. The results of splenectomy were better when the history was less than 100 days. Three patterns of response to splenectomy were observed: complete remission, symptomatic remission, and relapse. The prognosis can be determined by the level of the platelet count six weeks after splenectomy. Corticosteroid treatment for more than three weeks before splenectomy noticeably increased the incidence of complications after operation. Splenectomy can safely be performed in pregnancy. The decision to operate should be made on the maternal condition and its response to corticosteroids.
Injury to child pedestrians
Authors: H. Soori, R S Bhopal
Journal: BMJ (1995)

EDITOR,—Ian Roberts concludes that the key to preventing injuries to children by motor vehicles is a change in transport policy.1 He argues his case on the basis that the recent decrease in death rates probably reflects reduced exposure (fewer pedestrians), that personal characteristics are not strong predictors of injury, that education has had little effect on rate of injury, and that traffic management has been shown to work.

While transport policy is a key item …