tbuckley/cabot-search huggingface dataset:
Antiphospholipid Thrombosis: Clinical Course after the First Thrombotic Event in 70 Patients
Authors: Michael H. Rosove, Petronella M. C. Brewer
Journal: Annals of Internal Medicine (1992)

▪Objective: To determine the clinical course and influence of antithrombotic therapy in patients with lupus anticoagulant or anticardiolipin antibodies, or both, after the first thromboembolic event. ▪Design: Retrospective survey of consecutive patients treated according to their physician's best judgment. ▪Setting: Secondary and tertiary referral practice. ▪Patients: Seventy patients (48 women [69%]) with a mean age (±SD) of 45.5 ± 17.3 years. The antiphospholipid syndrome was primary in 51 patients (73%) and secondary to systemic lupus erythematosus in 14 patients (20%) and to chronic idiopathic thrombocytopenic purpura in 5 patients (7%). ▪Measurements: Site of initial and recurrent thrombotic events (venous or arterial), as well as kind (aspiring, heparin, or warfarin) and intensity of anticoagulation. ▪Results: Total follow-up after the first thrombotic event was 361.0 patient-years (mean [±SD], 5.2 ± 5.6 years per patient). Thirty-seven patients (53%) had 54 recurrent events, with 2 patients experiencing fatal events. Arterial events were followed by arterial events, and venous events by venous events, in 49 of 54 instances (91%). Recurrence rates during "no treatment;" aspirin therapy; or low-, intermediate-, or high-intensitywarfarin therapy (international normalized ratios [INRs] <1.9, 2.0 to 2.9, and >3.0, respectively, or rabbit brain thromboplastin prothrombin time ratios of approximately <1.3,1.3 to 1.5, and >1.5, respectively) were 0.19, 0.32, 0.57, 0.07 (P = 0.12), and 0.00 (P < 0.001) per patient-year. The follow-up periods for the five types of therapy were 161.2, 37.8, 11.3, 40.9, and 110.2 patient-years, respectively. The highest INR coincident with thrombosis was 2.6. Five warfarin-treated patients had five significant bleeding events (0.031 per patient-year). ▪Conclusions: Recurrent thrombosis is a potentially serious problem for patients with lupus anticoagulant or anticardiolipin antibodies or both. The site of the first event (arterial or venous) tended to predict the site of subsequent events. Intermediate- to high-intensity warfarin therapy may confer better antithrombotic protection than low- to intermediate-intensity warfarin therapy or aspirin therapy. Further studies are needed to define more precisely the rethrombosis rate and optimal type, intensity, and duration of antithrombotic therapy.
Medical Care for the Elderly
Authors: JOSEPHINE A. LOCKWOOD
Journal: Annals of Internal Medicine (1975)

Comments and Correction1 November 1975Medical Care for the ElderlyJOSEPHINE A. LOCKWOOD, M.D.JOSEPHINE A. LOCKWOOD, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-83-5-741_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: I have followed with interest the paper of Dr. Brickner and colleagues concerning his program for care of the elderly at home (Ann Intern Med82:1-6, 1975) and the editorials and letters engendered by it. Doctor Mumford and associates' letter of July 1975 (Ann Intern Med83:125-126, 1975) was most interesting and delineated programs long in existence for the chronically ill elderly patients of New York City through the New York City Health & Hospitals Corporation. Doctor Brickner's reply to this letter was inaccurate in that he apparently is under the impression that services delivered to patients... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Department of Community Medicine New York Medical College New York, New York PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 November 1975Volume 83, Issue 5Page: 741-741KeywordsElderly Issue Published: 1 November 1975 PDF DownloadLoading ...
Uromodulin and Translational Medicine
Authors: John R. Sedor
Journal: Journal of the American Society of Nephrology (2010)

Tamm-Horsfall protein (THP) was originally described in 1895 as “urinary mucoprotein” and biochemically characterized approximately 50 years ago. Kidney epithelial cells of all placental mammals synthesize THP, and it is the most abundant protein in normal urine.1,2 Pirica, a novel THP-like gene that is induced in response to predation, was recently identified in tadpoles, suggesting that THP family proteins are also present in invertebrate species.3 Uromodulin was originally reported as a unique immunosuppressive glycoprotein from the urine of pregnant women,4 and its amino acid composition is identical to THP.5 Standard nomenclature for THP is now uromodulin.

Uromodulin provides a protein infrastructure for urinary casts used to diagnosis various kidney diseases in the clinic. Experimentalists have used both in vitro and in vivo models to define the biology of uromodulin in the urinary tract, and protein chemists have extensively characterized its biochemical properties and domains.6–10 Despite these efforts, the function of uromodulin remains an enigma. Published data suggest uromodulin is glycosyl phosphatidyl inositol-anchored along the apical domain of some kidney epithelia and secreted into urine and blood. It inhibits both bacterial colonization of the urinary track and stone formation, binds and activates leukocytes, and generates the water impermeability of the thick ascending limb of Henle by assembly into filaments through its zona pelucida domain. Tissue distribution of pirica, the amphibian uromodulin-like protein, also supports the hypothesis that uromodulin regulates the water permeability of tissue.3

Mutations in UMOD , the gene that encodes uromodulin, cause rare, autosomal dominant, primary tubulointerstitialkidney diseases, particularly familial juvenile hyperuricemicnephropathy (FJHN; OMIM 191845) and a form of medullary cystic kidney disease (MCKD2; …
Polypectomy of a colonic muco-submucosal elongated polyp
Authors: K. Kume, H. Sakata, I. Yoshikawa, T. Watanabe, M. Harada
Journal: Endoscopy (2009)

A 66-year-old man was referred to our department for screening colonoscopy. He had no gastrointestinal symptoms. Barium enema revealed a curiously elongated polypoid lesion, 12 cm in length, in the transverse colon ([Fig. 1]).
Thromboembolism
Authors: J. F. MUSTARD, M. A. PACKHAM
Journal: Circulation (1970)

Thromboembolism may be considered as one of the manifestations of the response of blood to injury. Other manifestations of this include hemostasis, increased vessel permeability, and vasculitis; disturbances of the microcirculation may lead to tissue injury and organ dysfunction. The factors that can initiate these changes by stimulation of platelets are exposure of subendothelial tissue (collagen, basement membrane) and intravascular stimuli such as antigen-antibody complexes, viruses, bacteria, and endotoxin. These stimuli have a number of effects on blood; the interaction of the platelets with the above stimuli leads to the release of platelet constituents including ADP; the ADP causes the platelets to adhere to each other; the aggregated platelets cause acceleration of clotting; this and changes in blood flow promote the formation of fibrin around the platelet aggregates. Some of the stimuli such as collagen and antigen-antibody complexes also activate blood coagulation through factor XII; some of the materials released from these platelets affect the vessel wall. The initial platelet mass is transformed to a fibrin mass. There are compounds that inhibit the platelet release reaction, platelet aggregation, and blood coagulation and activate the fibrinolytic mechanism. It appears that by the selective use of these compounds we can improve our management of all aspects of thromboembolic disease related to vascular and intravascular stimuli.
Survival of Mature CD4 T Lymphocytes Is Dependent on Major Histocompatibility Complex Class II–expressing Dendritic Cells
Authors: Thomas Brocker
Journal: The Journal of Experimental Medicine (1997)

Thymic T cell development is controlled by T cell receptor (TCR)–major histocompatibility complex (MHC) interactions, whereas a further dependence of peripheral mature T cells on TCR–MHC contact has not been described so far. To study this question, CD4 T cell survival was surveyed in mice lacking MHC class II expression and in mice expressing MHC class II exclusively on dendritic cells. Since neither of these mice positively select CD4 T cells in the thymus, they were grafted with MHC class II–positive embryonic thymic tissue, which had been depleted of bone marrow derived cells. Although the thymus grafts in both hosts were repopulated with host origin thymocytes of identical phenotype and numbers, an accumulation of CD4+ T cells in peripheral lymphoid organs could only be observed in mice expressing MHC class II on dendritic cells, but not in mice that were completely MHC class II deficient. As assessed by histology, the accumulating peripheral CD4 T cells were found to be in close contact with MHC class II+ dendritic cells, suggesting that CD4 T cells need peripheral MHC class II expression for survival and that class II+ dendritic cells might play an important role for the longevity of CD4 T cells.
Lifestyle Modification and Heart Disease
Authors: Mike Mitka
Journal: JAMA (2009)

NEWORLEANS—Twomajortrialsexploring thebenefitsof lifestylemodifications forprimaryandsecondarypreventionof cardiovascular events failed to achieve their primary end points, which were to lower levels of low-density lipoprotein cholesterol (LDL-C) and mortality and hospitalization. But the researchers presenting thestudies’ findingsat theScientific Sessions of the American Heart AssociationhereinNovemberarestillcalling their studies successful. One of these studies, a randomized controlled trial called FIT Heart (a Family-Based Intervention Trial to Improve Heart Health), enrolled 501 healthy adult family members (66% of whom were female and 36% were nonwhite, with a mean age of 48 years) to test the hypothesis that the hospitalization of a family member with cardiovascular disease could provide a “teachable moment” for motivating adult family members to adopt lifestyle changes that would lower their LDL-C level. These family memberswere screened forcardiovascular risk factors and counseled about lifestyle changes (consuming a healthier diet and engaging in exercise), and their physicians received progress reports. However, at 1-year follow-up, participants in both the experimental group and the control group (who received only a brief prevention message and a letter to their health care clinician only if they had a critical risk factor for the levels reported) had comparable decreases in LDL-C levels, about 4.4 mg/dL from a mean baseline of about 129.5 mg/dL (Mosca L et al. Circ Cardiovasc Qual Outcomes. 2008;1[2]98-106). The second study, called HF-ACTION (for Heart Failure: a Controlled Trial Investigating Outcomes of Exercise Training), tested whether patients with heart failure participating in a highly structured exercise program in addition to usual care would experience a reduction in all-cause mortality and all-cause hospitalizations. But after an average of 2.5 years’ follow-up, mortality and
Nordic livertransplantation register and prognostic study
Authors: S. Keiding, L. Barkholt, B.G. Ericzon, S. Erikssion, A. Hiortug, K. Hückerstedt, H. Isoniomi, I. Karlberg, Ø. Mathisen, H. Person, K. Salmela, E. Schrumgf
Journal: Journal of Hepatology (1991)
Transcriptional regulation of the human transferrin gene by GADD153 in hepatoma cells
Authors: Kyung-Ran You, Ming-Jie Liu, Xue-Ji Han, Zee-Won Lee, Dae-Ghon Kim
Journal: Hepatology (2003)

The transcription factor CHOP/GADD153 is reportedly induced by cellular stresses such as UV light, genotoxic agents, and protein misfolding in the endoplasmic reticulum. However, the mechanism whereby induction of the GADD153 gene is linked to a downstream pathway is still unclear. Previously, we observed that a synthetic retinoid N –(4–hydroxyphenyl)retinamide (4HPR) effectively impaired cell growth and survival (induction of growth arrest and apoptosis) in human hepatoma cells, which was accompanied by over expression of GADD153. Furthermore, GADD153 –transfected Hep 3B cells were growth arrested and were sensitized to drug–induced apoptosis. Thus, in this study, we used suppression subtractive hybridization (SSH) to identify GADD153 target genes that were up–regulated or down–regulated in the GADD153 transfectants. We screened 614 sequence–verified clones by Northern blotting, of which 42 genes were scored as over expressed and 17 genes as under expressed in GADD153 transfectants compared with control vector transfectants. Of those genes, 49 corresponded to known genes in public databases. Among them, we further verified that the expression of transferrin (Tf), which is a negative acute–phase protein and is essential to cell survival as a growth factor, was highly modulated by drug–induced GADD153 over expression or by in vitro transfection. GADD153 significantly antagonized the C/EBP (C/EBP–α, –β, and –δ)–mediated transcriptional activation of the Tf gene. In conclusion, Tf and other target genes identified may play a functional role in the downstream pathway of GADD153.
Development of generic skills
Authors: D. Pencheon
Journal: BMJ (1998)

As doctors, we learn four sets of skills: firstly, the basic medical sciences that medical schools purport to teach us; secondly, the specialist skills that we learn (despite our professional examinations); thirdly, the special interest skills that most of us develop in our substantive posts; and fourthly, least acknowledged, but equally important, are the many generic skills (see box) that we pick up by that well trusted, educational technique of subconscious osmosis. By muddling through, many doctors become reasonably competent at these generic skills. We should, however, be more explicit about the most important of these skills and how they might be acquired.

Curriculums are becoming increasing explicit in what competencies are expected. A competency (defined as the ability to perform an activity within an occupation to a set standard) is a natural unit of curriculum and professional development. Unfortunately, it is not clear how to develop these competencies systematically or how to measure them objectively. This is more true of generic competencies (for example, managing a meeting) than of technical competencies (for example, performing a lumbar puncture). There is rarely a systematic approach to learning generic skills. How many of us, needing to write a business plan and project manage a research bid, suddenly appreciate the concept of a learning need?

Generic skills are those that we all need to manage the world around us so that we can use our technical skills more effectively.

#### Some essential generic skills

Managing yourself is usually called “time management,” as though it is something external that is being managed. When you …
Direct Angioplasty for Acute Myocardial Infarction
Authors: Mark H. Eckman, John B. Wong, Deeb N. Salem, Stephen G. Pauker
Journal: Annals of Internal Medicine (1992)

Purpose: To review the usefulness of angioplasty done early in the course of an acute myocardial infarction without preceding thrombolytic therapy. Data Sources: The English-language literature was searched from 1983 through October 1991 using MEDLINE; bibliographies from selected articles were searched by hand. Study Selection: Series reporting results for direct angioplasty without preceding thrombolytic therapy were reviewed. Twenty-three articles describing a total of 4368 patients were found. Data Extraction: After duplicate patient series were eliminated, weighted average short- and long-term mortality rates were calculated for the remaining 2073 patients in 10 series and for selected clinical subsets. Results of Data Synthesis: Average hospital mortality for patients with acute myocardial infarction having direct angioplasty was 8.3% (95% Cl, 7.1% to 9.5%). Patients in cardiogenic shock had the highest mortality (44.2%; Cl, 35.9% to 52.5%); patients with one-vessel disease had the lowest (1%; Cl, 0% to 2.3%). For patients in cardiogenic shock, data on direct angioplasty appeared superior to data for similar patients receiving thrombolytic therapy. Although few data exist, a survival advantage was also suggested for patients with a history of previous bypass surgery (hospital mortality, 11.1% [Cl, 4.4% to 17.8%]). Conclusions: Direct angioplasty has an overall mortality similar to that of thrombolytic therapy. Patients who may benefit more from mechanical revascularization than from thrombolytic therapy include those at increased risk for thrombolytic therapy (uncontrolled hypertension, recent major surgery, cerebrovascular accident, prolonged cardiopulmonary resuscitation, or bleeding diathesis), and those with cardiogenic shock. The efficacy in several other patient subsets (age > 65 years, previous coronary artery bypass grafting, prolonged delay before reperfusion) warrants further study.
Diabetes and Coronary Revascularization
Authors: James D. Flaherty
Journal: JAMA (2005)

Patients with diabetes mellitus account for approximately 25% of the nearly 1.5 million coronary revascularization procedures performed each year in the United States and experience worse outcomes compared with nondiabetic patients.To summarize the current state of evidence comparing the effectiveness and safety of coronary artery bypass graft (CABG) surgery and percutaneous coronary intervention (PCI) in diabetic patients and to examine developments that may affect future outcomes in this high-risk group.Using the key terms diabetes mellitus, revascularization, coronary artery bypass, angioplasty, and coronary intervention, we searched MEDLINE from 1985 to 2004 for all randomized controlled trials (RCTs) comparing CABG surgery and PCI that reported outcomes in diabetic patients. Bibliographies and the Web sites of cardiology conferences were also reviewed. Studies comparing drug-eluting stents and bare-metal stents were identified in a similar fashion. The literature was reviewed to identify clinical measures that may impact revascularization outcomes in diabetic patients.We identified 6 RCTs comparing CABG surgery and PCI in a total of 950 diabetic patients. A mortality benefit for CABG over balloon-only PCI has been demonstrated in diabetic patients with multivessel coronary artery disease but has not been clearly established against stent-assisted PCI or in high-risk CABG patients. Use of glycoprotein IIb/IIIa receptor inhibitors has improved survival in diabetic patients undergoing PCI. Restenosis after PCI in diabetic patients has led to substantially higher repeat revascularization rates than after CABG. The use of drug-eluting stents has led to dramatic reductions in restenosis in diabetic patients. Ongoing RCTs comparing CABG and PCI using drug-eluting stents in diabetic patients will clarify the impact of these advances on outcomes.There is a relative lack of data from RCTs specifically comparing CABG surgery and PCI as currently practiced in diabetic patients. The mortality advantage and decreased rates of revascularization seen with CABG in subgroups from early trials may not be applicable in the era of drug-eluting stents, glycoprotein IIb/IIIa inhibitors, and the latest medical therapies.
Vaccination for Influenza — Any Alternatives?
Authors: Stephen C. Schoenbaum
Journal: New England Journal of Medicine (1978)

Inactivated influenza vaccine is the most widely used vaccine in the United States, with annual sales of approximately 15 to 20 million doses. It is also one of the least satisfactory immunizing agents, with only 60 to 70 per cent effectiveness when optimally constituted. The vaccine needs frequent updating to keep up with changes in the virus, and with major antigenic shifts it has usually not been possible to make sufficient vaccine in time. The vaccine causes a substantial number of local and systemic reactions, which tend to be even more frequent in children. Judging from experience with the National . . .
Highly conserved non-coding elements on either side of SOX9 associated with Pierre Robin sequence
Authors: Sabina Benko, Judy A Fantes, Jeanne Amiel, Dirk-Jan Kleinjan, Sophie Thomas, Jacqueline Ramsay, Negar Jamshidi, Abdelkader Essafi, Simon Heaney, Christopher T Gordon, David McBride, Christelle Golzio, Malcolm Fisher, Paul Perry, Véronique Abadie, Carmen Ayuso, Muriel Holder-Espinasse, Nicky Kilpatrick, Melissa M Lees, Arnaud Picard, I Karen Temple, Paul Thomas, Marie-Paule Vazquez, Michel Vekemans, Hugues Roest Crollius, Nicholas D Hastie, Arnold Munnich, Heather C Etchevers, Anna Pelet, Peter G Farlie, David R FitzPatrick, Stanislas Lyonnet
Journal: Nature Genetics (2009)
Correlation of the width of the QRS complex with the pathologic anatomy of the cardiac conduction system in patients with chronic complete atrioventricular block.
Authors: S Ohkawa, D B Hackel, R E Ideker
Journal: Circulation (1981)

A study correlating the electrocardiographic findings and the histology of the atrioventricular (AV) conduction system was carried out in 14 cases with chronic complete AV block and in 13 cases without chronic complete AV block. Patients with chronic complete AV block were divided into two groups, based on the width of the QRS complex. The QRS complexes were narrow (less than 0.12 second) in four cases (group 1) and wide (greater than or equal to 0.12 second) in 10 cases (group 2). In group 1, the main lesion was located in the penetrating portion of His bundle (Hisp) in one heart, in the branching portion of the His bundle (Hisb) in another and in the combined regions of Hisb and the left bundle branch in two. Three of the four cases in group 1 had idiopathic fibrosis of the conduction system and one had calcific nodules in the central fibrous body. In group 2, the main lesion was located in Hisb in two cases, in the combined regions of Hisb and the right bundle branch in one, in the Hisb and in the bilateral bundle branches in two, and in the bilateral bundle branches in five. All cases in group 2 were of the idiopathic type, except case 5, which had calcific aortic stenosis. In 13 cases without chronic complete AV block the AV conduction system was histologically normal, except for slight-to-moderate aging changes in the His bundle or the bundle branches. Lesions of the Hisb, which is believed to be the "distal His" electrophysiologically, may induce complete AV block with narrow or wide QRS complexes, depending upon the severity of the lesions in Hisb or adjacent bundle branches.
Test early for verotoxin producing <i>Escherichia coli</i>
Authors: Roland L Salmon, Meirion R Evans, Brendan W Mason, Dirk Werber
Journal: BMJ (2008)

Murphy’s article on the management of bloody diarrhoea in children in primary care (and indeed his interests, judging from his reference 1) seems to be orientated towards the early diagnosis and treatment of inflammatory bowel disease.1 Some of his recommendations, however, particularly figure 1, should therefore be expanded so as not to be problematic for the management of infection, in general, and verotoxin producing …