tbuckley/cabot-search huggingface dataset:
Microalbuminuria as a potential novel cardiovascular biomarker in patients with COPD
Authors: C. Casanova, B. R. Celli
Journal: European Respiratory Journal (2014)

Chronic obstructive pulmonary disease (COPD) is now recognised as the third cause of death in the world [1]. Patients with COPD are more likely to have pre-existing cardiovascular disease (CVD) and are at high risk of acute events, hospitalisations and death from CVD [2, 3]. Furthermore, this strong association is independent of the degree of airflow limitation. Because of this, the Global Initiative for Chronic Obstructive Lung Disease initiative recognises CVD as the most important disease coexisting with COPD and suggests it should be routinely looked for, but makes no recommendation on how to do it [4].

Over the past two decades, interest in CVD prevention has expanded and now promotes not only primary prevention, but also identification of factors that could help clarify CVD pathophysiology, offer targets for intervention or lead to improved risk stratification beyond that allowed by the Framingham equations [5]. Currently, only a few biomarkers have been accepted as being clinically useful [6]. In this regard, the recent consensus of the American College of Cardiology/American Heart Association recognises family history as being useful and haemoglobin A1c measurement as reasonable in all adults. They also categorise microalbuminuria (MAB) assessment as reasonable in adults with hypertension or diabetes [7].

The discovery of novel “biomarkers” that could help identify cardiovascular risk in patients with COPD could help personalise therapy for that particular phenotype. To be clinically useful, the biomarker should be inexpensive, noninvasive and easily measurable. Therefore, MAB could be a …
Salmonella Septicemia from Platelet Transfusions
Authors: FRANK S. RHAME
Journal: Annals of Internal Medicine (1973)

Between 12 August 1970 and 3 February 1971, seven cases of Salmonella cholerae-suis septicemia occurred in immunologically compromised patients hospitalized at the Clinical Center of the National Institutes of Health. One patient died, and two had long-term recurrences. Epidemiologic evidence implicated platelets as the common source, and one donor who donated to all seven patients was detected. S. cholerae-suis of the epidemic strain was isolated from the donor's plasma on three occasions. Clinical evaluation of the donor showed chronic osteomyelitis of the tibia. Thirty-four patients received platelets from this donor during the epidemic period, and a chart review showed a probable additional case of S. cholerae-suis septicemia. The most significant difference between patients who became ill and those who had no septicemia was coincidental administration of antibiotics to the latter group after transfusion with the contaminated platelets.
Carnitine-Acyltransferase System Inhibition, Cancer Cell Death, and Prevention of Myc-Induced Lymphomagenesis
Authors: Annalisa Pacilli, Maria Calienni, Sabrina Margarucci, Maria D’Apolito, Orsolina Petillo, Laura Rocchi, Gianandrea Pasquinelli, Raffaella Nicolai, Aleardo Koverech, Menotti Calvani, Gianfranco Peluso, Lorenzo Montanaro
Journal: JNCI Journal of the National Cancer Institute (2013)

The metabolic alterations of cancer cells represent an opportunity for developing selective antineoplastic treatments. We investigated the therapeutic potential of ST1326, an inhibitor of carnitine-palmitoyl transferase 1A (CPT1A), the rate-limiting enzyme for fatty acid (FA) import into mitochondria.ST1326 was tested on in vitro and in vivo models of Burkitt's lymphoma, in which c-myc, which drives cellular demand for FA metabolism, is highly overexpressed. We performed assays to evaluate the effect of ST1326 on proliferation, FA oxidation, and FA mitochondrial channeling in Raji cells. The therapeutic efficacy of ST1326 was tested by treating Eµ-myc mice (control: n = 29; treatment: n = 24 per group), an established model of c-myc-mediated lymphomagenesis. Experiments were performed on spleen-derived c-myc-overexpressing B cells to clarify the role of c-myc in conferring sensitivity to ST1326. Survival was evaluated with Kaplan-Meier analyses. All statistical tests were two-sided.ST1326 blocked both long- and short-chain FA oxidation and showed a strong cytotoxic effect on Burkitt's lymphoma cells (on Raji cells at 72 hours: half maximal inhibitory concentration = 8.6 μM). ST1326 treatment induced massive cytoplasmic lipid accumulation, impairment of proper mitochondrial FA channeling, and reduced availability of cytosolic acetyl coenzyme A, a fundamental substrate for de novo lipogenesis. Moreover, treatment with ST1326 in Eµ-myc transgenic mice prevented tumor formation (P = .01), by selectively impairing the growth of spleen-derived primary B cells overexpressing c-myc (wild-type cells + ST1326 vs. Eµ-myc cells + ST1326: 99.75% vs. 57.5%, difference = 42.25, 95% confidence interval of difference = 14% to 70%; P = .01).Our data indicate that it is possible to tackle c-myc-driven tumorigenesis by altering lipid metabolism and exploiting the neoplastic cell addiction to FA oxidation.
The effects of statins on osteoarthritis structural progression: another glimpse of the Holy Grail?
Authors: Philip G Conaghan
Journal: Annals of the Rheumatic Diseases (2012)

While the last 2 decades have seen major advances and novel treatments for inflammatory arthritides, treatments for osteoarthritis (OA) have not advanced. Meanwhile, OA represents a huge problem for both individuals and health economies, with the OA burden rising quickly in ageing Western societies. Recent evidence-based guidelines provide a range of options for pain relief,1 2 often associated with small to moderate effect sizes.3 True structure modification, with its implication for an associated reduction (or at least reduced progression) of symptoms, is often referred to as the Holy Grail of OA research.4 5

In the context of chasing this Grail, the interesting report from Clockaerts and colleagues6 adds to a growing strand of research concerning the potential role of statins as structure modifiers in OA. A number of questions arise as a result of this work: Is there a plausible mechanism of action for statins in this context? Is there a real signal of reduced OA structural progression from this and other clinical studies of statins?

Statins are best known as competitive inhibitors of hydroxymethyl-glutaryl-coenzyme A reductase that reduce cholesterol biosynthesis. However, for some years it has been recognised that these agents also have significant anti-inflammatory and immune-modulating effects.7,–,9 So, it is possible that these agents may benefit the OA joint through a number of non-mutually exclusive mechanisms on different targets.

Inflammation appears universal in symptomatic OA joints, with inflammatory mediators produced by cartilage, bone and synovial cells;10 11 this inflammation is thought to be important in subsequent cartilage degradation. A multitude of anti-inflammatory effects of statins have been reported at the cellular level including inhibition of leucocyte–endothelial adhesion, reduced levels of inducible nitric oxide synthase, inhibition of production and reduced chemoattraction of monocyte chemotactic protein-1, and reduced …
BIBA but LGFTD
Authors: G. Dunea
Journal: BMJ (1999)

The purist element in most of us dislikes the use of abbreviations. We tend to view them as unsightly, a blot on the language, a sign of laziness or ignorance. We are irritated that only a select few (but others than ourselves) understand what they mean.

Take AB, a 59yo BM (a non-scatological term) S/P TURP/DES, BBPR, with elevated JVP from CCH (English), or JVD from CHF (American), Dx GOK or NYD. Or Dr William Bean's patient …
A Summary of the Methods That the National Clinical Guideline Centre Uses to Produce Clinical Guidelines for the National Institute for Health and Clinical Excellence
Authors: Jennifer Hill, Ian Bullock, Phil Alderson
Journal: Annals of Internal Medicine (2011)

The National Clinical Guideline Centre develops evidence-based clinical guidelines on behalf of the National Institute for Health and Clinical Excellence in the United Kingdom. These guidelines are developed for the National Health Service in England, Wales, and Northern Ireland and establish recommendations on best practice. The authors summarize the main methods used in development, how evidence from systematic reviews is interpreted to form recommendations, who is involved in the process, and the main outputs that are published.
Mechanism of the Redistribution of Renal Cortical Blood Flow during Hemorrhagic Hypotension in the Dog
Authors: Jay H. Stein, Sampanta Boonjarern, Richard C. Mauk, Thomas F. Ferris
Journal: Journal of Clinical Investigation (1973)

Studies were performed to define the mechanisms involved in the redistribution of renal cortical blood flow to inner cortical nephrons which occurs during hemorrhagic hypotension in the dog. The radioactive microsphere method was utilized to measure regional blood flow in the renal cortex. Renal nerve stimulation decreased renal blood flow 40% but had no effect on the fractional distribution of cortical blood flow. Pretreatment with phenoxybenzamine, phentolamine, propranolol, or atropine did not alter the redistribution of cortical flow during hemorrhage. A reduction in renal perfusion pressure by aortic constriction caused a qualitatively similar alteration in regional blood flow distribution as occurred during hemorrhage. When perfusion pressure was kept constant in one kidney by aortic constriction followed by hemorrhage, no redistribution occurred in the kidney with a constant perfusion pressure while the contralateral kidney with the normal perfusion pressure before hemorrhage had a marked increase in the fractional distribution of cortical flow to inner cortical nephrons. Additionally, retransfusion had no effect on the fractional distribution of flow in the kidney in which perfusion pressure was maintained at the same level as during hemorrhage while in the contralateral kidney in which pressure increased to normal there was a redistribution of flow to outer cortical nephrons. These studies indicate that the redistribution of renal cortical blood flow which occurs during hemorrhage is not related to changes in adrenergic activity but rather to the intrarenal alterations which attend a diminution in perfusion pressure.
National Kidney Disease Education Program
Authors: Thomas H. Hostetter, Mimi Lising
Journal: Journal of the American Society of Nephrology (2003)

The National Kidney Disease Education Program (NDKEP) is a program of the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health. It seeks to increase awareness of CKD among high risk groups and primary care providers. The NKDEP is a response to the rapidly escalating incidence of ESRD in the United States in the face of new treatment to prevent and mitigate CKD. The hope is that awareness will lead to action, testing, and treatment. E-mail: HostetterT@extra.niddk.nih.gov
Pretreatment, Prediagnosis Immunoglobulin, and Alpha&lt;sub&gt;1&lt;/sub&gt;-Antitrypsin Levels in Patients With Bronchial Carcinoma
Authors: Donald R. Nash, Ph.D., Jerry W. McLarty, Ph.D., Noble G. Fortson, M.A.
Journal: JNCI Journal of the National Cancer Institute (1980)

Sera from 148 patients suspected of having bronchial carcinoma were evaluated for concentrations of IgA, IgM, IgG, and alpha1-antitrypsin (α1-AT). Histologically, 137 tumor specimens obtained by bronchoscopy or surgical biopsy were diagnosed as squamous cell carcinoma (55%), adenocarcinoma (18%), undifferentiated small cell carcinoma (20%), or undifferentiated large cell carcinoma (7%). The tumor types of the remaining 11 patients were not identifiable from the records but were included as a separate group. Serum protein values were compared with those of a control group of 60 healthy adult volunteers. Regression analysis of age, race, and sex effects on the results of comparisons between test and control groups Indicated that, with the possible exception of age and IgM, these three independent variables did not significantly influence the observations. Both serum IgA and α1-AT were significantly elevated in all tumor groups when compared to the control levels. This was not the situation for serum IgG. Results for serum IgM were equivocal and depended on the statistical methods used. Although the serum immunoglobulin concentrations for the small cell carcinoma group were consistently lower than those for the other tumor cell types, no statistically significant difference existed between the five tumor groups in this regard.
Neoadjuvant Treatment of Colorectal Cancer with Bevacizumab: The Perioperative Angiogenic Balance Is Sensitive to Systemic Thrombospondin-1 Levels
Authors: Christine Brostjan, Kristina Gebhardt, Birgit Gruenberger, Verena Steinrueck, Halina Zommer, Harald Freudenthaler, Sebastian Roka, Thomas Gruenberger
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Colorectal cancer patients receiving neoadjuvant treatment with bevacizumab, a monoclonal antibody neutralizing vascular endothelial growth factor (VEGF), may suffer from wound healing complications after surgery as the antibody persists in patient blood. We characterized the systemic angiogenic balance in the perioperative period to evaluate its effect on physiologic angiogenesis. Experimental Design: Nineteen patients receiving combination chemotherapy and bevacizumab for six neoadjuvant cycles were compared with 14 patients receiving chemotherapy without bevacizumab. Plasma from perioperative days −1, +1, +7, and +21 was analyzed for VEGF, thrombospondin-1 (TSP-1), and PD-ECGF concentrations. The angiogenic capacity was further tested in an in vitro assay of endothelial cell proliferation and migration. Results: On day +1, the onset of wound healing was reflected in a change of balance, i.e., an increase of proangiogenic factors VEGF and platelet-derived endothelial cell growth factor compared with low TSP-1 inhibitor levels in both treatment groups. Patients with bevacizumab therapy showed significantly higher blood levels of total VEGF throughout the evaluation period. However, most VEGF molecules were inactive, i.e., complexed with antibody. Nevertheless, the capacity to stimulate endothelial growth was higher for these plasma samples and was reflected in low TSP-1 levels and an altered TSP-1 sensitivity. When purified TSP-1 protein was added, plasma samples of the bevacizumab but not the chemotherapy group showed reduced endothelial growth. Conclusions: Feedback mechanisms of bevacizumab therapy are not restricted to VEGF expression but seem to involve additional factors, such as TSP-1, which influences the systemic angiogenic balance and permits endothelial growth.
Endoscopic surveillance of premalignant gastric lesions
Authors: S Sebastian
Journal: Gut (2002)

We read with interest the study by Whiting and colleagues ( Gut 2002: 50 :378–81). The study has further highlighted the importance of early detection of gastric cancer and also given further emphasis on ways to prevent the multistep progression in gastric carcinogenesis. However, we would like to make the following comments.

Firstly, one in five patients in this group had lesions which, according to Whiting et al , should be followed up by yearly …
Tissue Culture Studies on Murine Virus-induced Leukemia Cells: Isolation of Single Cells in Agar-Liquid Medium
Authors: Maria C. Patuleia, Charlotte Friend
Journal: Cancer Research (1967)

Summary  Maturation along the erythrocytic line is observed in long-term cell cultures of murine virus-induced leukemic cells. In attempts to determine the relationship between the different morphologic types in these cultures, an adaptation of the Sanders technic of plating and cloning cells utilizing an agar-liquid medium was devised. This method permitted the cloning of single cells. The progeny of each clone consisted of primitive cells, proerythroblasts, and erythroblasts. From these data the possibility is considered that the primitive cell characteristic of the murine leukemia under study is an erythrocyte precursor.
United States limits resident physicians to 80 hour working week
Authors: J. Hopkins Tanne
Journal: BMJ (2003)

From 1 July 2003, the Accreditation Council on Graduate Medical Education will limit the work of the United States's almost 100 000 resident physicians in 7800 programmes to 80 hours a week. Shifts are never to last more than 24 hours, and residents will have one day off in seven and get a 10 hour break between being on call and working a shift.

Resident groups and the consumer advocate group Public Citizen called the new rules deeply flawed. They say that they are unlikely to be adequately enforced, because they do not have the force of law. Some groups would like to see federal legislation introduced, but the last attempt to do so failed in the last session of Congress.

The issue of regulating …
Hippocampal and Anterior Cingulate Activation Deficits in Patients With Geriatric Depression
Authors: J M de Asis, E Stern, G S Alexopoulos, H Pan, W Van Gorp, H Blumberg, B Kalayam, D Eidelberg, D Kiosses, D A Silbersweig
Journal: American Journal of Psychiatry (2001)

The authors assessed frontotemporal function in patients with geriatric depression, a debilitating and increasingly prevalent disorder that has not been examined with brain activation paradigms.Six depressed elderly patients and five healthy comparison subjects underwent high-sensitivity [(15)O]H(2)O positron emission tomography scans during a paced word generation task and a resting condition.Bilateral activation deficits were noted in the dorsal anterior cingulate gyrus and hippocampus of the depressed geriatric patients relative to the comparison subjects. Patients had memory deficits that correlated with lower hippocampal activity during both rest and activation.These initial findings suggest that hippocampal and dorsal anterior cingulate hypoactivation may constitute contributing neural substrates of geriatric depression. They also suggest that hippocampal dysfunction is related to the memory dysfunction characteristic of this disorder.
Inhibition of Neutrophil Superoxide Production by Uremic Concentrations of Guanidino Compounds
Authors: AKI HIRAYAMA, ALBERTO A. NORONHA-DUTRA, MICHAEL P. GORDGE, GUY H. NEILD, JOHN S. HOTHERSALL
Journal: Journal of the American Society of Nephrology (2000)

Abstract. In uremia, diminished reactive oxygen intermediate production is an important consequence of impaired neutrophil function. The effects of guanidino compounds, which are known uremic toxins, on neutrophil reactive oxygen intermediate production in vitro were studied. Neutrophils from healthy volunteers were exposed for 3 h to individual guanidino compounds or mixed guanidino compounds (GC mix ), at concentrations observed in uremic plasma. After removal of the guanidino compounds, the neutrophils were activated by adhesion, N -formylmethionylleucylphenylalanine, phorbol myristate acetate, or opsonized zymosan, and superoxide production was measured by monitoring lucigenin chemiluminescence. The direct effects of guanidino compounds on superoxide production in activated neutrophils were also measured. The energy status (ATP and creatine phosphate), antioxidant status (total glutathione), and glycolytic flux (lactate production) were measured. GC mix pretreatment decreased superoxide production in activated neutrophils (activated by N -formylmethionylleucylphenylalanine or zymosan) by 50% ( P &lt; 0.01), decreased ATP concentrations by 60% ( P &lt; 0.05), and inhibited glycolytic flux (lactate production) by 45% ( P &lt; 0.01) but did not alter glutathione concentrations. Simultaneous GC mix exposure and activation did not inhibit NADPH oxidase activity in cell lysates but inhibited superoxide formation in zymosan-activated intact neutrophils; this inhibition was reversed after removal of the guanidino compounds. Guanidinosuccinic acid, guanidinopropionic acid, and guanidinobutyric acid, when tested individually, were each as potent as GC mix . The inhibition of neutrophil superoxide generation by guanidino compounds results from decreased energy status. Micromolar concentrations of guanidino compounds significantly inhibit neutrophil metabolism, with serious implications for the functions of neutrophils in host defenses.
Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial
Authors: Florian Lordick, Yoon-Koo Kang, Hyun-Cheol Chung, Pamela Salman, Sang Cheul Oh, György Bodoky, Galina Kurteva, Constantin Volovat, Vladimir M Moiseyenko, Vera Gorbunova, Joon Oh Park, Akira Sawaki, Ilhan Celik, Heiko Götte, Helena Melezínková, Markus Moehler
Journal: The Lancet Oncology (2013)
THE LATHYROGENIC EFFECT OF ISONICOTINIC ACID HYDRAZIDE (INAH) ON THE CHICK EMBRYO AND ITS REVERSAL BY PYRIDOXAL
Authors: C. I. Levene
Journal: The Journal of Experimental Medicine (1961)

When applied to the chorio-allantoic membrane of the chick embryo, isoniazid was shown to produce an increase in the fragility of the embryo and in the amount of collagen which was extractable from the bones with cold 1 M sodium chloride. The administration of pyridoxal reversed these phenomena almost completely. The effect of isoniazid differed from that of beta-aminopropionitrile in that the latter was of greater magnitude, and was not affected by pyridoxal; whereas beta-aminopropionitrile caused skeletal deformities, isoniazid even at 12 times the concentration produced no deformities. The aldehyde group of pyridoxal was shown to be necessary for its interaction with isoniazid.
Functional instability in non-contact ankle ligament injuries
Authors: Alison Rose, Robert J Lee, Rachel M Williams, Lindsay C Thomson, Anne Forsyth
Journal: British Journal of Sports Medicine (2000)

Objectives —To measure objectively functional standing balance in the acute stages of non-contact ankle sprain, and to compare patients with controls. Methods —A Chattanooga balance machine was used to measure postural stability in patients with acute ankle sprain and uninjured controls over a two week period, in one and two legged stance, with eyes open and closed. Participants also completed the Olerud and Molander questionnaire to provide a subjective measure of ankle function. Results —There was a highly significant improvement in questionnaire scores for the patients during the study period (p&lt;0.0001). Patients appeared to be less stable than controls in all balance tests, although the difference did not reach significance. There was evidence of improvement over time in the number of tests successfully completed on the injured leg in single legged stance with eyes closed (p = 0.043) between visits 1 and 3. Conclusions —The patient group showed a subjective improvement, which supports clinical experience of treating acute ankle injuries. There is some evidence that on average the patient group appeared to be less stable than controls in all balance tests, although the difference did not reach statistical significance, even on the uninjured leg. There is a need to carry out further studies to confirm the results found in this pilot study and to investigate the hypotheses generated. It would be useful to evaluate a simple test that could be used clinically to monitor progress after ankle injury, and also to identify athletes with decreased functional stability, who may be more at risk of sustaining ankle injury.