tbuckley/cabot-search huggingface dataset:
The cardiac response to exercise in cirrhosis
Authors: F Wong, N Girgrah, J Graba, Y Allidina, P Liu, L Blendis
Journal: Gut (2001)

BACKGROUND Impaired exercise capacity and oxygen consumption are common in cirrhosis. AIM To explore the relationship between possible myocardial dysfunction and exercise tolerance in cirrhosis. METHODS Cardiac responses to exercise, using radionuclide angiography and graded upright cycle ergometry with oxygen consumption, were assessed before and after exercise in 39 cirrhotics patients and compared with 12 age and sex matched healthy volunteers. Baseline cardiac chamber dimensions and wall thickness, ejection fraction, and diastolic function were measured using two dimensional echocardiography is all subjects. RESULTS Baseline diastolic dysfunction with prolonged isovolumic relaxation times (p=0.02), left atrial enlargement, and left ventricular wall thickening were present in all cirrhotics (p=0.02), despite increased mean ejection fraction. With graded exercise, cirrhotics achieved 71 (4)% (p=0.03) (pre-ascitics) and 46 (3)% (p&lt;0.001) (ascitics) of predicted work loads, respectively, without significant increases in ejection fraction. The smaller absolute and percentage increases in cardiac output (p=0.003) in the cirrhotics were associated with significantly reduced oxygen consumption (p=0.003) and anaerobic threshold (p&lt;0.001), and correlated significantly with work and metabolic parameters. CONCLUSIONS Impaired exercise capacity in cirrhosis is associated with myocardial thickening and ventricular stiffness leading to decreased diastolic function, inotropic and chronotropic incompetence under conditions of stress, with metabolic consequences. This picture is compatible with the condition now known as cirrhotic cardiomyopathy.
Alimentary Fibropapilloma in Cattle: A Spontaneous Tumor, Nonpermissive for Papillomavirus Replication2
Authors: William F. H. Jarrett, M. Saveria Campo, Mark L. Blaxter, Brian W. O'neil, Helen M. Laird, Martin H. Moar, M. Luisa Sartirana
Journal: JNCI Journal of the National Cancer Institute (1984)

Fibropapillomatosis of the upper alimentary canal of cattle is described. The tumors, found in the esophagus, esophageal groove, and rumen, showed involvement of the subepithelial fibroblasts as well as of the squamous epithelial layer. Although the fibropapilloma cells harbored multiple episomal copies of the genome of bovine papillomavirus type 2 (BPV-2) easily detected by hybridization techniques, no mature virus could be isolated from these lesions or seen by electron microscopy, and no viral antigen could be detected by immunohistochemical methods. It would appear, therefore, that within the limitations of the techniques employed the alimentary canal epithelium and the underlying fibroblasts, while allowing BPV-2 DNA replication, are nonpermissive for the expression of the viral vegetative functions and that transformation of the epithelial cells, like transformation of fibroblasts, can take place in the absence of infectious viral progeny.
Children should have blood pressure and cholesterol checked by age of 5
Authors: J. Hopkins Tanne
Journal: BMJ (2002)

Because cardiovascular disease is the leading cause of death in the United States, doctors should start promoting cardiovascular health among their patients from birth, an American Heart Association committee said last week.

The committee recommends that doctors aim to increase children's physical activity, prevent or treat obesity, counsel children and their parents, assess insulin resistance as a risk for type II diabetes, check for high blood pressure and high cholesterol concentrations, and prevent cigarette smoking. The guidelines are published in Circulation (2002;106:143-60).

Also last week, Pediatrics , the journal of the American Academy of Pediatrics, published a supplement on ways to combat obesity …
Transition from Colitis to Cancer: High Wnt Activity Sustains the Tumor-Initiating Potential of Colon Cancer Stem Cell Precursors
Authors: Anitha K. Shenoy, Robert C. Fisher, Elizabeth A. Butterworth, Liya Pi, Lung-Ji Chang, Henry D. Appelman, Myron Chang, Edward W. Scott, Emina H. Huang
Journal: Cancer Research (2012)

Abstract Ulcerative colitis (UC) increases the risk of colorectal cancer (CRC), but the mechanisms involved in colitis-to-cancer transition (CCT) are not well understood. CCT may involve a inflammation-dysplasia-carcinoma progression sequence compared with the better characterized adenoma-carcinoma progression sequence associated with sporadic CRC. One common thread may be activating mutations in components of the Wnt/β-catenin signaling pathway, which occur commonly as early events in sporadic CRC. To examine this hypothesis, we evaluated possible associations between Wnt/β-catenin signaling and CCT based on the cancer stem cell (CSC) model. Wnt/β-catenin immunostaining indicated that UC patients have a level of Wnt-pathway-active cells that is intermediate between normal colon and CRC. These UC cells exhibiting activation of the Wnt pathway constituted a major subpopulation (52% + 7.21) of the colonic epithelial cells positive for aldehyde dehydrogenase (ALDH), a putative marker of precursor colon CSC (pCCSC). We further fractionated this subpopulation of pCCSC using a Wnt pathway reporter assay. Over successive passages, pCCSCs with the highest Wnt activity exhibited higher clonogenic and tumorigenic potential than pCCSCs with the lowest Wnt activity, thereby establishing the key role of Wnt activity in driving CSC-like properties in these cells. Notably, 5/20 single cell injections of high-Wnt pCCSC resulted in tumor formation, suggesting a correlation with CCT. Attenuation of Wnt/β-catenin in high-Wnt pCCSC by shRNA-mediated downregulation or pharmacological inhibition significantly reduced tumor growth rates. Overall, the results of our study indicates (i) that early activation of Wnt/β-catenin signaling is critical for CCT and (ii) that high levels of Wnt/β-catenin signaling can further demarcate high-ALDH tumor-initiating cells in the nondysplastic epithelium of UC patients. As such, our findings offer plausible diagnostic markers and therapeutic target in the Wnt signaling pathway for early intervention in CCT. Cancer Res; 72(19); 5091–100. ©2012 AACR.
Osteoclasts are dispensable for hematopoietic stem cell maintenance and mobilization
Authors: Kana Miyamoto, Shigeyuki Yoshida, Miyuri Kawasumi, Kazuaki Hashimoto, Tokuhiro Kimura, Yuiko Sato, Tami Kobayashi, Yoshiteru Miyauchi, Hiroko Hoshi, Ryotaro Iwasaki, Hiroya Miyamoto, Wu Hao, Hideo Morioka, Kazuhiro Chiba, Takashi Kobayashi, Hisataka Yasuda, Josef M. Penninger, Yoshiaki Toyama, Toshio Suda, Takeshi Miyamoto
Journal: The Journal of Experimental Medicine (2011)

Hematopoietic stem cells (HSCs) are maintained in a specific bone marrow (BM) niche in cavities formed by osteoclasts. Osteoclast-deficient mice are osteopetrotic and exhibit closed BM cavities. Osteoclast activity is inversely correlated with hematopoietic activity; however, how osteoclasts and the BM cavity potentially regulate hematopoiesis is not well understood. To investigate this question, we evaluated hematopoietic activity in three osteopetrotic mouse models: op/op, c-Fos-deficient, and RANKL (receptor activator of nuclear factor kappa B ligand)-deficient mice. We show that, although osteoclasts and, by consequence, BM cavities are absent in these animals, hematopoietic stem and progenitor cell (HSPC) mobilization after granulocyte colony-stimulating factor injection was comparable or even higher in all three lines compared with wild-type mice. In contrast, osteoprotegerin-deficient mice, which have increased numbers of osteoclasts, showed reduced HSPC mobilization. BM-deficient patients and mice reportedly maintain hematopoiesis in extramedullary spaces, such as spleen; however, splenectomized op/op mice did not show reduced HSPC mobilization. Interestingly, we detected an HSC population in osteopetrotic bone of op/op mice, and pharmacological ablation of osteoclasts in wild-type mice did not inhibit, and even increased, HSPC mobilization. These results suggest that osteoclasts are dispensable for HSC mobilization and may function as negative regulators in the hematopoietic system.
Planning for Avian Influenza
Authors: John G. Bartlett
Journal: Annals of Internal Medicine (2006)

Avian influenza, or influenza A (H5N1), has 3 of the 4 properties necessary to cause a serious pandemic: It can infect people, nearly all people are immunologically naive, and it is highly lethal. The Achilles heel of the virus is the lack of sustained human-human transmission. Fortunately, among the 124 cases reported through 30 May 2006, nearly all were acquired by direct contact with poultry. Unfortunately, the capability for efficient human-human transmission requires only a single mutation by a virus that is notoriously genetically unstable, hence the need for a new vaccine each year for seasonal influenza. Influenza A (H5N1) is being compared to another avian strain, the agent of the "Spanish flu" of 1918-1919, which traversed the world in 3 months and caused an estimated 50 million deaths. The question is, are we ready for this type of pandemic? The answer is probably no. The main problems are the lack of an effective vaccine, very poor surge capacity, a health care system that could not accommodate even a modest pandemic, and erratic regional planning. It's time to get ready, and in the process be ready for bioterrorism, natural disasters, and epidemics of other infectious diseases.
Natural selection drives recurrent formation of activating killer cell immunoglobulin-like receptor and Ly49 from inhibitory homologues
Authors: Laurent Abi-Rached, Peter Parham
Journal: The Journal of Experimental Medicine (2005)

Expression of killer cell Ig-like receptors (KIRs) diversifies human natural killer cell populations and T cell subpopulations. Whereas the major histocompatibility complex class I binding functions of inhibitory KIR are known, specificities for the activating receptors have resisted analysis. To understand better activating KIR and their relationship to inhibitory KIR, we took the approach of reconstructing their natural history and that of Ly49, the analogous system in rodents. A general principle is that inhibitory receptors are ancestral, the activating receptors having evolved from them by mutation. This evolutionary process of functional switch occurs independently in different species to yield activating KIR and Ly49 genes with similar signaling domains. Selecting such convergent evolution were the signaling adaptors, which are older and more conserved than any KIR or Ly49. After functional shift, further activating receptors form through recombination and gene duplication. Activating receptors are short lived and evolved recurrently, showing they are subject to conflicting selections, consistent with activating KIR's association with resistance to infection, reproductive success, and susceptibility to autoimmunity. Our analysis suggests a two-stage model in which activating KIR or Ly49 are initially subject to positive selection that rapidly increases their frequency, followed by negative selection that decreases their frequency and leads eventually to loss.
Predictors of success and failure in pulmonary rehabilitation
Authors: R. Garrod, J. Marshall, E. Barley, P. W. Jones
Journal: European Respiratory Journal (2006)

The purpose of the present study was to identify prognostic features of chronic obstructive pulmonary disease (COPD) associated with success or failure in pulmonary rehabilitation. Patients were stratified according to the Medical Research Council (MRC) dyspnoea score. A total of 74 stable COPD patients (mean± sd age 68±10 yrs), 21 MRC dyspnoea score grade 1/2, 29 grade 3/4 and 24 grade 5, with a mean forced expiratory volume in one second of 1.1±0.6 L, attended for rehabilitation. Assessments consisted of the following: quadriceps torque, 6-minute walking distance (6MWD), Brief Assessment Depression Cards and St George's Respiratory Questionnaire (SGRQ). Predictors of drop-out and of response (a change in SGRQ of four points or 6MWD of 54 m) were tested using binary logistic regression. In total, 51 patients completed the study. Of these, 39 (77%) showed a clinically significant benefit in either 6MWD or SGRQ. Baseline variables were poor predictors of response in each case. Significant differences were seen between MRC dyspnoea score groups for change in 6MWD and SGRQ Score. Only grade 1/2 and 3/4 patients improved. Depression was a risk factor for subject drop-out compared with nondepressed patients. Baseline state is a poor predictor of response to rehabilitation, although Medical Research Council dyspnoea score grade 5 patients showed smaller magnitudes of improvement than patients with less severe Medical Research Council dyspnoea score grades. Risk of drop-out is significantly greater in depressed compared with nondepressed patients.
ABO blood type B and fucosyltransferase 2 non-secretor status as genetic risk factors for chronic pancreatitis
Authors: Frank Ulrich Weiss, Claudia Schurmann, Alexander Teumer, Julia Mayerle, Peter Simon, Henry Völzke, Andreas Greinacher, Jens-Peter Kuehn, Martin Zenker, Uwe Völker, Georg Homuth, Markus M Lerch
Journal: Gut (2015)

Sir,

We thank Kirsten et al 1 for their comments on our recent study,2 in which we reported a genome-wide analysis on ∼4000 volunteers from the population-based Study of Health in Pommerania (SHIP) cohort3 with replication in 1444 blood donors. We had found a significant association between higher serum lipase activities and three single nucleotide polymorphisms (SNP) as well as the fucosyltransferase-2 (FUT2) non-secretor status (homozygosity for the FUT2 p.W134X mutation) and the ABO blood type B (figure 1). In more than 1000 patients with pancreatitis, we confirmed that FUT2 non-secretor status and blood type B are also disease risk factors, with a greater than twofold OR for blood type B compared with blood type O.



Figure 1 
Distribution of ABO blood types in blood donor subgroups with increasing mean serum lipase activity. One thousand four hundred and forty-four blood donors were stratified into subgroups (cohort size in brackets) of increasing serum …
Medical complications of an aquatic innovation
Authors: M Mountjoy, I Gordon, J McKeown, N Constantini
Journal: British Journal of Sports Medicine (2009)

The sport of swimming has been affected by the innovations of technology with the evolution of the swimsuit. The health benefits of swimming are numerous and are well documented in the scientific literature. As swimming is a low-impact sport, injuries are relatively uncommon. As a direct result of the new swimsuits, team physicians have identified the emergence of a new trend in injury in the aquatic athlete. Extensive blistering and ulceration of the finger tips and distal interphalangeal joints in addition to ecchymoses of the lower limb are now common in the aquatic athlete wearing the new swimsuits. Team physicians working with elite swimmers should be aware of this phenomenon and institute preventive measures.
Prospective randomised controlled trial of laparoscopic versus open inguinal hernia mesh repair: five year follow up
Authors: M Douek
Journal: BMJ (2003)

but was limited in basic problems found on the wards"; "Not enough emphasis on real life situations"; "Not enough time shadowing PRHO prior to commencing work."Six also commented that, in their view, the practicalities of the job could be learnt quickly, for example: "Felt inadequately prepared for surgical house jobs-but you can pick it up
Resolution of Insulin-Requiring Diabetes after Cessation of Chemotherapy for Tuberculosis
Authors: Mona Waterhouse, Claire Wilson, Veronica L C White, Tahseen A Chowdhury
Journal: Journal of the Royal Society of Medicine (2005)

Drugs that increase the risk of diabetes include corticosteroids, thiazides and beta blockers.1 In addition certain antipsychotic2 and antiretroviral drugs3 have been associated with hyperglycaemia and the metabolic syndrome. Such effects have not been reported with antituberculosis chemotherapy.
Overexpression of Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Induces Intramyocardial Vasculopathy in Apolipoprotein E–Null Mice
Authors: Kazuhiko Inoue, Yuji Arai, Hiroki Kurihara, Toru Kita, Tatsuya Sawamura
Journal: Circulation Research (2005)

Endothelial dysfunction induced by oxidized low-density lipoprotein (OxLDL) has been implicated in the pathogenesis of atherosclerosis and vasculopathy. Increased expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), the receptor for OxLDL in endothelial cells, has been demonstrated in the atherosclerotic plaques from experimental atherosclerotic animal models and human clinical samples. In vitro, activation of LOX-1 alters the expression of several endothelial cell genes that are involved in endothelial dysfunction. To investigate the role of LOX-1 in terms of both endothelial dysfunction and resultant vascular changes, we generated mice overexpressing LOX-1 (LOXtg) in C57BL/6 and apolipoprotein E–null mice (apoEKO) backgrounds. We found that the expression of the transgene was prominent in coronary vessels and cardiomyocytes. The enhancement of OxLDL uptake in LOXtg mice was consistent with the expression level of LOX-1. Under hyperlipidemic conditions, both OxLDL and 8-hydroxy-2′-deoxyguanosine accumulated in the coronary arteries of LOXtg/apoEKO mice. The expression of ICAM-1 and VCAM-1, as well as the number of macrophages around blood vessels, were significantly increased in LOXtg/apoEKO mice compared with control littermates. There were no differences in either the hemodynamic profile or the plasma lipid profile between the 2 groups of animals. LOXtg/apoEKO mice displayed accelerated intramyocardial vasculopathy, and the atheroma-like lesion area was increased 10-fold in the LOXtg/apoEKO mice compared with nontransgenic littermates after 3-weeks on the high-fat diet. Thus, it is demonstrated that LOX-1 overexpression promotes inflammatory intramyocardial vasculopathy in a hyperlipidemic mouse model, and this effect is probably mediated through the endothelial dysfunction induced by overexpression of LOX-1.
2-Chlorodeoxyadenosine (2-CDA) therapy in previously untreated patients with follicular stage III–IV non-Hodgkin's lymphoma
Authors: D.C. Betticher, E. Zucca, A. von Rohr, T. Egger, J.A. Radford, A. Ambrosetti, K. Bürki, B. Rufener, S.F. Hsu Schmitz, T. Cerny
Journal: Annals of Oncology (1996)
THE TREATMENT OF CHRONIC CONSTIPATION
Authors: W. K. Sibley
Journal: BMJ (1906)

TREATMENT OF CHRONIC CONSTIPATION.I[DEc.I, iSo6.almost indistinguishable to the eye from Spirockaeta paUida.Some of the spirochaetes were limp and irregular, and others were mere ghosts of dead spirochaetes.Most, how- ever, were crisp and well stained with Giemsa.Dr. A. Castellani has reported (Lancet, May 19th, 1906) two cases of haemoptysis in which he found spirochaetes of various types, whicll stained with ordinary aniline dyes.In both these he failed to find tubercle or other cause for the haemorrhage.He speaks of the condition as a haemorrhagic bronchitis.In my case it is to be noted that I failed to find the spirochaetes in the lung tissue, in the cavity, and in the mucus of a small bronchus.From their position and associations in the sputum, as well as their numbers, it is impossible that they were derived from the moutlh.But, at the same time, they were distributed very irregularly in the sputum, none at all being found in some smears.In ulcers I have found Spirochaeta refringens and another almost straight spirochaete to be associated with a peculiar glairy mucoid secretion.The tenacity of the sputum in my case was quite remarkable.While my observations, therefore, do not tend to prove anything but a saprophytic existence of the spirocliaetes in the large bronchi, yet it is possible that their presence is connected causatively with the viscid character of the sputum.And the cases of Castellani make it very probable that some spirochaetes do have an effect on the bronchial mucous membrane.
RAC2, AEP, and ICAM1 expression are associated with CNS disease in a mouse model of pre-B childhood acute lymphoblastic leukemia
Authors: Mark Holland, Fernanda V. Castro, Seema Alexander, Duncan Smith, Jizhong Liu, Michael Walker, Danny Bitton, Kate Mulryan, Garry Ashton, Morgan Blaylock, Steve Bagley, Yvonne Connolly, John Bridgeman, Crispin Miller, Shekhar Krishnan, Clare Dempsey, Ashish Masurekar, Peter Stern, Anthony Whetton, Vaskar Saha
Journal: Blood (2011)
Presentation and outcome of gastrointestinal involvement in hepatitis C virus-related systemic vasculitis: a case–control study from a single-centre cohort of 163 patients
Authors: Benjamin Terrier, David Saadoun, Damien Sène, Sami Scerra, Lucile Musset, Patrice Cacoub
Journal: Gut (2010)

During primary systemic vasculitides gastrointestinal (GI) involvement is associated with a poor outcome, leading to the use of immunosuppressive therapy. The significance of GI involvement during hepatitis C virus (HCV)-related systemic vasculitis has never been evaluated.To evaluate the significance of GI involvement during HCV-related systemic vasculitis in the antiviral therapy era.Data from 163 patients were retrospectively reviewed to describe the presentation and outcome of patients with HCV-related systemic vasculitis with GI involvement (GI+), and to compare them with patients without GI involvement (GI-).GI manifestations were present in 12 (7.4%) patients. Abdominal pain was consistently present in GI+ patients, and half of patients presented with surgical abdomen and/or intestinal bleeding. GI+ compared to GI- patients had more frequent renal (75% vs 30%; p=0.003) and cardiac involvement (25% vs 2%; p=0.006), medium-vessel vasculitis (67% vs 22%; p=0.003) and higher mixed cryoglobulinaemia levels (2.2 g/l vs 1.2 g/l; p=0.07). After treatment, GI+ and GI- patients had similar rates of overall clinical response of the vasculitis and immunological and virological responses. HCV-MC vasculitis patients with GI involvement did not have poorer overall survival than those without.GI involvement is a rare manifestation of HCV-related vasculitis, associated with acute-onset and life-threatening manifestations. In contrast with primary vasculitides, GI+ patients do not seem to have poorer overall survival than GI- patients.