tbuckley/cabot-search huggingface dataset:
Cystatin C Concentration as a Risk Factor for Heart Failure in Older Adults
Authors: Mark J. Sarnak, Ronit Katz, Catherine O. Stehman-Breen, Linda F. Fried, Nancy Swords Jenny, Bruce M. Psaty, Anne B. Newman, David Siscovick, Michael G. Shlipak
Journal: Annals of Internal Medicine (2005)

Background: Previous studies that evaluated the association of kidney function with incident heart failure may be limited by the insensitivity of serum creatinine concentration for detecting abnormal kidney function. Objective: To compare serum concentrations of cystatin C (a novel marker of kidney function) and creatinine as predictors of incident heart failure. Design: Observational study based on measurement of serum cystatin C from frozen sera obtained at the 1992–1993 visit of the Cardiovascular Health Study. Follow-up occurred every 6 months. Setting: Adults 65 years of age or older from 4 communities in the United States. Participants: 4384 persons without previous heart failure who had measurements of serum cystatin C and serum creatinine. Measurements: Incident heart failure. Results: The mean (±SD) serum concentrations of cystatin C and creatinine were 82 ± 25 nmol/L (1.10 ± 0.33 mg/L) and 89 ± 34 µmol/L (1.01 ± 0.39 mg/dL), respectively. During a median follow-up of 8.3 years (maximum, 9.1 years), 763 (17%) participants developed heart failure. After adjustment for demographic factors, traditional and novel cardiovascular risk factors, cardiovascular disease status, and medication use, sequential quintiles of cystatin C concentration were associated with a stepwise increased risk for heart failure in Cox proportional hazards models (hazard ratios, 1.0 [reference], 1.30 [95% CI, 0.96 to 1.75], 1.44 [CI, 1.07 to 1.94], 1.58 [CI, 1.18 to 2.12], and 2.16 [CI, 1.61 to 2.91]). In contrast, quintiles of serum creatinine concentration were not associated with risk for heart failure in adjusted analysis (hazard ratios, 1.0 [reference], 0.77 [CI, 0.59 to 1.01], 0.85 [CI, 0.64 to 1.13], 0.97 [CI, 0.72 to 1.29], and 1.14 [CI, 0.87 to 1.49]). Limitations: The mechanism by which cystatin C concentration predicts risk for heart failure remains unclear. Conclusions: The cystatin C concentration is an independent risk factor for heart failure in older adults and appears to provide a better measure of risk assessment than the serum creatinine concentration. *For a full list of participating Cardiovascular Health Study investigators and institutions, see www.chs-nhlbi.org.
A simple, fluorescent method to internally label platelets suitable for physiological measurements
Authors: Georgiann R. Baker, Paul M. Sullam, Jack Levin
Journal: American Journal of Hematology (1997)

Current methods for studying platelet survival in vivo are limited by the use of radioisotopes, with their inherent safety and regulatory concerns, systemic drug administrations that produce biochemical modifications of platelet functions, or external labeling techniques, which may produce artifacts due to surface modifications. For these reasons, we sought to develop a simple, nonisotopic method for labeling platelets internally, thereby producing platelets more likely to have in vivo properties equivalent to native cells. Murine platelets in protein-free buffer were fluorescently labeled internally by incubation with 2.5 μM 5-chloromethyl fluorescein diacetate (CMFDA), and without washing, were injected into mice for platelet survival studies. CMFDA-labeled platelets were unactivated, as shown by minimal P-selectin expression. When tested in vitro for function by aggregometry, the response of CMFDA-labeled platelets to collagen and thrombin was identical to that of unlabeled platelets. Flow cytometric analysis demonstrated that CMFDA platelets were an intensely stained, unimodal population that was completely separated from unlabeled platelets. The mean half-life of labeled platelets in the murine circulation was 37.5 ± 4.5 hr (±1 SD), and the mean survival time was 3.1–3.3 days (n = 24), similar to results reported using 51Cr and 111In. No evidence of in vivo transfer of dye from labeled platelets to unlabeled cells was observed. CMFDA produces a population of platelets that are nonradioactively, internally labeled with a highly fluorescent, stable product. The labeled platelets function equivalently to native platelets, as demonstrated by immunocytometry and aggregometry, and importantly, in vivo, by normal platelet survival. Am. J. Hematol. 56:17–25, 1997. © 1997 Wiley-Liss, Inc.
229. Use of rAAV Transduced Endothelial Progenitor Cells for the Treatment of Myocardial Infarction in Rat Model
Authors: Sabyasachi Sen, Juan Merchan, Jarrod Dean, Marcia Silver, Mary Gavin, Elizabeth Eaton, Tengiz Tkebuchava, Maasaki Ii, Young-Sup Yoon, Douglas W. Losordo, Ryuichi Aikawa
Journal: Molecular Therapy (2006)

• Background_ The regenerative potential of bone marrow_derived endothelial progenitor cells (EPCs) has been adapted for the treatment of myocardial and limb ischemia via ex vivo expansion. Biotechnologically, it is plausible to constitute a potential means of addressing enhancement of EPC functions by efficient genetic modification of EPCs. Recombinant adeno_associated virus (rAAV) is currently being recognized as a gene delivery tool, and we recently demonstrated that rAAV vectors are capable of transducing bone marrow cells. Insulin_like growth factor_1 (IGF_1), which belongs to the insulin family of peptides and acts on a variety of functions such as anti_apoptosis, angiogenesis and proliferation of cells. • Aim_ In the present study, we first explored whether rAAV can transduce EPCs and whether the transduction is augmented by a certain drug. We next created rAAV_IGF_1 vector encoding human IGF_1 cDNA and tried to treat rat myocardial infarction model using EPCs transduced by rAAV_IGF_1 and followed to note if post_MI function improves. • Methods_ 1ml peripheral blood was obtained from the heart of each rat and EPCs were expanded ex vivo as previously shown. 3000 particles/cell of rAAV_lacZ control vectors were infected. The cytotoxicity of genistein, LLnL and hydroxyurea on EPC was assessed by MTT assay. rAAV mediated EPC transduction efficacy was examined by LacZ enzymatic assay and gene expression was analyzed by RT_PCR. For in vivo study, adult rats (n=7) underwent myocardial infarction by LAD coronary artery occlusion, and they were transplanted with autologous EPCs, transduced by rAAV_ IGF_1 or rAAV_lacZ into the peri_infarct area. We examined IGF_1 effects on apoptosis by TUNEL assay and capillary density by isolectin B4 staining. • Results_ 23%(±1.2) EPCs were stained positive for b_gal, and the lacZ activity by enzymatic assay showed four_fold improvement when EPCs were pre_treated with a tyrosine kinase inhibitor, genistein. Pre_treatment with hydroxyurea showed most cytotoxicity for EPCs compared to the other two agents, tested. For in_vivo study, echocardiography demonstrated that cardiac function in IGF_1 group was significantly improved compared to lacZ control group in 12 weeks after MI. In addition, IGF_1 gene delivery demonstrated reduced apoptosis and increased new capillary density in the peri_ infarct area. There were 33 (±2.1) TUNEL positive nuclei per 105 cells in LacZ group compared to 15 (±1.3) TUNEL positive nuclei in IGF_1 group. Similarly, there were 88 (±4.4) /mm2 capillary number in rAAV_lacZ transduced EPC group compared to 162 (±8.6)/mm2 in rAAV_IGF_1 transduced group. • Conclusion_rAAV vectors markedly improved transduction of EPCs on pre_treatment with genistein. IGF_1 transduced EPC had an anti_apoptotic effect and showed new capillary formation in myocardium post_infarction.
Unanticipated Lessening of the Rise in Extracellular Potassium During Ischemia by Pinacidil
Authors: Akihiro Kanda, Ichiro Watanabe, Marcus L. Williams, Connie L. Engle, Shu Li, Gary G. Koch, Leonard S. Gettes
Journal: Circulation (1997)

Background The efflux of potassium (K) through the ATP- sensitive K channel is considered an important cause of the rise in extracellular K ([K + ] e ) during no-flow ischemia. We postulated that agents that enhance K conductance in this channel would enhance the rise in [K + ] e. Methods and Results We studied the effects of 10 and 25 μmol/L pinacidil, an ATP-sensitive K channel opener that provides metabolic protection to the ischemic myocardium, on the rise in [K + ] e recorded by K-sensitive electrodes, the change in action potential duration (APD) recorded by microelectrodes, and the changes in activation during ischemia in in situ pig hearts and Tyrode-perfused rabbit interventricular septa. Pinacidil 25 μmol/L unexpectedly lessened the rise in [K + ] e and the activation delay in both preparations. Pinacidil 10 μmol/L had no effect in the rabbit and only a slight effect in the pig. Both concentrations significantly exaggerated the APD shortening induced by ischemia. By varying stimulation frequency, we demonstrated that the rise in [K + ] e during ischemia, both before and after pinacidil, correlated with the time that the action potential was at its plateau voltage. Conclusions Our results indicate that the rise in [K + ] e during ischemia is due to multiple factors, including K conductance across membrane channels, K driving force as reflected by the time that the action potential is at its plateau voltage, and the metabolic effects of ischemia. The unanticipated lessening of the rise in [K + ] e by pinacidil reflects the balance of its effects on these several parameters.
SECONDARY TUMORS OF THE BRAIN
Authors: WALTER D. SHELDEN
Journal: JAMA (1926)

Approximately 5 per cent of the tumors of the brain examined at the Mayo Clinic have metastasized from malignant disease elsewhere in the body. The precise frequency of these secondary tumors of the brain is doubtless somewhat higher, but only by universal necropsy service could accurate data be acquired. The occurrence of metastasis to the brain during the course of malignant disease, whether or not it is productive of symptoms, is of especial interest to the pathologist; but when a considerable number of patients present themselves for diagnosis with symptoms and signs of brain tumor as the initial evidence of malignant disease elsewhere, the problem is one of serious import to the physician. It is this phase of the subject of secondary tumors of the brain that I wish to discuss in the hope that an unsatisfactory state of diagnosis may be improved and that, if possible, the embarrassment of
Hyperalimentation in Cancer
Authors: W. W. Souba, E. M. Copeland
Journal: CA A Cancer Journal for Clinicians (1989)

When response rates to antineoplastic therapy are good and the associated nutritional morbidity is high, TPN is recommended when the gastrointestinal tract is unavailable for use. Patients should not be denied adequate cancer treatment because of the fear of complications secondary to malnutrition. On the other hand, prolongation of pain and suffering for the terminally ill cancer patient is obviously not an indication for TPN. Appropriate clinical judgment is required in proper selection of the TPN candidate. Malnutrition is almost always a prerequisite, as is failure of the gastrointestinal tract. Therapies designed to direct nutritional support to preferentially benefit the host and "starve" the tumor have had only limited short-term success in animal models. The use of diets that are glutamine- and arginine-supplemented are only now being examined in animal experiments. Since TPN allows total and complete control of exogenous nutrients, it should be used to explore alternative therapies in the form of nutrient composition. For example, if tumors are preferential glutamine utilizers, then TPN-enriched solutions might be employed to increase the number of cells in a phase of mitosis that makes them more susceptible to attack by cell-cycle specific chemotherapeutic agents. Stimulation of tumor growth by TPN in patients is not scientifically documented. Only anecdotal reports appear in the literature. Thousands of cancer patients worldwide have received TPN. Were stimulation of tumor growth to be a major problem with TPN solutions as currently formulated, it should be known by now.
Mortality among Former Love Canal Residents
Authors: Lenore J. Gensburg, Cristian Pantea, Edward Fitzgerald, Alice Stark, Syni-An Hwang, Nancy Kim
Journal: Environmental Health Perspectives (2008)

The Love Canal is a rectangular 16-acre, 10-ft deep chemical waste landfill situated in a residential neighborhood in Niagara Falls, New York. This seriously contaminated site first came to public attention in 1978. No studies have examined mortality in the former residents of the Love Canal neighborhood (LC).The aim of this study was to describe the mortality experience of the former LC residents from the years 1979-1996.From 1978 to 1982, 6,181 former LC residents were interviewed. In 1996, 725 deaths from 1979-1996 were identified in this cohort, using state and national registries. We compared mortality rates with those of New York State (NYS) and Niagara County. Survival analysis examined risks by potential exposure to the landfill.We were unable to demonstrate differences in all-cause mortality for either comparison population for 1979 1996. Relative to NYS, the standardized mortality ratio (SMR) was elevated [SMR = 1.39; 95% confidence interval (CI), 1.16-1.66] for death from acute myocardial infarction (AMI), but not relative to Niagara County. Death from external causes of injury was also elevated relative to both NYS and Niagara County, especially among women (SMR = 1.95; 95% CI, 1.25 2.90).The role of exposure to the landfill in explaining these excess risks is not clear given limitations such as multiple comparisons, a qualitative exposure assessment, an incomplete cohort, and no data on deaths prior to 1978. Lack of elevation for AMI when compared with Niagara County but not NYS suggests possible regional differences. However, direct cardiotoxic or neurotoxic effects from landfill chemicals or indirect effects mediated by psychological stress cannot be ruled out. Revisiting the cohort in the future could reveal patterns that are not yet apparent.
Is Age a Good Discriminator When Deciding Whether to Perform Gastroscopy?
Authors: F. Froehlich
Journal: Endoscopy (2003)

How to select patients for upper gastrointestinal endoscopy is a question of paramount clinical importance given the high prevalence of upper gastrointestinal symptoms (in particular of dyspepsia) and the relapsing nature of these complaints. Indeed, about 1 % [1] [2] to 1.8 % [3] of the population undergo gastroscopy each year. The decision to perform a diagnostic procedure such as gastroscopy must take into account the probability and net benefit of identifying disease; in contrast, the decision not to perform it must take into account the risk of missing significant disease [4] for which early, appropriate treatment can improve outcome.
Benign Familial Hematuria
Authors: Israel Zelikovic
Journal: JAMA (1988)

<h3>To the Editor.—</h3> We read with interest the article by Blumenthal et al<sup>1</sup>concerning the importance of examining the urine sediment of patients and family members in establishing the diagnosis of benign familial hematuria. We concur with their notion of reducing the number of painful and costly urologic and radiological procedures in patients with hematuria but believe that the authors have failed to evaluate and discuss an important cause of hematuria, at least in children. This cause is idiopathic hypercalciuria, an entity with a familial occurrence pattern that is being recognized as a major cause of gross and microscopic hematuria in children.<sup>2,3</sup> Hypercalciuria, defined as urinary calcium excretion of more than 4 mg/kg of body weight every 24 hours or as a calcium/creatinine ratio of more than 0.21 (mg/mg) in a urine sample collected over a two-hour period,<sup>3</sup>was prospectively found in 78 (36%) of 215 children
Nephrotic Proteinuria in Obesity
Authors: ADAN GONZALEZ
Journal: Annals of Internal Medicine (1975)

Comments1 January 1975Nephrotic Proteinuria in ObesityADAN GONZALEZ, M.D., ROBERT SODERBLOM, M.D., SIEGMUND TEICHMAN, M.D.ADAN GONZALEZ, M.D.Search for more papers by this author, ROBERT SODERBLOM, M.D.Search for more papers by this author, SIEGMUND TEICHMAN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-82-1-122_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In a recent paper Weisinger and associates (Ann Intern Med 81:440-447, 1974) postulate that the cause of the reversible nephrotic proteinuria in their obese patients is renal venous hypertension. We would like to comment on this view and to propose an alternative explanation of their findings.Although it has been shown that progressive constriction of the renal veins leads to proteinuria (1), this is usually well under the range of nephrotic syndrome even when the venous pressure is increased four to five times normal. Second, the evidence that elevated renal vein pressure is the mechanism responsible for the...References1. WEGRIACAPECIGLUMENTHAL RNM: The pathogenesis of proteinuria in the acutely congested kidney. J Clin Invest 34:737-743, 1955 CrossrefMedlineGoogle Scholar2. HILTONJONESTIGHE PNJ: Nephrotic syndrome with heart disease—a reappraisal. Br Med J 3:584-586, 1968 CrossrefMedlineGoogle Scholar3. VASSALLIMCCLUSKEY PR: The coagulation process and glomerular disease. Am J Med 39:179-183, 1965 CrossrefMedlineGoogle Scholar4. GOLD RICK R: Fibrinolysis, blood clotting, serum lipids and body build in natives of New Guinea and Australians. Aust Ann Med 10:20-28, 1961 MedlineGoogle Scholar5. BENNETOGSTONMCANDREW NCG: Studies on the fibrinolytic enzyme system in obesity. J Clin Pathol 19:241-243, 1966 CrossrefMedlineGoogle Scholar6. OGSTONMCANDREW DG: Fibrinolysis in obesity. Lancet 2: 1205-1207, 1964 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Department of Medicine Loma Linda University Loma Linda, California PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByRenal hemodynamics in overweight and obesity: pathogenetic factors and targets for interventionRenal dysfunction 1 January 1975Volume 82, Issue 1Page: 122-122KeywordsHypertensionObesityOverweightProteinuriaVeins Issue Published: 1 January 1975 PDF DownloadLoading ...
Comparative Effectiveness of Warfarin and New Oral Anticoagulants for the Management of Atrial Fibrillation and Venous Thromboembolism
Authors: Soheir S. Adam, Jennifer R. McDuffie, Thomas L. Ortel, John W. Williams
Journal: Annals of Internal Medicine (2012)

Background: New oral anticoagulants (NOACs), including direct thrombin inhibitors (DTIs) and factor Xa (FXa) inhibitors, are emerging alternatives for prophylaxis and treatment of atrial fibrillation (AF) and venous thromboembolism (VTE). Purpose: To compare the benefits and harms of NOACs versus warfarin for AF and VTE. Data Sources: MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews from January 2001 through July 2012; U.S. Food and Drug Administration (FDA) database for adverse event reports. Study Selection: English-language, randomized, controlled trials (RCTs) comparing NOACs with warfarin for management of AF or VTE and observational studies and FDA reports on adverse effects. Data Extraction: Two independent reviewers abstracted data and rated study quality and strength of evidence. Data Synthesis: Six good-quality RCTs compared NOACs (2 DTI studies, 4 FXa inhibitor studies) with warfarin. In AF, NOACs decreased all-cause mortality (risk ratio [RR], 0.88 [95% CI, 0.82 to 0.96]); in VTE, NOACs did not differ for mortality or VTE outcomes. Across indications, adverse effects of NOACs compared with warfarin were fatal bleeding (RR, 0.60 [CI, 0.46 to 0.77]), major bleeding (RR, 0.80 [CI, 0.63 to 1.01]), gastrointestinal bleeding (RR, 1.30 [CI, 0.97 to 1.73]), and discontinuation due to adverse events (RR, 1.23 [CI, 1.05 to 1.44]). Subgroup analyses suggest a higher risk for myocardial infarction with DTIs than with FXa inhibitors. Bleeding risk for NOACs may be increased in persons older than 75 years or those receiving warfarin who have good control. Limitation: There were no head-to-head comparisons of NOACs and limited data on harms. Conclusion: New oral anticoagulants are a viable option for patients receiving long-term anticoagulation. Treatment benefits compared with warfarin are small and vary depending on the control achieved by warfarin treatment. Primary Funding Source: Department of Veterans Affairs.
Adaptationism, exaptationism, and evolutionary behavioral science
Authors: Paul W. Andrews, Steven W. Gangestad, Dan Matthews
Journal: Behavioral and Brain Sciences (2002)

In our target article, we discussed the standards of evidence that could be used to identify adaptations, and argued that building an empirical case that certain features of a trait are best explained by exaptation, spandrel, or constraint requires the consideration, testing, and rejection of adaptationist hypotheses. We are grateful to the 31 commentators for their thoughtful insights. They raised important issues, including the meaning of “exaptation”; whether Gould and Lewontin's critique of adaptationism was primarily epistemological or ontological; the necessity, sufficiency, or utility of design evidence, phylogenetic analyses, homology, and molecular genetics in distinguishing exaptations from adaptations; whether adaptationists accept adaptationist hypotheses too quickly; and the real utility of adaptationism to human behavioral science. We organize our response along the major points of the target article, in some situations defending our original claims and in others modifying them. While debate on these issues will undoubtedly continue, we are cautiously optimistic that the main points of the target article (as modified by our response) will help move the debate in a positive direction.
The Effect of Corticotropin and Adrenal Steroids on Adrenocortical and Pituitary Responsiveness.
Authors: Walter L. Palmer
Journal: Annals of Internal Medicine (1964)

s1 February 1964The Effect of Corticotropin and Adrenal Steroids on Adrenocortical and Pituitary Responsiveness.Walter L. Palmer, M.D., F.A.C.P., Peter I. Reed, M.D., Charles B. Clayman, M.D., F.A.C.P.Walter L. Palmer, M.D., F.A.C.P.Search for more papers by this author, Peter I. Reed, M.D.Search for more papers by this author, Charles B. Clayman, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-60-2-331_4 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptClinical experience has shown that the effect of adrenocorticotrophic hormone (ACTH) and the adrenal hormones, while frequently dramatic, is nevertheless variable and often disappointing. Relatively little information is available on the adrenocortical and pituitary responsiveness in disease states and how this is influenced by both short and long-term treatment with ACTH and adrenal steroids. Our study has yielded preliminary data and warrants certain tentative conclusions.Of the 20 patients studied, 13 had received ACTH only for periods of 2 weeks to 8½ years, 5 were on adrenal steroids for 3 days to 3¾ years and the remaining 2 patients had... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Walter L. Palmer, M.D., F.A.C.P.; Peter I. Reed, M.D.; Charles B. Clayman, M.D., F.A.C.P.Affiliations: Chicago, Illinois PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAdrenocortical Function During Intermittent Corticosteroid TherapyDONALD A. ADAMS, M.D., ERNEST M. GOLD, M.D., HARVEY C. GONICK, M.D., F.A.C.P., MORTON H. MAXWELL, M.D., F.A.C.P. 1 February 1964Volume 60, Issue 2_Part_1Page: 331-332KeywordsAdrenocorticotropic hormoneSteroids ePublished: 1 December 2008 Issue Published: 1 February 1964 PDF downloadLoading ...