tbuckley/cabot-search huggingface dataset:
PTH-085 Systematic Review Of Performance Of Alt In Predicting Liver Fibrosis: Alt Is A Sensitive, But Not A Specific Marker Of Liver Fibrosis In Populations With/suspected Liver Disease
Authors: J Coad, S Olsen, W Rosenberg, P Roderick, J Parkes
Journal: Gut (2014)

<h3>Introduction</h3> ALT is one of the most commonly used tests to detect liver disease for further investigation, but its accuracy is uncertain. Currently there is no systematic review of diagnostic accuracy of ALT in detecting liver fibrosis using liver biopsy as reference standard. <h3>Methods</h3> Standardised methods for conducting systematic reviews were used. MEDLINE, EMBASE, and reference lists from articles were searched. Studies were included if they evaluated paired samples of liver biopsy and serum, with extractable data for ALT, &gt;30 participants, and presented data as sensitivity, specificity, predictive values, likelihood ratios, or ROC curves or included sufficient data to calculate these parameters. ALT above upper limit of normal threshold were defined using local values and ranged from 30 to 60 u/l. <h3>Results</h3> Initial search located 9563 abstracts, 344 papers were assessed, of which 9 met inclusion criteria. The majority of included studies were published in last 10 years, were from secondary specialist care, and conducted in USA (3), Europe (3), and rest of world (3). Median study size was 206 (IQR 124–341). Median proportion of moderate/severe fibrosis on biopsy was 22% (range 6–34), any fibrosis 81% (range 58–100). Pooled sensitivity for ANY fibrosis was 87% (95% CI: 85–88) specificity 34% (95% CI: 30–38), positive likelihood ratio 1.3 (95% CI: 1.2–1.4). Moderate/severe fibrosis sensitivity was 89% (95% CI: 87–91), specificity 35% (95% CI: 32–37), positive likelihood ratio 1.36 (95% CI: 1.3–1.42). AUROC values were reported in 2 studies - moderate/severe fibrosis AUROC=0.815, and severe fibrosis AUROC=0.59. <h3>Conclusion</h3> ALT accuracy in predicting fibrosis has only been studied in specialist clinic populations where it has low specificity for both any or moderate/severe fibrosis, but high sensitivity for both. Predictive values in clinic populations with prevalences found in these studies show that ALT has high PPV for any fibrosis (because of high prevalence) but low NPV. In contrast it has high NPV for ruling out moderate/severe fibrosis but poor PPV. Results from this review suggest that ALT should be used in conjunction with other tests and clinical features and not alone to identify liver fibrosis in clinic populations. Spectrum effects are likely to be important especially in those with no fibrosis so affecting the specificity. Further studies are needed in primary care populations of the accuracy of ALT versus robust non invasive markers, but these findings would suggest that a normal ALT can rule out moderate/severe fibrosis with reasonable certainty due to its high sensitivity and likely low prevalence in primary care though this may not be the case for mild fibrosis. <h3>Disclosure of Interest</h3> None Declared.
The cervical spine in rheumatoid arthritis.
Authors: J A Mathews
Journal: BMJ (1993)

research for the first comprehensive national study of police surgeons.Our researches confirm that intoxication is implicated in many call outs.However, it was often not the prime reason for the call out, typically occurring in combination with other factors, usually some form of physical injury.In cases focusing on fitness to be detained it was the injury rather than the intoxication that was the prime reason for the call out.In cases involving the assessment of fitness to be interviewed, mental state assumed a greater importance.Overall, injury and assault accounted directly for 36% of consultations and alcohol for 19%.This finding concurs with the personal study of Payne-James.' With regard to the assessment of fitness for interview, a key issue is the need for any standardised approach to incorporate a record of the reasons for particular decisions.We believe that the present system within the Metropolitan Police District carries a potential for discrepancy between custody records, surgeons' notes, and records of a surgeon's attendance.Only a minority of police surgeons' decisions subsequently receive in depth scrutiny and our work found no reason to doubt the quality of the service, but this shortcoming should be addressed.
Patients with adenomatous polyps and carcinomas have increased colonic mucosal prostaglandin E2.
Authors: S Pugh, G A Thomas
Journal: Gut (1994)

Colorectal carcinoma in humans and animal models is associated with increased synthesis of prostaglandin E2 (PGE2). PGE2 synthesis was measured in normal and neoplastic human colorectal mucosa to investigate its role in the adenoma-carcinoma sequence. Paired mucosal biopsy specimens for PGE2 synthesis and histological examination were obtained during 39 diagnostic colonoscopies. Twelve control patients in whom colonoscopies and histology were normal synthesised similar amounts of PGE2 at all sites. Their results were (mean (SD) pg PGE2/mg tissue) caecum 102.8 (15.9) (n = 6), ascending colon 110.8 (24.3) (n = 10), transverse colon 103.9 (19.5) (n = 11), descending colon 102.9 (23.2) (n = 12), sigmoid colon 96.4 (18.0) (n = 12), and rectum 107.1 (17.6) (n = 12). Nineteen patients had a total of 27 adenomatous polyps (rectum (1), sigmoid (22), descending (1), transverse (1), and ascending colon (1): histology-tubular (16), tubulo-villous (8), and villous adenomous (3)). The polyps (178.0 (55.0), n = 27) synthesised more PGE2 than controls (p &lt; 0.001), but the values in polyp-associated mucosa (mean (SD) 115.4 (21.9), n = 15) were not different to control results. Eight patients had carcinomas (rectal (2), sigmoid (4), and caecal (2)) all of which were adenocarcinomas. The cancers (193.6 (40.2), n = 8) synthesised more PGE2 than control specimens (p &lt; 0.001), but were not different to polyps. Cancer-associated mucosa (140.3 (27.7) n = 8) synthesised more PGE2 than control and polyp-associated mucosa. Colorectal neoplasia is associated with a progressive increase in PGE2 synthesis which may have a role in tumourigenesis and be a pathophysiological explanation for the beneficial effects of NSAIDs in animal models and human disease.
a5b1 integrin mediates survival of breast cancer cells in 3-dimensional culture that can be specifically targeted for therapy.
Authors: J Nam, HJ Zhang, Y Chung, CC Park
Journal: Cancer Research (2009)

Abstract Abstract #4126 Background: β1 integrin signaling has been implicated in breast cancer progression and has been shown to facilitate resistance to radiation that could be abrogated using β1 integrin inhibitory antibody, AIIB2. In the present study, we investigated whether a specific alpha heterodimer of β1 integrin was preferentially mediating a pro-survival signal in human breast cancer cells, and if it could specifically be targeted for therapy.&amp;#x2028; Materials and Methods: We used three-dimensional (3D) laminin-rich extracellular matrix (lrECM) culture to compare the relative levels of alpha heterodimer expression in malignant HMT3522-T4-2 and nonmalignant cell line HMT3522-S-1. Total cell lysates were probed by western blot to detect several possible alpha integrins. In addition, to investigate whether α5β1 mediated an important pro-survival signal, we treated 3D lrECM cultures with a small peptide inhibitor of α5β1 integrin and fibronectin interaction, Ac-PHSCN-NH2 (ATN-161) and measured apoptotic response using TUNEL (terminal deoxynucleotidyl transferase (TdT)-mediated nick end labeling) assay.&amp;#x2028; Results: We found that expression of α5β1 was upregulated in HMT3522-T4-2 malignant breast cell line compared to nonmalignant cell line HMT3522-S-1. Inhibition using ATN-161 resulted in a significant dose-dependent increase in TUNEL positive cells.&amp;#x2028; Discussion: We have previously shown that inhibitory antibody to β1 integrin, AIIB2, leads to selective apoptosis and decreased proliferation in human breast cancer cells in 3DlrECM culture and in vivo. In addition, combining β1 integrin inhibition with IR allowed for reduction of IR dose necessary to achieve growth inhibition in vivo. Here, we show that in HMT3522-T4-2 breast cancer cell line, inhibition of α5 integrin and fibronectin interaction using ATN-161 significantly enhanced apoptosis in 3D lrECM. These data indicate that fibronectin and its receptor, α5β1 are important for survival signaling in breast cancer and may be an important target to enhance radiotherapy efficacy. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4126.
Theory of Use of Indicators to Measure Blood Flow and Extracellular Volume and Calculation of Transcapillary Movement of Tracers
Authors: KENNETH L. ZIERLER
Journal: Circulation Research (1963)

For indicators or tracers injected into the vascular system and sampled at some other portion of the vascular system, the indicator dilution curve supplies a measure of blood or plasma flow through the system even if the indicator is not confined to the blood vessels, providing only that it eventually all return to the circulation prior to the sampling site. Mean transit time of the indicator through the system multiplied by the measured flow determines the volume through which the indicator is distributed. This volume is independent of capillary permeability to the indicator if the indicator enters interstitial fluid at all. Of indicator coursing through the vascular system, the fraction crossing capillaries into interstitial fluid is inversely proportional to the mean transit time of the indicator across capillaries, through interstitial fluid and back into capillaries. The constant of proportionality is the ratio of interstitial fluid volume to plasma flow through the system. The fraction of a substance crossing capillary walls and returning can be calculated if the frequency function of transit times into, through and out of interstitial fluid can be measured. The equations cannot be solved if this frequency function is not measured. However, because this frequency function falls to zero much more slowly than other frequency functions through which tracer concentration is apt to be convoluted, capilary permeability may be estimated graphically. The graphic estimate applies even to substances that do not return completely to the vascular bed.
Review: Lipid-lowering drugs decrease all-cause and cardiac mortality and CV events in CKD
Authors: G. V. Ramesh Prasad
Journal: Annals of Internal Medicine (2012)

ACP Journal Club20 November 2012Review: Lipid-lowering drugs decrease all-cause and cardiac mortality and CV events in CKDG. V. Ramesh Prasad, MBBS, FRCPCG. V. Ramesh Prasad, MBBS, FRCPCUniversity of Toronto, Toronto, Ontario, Canada (G.V.R.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-157-10-201211200-02005 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationUpadhyay A, Earley A, Lamont JL, et al. Lipid-lowering therapy in persons with chronic kidney disease: a systematic review and meta-analysis. Ann Intern Med. 2012;157:251-62. https://pubmed.ncbi.nlm.nih.gov/22910936Clinical Impact RatingsGIM/FP/GP: Cardiology: Nephrology: References1 Foley RN, Parfrey PS, Sarnak MJ. Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis. 1998;32:S112-9. [PMID: 9820470] Google Scholar2 Wanner C, Ritz E. Reducing lipids for CV protection in CKD patients—current evidence. Kidney Int Suppl. 2008;111:S24-8. [PMID: 19034322] Google Scholar3 Campese VM, Park J. HMG-CoA reductase inhibitors and the kidney. Kidney Int. 2007;71:1215-22. [PMID: 17495867] Google Scholar Author, Article, and Disclosure InformationAffiliations: University of Toronto, Toronto, Ontario, Canada (G.V.R.)This article was published at Annals.org on 6 November 2012. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoReview: Statins decrease mortality and major CV events in adults with CKD not receiving dialysis G. V. Ramesh Prasad Metrics 20 November 2012Volume 157, Issue 10Page: JC5-5KeywordsChronic kidney diseaseDrugsHyperlipidemiaMedical dialysisRenal transplantationRevascularizationStatinsSystematic reviews ePublished: 20 November 2012 Issue Published: 20 November 2012 CopyrightCopyright © 2012 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Recurrent ulcer after vagotomy and pyloroplasty: the X-ray appearances and their value in diagnosis
Authors: J. A. Williams, D. K. M. Toye
Journal: Gut (1970)

Barium meal studies have shown evidence of a recurrent ulcer or of stenosis in 12 out of 24 patients with recurrent dyspepsia after vagotomy and pyloroplasty. These 12 patients have been subsequently proved to have had recurrences and all but one are now cured by further surgery. Barium meals in 12 patients show no evidence of recurrence or stenosis, and follow-up clinical studies suggest that they do not have recurrent ulcer. Radiological studies appear to have great value in the interpretation of recurrent dyspeptic symptoms after vagotomy and pyloroplasty.
Adaptive cellular immunity in aortic aneurysms: cause, consequence, or context?
Authors: John A. Curci, Robert W. Thompson
Journal: Journal of Clinical Investigation (2004)

Abdominal aortic aneurysms are common and life threatening. Although CD4+ T cells are abundant in aneurysm tissue, their role in disease progression remains unclear. A new study shows that mouse aortic allografts placed in animals lacking IFN-γ receptors develop a Th2 inflammatory response with aortic aneurysms, whereas Th1 responses promote intimal hyperplasia. It is expected that these surprising findings will stimulate further efforts to clarify whether adaptive cellular immunity in aneurysm disease is detrimental or potentially beneficial.
ST segment changes post-infarction: predictive value for multivessel coronary disease and left ventricular aneurysm.
Authors: D A Weiner, C McCabe, M D Klein, T J Ryan
Journal: Circulation (1978)

To ascertain whether exercise testing might predict multivessel coronary disease and left ventricular aneurysm after a myocardial infarction, 154 patients with a single documented myocardial infarction who had both exercise testing and coronary angiography were grouped according to whether they had greater than or equal to 1 mm ST depression, greater than or equal to 1 mm ST elevation, or neither during exercise testing: 83 patients developed ST depression alone (group 1); 22 patients had ST elevation with concomitant ST depression in other leads (group 2); 19 patients had ST elevation alone (group 3); and 30 patients had no ST changes (group 4). Multivessel disease, defined as greater than or equal to 70% luminal narrowing in two or more coronary vessels, was present in 76% (63 of 83) of group 1, 91% (20 of 22) of group 2, 21% (four of 19) of group 3, and 13% (four of 30) of group 4. A left ventricular aneurysm was present in 31% (26 of 83) of group 1, 68% (15 of 22) of group 2, 79% (15 of 19) of group 3, and 40% (12 to 30) of group 1. We conclude that ST changes during exercise testing in patients after a myocardial infarction can reliably predict the extent of coronary disease and the presence of a left ventricular aneurysm; ST depression with or without ST elevation predicts multivessel disease; ST elevation alone or a negative exercise test suggests single vessel involvement; and ST elevation with or without ST depression predicts left ventricular aneurysm.
Disorders of Suppressor Immunoregulatory Cells in the Pathogenesis of Immunodeficiency and Autoimmunity
Authors: THOMAS A. WALDMANN
Journal: Annals of Internal Medicine (1978)

A series of suppressor cell systems regulate virtually all immunologic processes. Disorders of these systems have been identified in association with a number of diseases. An abnormal number of activated suppressor T-cells have been seen in some patients with common variable hypogammaglobulinemia and in some with selective IgA deficiency. Suppressor T-cells that inhibit immunoglobulin synthesis also develop in an animal model of immunodeficiency, the agammaglobulinemia of the bursectomized bird. Non-T-cell suppressor cells are a pathogenic factor in the humoral immunodeficiency associated with multiple myeloma. At the other end of the spectrum of immunologic response, a reduction in functional activity of suppressor T-cells has been implicated in the pathogenesis of autoimmune diseases. The disorders of suppressor cells that have been shown in immunodeficiency and autoimmunity are important when developing rational strategies for prevention and therapy of these immunologic disorders.
ABC of clinical electrocardiography: Bradycardias and atrioventricular conduction block
Authors: D. Da Costa
Journal: BMJ (2002)

By arbitrary definition, a bradycardia is a heart rate of <60 beats/min. A bradycardia may be a normal physiological phenomenon or result from a cardiac or non-cardiac disorder.

Many patients tolerate heart rates of 40 beats/min surprisingly well, but at lower rates symptoms are likely to include dizziness, near syncope, syncope, ischaemic chest pain, Stokes-Adams attacks, and hypoxic seizures 

Sinus bradycardia is common in normal individuals during sleep and in those with high vagal tone, such as athletes and young healthy adults. The electrocardiogram shows a P wave before every QRS complex, with a normal P wave axis (that is, upright P wave in lead II). The PR interval is at least 0.12 s.

#### Pathological causes of sinus bradycardia

The commonest pathological cause of sinus bradycardia is acute myocardial infarction. Sinus bradycardia is particularly associated with inferior myocardial infarction as the inferior myocardial wall and the sinoatrial and atrioventricular nodes are usually all supplied by the right coronary artery.

Sick sinus syndrome is the result of dysfunction of the sinoatrial node, with impairment of its ability to generate and conduct impulses. It usually results from idiopathic fibrosis of the node but is also associated with myocardial ischaemia, digoxin, and cardiac surgery.

#### Conditions associated with sinoatrial node dysfunction

The possible electrocardiographic features include persistent sinus bradycardia, periods of sinoatrial block, sinus arrest, junctional or ventricular escape rhythms, tachycardia-bradycardia syndrome, paroxysmal atrial flutter, and atrial fibrillation. The commonest electrocardiographic feature is an inappropriate, persistent, and often severe sinus bradycardia.



Severe sinus bradycardia



Sinoatrial block is characterised by a transient failure of impulse conduction to the atrial myocardium, resulting in intermittent pauses between P waves. The pauses are the length of two …
REPORT LXX. ABSTRACT OF A REPORT ON THE FORMATION OF LYMPH BY THE LIVER
Authors: F. A. Bainbridge
Journal: BMJ (1902)

oedematous, and the abdominal wall greatly distended with oedema, although there did not seem to be much free fluid in the peritoneal cavity.During this time she was passing an average of 40 to 50 oz. of urine in the twenty-four hours, and was very restless and sleepless.Her blood at this period, as seen in the above table, presented a very interesting feature, namely, a blood crisis-the blood films contained a great number of nucleated red corpuscles.Many of their nuclei were bilobed or trilobed as if dividing.It will be remem- bered that a somewhat similar condition of the blood was found in Case iII where she was most oedematous.The pre- sence of a blood crisis is said to be a favourable sign in prognosis.From this period until the present date she made a gradual improvement, and her oedema almost entirely dis- appeared.From April 8th to the igth, while her oedema was passing off, she passed from 130 to 150 oz. of urine in the twenty-four hours.HAEMORREAGE.VII.-The next case is one of haemorrhage that presented the clinical appearance of pernicious anaemia, he had, how- ever, bleeding piles and made a remarkable recovery.On
Abstract 5766: The Hsp90 inhibitor PU-H71 is a potent suppressor of metastasis in triple-negative breast cancer models
Authors: Eloisi Caldas Lopes, Paula Bos, Hector Peinado, Leandro Cerchietti, Simon Lavotshkin, Ari Melnick, David Lyden, Gabriela Chiosis
Journal: Cancer Research (2010)

Abstract Background: Triple-negative breast cancer (TNBC) characterized by estrogen and progesterone receptor and HER-2-negativity is a particularly aggressive tumor with currently no effective targeted therapies. Our previous findings demonstrated that Hsp90 inhibition by the purine-scaffold inhibitor PU-H71 is a promising therapeutic approach in this tumor type. In TNBC cells, a multitude of malignancy driving proteins, including EGFR, HER3, Akt, PDK1, Bcl-xL and Raf-1, were in a complex with Hsp90 and were preferentially targeted for degradation by PU-H71 (Abstract 5637, AACR-Annual Meeting 2008/2009). In TNBC xenografts, PU-H71 exhibited potent and durable anti-tumor activity inducing complete responses without toxicity to the host. PU-H71 also inhibited the invasiveness of TNBC cells through a mechanism involving downregulation and inhibition of several pro-metastatic proteins such as NF-kB, p-Akt, ERK2, TYK2 and PKC, suggesting a potential effect of PU-H71 on TNBC metastasis. Study design: In order to determine whether in vivo PU-H71 also inhibits TNBC metastasis, we analyzed the effect of the Hsp90 inhibitor on lung colonization and metastastic body formation in immunocompromised mice. A lung tropic MDA-MB231 derivative expressing luciferase was used to establish the experimental models of metastasis. Animals were treated with 75mg/kg PU-H71 three times/week and lung metastases were monitored periodically by bioluminiscence imaging (IVIS system). Results: At completion of treatment both bioluminescent imaging and histological analyses demonstrated significant reduction of the metastastatic burden in mice treated with PU-H71 compared to the vehicle treated group. Importantly, flow cytometry analysis demonstrated that circulating hematopoietic precursors related to metastatic spread were reduced after treatment with PU-H71 and several hematopoietic cell types recruited to metastatic sites such as CD11b+/Gr1+ were reduced after the treatment. In addition, analysis of metastatic lungs demonstrated that CD24low/CD44+ cells were attracted to metastatic lung in MDA-MB231 bearing mice and strongly reduced after PU-H71 treatment. Conclusion: These data demonstrate that in addition to inhibition of primary tumors, PU-H71 leads to potent impairment of lung metastasis in an in vivo model of TNBC, supporting the use of PU-H71 for clinical trials involving patients with advanced and metastatic disease. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5766.