tbuckley/cabot-search huggingface dataset:
ABC of clinical haematology: Platelet disorders
Authors: R J Liesner, S J Machin
Journal: BMJ (1997)

Platelets are produced predominantly by bone marrow megakaryocytes as a result of budding of the cytoplasmic membrane.Megakaryocytes are derived from the haemopoietic stem cell, which is stimulated to differentiate to mature megakaryocytes under the influence of various cytokines, including thrombopoietin.Once released from the bone marrow, young platelets are trapped in the spleen for 36 hours before entering the circulation, where they have a primary haemostatic role. Normal haemostasisThe platelet membrane has integral glycoproteins essential in the initial events of adhesion and aggregation, leading to formation of the platelet plug during haemostasis.Glycoprotein receptors react with aggregating agents such as collagen on the damaged endothelial surface (for example, blood vessels), fibrinogen, and von Willebrand's factor to facilitate platelet-platelet and platelet-endothelial cell adhesion.Storage organelles within the platelet include the "dense" granules, which contain nucleotides, calcium, and serotonin, and granules containing fibrinogen, von Willebrand's factor, platelet derived growth factor, and many other clotting factors.After adhesion, platelets are stimulated to release the contents of their granules essential for platelet aggregation.Platelets also provide an extensive phospholipid surface for the interaction and activation of clotting factors in the coagulation cascade.
846-5 Improvement initiatives should specifically target patients admitted with acute myocardial infarction who undergo coronary artery bypass surgery before hospital discharge: Lessons from the guidelines applied in practice projects
Authors: Rajhendra H Mehta, Anthony C DeFranco, Cecelia K Montoye, Canopy Roychoudhury, Benrong Chen, Patricia L Baker, Arthur L Riba, Kim A Eagle
Journal: Journal of the American College of Cardiology (2004)
Increased Right Ventricular Glucose Metabolism in Patients With Pulmonary Arterial Hypertension
Authors: Mehmet Mustafa Can, Cihangir Kaymaz, Ibrahim Halil Tanboga, Hacer Ceren Tokgoz, Nesrin Canpolat, Erdem Turkyilmaz, Kenan Sonmez, Nihal Ozdemir
Journal: Clinical Nuclear Medicine (2011)

We aimed to assess the characteristics of glucose utilization in left and right ventricle (LV, RV) myocardium with F-18 fluorodeoxyglucose (FDG) on positron emission tomography in patients with pulmonary arterial hypertension (PAH), and to evaluate whether predominance of RV glucose metabolism as compared with that in LV relates to clinical, hemodynamic, echocardiographic, and neurohormonal parameters.The study group comprised 23 patients with PAH and 16 healthy controls who underwent FDG positron emission tomography. The ratio of RV uptake (u) of FDG to those of LV was used as a marker for the glucose utilization by RV myocardium. Six-minute walking distance, plasma brain natriuretic peptide (BNP), planimetric echo measures of RV and LV areas, pulmonary arterial systolic pressure estimated by Doppler, Tei index, tricuspid annular excursion, and systolic tissue velocity (St) were used to assess the RV function.The patients with PAH had significantly higher FDG SUV ratios as compared with controls. The RV to LV FDGu ratio showed a high correlation with PAPs (r=0.87, P<0.05), BNP (r=0.63, P<0.05), and planimetric echo measures of RV to LV area ratio (r=0.61, P<0.05); a mild correlation with Tei index (r=0.47, P<0.05); and a high and inverse correlation with tricuspid annular excursion (r=-0.80, P<0.05), 6-minute walking distance (r=-0.74, P<0.05), and St (r=-0.68, P<0.05).Increased RV myocardium FDG accumulation indicates increased RV loading that correlates with prognostic markers in pulmonary hypertension including reduced exercise capacity, elevated BNP, and echo variables of tricuspid annular function. Moreover, identification of increased RV FDG accumulation predicts the presence but not the severity of elevated pulmonary systolic pressure.
The Time in Which We Live
Authors: Hugh H. Hussey
Journal: JAMA (1975)

Fifty years ago, a 15-year-old boy, having finished his homework for that school day, performed his usual evening exercise in the best tradition of the boys' stories he had read. With his lively little mongrel, he walked about a mile to a park gate, entered, and soon found a brick path on which he ran as hard as he could for the mile and a half that brought him to another gate. By then, the moon had risen to enhance the light of the gas lampposts on his ten-block walk back to the row house that was typical of his middle-class neighborhood. All the way, the dark had been a little scary; but not the passersby he had encountered. There was no reason to fear attack. Robert A. Heinlein, in one of his science fiction stories, wrote about changes that had occurred approximately a generation later.<sup>1</sup> Law-abiding people hardly
Crystalluria Potential of Cholecystographic Agents
Authors: Eino Nelson
Journal: New England Journal of Medicine (1963)

A FATAL case of acute renal insufficiency that followed administration of a cholecystographic agent, bunamiodyl sodium, to a forty-four-year-old woman was recently reported in this journal.1 Since the nature of the nephrotoxicity of this and similar agents is not known and, further, since it was reported that at autopsy in this case, the kidney tubules contained "crystals" it was thought of interest to consider what potential exists for occurrence of crystalluria from the use of cholecystographic agents. Some recent work has shown that it is possible to evaluate the crystalluria potential of sulfonamides as well as to estimate minimum rates . . .
Radionuclide Angiocardiography: Use in the Detection of Myocardial Rhabdomyoma
Authors: ROBERT J. STARSHAK, JOHN R. STY
Journal: Clinical Nuclear Medicine (1978)

A neonate with a large rhabdomyoma of the heart was evaluated with radionuclide angiocardiography. The images revealed a "cold" area on the inferior surface of the heart which displaced the left ventricle. The findings were correlated with radiographic angiocardiography and were verified at surgery and autopsy. The value of this noninvasive technique in the evaluation of a seriously ill neonate is stressed.
Influence of Carbon Dioxide on Respiratory Function during Posterior Retroperitoneoscopic Adrenalectomy in Prone Position
Authors: Isoji Sasagawa, Hitoshi Suzuki, Takuji Izumi, Norifumi Shoji, Teruhiro Nakada, Seiji Takaoka, Yoshihide Miura, Hikura Hoshi, Sumio Amagasa, Hideo Horikawa
Journal: European Urology (1999)
Membrane-type matrix metalloproteinase-1(MT1-MMP) gene is overexpressed in highly invasive hepatocellular carcinomas
Authors: Tomika Harada, Shigeki Arii, Masahiro Mise, Takashi Imamura, Hiroaki Higashitsuji, Masaharu Furutani, Mototaka Niwano, Shun-ichi Ishigami, Manabu Fukumoto, Motoharu Seiki, Hiroshi Sato, Masayuki Imamura
Journal: Journal of Hepatology (1998)
Immune-Complex Assays: The State of the Art
Authors: Peter H. Schur
Journal: New England Journal of Medicine (1978)

From studies in laboratory animals there is considerable evidence that circulating complexes of antigen and antibody, or immune complexes, can deposit in tissues and induce pathologic lesions, especially vasculitis and glomerulonephritis.1 The clinical and pathological similarity of a number of human diseases to these experimental models has stimulated efforts to search for immune complexes, particularly in renal, dermatologic and rheumatic diseases. In some cases unequivocal evidence of antigen–antibody complexes has been obtained. Examples are the detection of rheumatoid factor-IgG complexes in the serum and joint fluids of some patients with rheumatoid arthritis,1 of DNA and anti-DNA in the glomeruli or . . .
Induction of hypertrophy in cultured proximal tubule cells by extracellular NH4Cl.
Authors: K Golchini, J Norman, R Bohman, I Kurtz
Journal: Journal of Clinical Investigation (1989)

Ammonia production increases in several models of renal hypertrophy in vivo. The present study was designed to determine whether ammonia can directly modulate the growth of renal cells in the absence of a change in extracellular acidity. In serum-free media NH4Cl (0-20 mM) caused JTC cells and a primary culture of rabbit proximal tubule cells to hypertrophy (increase in cell protein content) in a dose-dependent fashion without a change in DNA synthesis. Studies in JTC cells revealed that the cell protein content increased as a result of both an increase in protein synthesis and a decrease in protein degradation. Total cell RNA content and ribosome number increased after NH4Cl exposure and the cell content of the lysosomal enzymes cathepsin B and L decreased. Inhibition of the Na+/H+ antiporter with amiloride did not prevent the hypertrophic response induced by NH4Cl. The results indicate that ammonia is an important modulator of renal cell growth and that hypertrophy can occur in the absence of functioning Na+/H+ antiport activity.
Autoimmune Lymphoproliferative Syndrome with Somatic<i>Fas</i>Mutations
Authors: Eliska Holzelova, Cédric Vonarbourg, Marie-Claude Stolzenberg, Peter D. Arkwright, Françoise Selz, Anne-Marie Prieur, Stéphane Blanche, Jirina Bartunkova, Etienne Vilmer, Alain Fischer, Françoise Le Deist, Frédéric Rieux-Laucat
Journal: New England Journal of Medicine (2004)

Impaired Fas-induced apoptosis of lymphocytes in vitro is a principal feature of the autoimmune lymphoproliferative syndrome (ALPS). We studied six children with ALPS whose lymphocytes had normal sensitivity to Fas-induced apoptosis in vitro.
Anti-Saccharomyces cerevisiae IgA antibodies are raised in ankylosing spondylitis and undifferentiated spondyloarthropathy
Authors: I E A Hoffman
Journal: Annals of the Rheumatic Diseases (2003)

Objectives: To investigate whether anti- Saccharomyces cerevisiae antibodies (ASCA), a marker for Crohn's disease (CD), are present in spondyloarthropathies (SpA) and in the subgroups ankylosing spondylitis (AS), undifferentiated SpA (uSpA), and psoriatic arthritis (PsA), in comparison with healthy and inflammatory controls (patients with rheumatoid arthritis (RA)). Methods: ASCA IgA and IgG levels were measured with an enzyme linked immunosorbent assay (ELISA) kit (Medipan, Germany) in 26 patients with CD, 108 patients with SpA (43 patients with AS, 20 patients with uSpA, 45 patients with PsA), 56 patients with RA and 45 healthy controls. Gut biopsy samples were available in 18 AS and 10 patients with uSpA, these samples were screened for the presence of inflammation. Results: Both ASCA IgG and IgA levels were raised in CD compared with healthy controls and patients with RA. ASCA IgA, but not IgG levels, were higher in SpA than in both healthy and RA controls. ASCA IgA levels were raised in AS and uSpA, but not in PsA. No significant differences in ASCA IgA levels were noted between patients with SpA with and without histological gut inflammation. Conclusion: ASCA IgA levels are significantly higher in SpA, and more specifically in AS, than in healthy controls and patients with RA. This is the first serum marker associated with SpA. No correlation between the presence of subclinical bowel inflammation and ASCA IgA levels was noted. However, it remains to be evaluated whether patients with SpA with ASCA have an increased risk of developing CD.
Nitric oxide reduces SLC29A1 promoter activity and adenosine transport involving transcription factor complex hCHOP–C/EBPα in human umbilical vein endothelial cells from gestational diabetes
Authors: Marcelo Farías, Carlos Puebla, Francisco Westermeier, Miguel J. Jo, Marçal Pastor-Anglada, Paola Casanello, Luis Sobrevia
Journal: Cardiovascular Research (2009)

Reduced expression of human equilibrative nucleoside transporter 1 (hENT1) results from nitric oxide (NO)-dependent reduced SLC29A1 transcriptional activity in human umbilical vein endothelial cells (HUVECs) from gestational diabetes. As expression of the transcription factor C/EBP homologous protein 10 (hCHOP, which forms heterodimers with C/EBPα transcription factor) is activated by NO and induced in diabetes mellitus, we hypothesize that hCHOP plays a role in the gestational diabetes-reduced hENT1 expression in HUVECs. HUVEC primary cultures from 42 normal and 42 gestational diabetic pregnancies were used for adenosine uptake assays. Real-time PCR (mRNA quantification), western blotting (protein abundance), and luciferase activity (SLC29A1 promoter activity) were used. hCHOP–C/EBPα activity was assayed by chromatin immunoprecipitation. Overlap extension mutagenesis was used to generate a mutated hCHOP–C/EBPα consensus site at the SLC29A1 promoter, and endothelial NO synthase (eNOS) siRNA recombinant adenovirus was used to knock down eNOS. hCHOP nuclear protein abundance and binding to DNA were higher in gestational diabetes, paralleled by reduced SLC29A1 promoter activity, hENT1 expression, and transport activity. These changes were blocked by hCHOP consensus sequence mutation (−1845G > T and −1844C > A), eNOS-siRNA-induced knockdown, and NG-nitro-l-arginine methyl ester (NOS inhibitor), and were mimicked by S-nitroso-N-acetyl-l, d-penicillamine (NO donor) in cells from normal pregnancies. hCHOP and C/EBPα overexpression mimicked gestational diabetes effects in cells from normal pregnancies, but did not alter SLC29A1 promoter activity or hENT1-adenosine transport in cells from gestational diabetes. The hCHOP–C/EBPα complex down-regulates SLC29A1 expression in an NO-dependent manner in HUVECs from gestational diabetes.
Serum Salicylate Levels in Blood Donors
Authors: William P. McCann
Journal: JAMA (1970)

Salicylate levels were determined in serum from 240 volunteer blood donors who had denied recent drug exposure. Twenty-seven serum samples had levels ranging from 1.6 to 13.6 mg/100 ml, indicating exposure to salicylate preparations, which presumably were not considered by donors to be drugs. The observed elevated salicylate levels might affect adversely an extremely hypersensitive blood or plasma recipient. Salicylate ingestion might also suppress fever in donors.
Isolated Systolic and Diastolic Ventricular Interactions in Pacing-Induced Dilated Cardiomyopathy and Effects of Volume Loading and Pericardium
Authors: David J. Farrar, Edna Chow, Craig D. Brown
Journal: Circulation (1995)

Interactions between the closely coupled right and left ventricles are known to play important roles as determinants of ventricular function, and the purpose of this study was to evaluate their effects in a model of heart failure.A dilated cardiomyopathy resulting in congestive heart failure (CHF) was produced in pigs by rapid ventricular pacing at 230 beats per minute for 1 week. Blood was rapidly withdrawn from the left ventricular (LV) apex into a prosthetic ventricle, and the instantaneous effects on the right ventricle were studied during volume loading and before and after pericardiectomy. The systolic interaction gain between the right and left ventricles (Gs) was calculated as the ratio of changes in mean systolic pressure during isolated systolic LV unloading. Diastolic ventricular interaction gain (Gd) was calculated as the ratio of changes in mean diastolic pressures during LV unloading in the last 150 ms of diastole. With the pericardium closed, all interaction gains were significantly increased during volume loading from a right ventricular end-diastolic pressure of 3 to 9 mm Hg: Gs from 0.045 +/- 0.014 to 0.063 +/- 0.020 mm Hg/mm Hg (normal pigs) and from 0.077 +/- 0.040 to 0.103 +/- 0.019 (CHF pigs) and Gs from 0.196 +/- 0.116 to 0.493 +/- 0.117 mm Hg/mm Hg (normal pigs) and from 0.174 +/- 0.101 to 0.341 +/- 0.165 (CHF pigs). When the pericardium was opened, Gd was significantly reduced to 0.145 +/- 0.071 and 0.129 +/- 0.026 mm Hg/mm Hg (normal and CHF pigs, respectively), but Gs showed no significant change (0.067 +/- 0.027 and 0.109 +/- 0.012 mm Hg/mm Hg for normal and CHF pigs, respectively), and both were also significantly increased during volume loading. Gs was significantly greater in CHF versus normal pigs under all conditions, but there were no differences in Gd between CHF and normal pigs.These results suggest that dilated cardiomyopathy increases systolic but not diastolic interactions, that the pericardium increases diastolic but not systolic ventricular interactions, and that volume loading with and without the pericardium opened increases both systolic and diastolic interactions.
Journals sponsored by single companies
Authors: M. Partridge
Journal: BMJ (1995)

EDITOR,--The BMJ, like most journals and many postgraduate educational activities, is subsidised by the support of pharmaceutical companies. This is usually in the form of advertisements from many companies, and readers hope that that support, freely coming from numerous companies, in no way influences editorial content. Some other journals, however, now receive support from a single company, which is not immediately apparent. This is material to the assessment of …
Who Defines Futility?
Authors: Stuart J. Youngner
Journal: JAMA (1988)

Youngner responds to D.J. Murphy's article in this issue of JAMA in which Murphy advocates unilateral decision making by physicians concerning do-not-resuscitate (DNR) orders for some aged, chronically ill patients in long-term care (LTC) facilities. Youngner takes issue with Murphy's arguments for unilateral decision making, which involve the physician's assessment of the futility of treatment, the paternalistic desire to spare the patient and family members, and the need to reallocate medical resources. While agreeing with Murphy that CPR is contraindicated in many LTC patients, Youngner rejects his proposal to exclude patients and family members from the decision making process, and to not inform them of the physician's unilateral DNR decision. Youngner, a physician as is Murphy, warns that doctors must not substitute their values for those of their patients "under the guise of medical expertise and concern for resource allocation."
Age decreases nitric oxide synthesis and responsiveness in human platelets and increases formation of monocyte–platelet aggregates☆
Authors: I GOUBAREVA, E GKALIAGKOUSI, A SHAH, L QUEEN, J RITTER, A FERRO
Journal: Cardiovascular Research (2007)

Ageing is associated with an increase in atherothrombotic disease. Platelet-derived nitric oxide (NO) inhibits platelet activation, but the effect of age on platelet NO signaling is unknown. We investigated platelet NO biosynthesis and responsiveness in older (> 45 years old) as compared with younger (< 30 years old) healthy human subjects.Platelet NO synthase (NOS) activity was evaluated by l-[3H]-arginine to l-[3H]-citrulline conversion, and cGMP was determined by radioimmunoassay. Platelet expression of NOS3, phosphoserine-1177-NOS3 and soluble guanylyl cyclase (sGC) were quantified by Western blotting. Circulating monocyte-platelet aggregates (MPA) were measured by flow cytometry.Basal NOS activity was similar in both groups. By contrast, whereas both albuterol and collagen stimulated platelet NOS in younger subjects, stimulation was absent in older subjects. Platelet NOS3 expression was similar in both age groups, but NOS3 serine-1177 phosphorylation was greater in younger subjects. Basal, albuterol- and collagen-stimulated cGMP, as well as sGC expression, were all greater in younger than older subjects, and within the younger group both cGMP (basal and stimulated) and sGC expression were greater in women than in men. Circulating MPA were greater in older subjects and, whilst NOS inhibition increased MPA further in both groups, it did so to a lesser extent in the older age bracket.These data suggest that platelet NO production and responsiveness decrease with age, and this is reflected in increased circulating MPA.
Migration of Urbanites to Small Towns for Medical Care
Authors: Glen E. Garrison
Journal: JAMA (1974)

In recent decades, the concentration of medical manpower and facilities in large metropolitan areas has paralleled the rapid urban centralization of most products and services in the United States. Predictably, people living in small towns and rural areas go to large cities for some of their medical services. However, it is generally not appreciated that physicians practicing in small towns spend a sizeable proportion of their time providing medical care to people who live in somewhat distant, large, metropolitan areas. Apparently, these urban citizens perceive the presence of a type of medical care in small towns that is more desirable than that provided in large cities.
T6 Thrombocytosis is Associated with Increased Short and Long Term Mortality After Exacerbation of Chronic Obstructive Pulmonary Disease
Authors: MT Harrison, P Short, P Williamson, A Singanayagam, AR Akram, JD Chalmers, S Schembri
Journal: Thorax (2012)

<h3>Introduction</h3> There is increasing evidence suggesting that platelets play a significant role in inflammation in addition to their established role in thrombosis. Systemic inflammation is linked to poor short and long term outcomes in COPD Increased platelet activation has been reported in acute exacerbations of COPD (AECOPD). We investigated whether thrombocytosis is associated with poor outcomes following AECOPD. <h3>Methods</h3> A prospective observational cohort study of patients hospitalised with AECOPD was performed. The dataset consists of patients &gt;40 years, with spirometrically confirmed COPD admitted with exacerbations between 2009–2011. Platelet count was recorded on admission. The primary outcome was in-hospital mortality with secondary outcomes of 1 year all-cause mortality, cardiovascular events and mortality. Analyses were conducted using cox-proportional hazards regression after adjustment for demographics, co-morbidities, chronic treatments and severity of exacerbations. <h3>Results</h3> 1343 patients (49% male) were included with a median age of 72 years (interquartile range 63–79 years). 157 patients (11.7%) had thrombocytosis (platelet count &gt;400×109 cells/mm3). Thrombocytosis correlated with established markers of poor outcome in COPD, including hypoalbuminaemia (34 IQR 31–38 vs 37 33–40, p&lt;0.0001), low BMI (BMI &lt;18.5 in 14.6% vs 9.1%, p=0.03) and frequent exacerbations in the previous year (mean 1.42 standard deviation(SD) 1.9 vs mean 1.1 SD 1.8, p=0.02). Thrombocytosis was significantly associated with in-hospital mortality: Hazard ratio (HR) 1.96 (1.15–3.32) and 1 year mortality after discharge HR 1.48 (1.12–1.97). The relationships with cardiovascular hospitalisation HR 1.17 (0.84–1.64) and 1 year cardiovascular mortality HR 1.33 (0.82–2.14) were not statistically significant. To determine if the increased risk associated with thrombocytosis was potentially modifiable, we studied whether antiplatelet treatment (chronic prescription of aspirin or clopidogrel) would attenuate the risks associated with thrombocytosis. Anti-platelet treatment was associated with reduced 1 year mortality HR 0.75 (0.59–0.97) with a trend towards reduced in-hospital mortality HR 0.66 (0.40–1.09), cardiovascular hospitalisation HR 0.81 (0.61–1.08) and cardiovascular death HR 0.85 (0.57–1.26). <h3>Conclusion</h3> Thrombocytosis was associated with increased in-hospital and 1 year mortality. This relationship was only partly attributable to increased cardiovascular mortality. Anti-platelet medications correlated with significantly lower 1 year mortality and may have a protective role to play in COPD.