tbuckley/cabot-search huggingface dataset:
Abstract 9418: Preventive Effects of Tumor Necrosis Factor-Stimulated Gene-6 on Atherosclerosis
Authors: Rena Watanabe, Kaho Watanabe, Remina Shirai, Hanae Konii, Kengo Sato, Takuya Watanabe
Journal: Circulation (2014)

Introduction: Atherosclerosis is the complex lesion that consists of endothelial inflammation, macrophage foam cell formation, vascular smooth muscle cell (VSMC) proliferation, and extracellular matrix production. Tumor necrosis factor-stimulated gene-6 (TSG-6), an anti-inflammatory protein, was shown to be localized in the artery injury-induced rat neointima. However, the modulatory effect of TSG-6 on atherogenesis has not been reported. Objective and Methods: This study was performed to evaluate the atheroprotective effects of TSG-6 on human endothelial cells (ECs), human monocyte-derived macrophages, human aortic smooth muscle cells (HASMCs), and aortic lesions in apolipoprotein E-deficient (ApoE-/-) mice. Results: TSG-6 was expressed at higher levels in human ECs than monocytes, macrophages, and HASMCs. TSG-6 significantly suppressed oxidized low-density lipoprotein-induced foam cell formation associated with reduced expression levels of CD36 and acyl-CoA:cholesterol acyltransferase-1 (ACAT1) in human...
Lesson of the Week: Addison's disease presenting as reduced insulin requirement in insulin dependent diabetes
Authors: L. Armstrong, P. M Bell
Journal: BMJ (1996)

Diagnosing Addison's disease requires a high degree of clinical suspicion since it is rare and its presenting symptoms are often non-specific. An association between Addison's disease and insulin dependent diabetes is well recognised. Whereas about 10-18% of patients with Addison's disease have insulin dependent diabetes, Addison's disease remains relatively rare among patients with insulin dependent diabetes.1 2 3 We report two cases of patients with previously well controlled diabetes presenting with recurrent severe hypoglycaemia despite reduction in insulin doses.

A 43 year old man with a 15 year history of insulin dependent diabetes well controlled with a stable regimen of twice daily injections of human insulin was referred to the diabetic clinic, Royal Victoria Hospital, complaining of increased frequency of hypoglycaemic episodes on waking. On one occasion he required intramuscular glucagon administered by his wife. On a second occasion he collapsed at work and required medical assistance. He also complained of tiredness and nausea. He was advised to reduce his evening dose of long acting insulin and was given an appointment for further review.

Before …
Abstract #5554: DNA-PK is a new therapeutic target for adult T cell leukemia/lymphoma
Authors: Takashi Hisatomi, Rika Tomimasu, Naoko Aragane, Akemi Sato, Kazutoshi Komiya, Kazuya Okamoto, Eisaburo Sueoka
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Adult T-cell leukemia/lymphoma (ATLL) is caused by a retrovirus, human T-lymphotropic virus type I (HTLV-1), endemic to south Japan and various countries in the world. The polyclonal expansion of the HTLV-1 infected T-cells progresses to monoclonal proliferation during several decades of life resulting in subsequent occurrence of overt ATLL. Since ATLL is an aggressive disease and incurable by standard chemotherapy, a new strategy for overcome the drug resistance of ATLL cells is urgently required. Recent studies revealed that inhibition of DNA repair system is a new molecular target for improve the sensitivity of anti-cancer agents and radiotherapy. DNA-dependent protein kinase (DNA-PK) contributes to DNA repair in non-homologous end joining pathway, and we found catalytic subunit of DNA-PK was overexpressed in ATLL cells. So we paid our attention to inhibition of DNA repair mediated through inhibition of DNA-PK. We and other group found that NK314, a synthetic derivative of benzo[c]phenanthridine, is a bi-functional drug possessing inhibitory activity for topoisomerase II and DNA-PK activity. NK314 dose-dependently inhibited the growth of various ATLL cell lines, and the IC50 values were from 70 to 120 nM, which was comparable to that of etoposide. The growth inhibition mediated by G2/M arrest, followed by the induction of apoptosis was associated with degradation of DNA-PK catalytic subunits. In addition, we found that inhibitory activity of NK314 was stronger than etoposide. Since high activity of DNA repair system could play a role in ATLL acquisition of drug resistance, inhibition of DNA-PK could possibly overcome the drug resistance of ATLL cells. Inhibition of DNA-PK could be a promising therapeutic tool for this almost incurable disease ATLL.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5554.
Fatigue and an Elevated White Blood Cell Count
Authors: Meredith H. Sellers, Shira N. Dinner
Journal: JAMA (2015)

A 67-year-old woman presented with fatigue for 4 weeks; a history of type 2 diabetes mellitus, hypertension, hyperlipidemia, and allergic rhinitis; and leukocytosis with predominant granulocytes. What’s the diagnosis?
Acquisition of Clostridium difficile-Associated Diarrhea in Hospitalized Patients Receiving Tube Feeding
Authors: Donna Zimmaro Bliss
Journal: Annals of Internal Medicine (1998)

Background: Clostridium difficile is the most common infectious cause of nosocomial diarrhea, but its role in diarrhea associated with tube feeding has not been rigorously investigated. Objective: To determine the incidence of C. difficile acquisition and C. difficile-associated diarrhea in tube-fed and non-tube-fed patients. Design: Prospective cohort study. Setting: A university-affiliated Veterans Affairs Medical Center. Patients: 76 consecutive hospitalized, tube-fed patients and 76 hospitalized, non-tube-fed patients. The two cohorts were matched for age, unit location, duration of hospitalization before surveillance, and severity of illness. Measurements: Incidence of C. difficile acquisition, incidence of C. difficile-associated diarrhea, and C. difficile restriction endonuclease analysis typing results. Results: More tube-fed patients than non-tube-fed patients acquired C. difficile (15 of 76 patients [20%] compared with 6 of 76 patients [8%]; P = 0.03) and developed C. difficile-associated diarrhea (7 of 76 patients [9%] compared with 1 of 76 patients [1%]; P = 0.03). The mean proportion (±SD) of surveillance days with diarrhea was greater for tube-fed patients after the development of C. difficile-associated diarrhea than for tube-fed patients without this diarrhea (0.68 ± 0.4 compared with 0.22 ± 0.2 [95% CI for the mean difference, 0.08 to 0.84]). Postpyloric tube feeding (odds ratio, 3.14 [CI, 1.008 to 9.77]) and duration of surveillance (odds ratio, 1.08 [CI, 1.0009 to 1.16]) were risk factors for the acquisition of C. difficile. Nineteen restriction endonuclease analysis types of C. difficile were identified from 20 patients. Conclusions: Hospitalized, tube-fed patients, especially those receiving postpyloric tube feeding, are at greater risk for the acquisition of C. difficile and the development of C. difficile-associated diarrhea than are hospitalized, non-tube-fed patients. Clinicians should test for C. difficile in tube-fed patients with diarrhea.
Geriatric care in the United Kingdom: aligning services to needs Commentary: current system could be made to work
Authors: C. Bowman, M. Johnson, D. Venables, C. Foote, R. L Kane, G. Bennett
Journal: BMJ (1999)

Current provision and funding of health and social care for older people in the United Kingdom are undermined by a structural and operational misalignment of primary healthcare teams, acute hospital trusts, community trusts, and social services.The problem has been compounded by the fact that funding originates from at least three sources: the NHS, local social services departments, and personal or insured means.The inevitable result is obfuscation of responsibilities.The recent report from the Royal Commission on Long Term Care, With Respect To Old Age, 1 recommends the establishment of a national care commission to monitor trends, costs, accountability, and the interests of the consumer and to set national benchmarks.This builds logically on policy trends signalled in the government discussion paper Partnership in Action and Modernising Social Services, which suggest a national regulatory system and standards. 2 3In this article we outline a possible solution that integrates and aligns health and personal care for elderly people in a practical and incremental manner.To put our strategic proposals in a contemporary perspective we briefly outline some present issues.Long term care of elderly people has been shifted to residential homes ULRIKE PREUSS
Interactions of 3,3′-diindolylmethane with rat hepatic cytochrome P450s in vitro and in vivo.
Authors: Daniel Parkin, Yongjian Lu, Danuta Malejka-Giganti
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

5593 

3,3′-Diindolylmethane (DIM) is a major product formed in the acid pH of the stomach after oral intake of indole-3-carbinol (I3C). DIM has been reported to suppress the growth of breast and prostate cancer cells and also mammary tumors in rats. Its mechanism of action may be mediated via cytochrome P450 (CYP)-catalyzed metabolism of steroid hormones. DIM has been shown to inhibit the activities of CYP1A1 and CYP2B1/2 in hepatic microsomes of β-naphthoflavone (β-NF)- and phenobarbital (PB)-treated rats, respectively (Stresser et al. J Biochem Toxicol 1995). In our study, DIM was found to be a mixed inhibitor of CYP1A1 (EROD) activity with Vmax 3.11 nmol/min/mg, Km 0.287 μM, Kia 2.37 μM and Kib 27.5 μM in hepatic microsomes of I3C-treated, and with Vmax 2.32 nmol/min/mg, Km 0.167 μM, Kia 1.60 μM and Kib 22.0 μM in those of β-NF-treated rats. In PB-treated rats, DIM was an uncompetitive inhibitor of CYP2B1/2 activity assayed as BROD with Vmax 4.66 nmol/min/mg, Km 0.667 μM and Kib 0.471 μM. DIM was also a mixed inhibitor of this activity assayed as PROD with Vmax 1.29 nmol/min/mg, Km 1.30 μM, Kia 0.364 μM and Kib 0.600 μM. However, CYP3A1/2 (NIFOX) activity of dexamethasone (DEX)-treated rats was not inhibited by DIM in vitro. To determine whether the above interactions of DIM with CYPs occur in vivo, CYP mRNA expression levels, CYP activities and metabolism of 17β-estradiol (E2) were measured in hepatic microsomes of rats treated with PB (4 days at 75 mg/kg bwt), DEX (3 days at 50 mg/kg bwt), DIM (4 days at 42 mg/kg bwt) or DIM in combination with either PB or DEX. The relative mRNA expression levels of CYPs were increased as follows: CYP2B1 > CYP1A1 > CYP2B2 after DIM; CYP2B1 >> CYP2B2 >> CYP3A2 after PB; and CYP3A1 >> CYP3A2 >> CYP2B1 after DEX treatment. The CYP activities were increased as follows: BROD > EROD > PROD after DIM; BROD > PROD > EROD > NIFOX; and BROD > PROD > NIFOX after DEX treatment. Co-treatment with DIM had no effect on the PB- or DEX-induced increases in either CYP mRNA expression levels or activities. The rates of formation of E2 metabolites were increased as follows: 6β-OH-E2 > 2-OH-E2 after DIM; 6β-OH-E2 > 2-OH-E1 > 6α-OH-E2 > E3 > 2-OH-E2 > 4-OH-E2 > 6(α+β)-OH-E1 after PB; and 15α-OH-E2 > 6β-OH-E2 > 4-OH-E2 > 6(α+β)-OH-E1 > 2-OH-E2 > E1 after DEX relative to vehicle treatment. Co-treatment with DIM decreased the rates of formation of 2-OH-E2, 2-OH-E1, 4-OH-E2, 6β-OH-E2 and 6(α+β)-OH-E1 by 28, 63, 43, 47 and 49%, respectively, compared to PB-treated rats, but had no effect on the DEX-increased rates of E2 metabolite formation. The data indicate that inhibition of CYP1A1 and 2B1/2 activities by DIM in vitro is not reproducible in vivo, and suggest that a PB-inducible CYP(s) not analyzed in this study catalyzes metabolism of E2 and is inhibited by DIM. The inhibition of the adverse E2 metabolite formation by DIM in vivo might have a protective effect on E2-dependent carcinogenesis.
A dynamic model of patient consent to sharing of medical record data
Authors: W. G. Dixon, K. Spencer, H. Williams, C. Sanders, D. Lund, E. A. Whitley, J. Kaye
Journal: BMJ (2014)

The Health and Social Care Information Centre recently began its leaflet campaign “better information means better healthcare” to inform patients about how it will share health records to improve the quality of care and health services for all.1 As Sheather and Brannan predicted,2 this has sparked much debate. Although recent surveys have indicated four in five patients are in favour of …
Regular review: Effectiveness of interventions to help people stop smoking: findings from the Cochrane Library
Authors: Tim Lancaster, Lindsay Stead, Chris Silagy, Amanda Sowden
Journal: BMJ (2000)

Peto estimates that current cigarette smoking will cause about 450 million deaths worldwide in the next 50 years. Reducing current smoking by 50% would avoid 20–30 million premature deaths in the first quarter of the century and about 150 million in the second quarter.1 Preventing young people from starting smoking would cut the number of deaths related to tobacco, but not until after 2050. Quitting by current smokers is therefore the only way in which tobacco related mortality can be reduced in the medium term. There is evidence that some form of treatment aids an increasing number of successful attempts to quit.2 This review aims to summarise evidence for the effectiveness of the available interventions.

#### Summary points

Advice from doctors, structured interventions from nurses, and individual and group counselling are effective interventions

Generic self help materials are no better than brief advice but more effective than doing nothing; personalised materials are more effective than standard materials

All forms of nicotine replacement therapy are effective

The antidepressants bupropion and nortriptyline increased quit rates in a small number of trials; the usefulness of the antihypertensive drug clonidine is limited by side effects

Anxiolytics and lobeline are ineffective

The effectiveness of aversion therapy, mecamylamine, acupuncture, hypnotherapy, and exercise is uncertain

The Cochrane Tobacco Addiction Review group identifies and summarises the evidence for interventions to reduce and prevent tobacco use; it produces and maintains systematic reviews to inform policymakers, clinicians, and individuals wishing to stop smoking. Twenty systematic reviews are available in the Cochrane Library and have contributed to the evidence base for smoking cessation guidelines.3

Details of the methods and results of each review are available in the Cochrane Library (abstracts at www.update-software.com/ccweb/cochrane/revabstr/g160index.htm). The reviews summarise results from randomised controlled trials with at least six …
Abstract 18517: Single Vessel Disease - Surgical or Interventional treatment a Systematic Review With Meta-analysis of 3,491 Patients
Authors: Antje C Deppe, Oliver J Liakopoulos, Yeong-Hoon Choi, Elmar W Kuhn, Ingo Slottosch, Maximillian Scherner, Parwis B Rahmanian, Thorsten Wahlers
Journal: Circulation (2014)

Introduction:  Minimally invasive direct coronary artery bypass grafting (MIDCAB) and percutaneous coronary intervention (PCI) are both established therapeutic options for single vessel disease of the left anterior descending artery (LAD). Internal mammary artery grafts (IMA) has proven survival benefits and 10 year patency rates greater than 90% after LAD revascularization. However, due to lower costs, quicker recovery and lesser invasiveness PCI with stenting it the most common used treatment for isolated LAD stenosis.   Hypothesis:  The present systematic review with meta-analysis aims to determine the current evidence for MIDCAB or PCI for revascularization of the LAD.   Methods:  We performed a meta-analysis of randomized (RCT) and observational trials (OT) that reported clinical outcome after isolated LAD revascularization. Pooled treatment effects (odds ratio (OR) or weighted mean difference (WMD), 95% confidence intervals (95%CI)) were assessed using a fixed or random effects model.   Results:  A total of 3,491 patients from 13 studies (6 RCT, 7 OT) were identified. Increased incidence for repeat target vessel revascularization (TVR) after PCI was already in existence six month after the procedure (OR 1.98; 95%CI 1.45-2.69; p   Conclusions:  Current evidence reported in this systematic review suggests MIDCAB for treatment of single vessel disease of the LAD.
Cell cycle responses to low-dose ionizing radiation.
Authors: Sarah A. Krueger, George D. Wilson, Michael C. Joiner, Brian Marples
Journal: Cancer Research (2006)

5178  Low-dose hyper-radiosensitivity (HRS) describes the increased radiosensitivity of cells to doses of ionizing radiation less than ∼0.5 Gy. While a complete understanding of the underlying molecular mechanism of this radiation response is not clear, our recent work has identified a connection between low-dose HRS survival, Ataxia Telangiectasia Mutated (ATM)-mediated repair pathways and an “early” ATM-dependent G2 cell-cycle checkpoint. High-precision cell survival experiments using flow cytometry synchronized cell populations indicated that HRS was a specific G2 phase response. Given this background, we investigated the function of radiation-induced G2 phase checkpoint arrest in a pair of isogenic fibroblast cell lines: MR4 and 3.7. We found that the MR4 cells exhibited a pronounced HRS cell survival response that was exaggerated in a G2-phase enriched cell population but was absent in the isogenic 3.7 cell line. Moreover, distinct temporal differences in G2 checkpoint response were observed between these two cell lines within the low dose radiation range (0-1 Gy). MR4 cells did not demonstrate an “early” G2-phase cell cycle delay in response to low doses (0-0.3 Gy) of irradiation although an immediate cell cycle delay was evident for 3.7 cells over the same dose range. Additionally, the dose response pattern for the induction of the “early” G2-phase cell cycle checkpoint in MR4 cells was concordant with ATM autophosphorylation on serine 1981, which further implicates the “early” checkpoint in the HRS response. Using ∈3H2AX as an index of the presence and repair of DNA double \. strand breaks, it was determined that the detection of radiation-induced strand breaks was comparable in a panel of cell lines that show disparate HRS status. This suggests that immediate radiation-mediated DNA events may not have a prominent role in determining HRS, although this result needs to be confirmed with pure G2-phase cell populations. Furthermore, recent work has suggested that apoptosis is likely the mode of cell death most closely associated with low-dose HRS. We observed in a series of 6 cell lines that caspase-3 activation in the low-dose range mirrored the presence of HRS. These data provide a possible route for clinical exploitation by combining radiotherapy with chemotherapeutic agents that promote or modulate apoptosis. Currently a number of mechanistically unique drugs are being investigated in this effort e.g. paxlitaxel, etoposide, carboplatin, BCNU (carmustine). Overall, the data remain consistent with the hypothesis that overcoming HRS is related to the control of a specific G2 checkpoint that responds to radiation-mediated DNA damage. Our current working model suggests that HRS is a consequence of radiation damaged G2 phase cells entering mitosis with unrepaired DNA damage after failing to activate checkpoint delays that otherwise would have initiated DNA repair mechanisms and improved overall cell survival.
Making Sense of Data: A Self-Instruction Manual on the Interpretation of Epidemiological Data
Authors: J. H. Abramson, Z. H. Abramson
Journal: Annals of Internal Medicine (1989)

Introduction 1. Basic concepts and procedures 2. Rates and other measures 3. How good are the measures? 4. Making sense of associations 5. Causes and effects 6. Meta-analysis - Putting it all together
DISSECTING ANEURYSM OF THE AORTA WITH A CASE REPORT
Authors: Reuben Finkelstein, Mendel Jacobi
Journal: Annals of Internal Medicine (1940)

Case Reports1 April 1940DISSECTING ANEURYSM OF THE AORTA WITH A CASE REPORTREUBEN FINKELSTEIN, M.D., F.A.C.P., MENDEL JACOBI, M.D., F.A.C.P.REUBEN FINKELSTEIN, M.D., F.A.C.P., MENDEL JACOBI, M.D., F.A.C.P.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-13-10-1991 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIt is a strange fact that dissecting aneurysm of the aorta, which presents such dramatic symptoms and about which so much has been written, is so rarely diagnosed during life. About 500 cases have been reported in the literature of which only 12 were diagnosed ante mortem. The condition usually occurs in patients between the ages of 40 and 70 years suffering from hypertension and arteriosclerosis. Syphilis, which is a questionable etiologic factor, appears to be present in only 10 per cent of the cases. The normal aorta can withstand great internal pressures, from 900 to 1500 millimeters of mercury....Bibliography1. SHENNAN T: Dissecting aneurysm, Special Report, Medical Research Council, Series No. 193, 1934, London, His Majesty's Stationaries Office. Google Scholar2. MCGEACHYPAULLIN TEJE: Dissecting aneurysm of the aorta, Jr. Am. Med. Assoc., 1937, cviii, 1690. CrossrefGoogle Scholar3. TYSON MD: Dissecting aneurysm, Am. Jr. Path., 1931, viii, 581. Google Scholar4. OPHULS W For a comprehensive review of the pathogenesis of arteriosclerosis see: : Arteriosclerosis, Cowdry, 1933, Macmillan Co., New York, p. 249. Google Scholar5. PEERY TM: Aneurysm of the aorta, Am. Heart Jr., 1936, xii, 650. CrossrefGoogle Scholar6. SHENNAN T: Completely healed dissecting aneurysm of the aorta with obliteration of the sac, Jr. Path. and Bact., 1932, xxxv, 161. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Brooklyn, New York*Received for publication August 5, 1938.From the Gastrointestinal Department and the Pathology Department, Beth El Hospital, Brooklyn, New York. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAneurysmenSurgical Treatment of Dissecting Aneurysm of the Aorta Analysis of Seventy-Two CasesDissecting Aneurysm of the AortaDissecting Aneurysm of the Aorta: Its Clinical, Electrocardiographic and Laboratory FeaturesTwo cases of dissecting aneurysm of the aorta, with ante-mortem diagnosis 1 April 1940Volume 13, Issue 10Page: 1991-1998KeywordsAneurysmsAortaHypertensionSyphilis ePublished: 1 December 2008 Issue Published: 1 April 1940 PDF downloadLoading ...