tbuckley/cabot-search huggingface dataset:
Pegylated interferon-α induced hypoferremia is associated with the immediate response to treatment in hepatitis C
Authors: John D. Ryan, Sandro Altamura, Emma Devitt, Sarah Mullins, Matthew W. Lawless, Martina U. Muckenthaler, John Crowe
Journal: Hepatology (2012)

Pegylated interferon-α (PEG-IFN-α) forms an integral part of the current treatment for hepatitis C virus (HCV) infection. PEG-IFN-α suppresses HCV production by augmenting the innate antiviral immune response. Recent studies have reported the induction of hepcidin, the iron regulatory hormone, by IFN-α in vitro. As hepcidin plays an important role in innate immunity, we hypothesized that this finding may be of clinical relevance to HCV and investigated the changes in iron homeostasis during the first 24 hours of treatment. Blood samples were obtained from HCV patients immediately prior to and 6, 12, and 24 hours following the first dose of PEG-IFN-α/ribavirin (RBV). Samples were analyzed for hepcidin, cytokine, iron levels, and HCV viral load, and hepcidin messenger RNA (mRNA) expression was quantified in peripheral blood mononuclear cells. Hepcidin induction by IFN-α was further analyzed in cell culture. In HCV patients a single dose of PEG-IFN-α/RBV resulted in a significant increase in serum hepcidin, peaking at 12 hours, coinciding with a 50% reduction in serum iron and transferrin saturation over the 24-hour period. Patients with a ≥ 2 log decline in HCV viral load over the first 24 hours had significantly lower SI and TS levels at 12 and 24 hours. Moreover, 24-hour SI levels were an independent predictor of the immediate HCV viral decline, an indicator of ultimate treatment outcome. In cell culture, a direct induction of hepcidin by IFN-α was seen, controlled by the STAT3 transcription factor.Hepcidin induction occurs following the initiation of PEG-IFN-α treatment for HCV, and is mediated by way of STAT3 signaling. The subsequent hypoferremia was greatest in those with the most significant decline in viral load, identifying systemic iron withdrawal as a marker of immediate interferon-α efficacy in HCV patients.
New Studies Fuel Controversy Over Universal Cholesterol Screening During Childhood
Authors: Beverly Merz
Journal: JAMA (1989)

MASS SCREENING for elevated serum cholesterol values should begin in childhood. This recommendation, counter to the current position taken by the American Academy of Pediatrics (AAP), was made by two teams of investigators at recent American Heart Association meetings. In a statement published in January (<i>Pediatrics</i>. 1989; 83:141-142), the AAP's committee on nutrition states, "a child with a family history of either early coronary heart disease or hyperlipidemia should have a complete evaluation, including serum or plasma measurement of cholesterol, other lipids, and lipoproteins. On the other hand, the Committee on Nutrition does not favor universal testing of blood cholesterol levels of children either in the hospital or in the office of the private physician." "We need a big push to change this kind of thinking and start screening for primary risk factors in kids," says Gerald S. Berenson, MD, chief of the Section of Cardiology at Louisiana State University
In situ detection of fragmented dna (tunel assay) fails to discriminate among apoptosis, necrosis, and autolytic cell death: A cautionary note
Authors: Bettina Grasl Kraupp, Branislav Ruttkay-Nedecky, Helga Koudelka, Krystyna Bukowska, Wilfried Bursch, Rolf Schulte-Hermann
Journal: Hepatology (1995)

Detection of DNA fragments in situ using the terminal deoxyribonucleotidyl transferase (TDT)-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay is increasingly applied to investigate active cell death (apoptosis). We studied the specificity of the assay in well-defined models of apoptosis and necrosis as well as in postmortem autolysis in rat liver. During involution of liver hyperplasia, which follows stopping treatment with the hepatomitogens cyproterone acetate (CPA) or nafenopin (NAF), numerous apoptotic hepatocytes could be observed with TUNEL-positive chromatin residues. A similar TUNEL-positive reaction appeared in necrotic hepatocytes after a cytotoxic dose of carbon tetrachloride (CCl 4 ) or N -nitrosomorpholine (NNM). Also, in insufficiently fixed, autolytic livers TUNEL-positive nuclei were observed. Thus, DNA fragmentation is common to different kinds of cell death; its detection in situ should not be considered a specific marker of apoptosis.
Electrocardiographic Predictors of Incident Congestive Heart Failure and All-Cause Mortality in Postmenopausal Women
Authors: Pentti M. Rautaharju, Charles Kooperberg, Joseph C. Larson, Andrea LaCroix
Journal: Circulation (2006)

Background— Information is limited about ECG predictors of the risk of incident congestive heart failure (CHF), particularly in women without overt manifestations of cardiovascular disease (CVD). Methods and Results— We evaluated hazard ratios for incident CHF and all-cause mortality using Cox regression in 38 283 participants of the Women’s Health Initiative (WHI) during a 9-year follow-up. All risk models were adjusted for demographic and available clinical and therapeutic variables (multivariable-adjusted models). A backward selection procedure was used to identify dominant predictors among those that were significant as individual ECG predictors. Eleven ECG variables were significant predictors of incident CHF, with none of them having a significant interaction with baseline CVD status. From 6 dominant ECG predictors, wide QRS/T angle had a nearly 3-fold increased risk in multivariable-adjusted single ECG variable models. Two other repolarization variables, STV 5 depression and high TV 1 amplitude, and 2 QRS-related variables, QRS non-dipolar voltage and myocardial infarction (MI) by ECG, were all associated with &amp;2-fold increase of incident CHF risk. Overall, 11 of the 12 ECG variables were significant predictors of all-cause mortality. Four variables had a significant interaction with CVD status requiring stratification. Three among these 4 were strong, dominant predictors in the CVD group: ECG MI, wide QRS/T angle, and low TV 5 amplitude had risk increase from &gt;2-fold to 3-fold, with considerably lower risks in the CVD-free group. Conclusions— Several repolarization variables in postmenopausal women are predictors of the risk of incident CHF and all-cause mortality as important as old ECG MI.
Surgical Techniques for Saccular and Giant Intracranial Aneurysms
Authors: Charles G. Drake
Journal: JAMA (1990)

This volume encompasses the surgical experience with intracranial aneurysms from 1969 to 1988 at the Mayo Clinic: 1634 cases of which 1096 were saccular, 215 globular, and 323 giant. It is Thoralf Sundt at his best. As he writes in the preface, it is "quite simply a 'how we do it book,'" and its pages are an atlas of the Mayo techniques. After a nice historical review, the book is divided into four parts that contain chapters on "Basic Considerations," "Aneurysms of the Anterior Circulation," "Aneurysms of the Posterior Circulation," and "Pediatric Aneurysms." "Basic Considerations" contains brief chapters on circulatory physiology, pathophysiology, clinical evaluation, and perioperative care wherein Dr Sundt's well-known personal management methods emerge—eg, administering isoproterenol and lidocaine in the management of vasospasm and highdose steroids to prevent its angiopathy. In delayed operations from 1969 through 1977 involving the first 310 patients, 7 died or moved to a lower
Abstract 5320: Novel computational methods reveal subtle clonal mosaicism
Authors: Paul Scheet, Rui Xia, F. Anthony San Lucas, Christina Hahn, Jerry Fowler, Selina Vattathil
Journal: Cancer Research (2014)

Abstract Recent genome-wide surveys have revealed age-related genetic mosaicism and established a link between clonal mosaicism and risk of hematological and solid-tumor cancers (Laurie et al, 2012, Nat Genet, 44:642; Jacobs et al, 2012, Nat Genet, 44:651; Forsberg et al, 2012, AJHG, 90:217). Existing methods to identify chromosomal aberrations leading to mosaic allelic imbalance (AI) rely on the detection of increased variance of the estimated within-sample allele frequencies at heterozygous loci, ignoring the dependence among allele frequencies in regions of an AI-inducing event, such as a deletion or copy-neutral loss of heterozygosity (LOH), expected from the loss or gain of a chunk of an inherited chromosome. As a result, they break down when the proportion of DNA from an aberrant source is below 10-15%. Here we present a suite of new methods (hapLOH, J-LOH, hapLOHseq) that harness the important information contained in the germline haplotypes to help distinguish signal from noise, accommodate multiple samples of different tumor purities (to deconvolute aberration type and tumor purity) and infer co-occurrence of aberrations in heterogeneous mixtures. For example, our initial method, hapLOH (Vattathil &amp; Scheet, 2013, Gen Res 23:152), can identify 10 Mb regions with just 4% of the signal coming from the tumor genome in data simulated from a series of experiments from a 317K SNP microarray. Application of hapLOH to data analyzed by Laurie et al (2012) indicates that we have substantially greater sensitivity to detect clonal mosaicism, particularly events harbored in a small proportion of cells (&amp;lt; 5-10%). We identify more than twice as many mosaic events, demonstrating the potential role for our methods to aid in profiling cancer risk. Our suite of tools is designed for both microarray and next-generation sequencing data and is available at scheet.org. Citation Format: Paul Scheet, Rui Xia, F. Anthony San Lucas, Christina Hahn, Jerry Fowler, Selina Vattathil. Novel computational methods reveal subtle clonal mosaicism. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5320. doi:10.1158/1538-7445.AM2014-5320
Low-Back Pain as the Presenting Symptom of Malignant Breast Tumors
Authors: Theodore D. Cohn, Harold Cohn
Journal: New England Journal of Medicine (1945)

PRIMARY malignant tumors of the female breast that have metastasized to the vertebral column and bony pelvis are not infrequently overlooked. These patients are at times erroneously treated for the numerous other causes of backache, such as "lumbago," "sciatica," sacroiliac strain and retroversion of the uterus. The frequency of diffuse skeletal metastases from relatively small malignant nodules in the breast is a well-recognized clinical fact, but the subject has not been extensively discussed or become crystallized in the literature.Lamarque1 in his discussion of sketetal metastases from breast cancer makes the point that many of his patients complained of vague . . .
Lead and PCBs as Risk Factors for Attention Deficit/Hyperactivity Disorder
Authors: Paul A. Eubig, Andréa Aguiar, Susan L. Schantz
Journal: Environmental Health Perspectives (2010)

Attention deficit/hyperactivity disorder (ADHD) is the most frequently diagnosed neurobehavioral disorder of childhood, yet its etiology is not well understood. In this review we present evidence that environmental chemicals, particularly polychlorinated biphenyls (PCBs) and lead, are associated with deficits in many neurobehavioral functions that are also impaired in ADHD.Human and animal studies of developmental PCB or lead exposures that assessed specific functional domains shown to be impaired in ADHD children were identified via searches of PubMed using "lead" or "PCB exposure" in combination with key words, including "attention," "working memory," "response inhibition," "executive function," "cognitive function," "behavior," and "ADHD."Children and laboratory animals exposed to lead or PCBs show deficits in many aspects of attention and executive function that have been shown to be impaired in children diagnosed with ADHD, including tests of working memory, response inhibition, vigilance, and alertness. Studies conducted to date suggest that lead may reduce both attention and response inhibition, whereas PCBs may impair response inhibition to a greater degree than attention. Low-level lead exposure has been associated with a clinical diagnosis of ADHD in several recent studies. Similar studies of PCBs have not been conducted.We speculate that exposures to environmental contaminants, including lead and PCBs, may increase the prevalence of ADHD.
PACEMAKER CLICKS CLARIFIED
Authors: A. M. HARRIS
Journal: Annals of Internal Medicine (1969)

Letters and Comments1 January 1969PACEMAKER CLICKS CLARIFIEDA. M. HARRIS, M.D.A. M. HARRIS, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-70-1-234_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor:With reference to the recent letter (Ann. Intern. Med. 69: 846, 1968) by Dr. Azam Ansari on the article entitled "Auscultatory Clicks Produced by Pacemaker Catheters," I would like to point out to these authors that this subject was fully dealt with by me in an article entitled "Pacemaker Heart Sound" published in theBritish Heart Journalin July 1967. This sound is due to intercostal muscle contraction, and in fact it was abolished by suxamethonium chloride.... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Cardiac Department St. George's Hospital London, S.W.1 England PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byElectronic spectra of jet-cooled isoindoline: Spectroscopic determination of energy difference between conformational isomers 1 January 1969Volume 70, Issue 1Page: 234-234KeywordsCathetersChloridesHeartMuscle contractionPacemakers Issue Published: 1 January 1969 PDF downloadLoading ...
Response of anaemia in rheumatoid arthritis to treatment with subcutaneous recombinant human erythropoietin.
Authors: B Gudbjörnsson, R Hällgren, L Wide, G Birgegård
Journal: Annals of the Rheumatic Diseases (1992)

Eleven patients with chronic inflammatory arthritides and haemoglobin concentrations less than 105 g/l with symptoms from their anaemia were treated with a dose of 250 IU/kg/week of recombinant human erythropoietin for six weeks. The treatment was given as subcutaneous injections five days a week. All patients had active inflammatory disease. Nine patients responded to treatment with an increase in haemoglobin of more than 15 g/l. The mean (SD) haemoglobin concentration increased from 93.0 (8.0) g/l before treatment to 115.0 (12.0) g/l after six weeks. There was no correlation between the initial serum concentration of erythropoietin and the response. It was concluded that anaemia in chronic inflammatory arthritides responds to treatment with subcutaneous injections of recombinant human erythropoietin.
Pharmacokinetics of Lidocaine-Reply
Authors: David J. Greenblatt
Journal: JAMA (1977)

<h3>In Reply.—</h3> We appreciate the opportunity to consider the comments of Dr Lawyer and of Drs Wheeler et al. The major point of our article was that judicious application of pharmacokinetic principles can enhance the likelihood of safe and effective pharmacotherapy with a drug such as lidocaine, for which there is reasonably good data suggesting a relation between blood concentration and clinical efficacy and toxicity. We chose representative data from a previous publication<sup>1</sup>to illustrate this point. Dr Lawyer raises an interesting issue regarding these data, but it is not really pertinent to our conceptual objective. Other more complicated pharmacokinetic schemes, such as those suggested by Drs Wheeler et al and by Jelliffe et al,<sup>2</sup>may come closer to "optimizing" lidocaine therapy than the one suggested by us. However, one must consider not only the potential benefits of more complex schemes, but also the possible disadvantages. These include
Effective predischarge triage at the emergency room with dobutamine stress echocardiography and cardiac troponin T
Authors: Radha Bholasingh, Jan H. Cornel, Otto Kamp, Jan P. van Straalen, Gerard T. Sanders, Jan G. Tijssen, Victor A. Umans, Cees A. Visser, Robbert J. de Winter
Journal: Journal of the American College of Cardiology (2002)
Decreased Microvascular Nitric Oxide–Dependent Vasodilation in Postural Tachycardia Syndrome
Authors: Marvin S. Medow, Christopher T. Minson, Julian M. Stewart
Journal: Circulation (2005)

Background— One variant of postural tachycardia syndrome (POTS), designated low-flow POTS, is associated with decreased peripheral blood flow related to impaired local vascular regulation. Methods and Results— To investigate the hypothesis that microvascular endothelial dysfunction produces decreased peripheral blood flow in low-flow POTS, we performed experiments using laser-Doppler flowmetry (LDF) combined with iontophoresis in 15 low-flow POTS patients, 17 normal-flow POTS patients, and 13 healthy reference volunteers varying in age from 14 to 22 years. We tested whether α-adrenergic vasoregulation was impaired using iontophoretic delivery of tyramine, phentolamine, and bretylium followed by a norepinephrine dose response. We tested endothelial-dependent and -independent receptor-mediated vasodilation by measuring acetylcholine and sodium nitroprusside dose responses. We tested whether nitric oxide–dependent vasodilation was different in these groups by testing the local thermal hyperemic response to saline used as a reference compared with the nitric oxide synthase inhibitor N G -nitro- l -arginine methyl ester (L-NAME). Adrenergic and receptor-dependent cutaneous vasoregulation was similar for low-flow POTS, normal-flow POTS, and reference subjects. Thermal hyperemia produced distinctly different findings: there was marked attenuation of the nitric oxide–sensitive plateau during prolonged heating, which was insensitive to L-NAME in low-flow POTS subjects. The pattern of thermal hyperemia response in low-flow POTS subjects during saline administration resembled the pattern in reference subjects during L-NAME administration and was minimally affected by L-NAME. Conclusions— The data suggest that flow-dependent nitric oxide release is reduced in low-flow POTS. This may account for local flow regulation abnormalities.
Comparative echocardiographic study of recovery of diastolic versus systolic function after brief periods of coronary occlusion: differential effects of intravenous nifedipine administered before and during occlusion
Authors: Yozo Fujibayashi, Shigeru Yamazaki, Bing-Lo Chang, Ram E. Rajagopalan, Samuel Meerbaum, Eliot Corday
Journal: Journal of the American College of Cardiology (1985)
Absence of immunoglobulin and T‐cell receptor gene rearrangements in myelodysplastic syndromes and acute nonlymphocytic leukemias
Authors: J. S. Wainscoat, M. F. Fey, S. Pilkington, C. Summers, D. G. Oscier
Journal: American Journal of Hematology (1988)

Abstract The arrangement of the immunoglobulin and T‐cell receptor genes has been analysed in 72 cases of primary myelodysplastic syndrome and 17 cases of acute nonlymphocytic leukemia. DNA was extracted from bone marrow aspirates, digested with at least two restriction enzymes, and hybridised with probes for the joining region of the immunoglobulin heavy chain gene, the constant region of the T‐cell receptor β chain gene, and the joining region of the T‐cell receptor γ chain gene. All cases showed germline arrangements of the immunoglobulin and the T cell receptor genes. Thus, true interlineage infidelity, myeloid to lymphoid, is a rare occurrence in myelodysplasia and in myeloid leukemias.
AN ELECTRON MICROSCOPE STITDY OF THE DEGRANULATION OF RAT PERITONEAL MAST CELLS BROUGHT ABOUT BY FOUR DIFFERENT AGENTS
Authors: PATRICIA R. MANN
Journal: British Journal of Dermatology (1969)

SUMMARY.— The degranulation of rat peritoneal mast cells produced by Compound 48 80, by two antigens and by hydration has been studied with the electron microscope. The different mediators of degranulation do not apparently act in the same way. Degranulation by antigens produces bizarre forms of granule and clumping of the granules, which does not occur with Compound 48/80 or hypotonic solutions. Hypotonic solutions produce swelling of cyto-plasmic membranes but no alteration in the granules. The differences are illustrated and discussed.
Monocyte Responsiveness to Chemotactic Stimuli is a Property of a Subpopulation of Cells that can Respond to Multiple Chemoattractants
Authors: George J. Cianciolo, Ralph Snyderman
Journal: Journal of Clinical Investigation (1981)

The chemotactic migration of leukocytes is preceded by an alteration in the cells' shape from round to a characteristic polar configuration. We have developed an assay that shows that human monocytes, when exposed to chemoattractant in suspension, assume this polarized shape. The three types of chemo-attractants studied, a chemotactic lymphokine, complement-activated serum, and the N-formylated oligopeptides, all induced polarization in a time, temperature, and dose-dependent fashion. Nonchemotactic agents such as mitogens or phorbol myristate acetate did not induce polarization. At 37°C, polarization was rapid (<1 min) and was inhibitable by cytochalasin B, sodium azide, or low temperature. A series of N-formylated oligopeptides were studied and their activity in inducing polarization correlated closely (r > 0.99) with their chemotactic activity. Of the entire population of circulating monocytes there is a subpopulation of cells that is capable of polarizing in response to chemotactic stimuli. The maximum percentage of monocytes which polarized to any chemotactic factor was ∼60%. Furthermore, the combination of several chemotactic factors could not increase the percentage of polarized monocytes above the maximum obtained with an optimal dose of any single chemoattractant. The data also demonstrate that high doses of a chemoattractant can induce a state of cross-desensitization in monocytes that blocks the response of the cells to other types of chemotactic factors. These results support the concept that the monocytes that do respond to chemotactic stimuli are capable of responding to any of several attractants.