tbuckley/cabot-search huggingface dataset:
Exercise Responses in Patients With IDDM
Authors: Anne-Marie Nugent, Ian C Steele, Firas Al-Modaris, Stephen Vallely, Ann Moore, Norman P S Campbell, Patrick M Bell, Keith D Buchanan, Elisabeth R Trimble, D Paul Nicholls
Journal: Diabetes Care (1997)

OBJECTIVE The hemodynamic, respiratory, and metabolic responses to exercise were studied in IDDM patients and control subjects to detect diabetic cardiomyopathy. RESEARCH DESIGN AND METHODS Eight subjects aged 25–40 years with diabetes of at least 10 years' duration were compared with eight control subjects aged 21–46 years. All subjects underwent a progressive incremental bicycle exercise test with measurement of gas exchange, blood glucose, lactate, fat metabolite, and catecholamine levels and two steady-state exercise tests with measurement of cardiac output by a CO2 rebreathing method. A new first-pass radionuclide method was used to measure cardiac ejection fractions (EFs) at rest, peak exercise, and steady-state exercise. RESULTS The peak achieved oxygen consumption was similar in the diabetic and control subjects (29.9 [25.1–34.6] and 31.4 [26.9–35.9] ml . min−1 . kg−1, respectively; mean [95% CI]). There were no significant differences in heart rate, double product, ventilation, respiratory exchange ratio, or ventilatory equivalents for oxygen and CO2 during the incremental test. Glucose levels were higher in the diabetic subjects, but there were no significant differences in levels of lactate, catecholamines, free fatty acids, glycerol, or β-hydroxybutyrate. Left ventricular EF fell from rest to peak exercise within the diabetic group (66.0% [59.6–72.4] at rest; 53.6% [45.6–61.6] at peak; P &amp;lt; 0.05) but this did not differ significantly from the control group (58.7% [52.3–65.1] at rest; 60.3% [48.9–71.7] at peak). Right ventricular EFs were similar in each group, and there was no reduction in peak filling rate to suggest diastolic dysfunction. The cardiac output responses to exercise were also similar in the two groups. CONCLUSIONS There is no evidence of impairment of the exercise response in subjects with long-standing diabetes, and the apparent fall in left ventricular EF at peak exercise could be related to hemodynamic adaptation.
Consideration of QT/QTc Interval Data in a Phase I Study in Patients with Advanced Cancer
Authors: Mary Varterasian, Howard Fingert, Marilyn Agin, Mark Meyer
Journal: Clinical Cancer Research (2004)

We commend the effort of these authors to undertake and report on their analysis of the QT/QTc interval during their phase I evaluation of combretastatin A4 phosphate and also for their inclusion of these data in this publication [(1)][1] . Capturing and interpreting such data can be challenging,
Comparison of the Hyperoxic Test and the Alternate Breath Test in Infants
Authors: BELKACEM BOUFERRACHE, SLAVI FILTCHEV, ANDRÉ LEKE, MICHEL FREVILLE, JORGE GALLEGO, CLAUDE GAULTIER
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Peripheral chemoreceptor function has been tested using either the hyperoxic test (HT), which decreases minute ventilation (V˙ e) by causing physiologic chemodenervation, or the alternate breath test (ABT), which induces V˙ e alternations by delivering rapid hypoxic stimuli through breath-by-breath alternations in fractional inspired O2 between normoxia (0.21) and hypoxia (0.15). No previous studies have compared ventilatory responses to both tests in the same infants. We hypothesized that the V˙ e decrease during HT would be significantly related to V˙ e alternations during ABT. Eighteen infants (postnatal age 21 ± 14 d) underwent two 30-s HTs and two ABTs (quiet sleep, face mask, and pneumotachograph; mass spectrometry measurement of inspired and expired O2 and CO2 fractions; and breath-by-breath analysis). The tests were done in random order. Decreases in V˙ e and mean inspiratory flow (tidal volume over inspiratory time, Vt/Ti) during HTs were significantly correlated to their respective percentage coefficients of alternation during ABTs (r = 0.69 and 0.70, respectively, p < 0.01). Principal components analysis showed that the V˙ e and Vt/Ti decreases during HTs were due chiefly to a fall in Vt, whereas V˙ e and Vt/Ti alternations were ascribable to alternations in both Vt and Ti. Intraindividual coefficients of variation of V˙ e changes were significantly lower during HTs than during ABTs. We conclude that (1) ventilatory responses to HT and ABT are significantly correlated despite differences in the mechanisms of the V˙ e changes; (2) the better reproducibility of the V˙ e response to HT as compared with ABT may be an advantage in clinical practice.
Abstract 174: MicroRNA signatures of castration resistant human prostate cancer
Authors: Tong Sun, Ming Yang, Shaoyong Chen, Steven Balk, Mark Pomerantz, Myles Brown, Philip W. Kantoff, Gwo-Shu Mary Lee
Journal: Cancer Research (2011)

Abstract Androgen-dependent (AD) prostate cancer (CaP) typically progresses to castration resistant prostate cancer (CRPC) after after some duration of androgen deprivation therapy (ADT). The mechanisms of this transition are at the beginning to be understood. MicroRNAs (miRs) are non-coding small RNAs (19-25nt) that play an important role in the regulation of gene expression. So far, only a few studies have looked at prostate cancer-specific miRNA signatures relevant to the development and progression of CaP. By performing genome-wide expression profiling of miRs, we found 7 miRs (miR-221, miR-222, miR-15a, miR-16-1, miR-203, miR-23b and miR-27b) differentially expressed in the AD prostate cancer LNCaP cell line and the LNCaP derived CRPC cell line- LNCaP-Abl. In particular miR-221 and miR-222, were most dramatically increased in the CRPC cell lines. Over-expression of miR-221 or -222 in LNCaP or another AD cell line, LAPC-4 significantly reduced the level of the dihydrotestosterone (DHT) induced up-regulation of PSA expression and increased androgen independent (AI) growth of LNCaP cells. Knocking down the expression level of miR-221 and -222 with antagonist miRs in the LNCaP-Abl cell line restored the response to DHT induction of PSA transcription and also increased the growth response of LNCaP-Abl cells to androgen. To determine the clinical relevance of the differential expression patterns of these miRs, we compared the expression levels of these 7 miRs in 86 normal prostate tissues, 34 localized hormone naïve primary tumors and 17 bone metastatic CRPC samples. Despite of the anticipated heterogeneity of CRPCs within each individual or among patients, surprisingly ∼90% of analyzed CRPC tumors can be characterized by significant up-regulation of miR-221/-222 and down-regulation of miR-23b/-27b. This finding suggests that the signature of altered miR-221/-222 and miR-23b/-27b expression is associated with the development of CRPC in human tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 174. doi:10.1158/1538-7445.AM2011-174
Fats, Oil, Health-Reply
Authors: Angela Gilchrist
Journal: JAMA (1990)

In Reply. —  As noted, the Council report was prepared in response to a House of Delegates Resolution that asked the Council to investigate the risk of using products containing coconut and/or palm  and, if appropriate, encourage food manufacturers, except manufacturers of infant formulas, to cease the use of these very atherogenic agents and to substitute oils of much lower atherogenicity (eg, corn, soybean, safflower, cottonseed, or similar oils).  The Council placed the use of tropical  in foods in perspective by pointing out the following: (1) These oils make only minor contributions to the total saturated fatty acid intake (
Myelotoxicity of vincristine‐prednisone therapy in treatment of chronic myelogenous leukemia in blastic transformation
Authors: Richard S. Stein, Daniel G. Roth
Journal: American Journal of Hematology (1976)

Abstract Therapy with vincristine and prednisone (VP) has produced remissions in 30% of patients with chronic myelogenous leukemia in blast transformation (CML‐BT). The possibility that therapy with VP can adversely affect the production of mature granulocytes in this setting has not been appreciated, as these drugs are generally considered free of myelotoxicity. In this report we review eight courses of VP administered to three patients with CML‐BT. Granulocytopenia developed following all five courses in which granulocyte counts were normal prior to therapy; granulocytopenia worsened in two of three courses in patients who were granulocytopenic prior to therapy. Progressive leukemia in the marrow was excluded as a cause of granulocytopenia. It is important to recognize that VP therapy rather than disease progression may be a cause of granulocytopenia in CML‐BT.
Free the slaves
Authors: K. Abbasi
Journal: BMJ (1999)

For the world's poorest countries debt burden is “the new slavery.” Jubilee 2000, a coalition of over 90 organisations including Oxfam, Christian Aid, and the British Medical Association, is demanding that those financial chains are broken as a celebration of the new millennium. By clamouring for the cancellation of the “unpayable” debt of the world's poorest countries,1 Jubilee 2000 has focused the spotlight firmly on the creditors: the world's richest countries, the International Monetary Fund, and the World Bank.

Jubilee 2000's campaign was officially launched in 1996 and gained prominence in 1998 when 70 000 supporters formed a human chain in Birmingham, UK, around the summit meeting of the G8 leaders—representing the world's richest nations. Later that year representatives of 39 national Jubilee 2000 campaigns gathered in Rome and called for cancellation, by the year 2000, of certain forms of debt: unpayable debt, which cannot be serviced without placing an undue burden on impoverished people; debt where the principal has already been repaid and only the interest remains; debt for improperly designed policies and projects; and debt incurred by repressive regimes.2

The campaign has gathered an irresistible momentum, with support from a mixed bag of international celebrities. Rock stars Bono and Annie Lennox, former boxer Muhammad Ali, writer Harold Pinter, …
Ombitasvir, Paritaprevir Co-dosed With Ritonavir, Dasabuvir, and Ribavirin for Hepatitis C in Patients Co-infected With HIV-1
Authors: Mark S. Sulkowski, Joseph J. Eron, David Wyles, Roger Trinh, Jay Lalezari, Chia Wang, Jihad Slim, Laveeza Bhatti, Joseph Gathe, Peter J. Ruane, Richard Elion, Fritz Bredeek, Robert Brennan, Gary Blick, Amit Khatri, Krystal Gibbons, Yiran B. Hu, Linda Fredrick, Gretja Schnell, Tami Pilot-Matias, Rakesh Tripathi, Barbara Da Silva-Tillmann, Barbara McGovern, Andrew L. Campbell, Thomas Podsadecki
Journal: JAMA (2015)

Patients co-infected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) are at high risk for liver disease progression. However, interferon-based treatments for HCV infection have significant toxicities, limiting treatment uptake.To assess the all-oral 3 direct-acting antiviral (3D) regimen of ombitasvir, paritaprevir (co-dosed with ritonavir [paritaprevir/r]), dasabuvir, and ribavirin in HCV genotype 1-infected adults with HIV-1 co-infection, including patients with cirrhosis.TURQUOISE-I is a randomized, open-label study. Part 1a of this pilot study was conducted at 17 sites in the United States and Puerto Rico between September 2013 and August 2014 and included 63 patients with HCV genotype 1 and HIV-1 co-infection who were HCV treatment-naive or had history of prior treatment failure with peginterferon plus ribavirin therapy. The study allowed enrollment of patients, including those with cirrhosis, with a CD4+ count of 200/mm3 or greater or CD4+ percentage of 14% or more and plasma HIV-1 RNA suppressed while taking a stable atazanavir- or raltegravir-inclusive antiretroviral regimen.Ombitasvir/paritaprevir/r, dasabuvir, and ribavirin for 12 or 24 weeks of treatment as randomized.The primary assessment was the proportion of patients with sustained virologic response (HCV RNA <25 IU/mL) at posttreatment week 12 (SVR12).Among patients receiving 12 or 24 weeks of 3D and ribavirin, SVR12 was achieved by 29 of 31 (94%; 95% CI, 79%-98%) and 29 of 32 patients (91%; 95% CI, 76%-97%), respectively. Of the 5 patients who did not achieve SVR, 1 withdrew consent, 2 had confirmed virologic relapse or breakthrough, and 2 patients had clinical history and phylogenetic evidence consistent with HCV reinfection. The most common treatment-emergent adverse events were fatigue (48%), insomnia (19%), nausea (18%), and headache (16%). Adverse events were generally mild, with none reported as serious or leading to discontinuation. No patient had a confirmed HIV-1 breakthrough of 200 copies/mL or greater during treatment.In this open-label, randomized uncontrolled study, treatment with the all-oral, interferon-free 3D-plus-ribavirin regimen resulted in high SVR rates among patients co-infected with HCV genotype 1 and HIV-1 whether treated for 12 or 24 weeks. Further phase 3 studies of this regimen are warranted in patients with co-infection.clinicaltrials.gov Identifier: NCT01939197.
Reorganisation in North Yorkshire
Authors: W R M Couper
Journal: BMJ (1977)

should be deprived of benefit from their husbands' war service.Interest at 3-50o compound, without tax relief, payable to secure war service pension compares very unfavourably with the miserable 210O simple-taxable-paid since 1948 on our compensation for loss of goodwill.A colleague of mine with six years of war service recently wrote to the appropriate department of the Ministry of Defence seeking confirmation of the dates of his war service.I understand th'at the reply
COVER-GLASS FORCEPS.
Authors: O. E. LINJER
Journal: JAMA (1896)

To those who are familiar with microscopic technique the following illustrations of a cover-glass forceps devised by me are self-explanatory. Clinical microscopy demands the simplest as well as most rapid methods consistent with accuracy. None of the many cover-glass forceps now in use are adapted to modern microscopic work. For staining sputum, pus, blood, etc., the complete process, from fixing to placing of cover-glass on slide, may be carried out while cover-glass is held in forceps. The following advantages are claimed for these forceps: 1. The cover-glass while on its flat side can be rapidly picked up from any surface whether glass, marble, wood or paper. 2. The cover-glass is held level, firmly and anatomically. 3. No possibility of cover-glass slipping out of or breaking while held in forceps. 4. Hands of operators are kept free from stains and acids. 5. The edge only of cover-glass being grasped and held
Prospective multicenter trial comparing repeated immunosuppressive therapy with stem-cell transplantation from an alternative donor as second-line treatment for children with severe and very severe aplastic anemia
Authors: Yoshiyuki Kosaka, Hiroshi Yagasaki, Kimihiko Sano, Ryoji Kobayashi, Hiroshi Ayukawa, Takashi Kaneko, Hiromasa Yabe, Masahiro Tsuchida, Hideo Mugishima, Akira Ohara, Akira Morimoto, Yoshitoshi Otsuka, Shouichi Ohga, Fumio Bessho, Tatsutoshi Nakahata, Ichiro Tsukimoto, Seiji Kojima
Journal: Blood (2007)
Ultrasonographic Determination of Ascitic Volume
Authors: J Inadomi, J P Cello, J Koch
Journal: Hepatology (1996)

The purpose of this study was to develop a method by which ascitic volume can be calculated using transcorporeal ultrasonography, and to determine the accuracy of this method by comparison with the volume of distribution of a radiolabeled tracer (indicator dilution technique [IDT]). Subjects with ascites confirmed by ultrasonography were recruited from the San Francisco General Hospital Gastroenterology and Liver Clinics. With subjects in the prone position on their hands and knees, ultrasonographic measurements were obtained along the ventral surface of the abdomen. The greatest vertical depth of ascitic fluid was recorded, and the abdominal circumference was measured from this point. The ascitic fluid volume was modeled as a segment of a sphere. IDT was performed as the reference method by injecting 99mTc–labeled macroalbumin into the peritoneal cavity and determining the volume of distribution of the indicator. Nine patients were evaluated. The median volume of ascites measured by the IDT was 11.2 L (range, 1.5–17.0 L). The median volume calculated by the ultrasonographic method was 10.3 L (range, 1.2–18.0 L). The correlation coefficient between the ultrasonographic and IDT was 0.96 ( P &lt; .001). Our technique accurately determines the volume of ascites using simple ultrasonographic measurements.
Studies on the genetic effects of phthalic acid esters on cells in culture.
Authors: B J Phillips, D Anderson, S D Gangolli
Journal: Environmental Health Perspectives (1986)

Mono(2-ethylhexyl) phthalate (MEHP) induced chromosome aberrations in cells of two culture lines, one derived from Chinese hamster ovary cells (CHO) and the other from rat liver cells (RL4). In CHO cells, the clastogenicity of MEHP was unaffected by the presence of an exogenous metabolic activation system (S-9 mix). 2-Ethylhexanol, o-phthalic acid, and phthalic anhydride were without effect. Cytochemical methods and assays for carnitine acetyltransferase and KCN-insensitive palmitoyl CoA oxidation were employed to determine whether chromosome damage was associated with peroxisome proliferation. No evidence of an increase in peroxisome numbers or of induction of marker enzymes was found in CHO cells treated with MEHP for up to 72 hr. Clofibric acid and BR931 were also ineffective. Observations on changes in CHO cell structure and permeability, and on the haemolytic effects of phthalate monoesters, suggest that the cytotoxicity of MEHP may be due primarily to its action on cell membranes. Since chromosome damage was observed only at cytotoxic concentrations, it is suggested that damage to lysosomal membranes and the release of endonucleases may be responsible for the observed clastogenicity of MEHP in vitro.
Dependence of highly enriched human bone marrow progenitors on hemopoietic growth factors and their response to recombinant erythropoietin.
Authors: C A Sieff, S G Emerson, A Mufson, T G Gesner, D G Nathan
Journal: Journal of Clinical Investigation (1986)

Human bone marrow cells were sequentially fractionated by three negative selection steps to remove adherent cells and Fc receptor-bearing cells, followed by immune adsorption (panning) to deplete maturing cells that react with a panel of monoclonal antibodies. This nonadherent Fc receptor and antibody negative fraction could be further enriched by a positive selection "panning" step, using an antibody to HLA-DR antigen; 12-27% of the cells formed erythroid burst-forming unit (BFU-E), erythroid colony-forming unit, granulocyte-monocyte colony-forming unit, and erythroid and granulocyte and/or monocyte colony-forming unit-derived colonies with recovery of 0.5-1% of the cells and 20-100% of the colony-forming cells. Sequential fractionation resulted in increasing dependence of a subset of BFU-E-derived colonies on exogenous burst-promoting activity (BPA) for proliferation in culture, but the most enriched progenitor fraction still contained a proportion of accessory cell or BPA-independent BFU-E that responded to either natural or biosynthetic erythropoietin when added to cultures on day 0 in the absence of BPA. If the addition of erythropoietin was delayed until day 3, the data suggest that this population of BFU-E either died or became unresponsive to erythropoietin. Delayed addition of erythropoietin to cultures of enriched progenitors provided a sensitive BPA assay, since BPA-independent but erythropoietin-responsive BFU-E were eliminated. The surviving BFU-E that were dependent for their proliferation on the presence of both BPA and erythropoietin showed a characteristic dose response to increasing BPA concentrations.
Serum histidine in rheumatoid arthritis: a family study
Authors: J. Kirkham, J. Lowe, H. A. Bird, V. Wright
Journal: Annals of the Rheumatic Diseases (1981)

We have compared free serum histidine in patients with rheumatoid arthritis, their blood relatives, and their non-blood relatives. The hypohistidinaemia of rheumatoid arthritis is acquired with the disease and does not provide a biochemical marker of those at risk.
The Metyrapone and Dexamethasone Suppression Tests for the Differential Diagnosis of the Adrenocorticotropin-Dependent Cushing Syndrome: A Comparison
Authors: Peter C. Avgerinos
Journal: Annals of Internal Medicine (1994)

Objective: To develop criteria for interpreting results of the metyrapone test for the differential diagnosis of the adrenocorticotropin (ACTH)-dependent Cushing syndrome and to compare its diagnostic accuracy with that of the high-dose dexamethasone suppression test. Design: Retrospective cohort study. Setting: Inpatient research ward. Patients: 186 patients believed to have the ACTH-Dependent Cushing syndrome who had the metyrapone test, the dexamethasone test, and a surgical procedure to remove the source of excessive ACTH. Measurements: The sensitivity, specificity, and diagnostic accuracy were determined for the metyrapone test using urine excretion of hydroxysteroid and plasma levels of 11-deoxycortisol. For the dexamethasone suppression test, urine excretions of 17-hydroxysteroid (17-OHS) and free cortisol were used. Main Results: 156 patients had pituitary disease, 15 had ectopic ACTH secretion, and 15 had no diagnosis after pituitary surgery. Of those 15 patients, 14 were ultimately classified as having pituitary disease on the basis of follow-up, and 1 was found to have ACTH-independent Cushing syndrome. After administration of metyrapone, stimulation of 17-OHS excretion greater than 70% or of a plasma 11-deoxycortisol level greater than 400-fold did not result in the misclassification of any of the patients with surgically confirmed cases of ectopic ACTH secretion. When these criteria were combined, the percentage of correct predictions (122 of 186 [71%; 95% CI, 62% to 79%]) was higher than that for either steroid alone (116 of 186 [62%; CI, 52% to 71%]) for excretion of 17-OHS and that for plasma 11-deoxycortisol (82 of 186 [44%; CI, 34% to 54%]). When the criteria for both the metyrapone test and the dexamethasone test were combined, the percentage of correct predictions (153 of 186 [82%; CI, 75% to 87%]) was higher than that obtained when the criteria for either test alone were used (P = 0.001). Similar results were found when the 15 patients with indeterminate surgery were assigned to the appropriate group on the basis of follow-up. When the criteria for both the metyrapone and dexamethasone tests were combined to identify patients with the pituitary Cushing syndrome, the sensitivity and diagnostic accuracy improved to 88% and 89%, respectively. Conclusions: The metyrapone test, which can be done in 48 hours, has a sensitivity and specificity for the diagnosis of the Cushing syndrome identical to that of the standard 6-day high-dose dexamethasone suppression test. Combining both tests results in greater accuracy than that obtained with either test alone.
Transient and persistent effects of IL-15 on lymphocyte homeostasis in nonhuman primates
Authors: Enrico Lugli, Carolyn K. Goldman, Liyanage P. Perera, Jeremy Smedley, Rhonda Pung, Jason L. Yovandich, Stephen P. Creekmore, Thomas A. Waldmann, Mario Roederer
Journal: Blood (2010)