tbuckley/cabot-search huggingface dataset:
Abstract 39: Frequency of the Angiotensin Converting Enzyme (I/D) and β1 Adrenergic Receptor (Arg389Gly) Gene Polymorphisms in a Sample of Mexican Population
Authors: Juan Pablo Cervantes Minjares, Manuel Alejandro De la Torre Zazueta, Guadalupe Hernández Pacheco
Journal: Circulation Research (2014)

Introduction: The angiotensin converting enzyme (ACE) is involved in blood pressure regulation. The I/D polymorphism of ACE has been associated with hypertension, left ventricular hypertrophy and metabolic syndrome. The β1 adrenergic receptor (ARβ1) is located mainly in the heart, its activation has a chronotropic and inotropic effect. The Arg389Gly polymorphism of ARβ1 has been associated with dilated cardiomyopathy, atrial fibrillation and vasovagal syncope. The identification of these polymorphisms in a control group, will reveal the frequencies in healthy mexican population so we can compare with the diseased population and seek association with different diseases. Objective: Identifying gene and allelic prevalence in a healthy population. Material and Methods: We worked with 45 samples from healthy individuals, 36 males and 9 females, with a median age of 35.8 ± 16.1 and a BMI of 25.81 ± 4.6. Extraction of DNA from 10 ml of peripheral blood. ACE polymorphism was determined by direct PCR. The determination of the Arg389Gly polymorphism was by PCR-RFLP. Results: The gene frequency of the ACE gene in 39 subjects was: DD 33.33% (13 of 39), ID 38.46% (15 of 39) and II 28.2% (11 of 39). The allelic frequency: I 47.43% and D 52.56%. Arg389Gly polymorphism frequency was in 11 subjects: ArgArg 9% (1 of 11), ArgGly 72.7% (8 of 11) and GlyGly 18.2% (2 of 11). The allele frequency: 45% Arg and Gly 55%. Conclusions: DD homozygote frequency differs from that observed in the study of Vargas et al., which is lower. This is important because the D allele is associated with greater activity and concentration of ACE, which may predispose to cardiovascular disease in our population. Regarding the Arg389Gly polymorphism, it has been observed that the Gly allele is linked to cardiovascular disease and the response to beta-blockers. Our population showed an increase of Gly allele carriers, so they may be more susceptible to these diseases. It is important to know the frequency of these polymorphisms in our population, and identify that they can impact in medical treatment or may serve as potential predictors of cardiovascular disease.
Abstract 3341: Chronic TNFα treatment enhances cancer stem cell-like phenotype via Notch1 activation in oral squamous cell carcinoma cells
Authors: Sung Hee Lee, Reuben Kim, Mo Kang, No-Hee Park, Ki-Hyuk Shin
Journal: Cancer Research (2012)

Abstract Although there is an increasing evidence of chronic inflammation-associated tumorigenesis, the molecular and cellular mechanisms linking chronic inflammation to tumorigenesis have not yet been fully understood. Recent studies have uncovered and validated the pathophysiological role of self-renewing cells, named cancer stem cells (CSC; also called tumor-initiating cells), in long-term sustenance of cancers. In this study, we investigated the effect of chronic inflammation on CSC phenotype of oral squamous cell carcinoma cells (OSCC). We treated OSCC cell lines with tumor necrosis factor alpha (TNFα), a major proinflammatory cytokine, for extended periods and examined the effect of chronic TNFα on CSC characteristics, i.e., undifferentiated tumor sphere forming ability, stem cell-associated genes expression and chemo-radioresistance. Chronic treatment of OSCC with TNFα enhanced CSC phenotype, which is shown by increased tumor sphere forming ability, greatly increased tumorigenicity and chemo-radioresistance, and increased expression of stemness-related genes. Moreover, activation of Notch1 signaling was detected in the TNFα treated cell, and suppression of Notch1 signaling inhibited CSC phenotype. Furthermore, we demonstrated that inhibition of Hes-1, the downstream target of Notch1, led to suppression of CSC phenotype. Taken together, the data suggest that proinflammatory cytokine exposure can generate or/and enrich OSCC CSC population, in part, by activation of the Notch1 signaling pathway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3341. doi:1538-7445.AM2012-3341
Splenic Infarction Evidenced by Whole-Body Tc-99m HMPAO-Labeled Leukocyte Scan
Authors: B J Cook, S Paknikar, N Lehman, E Adickes
Journal: Clinical Nuclear Medicine (1999)

Splenic infarction can be the result of an acute or chronic vascular event. The etiologic events commonly associated with splenic infarction include local vascular compromise secondary to trauma, atherosclerosis, arterial emboli, arteritis, erythrocyte sludging, or splenomegaly. In addition, there may be relative ischemia as a consequence of systemic conditions such as inflammatory disease, myeloproliferative syndromes or other neoplasias, bacteremia, or sickle cell disease. Patients with acute splenic infarction may be asymptomatic or have symptoms of left upper-quadrant pain. Diagnoses are often made based on clinical, pathologic, or radiologic information. The images show a splenic infarction that was first identified by radionuclide leukocyte imaging, later seen and followed by CT imaging, and confirmed by a pathologic diagnosis at autopsy.
Same quality, less radiation exposure
Authors: Bryony M. Mearns
Journal: Nature Reviews Cardiology (2012)

As the PROTECTION-III investigators point out in their recent report in JACC: Cardiovascular Imaging, "it is critically important to appropriately balance the desire to achieve low radiation exposures with the likelihood of obtaining useful diagnostic images".With this consideration in mind, they set out to compare two types of data acquisition technique during coronary CT angiography.PROTECTION-III was a multicenter, multivendor, investigator-led trial involving 400 individuals with low-to-intermediate risk of obstructive coronary artery disease.Half of the enrolled patients were randomly assigned to traditional, helical scanning, during which radiation is applied throughout the entire cardiac cycle.The remaining patients were assigned to prospective ECG-triggered axial scanning-a technique involving application of radiation only at predefined points in the cardiac cycle (usually during the diastolic phase).The primary end point of the trial was image quality.Secondary end points included radiation dose and need for further testing.Mean image quality score did not differ on the basis of scanning technique (3.36 ± 0.59 vs 3.37 ± 0.59 for axial vs helical scanning; P = 0.866; P <0.004 for diagnostic noninferiority), nor did the number of nondiagnostic (low quality) studies (13.0%vs 11.5%, respectively; P = 0.647).No significant differences in image quality were observed in various sub-group analyses, including those defined by heart rate, CT systems and manufacturers, or BMI.Prospective ECG-triggered axial scanning was associated with a 69% reduction in estimated effective radiation dose (3.5 ± 2.1 mSv vs 11.2 ± 5.9 mSv; P <0.0001) compared with the helical method.During 30 days of clinical follow-up, no difference in the rate of downstream testing (13.8% vs 15.9% for axial vs helical scanning; P = 0.555) was observed.On the basis of their findings, the PROTECTION-III investigators believe "the prospectively ECG-triggered axial scan technique should be used for coronary CT angiography in all patients with low and stable heart rates, in pursuit of the ultimate goal of obtaining diagnostic coronary CT angiography images with the lowest possible radiation dose".
AB0572 Meta-analysis of the key rheumatoid arthritis (RA) disease activity endpoints in patients treated with B-cell depleting therapies
Authors: S. Menon, K. Barker, E. Peeva, I. Gourley, A. Heatherington
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Two recent meta-analyses are available in the literature (Lee et al., 2010 and Volkmann et al., 2010). In this meta-analysis we included additional recently published studies (nine in all) and analyzed all the RA disease activity endpoints at week 24 focusing on both anti-TNF naïve and experienced patients. <h3>Objectives</h3> To compare and evaluate RA disease activity endpoints in several similar published studies in the last decade in order to examine the effect of B cell depleting therapy on RA disease activity. <h3>Methods</h3> Unlike the other meta-analysis that exclusively uses logit method, this analysis used the method of Mantel-Hansel (MH) for the analysis of the ACR20, 50 and 70. The MH method was chosen for the current analysis due to its relative simplicity and its wide use in the medical literature. For DAS28, the effect sizes were combined using the inverse variance as the weighting factor so that studies with larger sample sizes were given more weight than smaller studies. In addition, we looked at the disease activity at week 24 for all studies. <h3>Results</h3> The estimated effect was comparable in all studies at week 24 although the treatment effect is slightly lower in IMAGE study. The confidence intervals for the Ocrelizumab (ACTION) and Rituximab (EDWARDS) studies were wider due to the relative smaller sample size. The trends were similar for anti-TNF naïve and experienced patients. Similar observations were made for ACR50, ACR70 and DAS28. <h3>Conclusions</h3> This meta-analysis indicates that in recent trials with B-cell depleting therapy, the therapies have a large and highly reproducible effect on RA disease activity which is not affected by prior receipt of anti-TNF therapy. <h3>Disclosure of Interest</h3> None Declared
Mutations in Coagulation Factors in Women with Unexplained Late Fetal Loss
Authors: Ida Martinelli, Emanuela Taioli, Irene Cetin, Alessandra Marinoni, Sonia Gerosa, Maria V. Villa, Maddalena Bozzo, Pier M. Mannucci
Journal: New England Journal of Medicine (2000)

The Factor V Leiden and prothrombin-gene mutations are independent risk factors for venous thrombosis; it is debated whether a mutation in the gene encoding methylenetetrahydrofolate reductase, an enzyme involved in homocysteine metabolism, also increases the risk of venous thrombosis. Whether any of these mutations is associated with an increased risk of late fetal death is not known.
Clonal Development, Stem-Cell Differentiation, and Clinical Remissions in Acute Nonlymphocytic Leukemia
Authors: Philip J. Fialkow, Jack W. Singer, Wendy H. Raskind, John W. Adamson, Robert J. Jacobson, Irwin D. Bernstein, Lois W. Dow, Vesna Najfeld, Robert Veith
Journal: New England Journal of Medicine (1987)

To determine whether acute nonlymphocytic leukemia develops clonally, to study the pattern of differentiation of the involved stem cells, and to determine whether clinical remissions are true remissions, we studied 27 patients with acute nonlymphocytic leukemia who were heterozygous for the X-chromosome-linked glucose-6-phosphate dehydrogenase. In each case, leukemic blast cells manifested only one type of glucose-6-phosphate dehydrogenase, indicating that the malignant process had developed from a single cell. In six elderly patients, circulating erythrocytes, platelets, or both expressed only the glucose-6-phosphate dehydrogenase found in blast cells, indicating that these leukemias had arisen from stem cells with multipotent differentiative expression. In 16 younger adults and children, erythroid cells and platelets were predominantly derived from normal stem cells. In three other cases, the stem cell that gave rise to leukemic blasts apparently also gave rise to erythroid progenitors but not to mature erythrocytes. Heterogeneity was also found during remissions. In 8 of 13 patients, restoration of nonclonal hemopoiesis and repopulation of the marrow by normal stem cells was observed during remission. In the other five patients, marrow stem cells remained partially or completely clonal, even during remission. These data indicate that acute nonlymphocytic leukemia is a heterogeneous disease with respect to differentiation of the stem cells involved by leukemia and the nature of remissions.
THU0199 Successful outcomes of pregnancy in patients with ANCA vasculitis
Authors: A. Croft, S.W. Smith, S. Carr, S. Youssouf, A. Salama, C. Pusey, L. Harper, M. Morgan
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> There is a paucity of data on the outcome of pregnancy in patients with primary systemic vasculitis. The limited evidence available suggests frequent complications such as first-trimester miscarriages, pre-term births, premature rupture of membranes and relapse of disease resulting in fetal and maternal death. Many of these studies are old and based on isolated case reports. <h3>Objectives</h3> To describe the outcome of pregnancies in patients with anti-neutrophil cytoplasmic antibody (ANCA) associated small vessel vasculitis: Granulomatosis with Polyangiitis (GPA) and Microscopic Polyangitis (MPA). <h3>Methods</h3> Retrospective case analysis of all women who became pregnant following a diagnosis of ANCA associated vasculitis or whose disease developed de novo during pregnancy in the cohort of patients treated in 3 UK centres. <h3>Results</h3> Nine pregnancies were observed in 8 patients following a diagnosis of vasculitis. All patients identified had a diagnosis of ANCA associated vasculitis according to EMEA criteria (7 diagnosed with GPA and one with MPA). All patients were in clinical remission for at least 12 months with low or undetectable serum ANCA titres at the time of conception and had no other risk factors for antenatal complications including proteinuria and hypertension. Five patients received cyclophosphamide induction therapy prior to pregnancy with a cumulative dose between 3-10g. Methotrexate was discontinued in all patients with a planned pregnancy. One patient had a first trimester miscarriage following an unplanned pregnancy whilst taking methotrexate. Seven patients were switched to azathioprine prior to pregnancy in combination with prednisolone. One patient experienced a second trimester disease relapse which was treated successfully with immunoglobulin G and plasmapheresis and progressed with an otherwise uncomplicated pregnancy. Nine live births were observed with all infants born at full term by normal vaginal delivery with the exception of one patient with a twin pregnancy and one patient with a breech presentation who underwent an elective caesarean sections. There were no obstetric or neonatal complications and no disease relapse reported in the post-partum period. <h3>Conclusions</h3> Planned pregnancy in ANCA associated vasculitis is safe with a low incidence of fetal and maternal complications. Patients should be in remission at the time of conception and on appropriate immunosuppressant therapy. Disease relapse can be treated successfully without causing fetal complications. <h3>Disclosure of Interest</h3> None Declared
A patient who intrigued me: Ceremonial haemoglobinuria
Authors: B. McConkey
Journal: BMJ (1998)

A fit young infantry officer told me that he had passed deep red urine. It was only on one occasion—the Lord Mayor’s Show, London, 1949. Confident that this was march haemoglobinuria I gave him some containers and asked for urine samples before, at about half time, and after his next hard march. This turned out to be quite soon and the urine samples he then brought in looked normal; none contained methaemoglobin. 

We discussed the matter and he made the point that the difference between usual marches and the Lord Mayor’s Show was the ceremonial aspect. There was a sense of apprehension about doing well in the public gaze, a feeling not associated with other often more strenuous and stressful events. An opportunity to test the idea that the nature of the occasion made the difference soon came. He was due to command a unit carrying out the changing of the guard at Buckingham Palace. After he had done so he brought in two urine samples, one before and one after. The first was normal, the second was deep red and had the spectrum of methaemoglobin. He was otherwise quite well and we decided to let the matter drop. 

Some years later, coming across a note I had made about him, I wrote and traced him. He was still serving as an infantry officer and had been attached to the Parachute Regiment. He answered at some length to say that he had had red urine on only two more occasions. Both were during the Korean War. The first was as his unit, aboard ship, was drawing in to Pusan harbour in darkness, ship lights dimmed and he and his regiment keyed up with the expectation of what might lie ahead. The second was during the waiting period before a dawn attack. He went on to say that since then there had been many stressful episodes but no further red urine. He remained well. 

I recently submitted the above account to the BMJ and was advised to get the patient’s consent for publication. He is well and has had no further haemoglobinuria despite having “been under stress on many occasions in many theatres of operations in my career.” It is pleasing not only to hear that he is still well but also to have achieved a 48 year follow up. 

So far as I (and Medline) know, haemoglobinuria apparently precipitated by a stressful event has not previously been recorded. This account surely emphasises that stress can mean different things to different people. At the first consultation we went carefully into the question of the physical stress of marching but forced marches involving much more effort than his ceremonial duties had never been followed by haemoglobinuria. 

I might have written him up as a formal case report years ago if I had felt able to speculate usefully on an explanation to account for stress leading to haemoglobinuria. Unfortunately, I still cannot and have not found anyone who can. Any suggestions?
Enhanced Detection of Ischemic but Viable Myocardium by the Reinjection of Thallium after Stress-Redistribution Imaging
Authors: Vasken Dilsizian, Thomas P. Rocco, Nanette M.T. Freedman, Martin B. Leon, Robert O. Bonow
Journal: New England Journal of Medicine (1990)

The identification of ischemic but viable myocardium by thallium exercise scintigraphy is often imprecise, since many of the perfusion defects that develop in ischemic myocardium during exercise do not "fill in" on subsequent redistribution images. We hypothesized that a second injection of thallium given after the redistribution images were taken might improve the detection of ischemic but viable myocardium.We studied 100 patients with coronary artery disease, using thallium exercise tomographic imaging and radionuclide angiography. Patients received 2 mCi of thallium intravenously during exercise, redistribution imaging was performed three to four hours later, and a second dose of 1 mCi of thallium was injected at rest immediately thereafter. The three sets of images (stress, redistribution, and reinjection) were then analyzed.Ninety-two of the 100 patients had exercise-induced perfusion defects. Of the 260 abnormal myocardial regions identified by stress imaging, 85 (33 percent) appeared to be irreversible on redistribution imaging three to four hours later. However, 42 of these apparently irreversible defects (49 percent) demonstrated improved or normal thallium uptake after the second injection of thallium, with an increase in mean regional uptake from 56 +/- 12 percent on redistribution studies to 64 +/- 10 percent on reinjection imaging (P less than 0.001). Twenty patients were restudied three to six months after coronary angioplasty. Of the 15 myocardial regions with defects on redistribution studies that were identified as viable by reinjection studies before angioplasty, 13 (87 percent) had normal thallium uptake and improved regional wall motion after angioplasty. In contrast, all eight regions with persistent defects on reinjection imaging before angioplasty had abnormal thallium uptake and abnormal regional wall motion after angioplasty.These data indicate that the reinjection of thallium improves the detection of ischemic myocardium and that myocardial regions with improved thallium uptake on reinjection imaging represent viable but jeopardized myocardium.
UTILIZATION AND SAFETY OF CARDIAC RESYNCHRONIZATION THERAPY IN ELDERLY
Authors: Abhishek Deshmukh, Achint Patel, Nileshkumar Patel, Badal Thakkar, Shantanu Solanki, Samir Patel, Shilpkumar Arora, Nilay Patel, Nikhil Nalluri, Peter Noseworthy, Sadip Pant, Yogesh Reddy, Apurva Badheka, Chance Witt, Yong-Mei Cha, Paul Friedman, Samuel Asirvatham
Journal: Journal of the American College of Cardiology (2015)
Case 27-1998
Authors: Anthony Atala, Joseph Misdraji
Journal: New England Journal of Medicine (1998)

Presentation of CaseA 10-year-old girl was admitted to the hospital because of urinary retention.The patient had been in excellent health until two days earlier, when she experienced suprapubic “pressure” on voiding, with urinary frequency. The next day, the discomfort was so severe that she was unable to void. Examination at this hospital showed distention of the bladder to the umbilicus. An indwelling catheter was inserted and 600 ml of urine drained. A urine specimen was positive (+) for protein and had a pH of 7.0 and a specific gravity of 1.021. The sediment contained 4 red cells and . . .
Eosinophilic Inflammation in Asthma
Authors: Jean Bousquet, Pascal Chanez, Jean Yves Lacoste, Gilbert Barnéon, Nouchine Ghavanian, Ingrid Enander, Per Venge, Staffan Ahlstedt, Joelle Simony-Lafontaine, Philippe Godard, François-Bernard Michel
Journal: New England Journal of Medicine (1990)

The importance of eosinophils in the pathogenesis of bronchial asthma is not established. In an attempt to evaluate the role of eosinophilic inflammation in asthma, we compared 10 normal subjects with 43 patients with chronic asthma, 19 of whom had severe disease as assessed by a clinical scoring method described by Aas and by pulmonary-function tests. Eosinophils were counted in peripheral blood and bronchoalveolar-lavage fluid, and in biopsy specimens obtained from the patients and post mortem from 8 subjects without asthma, but not from the 10 normal controls. Eosinophil cationic protein was titrated by radioimmunoassay in the bronchoalveolar-lavage fluid from all subjects and studied by immunohistochemistry in the biopsy specimens.