tbuckley/cabot-search huggingface dataset:
Transforming Growth Factor-β1 Modulates Extracellular Matrix Production, Proliferation, and Apoptosis of Endothelial Progenitor Cells in Tissue-Engineering Scaffolds
Authors: Virna L. Sales, George C. Engelmayr, Bret A. Mettler, John A. Johnson, Michael S. Sacks, John E. Mayer
Journal: Circulation (2006)

Background— Valvular endothelial cells and circulating endothelial progenitor cells (EPCs) can undergo apparent phenotypic change from endothelial to mesenchymal cell type. Here we investigated whether EPCs can promote extracellular matrix formation in tissue engineering scaffolds in response to transforming growth factor (TGF)-β1. Method and Results— Characterized ovine peripheral blood EPCs were seeded onto poly (glycolic acid)/poly (4-hydroxybutyrate) scaffolds for 5 days. After seeding at 2×10 6 cells/cm 2 , scaffolds were incubated for 5 days in a roller bottle, with or without the addition of TGF-β1. After seeding at 15×10 6 cells/cm 2 , scaffolds were incubated for 10 days in a roller bottle with or without the addition of TGF-β1 for the first 5 days. Using immunofluorescence and Western blotting, we demonstrated that EPCs initially exhibit an endothelial phenotype (ie, CD31 + , von Willebrand factor + , and α–smooth muscle actin (SMA) − ) and can undergo a phenotypic change toward mesenchymal transformation (ie, CD31 + and α-SMA + ) in response to TGF-β1. Scanning electron microscopy and histology revealed enhanced tissue formation in EPC-TGF-β1 scaffolds. In both the 10- and 15-day experiments, EPC-TGF-β1 scaffolds exhibited a trend of increased DNA content compared with unstimulated EPC scaffolds. TGF-β1–mediated endothelial to mesenchymal transformation correlated with enhanced expression of laminin and fibronectin within scaffolds evidenced by Western blotting. Strong expression of tropoelastin was observed in response to TGF-β1 equal to that in the unstimulated EPC. In the 15-day experiments, TGF-β1–stimulated scaffolds revealed dramatically enhanced collagen production (types I and III) and incorporated more 5-bromodeoxyuridine and TUNEL staining compared with unstimulated controls. Conclusions— Stimulation of EPC-seeded tissue engineering scaffolds with TGF-β1 in vitro resulted in a more organized cellular architecture with glycoprotein, collagen, and elastin synthesis, and thus noninvasively isolated EPCs coupled with the pleiotropic actions of TGF-β1 could offer new strategies to guide tissue formation in engineered cardiac valves.
Effects of inorganic phosphate and ADP on calcium handling by the sarcoplasmic reticulum in rat skinned cardiac muscles
Authors: J.-Z. Xiang, J. C Kentish
Journal: Cardiovascular Research (1995)

The aim was to investigate whether, and how, increases in inorganic phosphate (Pi) and ADP, similar to those occurring intracellularly during early myocardial ischaemia, affect the calcium handling of the sarcoplasmic reticulum.Rat ventricular trabeculae were permeabilised with saponin. The physiological process of calcium induced calcium release (CICR) from the muscle sarcoplasmic reticulum was triggered via flash photolysis of the "caged Ca2+", nitr-5. Alternatively, calcium release was induced by rapid application of caffeine to give an estimate of sarcoplasmic reticular calcium loading. The initial rate of sarcoplasmic reticular calcium pumping was also assessed by photolysis of caged ATP at saturating [Ca2+]. Myoplasmic [Ca2+] (using fluo-3) and isometric force were measured.Pi (2-20 mM) significantly depressed the magnitude of CICR and the associated force transient. Sarcoplasmic reticular calcium loading was inhibited even more than CICR by Pi, suggesting that reduced calcium loading could account for all of the inhibitory effect of Pi on CICR and that Pi may slightly activate the calcium release mechanism. The reduced sarcoplasmic reticular calcium loading seemed to be due to a fall in the free energy of ATP hydrolysis (delta GATP) available for the calcium pump, since equal decreases in delta GATP produced by adding both Pi and ADP in various ratios caused similar falls in the calcium loading of the sarcoplasmic reticulum. The caged ATP experiments indicated that Pi (20 mM) did not affect the rate constant of sarcoplasmic reticular calcium uptake. ADP (10 mM) alone, or with 1 mM Pi, inhibited calcium loading. In spite of this, ADP (10 mM) did not alter CICR and, when 1 mM Pi was added, ADP increased CICR above control.An increase in intracellular Pi reduces sarcoplasmic reticular calcium loading and thus depresses the CICR. This could be an important contributing factor in the hypoxic or ischaemic contractile failure of the myocardium. However the detrimental effect of Pi may be offset to some extent by a stimulatory action of ADP on the calcium release mechanism of CICR.
Sporadic Anicteric Leptospirosis in South Vietnam
Authors: Steven J. Berman, Che-Chung Tsai, King Holmes, James W. Fresh, Raymond H. Watten
Journal: Annals of Internal Medicine (1973)

Leptospiral infections were a common cause of acute fever among American servicemen in Vietnam. In 150 men the clinical illness was characterized by the abrupt onset of fever, chills, and headache; myalgias and gastrointestinal complaints were common. The most characteristic physical findings were muscle tenderness (42%) and conjunctivitis (42%). Aseptic meningitis occurred in nine patents. Oliguria and azotemia of renal origin occurred in seven patients, but none required dialysis. Only two patients became jaundiced; however, some liver function tests were abnormal in 40% of the patients. There were no deaths. The clinical diagnosis depended on recognizing the syndrome of muscle tenderness, conjunctivitis, and gastroenteritis in a febrile patient from an endemic area. One third of the patients had no abnormal findings other than fever, and the leptospiral infection would not have been detected without serological surveillance of febrile patients from endemic areas.
243 TRANSLATION INHIBITORS SENSITIZE HEPATOMA CELLS TO APOPTOSIS INDUCED BY TUMOR NECROSIS FACTOR-RELATED APOPTOSIS-INDUCING LIGAND (TRAIL) BY ENHANCING BID CLEAVAGE
Authors: C.Y. Jin, C. Park, G.Y. Kim, S.K. Moon, W.J. Kim, Y.H. Choi
Journal: Journal of Hepatology (2009)
Neurological Outcomes After Immediate Aortic Repair for Acute Type A Aortic Dissection Complicated by Coma
Authors: Takuro Tsukube, Taro Hayashi, Toshihiro Kawahira, Tomonori Haraguchi, Ritsu Matsukawa, Shuichi Kozawa, Kyoichi Ogawa, Yutaka Okita
Journal: Circulation (2011)

Management of acute type A aortic dissection (AADA) complicated by coma remains controversial. We analyzed our experience in managing AADA complicated by coma to determine the relationship of duration of preoperative coma to postoperative neurological recovery.Between September 2003 and October 2010, 181 patients with AADA were treated, including 27 presenting with coma (Glasgow Coma Scale <11) on arrival. Twenty-one patients were repaired immediately (immediate group); time from onset of symptoms to operating room was <5 hours. For brain protection, deep hypothermia with antegrade cerebral perfusion was used, and postoperative therapeutic hypothermia with magnesium treatment was performed. Six patients initially were managed medically, and 3 of them were followed by eventual repair because time from onset was >5 hours (delayed group). The preoperative National Institutes of Health Stroke Scale score was 31.4 ± 6.6 in the immediate group and 28.3 ± 9.5 in the delayed group. Hospital mortality was 14% in the immediate group and 67% in the delayed group. Full recovery of consciousness was achieved in 86% of patients in the immediate group and in 17% in the delayed group. In immediate group, the postoperative National Institutes of Health Stroke Scale score significantly improved to 6.4 ± 8.4, cumulative survival rate was 71.8% in 3 years, and independence in daily activities was achieved in 52% (11/21).Aortic repair, if performed immediately from the onset of symptoms, showed satisfactory recovery of consciousness and neurological function in patients with AADA complicated by coma. In this patient population, immediate aortic repair is warranted.
Nanographene oxide-based radioimmunoconstructs for in vivo targeting and SPECT imaging of HER2-positive tumors
Authors: Bart Cornelissen, Sarah Able, Veerle Kersemans, Philip A. Waghorn, Sverre Myhra, Kerstin Jurkshat, Alison Crossley, Katherine A. Vallis
Journal: Biomaterials (2012)
Cancer and Psychosocial Traits, Continued
Authors: Georgia D. Andrianopoulos
Journal: JAMA (1990)

To the Editor.—  In the September 1, 1989, issue of JAMA , Zonderman et al 1 report that depression, as measured by the General Well-being Schedule and the Center for Epidemiologic Studies Depression scale, is not predictive of cancer morbidity or mortality in a 10-year follow-up. However, a breakdown of cancer morbidity by site was not reported.  Given that immunity is the most popular hypothetical mediating factor between depression and cancer, 2,3 the type of cancers that have been shown to be most sensitive to immune factors ought to be examined. Previous results have shown an increased incidence only of certain neoplasms in patients in chronic immunodeficiency states. 4-7 The incidence of lymphomas, carcinomas of the lip and skin, carcinomas of the vulva, in situ carcinomas of the uterine cervix, and leukemias is greater in organ transplant recipients and other chronically immunosupressed patients than in the general population. 7 The most frequently
Tungsten and Cobalt in Fallon, Nevada: Association with Childhood Leukemia
Authors: John Schell, Michael Pardus
Journal: Environmental Health Perspectives (2008)

Main et al. (2007) reported that elevated levels of polybrominated diphenyl ethers (PBDEs) in breast milk, but not placenta, were associated with congenital cryptorchidism in Danish and Finnish boys.For the Danish cohort, the researchers used a case-cohort design in which biological samples were collected from all study participants, whereas for the Finnish cohort, they used a nested case-control design.The matching criteria used for Finnish mothers who gave birth to boys with cryptorchidism (measured at birth) and matched Finnish controls included the following: parity, smoking (yes/no), diabetes (yes/no), gestational age (± 7 days), and date of birth (± 14 days).However, Main et al. (2007) did not provide information on adjustments made to account for the type/severity of diabetes (Virtanen et al. 2006), smoking habits (Kurahashi et al. 2005), alcohol consumption (Damgaard et al. 2007), cesarean section (Hjertkvist et al. 1989;Kurahashi et al. 2005), and other factors that may be associated with cryptorchidism.Interestingly, Main et al. did note that approximately 12% and 18% of breast milk samples and placentas, respectively, were obtained from diabetic Finnish mothers of cryptorchid boys, compared with 0% of controls (Main et al. 2007), but they conducted no further inquiry on this discrepancy.Damgaard et al. (2007) previously evaluated this same Danish-Finnish cohort and adjusted for confounders and effect modifiers for differences observed based on country, smoking, caffeine intake, alcohol consumption (including binge-drinking episodes), social class, maternal age, parity, maturity, and birth weight.Damgaard et al. (2007) noted an association between maternal alcohol consumption (≥ 5 drinks/week) and transient cryptorchidism.Despite these findings, Main et al. (2007) provided no information on stratified alcohol consumption or other potential confounders, such as caffeine intake or social class.Main et al. (2007) concluded that an association exists between PBDE levels in breast milk and cryptorchidism in boys, but we should be cautious of this interpretation, given that Main et al. (2007) may not have adequately addressed potential confounders.
Comparison of the steady state pharmacokinetics of two formulations of cyclosporin in patients with atopic dermatitis*
Authors: M. CHAWLA, M. ALI, R. MARKS
Journal: British Journal of Dermatology (1996)

A comparison was made of the efficacy, tolerability, safety and steady state pharmacokinetics of Sandimmun and Neoral in 11 stable atopic dermatitis patients already on Sandimmun. The study was of an open, crossover design. At entry into the trial, patients were switched to Neoral for 28 days. Treatment was switched back to Sandimmun for Days 28 to 42. The morning dose was given fasting, the evening dose after a standard meal. All measures of eczema severity improved during the Neoral treatment period. Neoral was markedly better tolerated with fewer side-effects. Switching from Sandimmun to Neoral at the same dose resulted in less variable pharmacokinetic profiles in both fasted and fed states. There was an increase in bioavailability with better, less variable and faster absorption, with a slightly reduced tmax, a higher mean Cmax (+43%) and a higher mean AUC (+30%) in fasted, but not fed patients. Higher trough levels (Cmin) occurred throughout for Neoral. These differences between the two formulations were not associated with any changes in safety parameters. Overall, Neoral was equivalent or superior to Sandimmun in tolerability and efficacy when given on a 1:1 dose basis.
Sudden Infant Death Syndrome: Problems of the Parents
Authors: Norman Lewak
Journal: JAMA (1974)

To the Editor.—  A consistent method of humane treatment of parents of sudden infant death syndrome (SIDS) victims is the aim of a California law that takes effect Jan 1, 1975. This is the first legislation in any state that provides for the measures necessary for prompt and sympathetic management of such cases. (Since one of 350 babies dies each year of SIDS, 800 to 1,000 deaths are expected in California in 1975.)  AB 409, Crown, mandates immediate autopsies in possible SIDS cases, immediate notification of the county health officer in the provisional diagnosis of the gross autopsy is SIDS, and notification of the parents by the health officer to explain SIDS to them (after consultation with the infant's physician).  Although this humane treatment should occur under existing procedures and, in fact, does occur at times in California as well as in scattered areas in the nation, the lack of
US board says censuring research on avian flu was necessary to prevent a potential catastrophe
Authors: B. Roehr
Journal: BMJ (2012)

A US government panel has defended its advice to two leading scientific journals to censure publication of methods used in research of human to human transmission of the H5N1 avian influenza virus as justified to protect public health. In the wrong hands the information could lead to the development of a virus for harmful purposes leading to “an epidemic of significant proportions,” the board says.

The US National Science Advisory Board for Biosecurity reviewed research papers on H5N1 transmissibility before publication in the journals Science and Nature . In December it recommended the journals withhold the methodological and other details ( BMJ 2011;343:d8333, doi:10.1136/bmj.d8333) igniting a firestorm of …
Recommendations for Off-Label Use of Intravenously Administered Immunoglobulin Preparations
Authors: Thomas A. Ratko
Journal: JAMA (1995)

<h3>Objective.</h3> —To summarize consensus recommendations for off-label uses of standard intravenous immunoglobulin (IVIG), as developed by a University Hospital Consortium (UHC) Expert Panel. These findings are intended to help guide clinicians in the appropriate and efficient use of IVIG. <h3>Participants.</h3> —The UHC-sponsored panel included eight physicians (board certified in critical care, hematology, immunology, neurology, oncology, pediatrics, or rheumatology) and two hospital pharmacists. <h3>Evidence.</h3> —MEDLINE and EMBASE were searched to identify all English-language review articles (n=201) and original reports (n=1904) on IVIG (human use only, excluding editorials, letters, and comments) published between January 1982 and March 1994. Relevant original reports (250) and review articles (87) were evaluated by the first author (T.A.R.). Extracted data included laboratory and clinical findings, objective measures, or clinical impressions. The evidence quality was graded by study design according to the US Preventive Services Task Force. <h3>Consensus Process.</h3> —Before the panel meeting, a draft literature review and recommendations were produced by one of the authors (T.A.R.). The recommendations herein represent consensus (100% agreement) based on the published evidence. <h3>Conclusions.</h3> —The UHC Expert Panel made specific recommendations for 53 off-label indications and the following general recommendations: (1) Usually IVIG is indicated only if standard approaches have failed, become intolerable, or are contraindicated; (2) IVIG products should be considered therapeutically equivalent and interchangeable; (3) interproduct pharmaceutical differences should be considered with the patient's clinical and physiological status when selecting an IVIG product; and (4) currently, IVIG manufacturers cannot guarantee freedom from viral contamination in the finished product. (<i>JAMA</i>. 1995;273:1865-1870)
Burden of Changes in Generic Pill Appearance
Authors: Stephen Pauker
Journal: Annals of Internal Medicine (2014)

Letters2 December 2014Burden of Changes in Generic Pill AppearanceStephen Pauker, MDStephen Pauker, MDFrom Tufts Medical Center, Boston, Massachusetts.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L14-5028-2 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Kesselheim and colleagues (1) provide data on the burden of changes in the appearance of generic drugs in terms of patients' discontinuing their generic medications. Although this is an important finding, it is only the tip of the iceberg of the risk associated with generic medications. As a caregiver for my elderly mother and as a patient—with both my mother and me having a suite of chronic conditions that require multiple medications—I believe that a far greater problem is that changes in the appearance of generic pills greatly increase the likelihood of medication errors.Although all medications ...Reference1. Kesselheim AS, Bykov K, Avorn J, Tong A, Doherty M, Choudhry NK. Burden of changes in pill appearance for patients receiving generic cardiovascular medications after myocardial infarction: cohort and nested case–control studies. Ann Intern Med. 2014;161:96-103. [PMID: 25023248] doi:10.7326/M13-2381 LinkGoogle Scholar Author, Article, and Disclosure InformationAuthors: Stephen Pauker, MDAffiliations: From Tufts Medical Center, Boston, Massachusetts.Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L14-0453. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoBurden of Changes in Pill Appearance for Patients Receiving Generic Cardiovascular Medications After Myocardial Infarction Aaron S. Kesselheim , Katsiaryna Bykov , Jerry Avorn , Angela Tong , Michael Doherty , and Niteesh K. Choudhry Burden of Changes in Generic Pill Appearance Kathleen Uhl and John R. Peters Burden of Changes in Generic Pill Appearance Aaron S. Kesselheim , Niteesh K. Choudhry , and Jerry Avorn Metrics 2 December 2014Volume 161, Issue 11Page: 839KeywordsCaregiversConflicts of interestDisclosureDrugsElderlyFood and Drug AdministrationSafetyVision ePublished: 2 December 2014 Issue Published: 2 December 2014 Copyright & PermissionsCopyright © 2014 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Institutional failure led to Ebola outbreak "spiralling out of control," says MSF
Authors: A. Gulland
Journal: BMJ (2015)

The international response to the epidemic of Ebola virus disease in west Africa has been characterised as a “global coalition of inaction” by the charity Medecins Sans Frontieres in a report marking the first year of the outbreak.

The report, published on 23 March, the first anniversary of the World Health Organization’s first warning of an emerging outbreak of Ebola virus disease in Guinea, is damning in its criticism of WHO and the international response.1

The charity’s general director, Christopher Stokes, said that the outbreak has often been described as a “perfect storm”: it occurred in a region that had never experienced Ebola and that had poor health systems, porous borders, and widespread movement of people. However, he said that this was too “convenient an explanation.” He added, “For the Ebola outbreak to spiral this far out of control required many institutions to …
Deaths From Unintentional Carbon Monoxide Poisoning and Potential for Prevention With Carbon Monoxide Detectors
Authors: Steven S. Yoon
Journal: JAMA (1998)

Unintentional carbon monoxide (CO) poisoning causes approximately 2100 deaths in the United States per year, but the use of CO detectors could potentially prevent many of these deaths.To describe the epidemiology of potentially preventable unintentional CO poisoning deaths in New Mexico.Descriptive analysis.A total of 136 deaths from CO poisoning investigated by the New Mexico Office of the Medical Investigator, 1980 through 1995.Characteristics of deaths from CO poisoning; estimates of the number of deaths potentially preventable with CO detectors.Of 136 people whose deaths were classified as "unintentional carbon monoxide poisoning, not fire related," 49 (36%) most likely were asleep when poisoned. Thirty-nine (49%) of 80 people whose deaths were identified as "residential fatalities" most likely were asleep vs 10 (18%) of 56 of those whose deaths were identified as occurring in or around motor vehicles. A blood-alcohol level greater than 0.01% was present in 56 (42%) of the decedents. Among decedents who had a negative blood-alcohol level (52 in residences and 26 in vehicles), an electronic audible CO detector may have prevented CO poisoning; whereas, among those who had a negative blood-alcohol level and most likely were awake at the time of CO exposure (28 in residences and 23 in vehicles), an electronic detector or a nonaudible, chemical reagent type detector may have prevented CO poisoning.Differences exist between deaths due to unintentional CO poisoning that occur in residences and those that occur in or around motor vehicles. Carbon monoxide detectors, whether the electronic or chemical reagent types, may have prevented approximately half of these deaths. The high proportion of decedents with alcohol in their blood indicates that effective public health campaigns must address the role of alcohol in CO poisoning deaths.