tbuckley/cabot-search huggingface dataset:
Hyperfibrinogenemia: An important risk factor for vascular complications in diabetes
Authors: Om P Ganda, Charles F Arkin
Journal: Diabetes Care (1992)

OBJECTIVE To evaluate the determinants of elevated fibrinogen levels and the impact of hyperfibrinogenemia on vascular complications in diabetes. RESEARCH DESIGN AND METHODS Plasma fibrinogen, glucose, HbA1, and lipids were measured in 116 ambulatory type I and type II diabetic patients with (n = 59) or without (n = 57) clinical evidence of micro- or macrovascular complications. In 56 of these patients, factor VII activity and CRP also were measured. Univariate and multivariate data analyses were conducted. RESULTS Overall mean ± SE fibrinogen levels in patients (339 ± 7.3 mg/dl) were elevated markedly compared with control subjects (248 ± 9.1 mg/dl). Fibrinogen levels were elevated disproportionately in patients with type II diabetes (P &amp;lt; 0.0001), hypertension (P = 0.0001), obesity (P &amp;lt; 0.0001), and vascular complications (P &amp;lt; 0.0001). Fibrinogen was correlated significantly with age (P &amp;lt; 0.001), cholesterol (P = 0.002), CRP (P &amp;lt; 0.001), and factor VII activity (P = 0.032), but not with plasma glucose, triglycerides, HDL cholesterol, or disease duration. Stepwise multiple regression analyses revealed that type II diabetes and presence of vascular complications were major determinants of fibrinogen. For vascular complications, fibrinogen emerged as one of only three independent predictors, the other two being diabetes duration and hypertension.
Suppression of experimental atherosclerosis by the Ca++-antagonist lanthanum. Possible role of calcium in atherogenesis.
Authors: D M Kramsch, A J Aspen, C S Apstein
Journal: Journal of Clinical Investigation (1980)

Agents inhibiting calcium deposition into arteries are known to suppress atherosclerosis in animals. However, the precise role of calcium in atherogenesis is unknown. In this study, the specific Ca2+-antagonist lanthanum was used to attempt suppression of experimental atherosclerosis and to gain more insight into the possible effects of calcium on atherogenesis. Rabbits were fed an atherogenic diet with and without increasing doses of LaCl3. All cholesterol-fed rabbits showed marked increases in serum cholesterol and ca2+. Untreated atherogenic animals revealed pronounced gross and microscopic atherosclerosis and striking increases in the aortic content of cholesterol, collagen, "elastin," and calcium as well as of elastin calcium, polar amino acids, and cholesterol. With increasing LaCl3 dosage these abnormalities progressively decreased and were completely abolished at the highest dose. The ingested La3+ was absorbed only in small quantities and had no discernible effect on the calcium and connective tissue content of bone, skin, lung, heart, and skeletal muscle nor on myocardial function (left ventricle pressure and left ventricle dp/dt) or myocardial and muscle content in ATP and creatine phosphate. The data suggest that shifts in arterial Ca2+-distribution may play a decisive part in atherogenesis, and provision of arterial calcium homeostasis by La3+ a pivotal role in its prevention, despite hypercholesteremia. Other inhibitors of calcium deposition into arteries may exert their protective effect by similar mechanisms. However, a direct inhibition of atherogenesis by La3+ cannot entirely be ruled out in this study, although no direct effects of La3+ on tissue metabolism have as yet been reported.
Reduction of Stent Thrombosis in Patients With Acute Coronary Syndromes Treated With Rivaroxaban in ATLAS-ACS 2 TIMI 51
Authors: C. Michael Gibson, Anjan K. Chakrabarti, Jessica Mega, Christophe Bode, Jean-Pierre Bassand, Freek W.A. Verheugt, Deepak L. Bhatt, Shinya Goto, Marc Cohen, Satishkumar Mohanavelu, Paul Burton, Gregg Stone, Eugene Braunwald
Journal: Journal of the American College of Cardiology (2013)
Menninger: The Family and the Clinic
Authors: Ralph Crawshaw
Journal: JAMA (1991)

Seldom do you travel to the funeral of a friend and mentor reading his biography. Even less commonly do you go with the information that, after reading his biography, your friend said, "My heart is broken," became depressed and entered a hospital, and died of carcinoma, if not a broken heart. Lawrence Friedman's detailed account of a remarkable period of development in medical-psychiatric history, which coalesced about the Menninger family, is based on the prolific writings of the family members, the extensive archives maintained by the Menninger Clinic, private papers, and extensive personal interviews. Friedman was given an absolutely clear, unfettered shot at writing the definitive history of the Menninger Clinic, and he melded his study of the interviews and documents into a book that was published without benefit of prior review by any of the significant characters. As the author remarks early on, "It is not entirely clear why
Dipstick haematuria and bladder cancer in men over 60: results of a community study.
Authors: J. P. Britton, A. C. Dowell, P. Whelan
Journal: BMJ (1989)

OBJECTIVE--To investigate the prevalence and relevance of dipstick haematuria in a group of men in the community. DESIGN--Prospective study of elderly men invited to attend a health centre for urine screening as part of a health check. SETTING--An inner city health centre in Leeds. SUBJECTS--578 Of 855 men aged 60-85 responding to an invitation to participate. INTERVENTIONS--The subjects had their urine tested with a dipstick (Multistix) for the presence of blood and then tested their urine once a week for the next 10 weeks. Those with one or more positive test results were offered full urological investigation. MAIN OUTCOME MEASURE--The prevalence of urological disease in those subjects with dipstick haematuria. RESULTS--78 Men (13%) had dipstick haematuria on a single test and a further 54 (9%) had evidence of dipstick haematuria when testing their urine once a week during a subsequent 10 week period. Investigation of 87 men disclosed urological disease in 45, including four with a bladder tumour and seven with epithelial dysplasia. CONCLUSION--Dipstick haematuria is a common incidental finding in men over 60 and is associated with appreciable urological disease. The introduction of less invasive methods of investigation, particularly flexible cystoscopy and ultrasonography, has made investigation of these patients simple and safe and makes screening for bladder cancer in the community more feasible.
Trisomy 21 enhances human fetal erythro-megakaryocytic development
Authors: Stella T. Chou, Joanna B. Opalinska, Yu Yao, Myriam A. Fernandes, Anna Kalota, John S. J. Brooks, John K. Choi, Alan M. Gewirtz, Gwenn-ael Danet-Desnoyers, Richard L. Nemiroff, Mitchell J. Weiss
Journal: Blood (2008)
Long-term observational study of afamelanotide in 115 patients with erythropoietic protoporphyria
Authors: G. Biolcati, E. Marchesini, F. Sorge, L. Barbieri, X. Schneider-Yin, E.I. Minder
Journal: British Journal of Dermatology (2014)

Background In erythropoietic protoporphyria (EPP), an inherited disease of porphyrin-biosynthesis, the accumulation of protoporphyrin in the skin causes severely painful phototoxic reactions. Symptom prevention was impossible until recently when afamelanotide became available. Afamelanotide-induced skin pigmentation has statistically significantly improved light-tolerance, although the clinical significance of the statistical effect was unknown. Objectives To assess clinical effectiveness by recording compliance and safety during prolonged use. Methods We report longitudinal observations of 115 ambulatory patients with EPP, who were treated with a total of 1023 afamelanotide implants over a period of up to 8 years at two porphyria centres; one in Rome, Italy, and the other in Zurich, Switzerland. Results Since the treatment first became available in 2006, the number of patients treated with 16 mg afamelanotide implants rose continuously until June 2014, when 66% of all patients with EPP known to the porphyria centres were treated. Only three patients considered afamelanotide did not meet their expectations for symptom improvement; 23% discontinued the treatment for other, mostly compelling, reasons such as pregnancy or financial restrictions. The quality of life (QoL) scores, measured by an EPP-specific questionnaire, were 31 ± 24% of maximum prior to afamelanotide treatment, rose to 74% after starting afamelanotide and remained at this level during the entire observation period. Only minor adverse events attributable to afamelanotide, predominantly nausea, were recorded. Conclusion Based on the improved QoL scores, high compliance and low discontinuation rates, we conclude that afamelanotide exhibits good clinical effectiveness and good safety in EPP under long-term routine conditions.
Abstract 812: Identification of novel anticancer drugs as substrates of organic anion transporting polypeptide 1B3 using a cell viability assay
Authors: Amanda L. Obaidat-Hays, Bruno Hagenbuch
Journal: Cancer Research (2012)

Abstract Organic anion transporting polypeptide 1B3 (OATP1B3) belongs to a superfamily of transport proteins that mediate the uptake of a wide range of endogenous and exogenous compounds into cells. Under normal conditions OATP1B3 is selectively expressed at the basolateral membrane of human hepatocytes. Recently, OATP1B3 expression has been detected in a variety of different cancers and because of its multispecificity OATP1B3 is thought to be a potential therapeutic target to enhance drug delivery into cancer cells. Thus far, only a few anticancer drugs have been identified as substrates of OATP1B3 including docetaxel, paclitaxel, methotrexate and imatinib. Given that OATP1B3 can potentially be used as a target for anticancer drug delivery we need to identify additional anticancer drug substrates of OATP1B3. Therefore, we aimed at establishing a cell based high throughput assay to screen the NCI approved oncology drug set for novel cytotoxic substrates of OATP1B3. Using a luminescent cell viability assay, we measured the viability of wild-type and OATP1B3-expressing Chinese Hamster Ovary (CHO) cells in the absence or presence of the anticancer drugs. After we identified positive hits we further characterized them with respect to concentration dependencies. We identified etoposide, bleomycin, oxaliplatin and plicamycin as compounds that kill OATP1B3-expressing CHO cells at much lower concentrations than wild-type CHO cells suggesting that these compounds are substrates of OATP1B3. Using secondary assays we confirmed that etoposide is a substrate of OATP1B3 and we are currently testing the remaining compounds for direct uptake by OATP1B3. In conclusion, this cell-based viability assay is a good tool to identify novel cytotoxic OATP1B3 substrates that can potentially be used to treat OATP1B3-expressing cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 812. doi:1538-7445.AM2012-812
P235 Prednisolone/cortisol Spot Test Of Non-adherence In Corticosteroid-dependent Asthma
Authors: A. Mansur
Journal: Thorax (2014)

<h3>Background</h3> About 40% of severe asthmatics require maintenance oral corticosteroids (OCS) for disease control. However, significant proportion of these patients continues to have poor disease control due to OCS unresponsiveness or non-adherence (Gamble 2009). <h3>Methods</h3> Using a validated in-house developed liquid chromatography/mass tandem spectrometry (LQ/MSMS), we conducted spot measurement of serum prednisolone, prednisone and cortisol in 111 patients attending our severe asthma clinic over a 12 months period. Patients not on maintenance OCS comprised the control group. Suppressed cortisol (20nmol/l, were considered as compatible with adherence to OCS, whilst unsuppressed cortisol and undetectable prednisolone were considered as non-adherent. For validation purposes the test was repeated multiple times in few cases. <h3>Results</h3> The prednisolone/cortisol spot test was conducted on 111 patients (79% females) with 44 (40%) were not on regular OCS (control group) and 67 (60%) on maintenance OCS. The spot test revealed non-adherence in 27/67 (40%) of patients and adherence in 40/67 (60%) of patients. The prednisolone/prednisone/cortisol assays were similar in non-adherent group and non-OCS group (figure). The mean daily prednisolone dose was 16.3, 20.1, and 0.0 mgs in the adherent, non-adherent and non-OCS groups respectively. Non-adherent patients had lower BMI, and higher exacerbations frequency, blood eosinophil count, and fraction exhaled nitric oxide than OCS adherent group. The non-adherent group resembled more the non-OCS group with regard to aforementioned parameters. We conclude that this prednisolone/cortisol spot test is reproducible and diagnostic of non-adherence to OCS in 40% of patients on maintenance OCS, and should be routinely measured in severe asthma clinics to improve patients management.
Effect of volume-overload hypertrophy on the coronary circulation in awake dogs
Authors: J. A GASCHO, T. M MUELLER, C. EASTHAM, M. L MARCUS
Journal: Cardiovascular Research (1982)

Journal Article Effect of volume-overload hypertrophy on the coronary circulation in awake dogs Get access JOSEPH A GASCHO, JOSEPH A GASCHO * From the Department of Internal Medicine, Division of Cardiovascular Disease and the Cardiovascular Center, University of Iowa and Veterans Administration Hospitals, Iowa City, Iowa *The current address of Dr Gascho is: Experimental Cardiology Laboratory, Department of Cardiology, Box 500, University of Virginia Medical Center, Charlottesville, VA 22908, USA. Search for other works by this author on: Oxford Academic PubMed Google Scholar THOMAS M MUELLER, THOMAS M MUELLER From the Department of Internal Medicine, Division of Cardiovascular Disease and the Cardiovascular Center, University of Iowa and Veterans Administration Hospitals, Iowa City, Iowa Search for other works by this author on: Oxford Academic PubMed Google Scholar CHARLES EASTHAM, CHARLES EASTHAM From the Department of Internal Medicine, Division of Cardiovascular Disease and the Cardiovascular Center, University of Iowa and Veterans Administration Hospitals, Iowa City, Iowa Search for other works by this author on: Oxford Academic PubMed Google Scholar MELVIN L MARCUS MELVIN L MARCUS From the Department of Internal Medicine, Division of Cardiovascular Disease and the Cardiovascular Center, University of Iowa and Veterans Administration Hospitals, Iowa City, Iowa Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 16, Issue 5, May 1982, Pages 288–292, https://doi.org/10.1093/cvr/16.5.288 Published: 01 May 1982
TRASH OR TREASURE?: Putting Coal Combustion Waste to Work
Authors: David J. Tenenbaum
Journal: Environmental Health Perspectives (2009)

A retrofit of the San Francisco Oakland Bay Bridge involves more than 30 different concrete mixes, each of which confers specific advantages.For instance, according to the U.S. EPA, concrete containing more than 50% fly ash resists the cracking and corrosion associated with seawater.
Loss of the Cholesterol Feedback System in the Intact Hepatoma-Bearing Rat
Authors: Lee A. Bricker, Harold P. Morris, Marvin D. Siperstein
Journal: Journal of Clinical Investigation (1972)

By means of the desmosterol suppression technique described in the previous paper, the influence of hepatomas on sterol metabolism has been studied in the intact rat. The major finding of this study is that all hepatoma-bearing rats demonstrate a consistent in vivo loss of the cholesterol feedback system that is characteristic of normal liver. The results also demonstrate that such tumors retain only minor amounts of the sterol they synthesize, releasing over 90% of such endogenous sterol into the circulation. Finally, the in vivo loss of cholesterol feedback control was found to occur in at least two minimal deviation hepatomas and in one highly malignant adenocarcinoma of hepatic origin. These findings indicate that even tumors that are capable of only very limited cholesterol synthesis in vitro, can contribute significant quantities of sterol to the bloodstream. It is concluded that as a result of their lack of normal cholesterol feedback control, hepatomas may represent a physiologically important source of sterols in the tumor-bearing animal, and that the absence of feedback control of sterol synthesis may provide a means of detecting the presence of such tumors in the intact animal.
Modes of action of trichloroethylene for kidney tumorigenesis.
Authors: L H Lash, J C Parker, C S Scott
Journal: Environmental Health Perspectives (2000)

This article focuses on the various models for kidney toxicity due to trichloroethylene (TCE) and its glutathione-dependent metabolites, in particular S-(1,2-dichlorovinyl)-l-cysteine. Areas of controversy regarding the relative importance of metabolic pathways, species differences in toxic responses, rates of generation of reactive metabolites, and dose-dependent phenomena are highlighted. The first section briefly reviews information on the incidence and risk factors of kidney cancer in the general U.S. population. Epidemiological data on incidence of kidney cancer in male workers exposed occupationally to TCE are also summarized. This is contrasted with cancer bioassay data from laboratory animals, that highlights sex and species differences and, consequently, the difficulties in making risk assessments for humans based on animal data. The major section of the article considers proposed modes of action for TCE or its metabolites in kidney, including peroxisome proliferation, alpha(2u)-globulin nephropathy, genotoxicity, and acute and chronic toxicity mechanisms. The latter comprise oxidative stress, alterations in calcium ion homeostasis, mitochondrial dysfunction, protein alkylation, cellular repair processes, and alterations in gene expression and cell proliferation. Finally, the status of risk assessment for TCE based on the kidneys as a target organ and remaining questions and research needs are discussed.
Therapeutic research protocol: should patient pay?
Authors: M. Siegler
Journal: JAMA (1982)

A physician responds to a question about whether patients participating in clinical trials should be required to pay for the drugs and physician services involved. He answers that patients should generally be expected to pay if they are taking part in therapeutic research on drugs that have already been approved by the Food and Drug Administration. Although physicians have a moral responsibility to needy patients, there is a positive virtue in retaining paying patients among those who consent to participate in clinical research.
Fibrinopeptide A levels indicative of pulmonary vascular thrombosis in patients with primary pulmonary hypertension.
Authors: P R Eisenberg, C Lucore, L Kaufman, B E Sobel, A S Jaffe, S Rich
Journal: Circulation (1990)

Although the mechanisms involved in the pathophysiology of primary pulmonary hypertension have not yet been delineated, thrombosis has been implicated. This study was designed to determine whether thrombin activity as reflected by plasma concentrations of fibrinopeptide A (FPA), a marker of the action of thrombin on fibrinogen, is increased in patients with primary pulmonary hypertension. To evaluate fibrinolytic activity, we measured plasma concentrations of tissue-type plasminogen activator, plasminogen activator inhibitor-1, and cross-linked fibrin degradation products. We studied 31 patients with primary pulmonary hypertension. Plasma FPA concentrations measured by radioimmunoassay, were elevated to 87.4 +/- 36.9 ng/ml (mean +/- SEM). Fifteen minutes after administration of heparin (5,000 U), FPA concentrations decreased to 6.8 +/- 1.4 ng/ml (p less than 0.001 compared with preheparin levels). In 21 of 30 patients (70%), FPA concentrations after heparin administration were less than half the preheparin levels, a response consistent with inhibition of thrombin by heparin and the short half-life of FPA. Despite evidence for marked thrombin activity, plasma concentrations of cross-linked fibrin degradation products were normal in all but four patients. Plasminogen activator inhibitor-1 activity was elevated in 19 of the 27 patients in whom it was measured, potentially limiting the fibrinolytic response. The elevations of FPA indicate that thrombin activity is increased in vivo in patients with primary pulmonary hypertension. Thus, sequential assays of plasma markers of thrombosis and fibrinolysis in vivo may help identify those patients who may benefit from treatment with anticoagulants.
Blocking the Adhesion Cascade at the Premetastatic Niche for Prevention of Breast Cancer Metastasis
Authors: Shin-Ae Kang, Nafis Hasan, Aman P Mann, Wei Zheng, Lichao Zhao, Lynsie Morris, Weizhu Zhu, Yan D Zhao, K Stephen Suh, William C Dooley, David Volk, David G Gorenstein, Massimo Cristofanilli, Hallgeir Rui, Takemi Tanaka
Journal: Molecular Therapy (2015)

Shear-resistant adhesion and extravasation of disseminated cancer cells at the target organ is a crucial step in hematogenous metastasis. We found that the vascular adhesion molecule E-selectin preferentially promoted the shear-resistant adhesion and transendothelial migration of the estrogen receptor (ER)(-)/CD44(+) hormone-independent breast cancer cells, but not of the ER(+)/CD44(-/low) hormone-dependent breast cancer cells. Coincidentally, CD44(+) breast cancer cells were abundant in metastatic lung and brain lesions in ER(-) breast cancer, suggesting that E-selectin supports hematogenous metastasis of ER(-)/CD44(+) breast cancer. In an attempt to prevent hematogenous metastasis through the inhibition of a shear-resistant adhesion of CD44(+) cancer cells to E-selectin-expressing blood vessels on the premetastatic niche, an E-selectin targeted aptamer (ESTA) was developed. We demonstrated that a single intravenous injection of ESTA reduced metastases to a baseline level in both syngeneic and xenogeneic forced breast cancer metastasis models without relocating the site of metastasis. The effect of ESTA was absent in E-selectin knockout mice, suggesting that E-selectin is a molecular target of ESTA. Our data highlight the potential application of an E-selectin antagonist for the prevention of hematogenous metastasis of ER(-)/CD44(+) breast cancer.
Dissociation Between Neutrophil Expression of the High Affinity IgE Receptor and Serum IgE Levels in Individuals with Allergic Asthma
Authors: J. Mora, E. Riggs, S. Fox, D.W. MacGlashan Jr., B. Yu, L. Thomas, M.C. Tobin, U. Tran
Journal: Journal of Allergy and Clinical Immunology (2009)