tbuckley/cabot-search huggingface dataset:
A POST-GRADUATE CLINICAL LECTURE on MITRAL STENOSIS, with SPECIAL REFERENCE to RECENT INVESTIGATIONS: Delivered at the London Hospital
Authors: A. E. Sansom
Journal: BMJ (1898)

IN the coivse of clinical lectures which I have delivered this session I have considered the clinical and pathological signs of mitral stenosis as evidenced by the cases under our obser- vation in this hospital.On this occasion I ehall confine myself chiefly to a review of the investigations which have been made in recent years towards the elucidation of some of the problems presented by this form of disease.We will, in the first instance, examine the patients who will serve as object lessons, and I will in the briefest terms state the circumstances with regard to these which I wish you to note.CASE I.-C.M., aged 31, female.From 18 years of age suffered from anaemia, palpitations, and shortness of breath.Six weeks before admission had haemoptysis, two attacks.No rheumatic historv.Pulse- rate 7 irregular.Slight thrill at apex.Long purring presystolic bruit, flnishiDg up suddenly at the first sound, which is short and sharp in character; double shock sound during diastole heard at apex.Pul- monary second sound accentuated.Patient improved very much while in hospital, her chief trouble being indigestion.Temperature normal; no albumen in urine: quantity passed normal in amount.CASE II.-E.P., aged 22, female.Patient had right hemiplegia.She could not write, but recognised her name.The heart examination showed all the signs of uncomplicated mitral stenosis, presystolic murmur, and tbrill, with double second sound.The hemiplegia gradiually cleared up, so that on discharge patient could walk well.The patient could copy print, etc, but could not write anylbing original.Intelligible speech was absent; she could only say "No."We had no doubt that this patient when admitted was suffering from embolism of the left middle cerebral artery.Nutrition was re-establisbed in the areas served by all the branches save that supplying the speech centres; in these a destructive lesion persisted.
Induction of Mammary Tumors in Virgin Female BALB/c Mice by Single Low Doses of 7,12-Dimethylbenz[α]anthracene<xref ref-type="fn" rid="fn2">2</xref><xref ref-type="fn" rid="fn3">3</xref>
Authors: S P Ethier, R L Ullrich
Journal: JNCI Journal of the National Cancer Institute (1982)

The induction of mammary tumors in virgin female inbred BALB/c mice after administration of 7,12-dimethylbenz[a]anthracene (DMBA) over a wide range of doses was studied. Mice were exposed at 12 weeks of age to single or multiple doses of DMBA ranging from 0.0025 to 12.0 mg by gastric intubation and were checked regularly for mammary tumors. The experiment was terminated when the mice were 800 days of age. In the dose range of 0.0025--0.125 mg DMBA, the incidence of mammary tumors was dose-dependent. At higher doses, the mammary tumor incidence became less dose-dependent and was nearly independent of doses above the 0.25-mg level. Analysis of the data for the rate of appearance of mammary tumors with age of the animals and for the age at death of non-mammary tumor-bearing animals indicated that in the low dose range induction of mammary tumors was the predominant effect of DMBA exposure, whereas at moderate to high doses the toxic and carcinogenic effects of DMBA on other tissues significantly influenced the final incidence of mammary tumors. Greater than 90% of the tumors that resulted from administration of low doses of DMBA were adenocarcinomas. In contrast, adenocarcinomas and adenoacanthomas were found in approximately equal proportions following administration of high doses of DMBA.
Doppler ultrasound investigation of uterine and ovarian blood flow in infertility and early pregnancy
Authors: R P Dickey
Journal: Human Reproduction Update (1997)

This review describes the current use of Doppler ultrasound to examine blood flow in the uterus and ovaries in infertile patients and during early pregnancy. The basics of Doppler ultrasound and the different methods of measuring blood flow are discussed from the viewpoint of the clinician who may be unfamiliar with Doppler physics and terminology. Normal values in the menstrual cycle and the relationship of uterine and ovarian blood flow to infertility and to implantation following in-vitro fertilization are presented. Normal values for uterine blood flow in the first 16 weeks of pregnancy and the effect of sex steroids and ovulation induction on their values are described. The possible relationship of defective uterine blood flow, and the effect of drugs are explored. The findings of this review indicate that Doppler blood flow studies may provide significant information about possible causes of some disorders of infertility and early pregnancy and methods of treatment for the same. Key words: abortion (miscarriage)/Doppler ultrasound/pregnancy first trimester/uterine blood flow
Safety and efficacy of ocrelizumab in combination with methotrexate in MTX-naive subjects with rheumatoid arthritis: the phase III FILM trial
Authors: William Stohl, Juan Gomez-Reino, Ewa Olech, Jean Dudler, Roy M Fleischmann, Cristiano A F Zerbini, Ali Ashrafzadeh, Susanna Grzeschik, Rebecca Bieraugel, Jennifer Green, Steven Francom, Wolfgang Dummer
Journal: Annals of the Rheumatic Diseases (2012)

<h3>BACKGROUND</h3> It remains controversial whether or not <i>Helicobacter pylori</i>infection causes altered gastric acid secretion. A novel test for evaluating gastric acid secretion (endoscopic gastrin test; EGT) has recently been developed. <h3>AIM</h3> To investigate by EGT the effects of <i>H pylori</i>eradication on the state of gastric acid secretion in patients with peptic ulcer. <h3>METHODS</h3> Twenty six patients with duodenal ulcer and 33 with gastric ulcer, for all of whom<i>H pylori</i> infection had been documented, were studied by EGT, histological examination of gastric mucosa, and measurement of plasma gastrin levels before and one and seven months after <i>H pylori</i> eradication. <h3>RESULTS</h3> In patients with duodenal ulcer, the mean EGT value before<i>H pylori</i> eradication was higher than that in<i>H pylori</i> negative controls, but it had decreased significantly seven months after the treatment. In contrast, the mean EGT value of patients with gastric ulcer before<i>H pylori</i> eradication was lower than that in<i>H pylori</i> negative controls, but it had increased one month after the treatment; this was followed by a slight decrease at seven months. In both groups, mean EGT values seven months after the treatment were not significantly different from the mean control value. <h3>CONCLUSIONS</h3> The reduced acid secretion in gastric ulcer patients and gastric acid hypersecretion in duodenal ulcer patients were both normalised after the clearance of <i>H pylori</i>.
Comparative genomics of Drosophila and human core promoters.
Authors: Peter C FitzGerald, David Sturgill, Andrey Shyakhtenko, Brian Oliver, Charles Vinson
Journal: Genome biology (2006)

Abstract Background The core promoter region plays a critical role in the regulation of eukaryotic gene expression. We have determined the non-random distribution of DNA sequences relative to the transcriptional start site in Drosophila melanogaster promoters to identify sequences that may be biologically significant. We compare these results with those obtained for human promoters. Results We determined the distribution of all 65,536 octamer (8-mers) DNA sequences in 10,914 Drosophila promoters and two sets of human promoters aligned relative to the transcriptional start site. In Drosophila , 298 8-mers have highly significant ( p ≤ 1 × 10 -16 ) non-random distributions peaking within 100 base-pairs of the transcriptional start site. These sequences were grouped into 15 DNA motifs. Ten motifs, termed directional motifs, occur only on the positive strand while the remaining five motifs, termed non-directional motifs, occur on both strands. The only directional motifs to localize in human promoters are TATA, INR, and DPE. The directional motifs were further subdivided into those precisely positioned relative to the transcriptional start site and those that are positioned more loosely relative to the transcriptional start site. Similar numbers of non-directional motifs were identified in both species and most are different. The genes associated with all 15 DNA motifs, when they occur in the peak, are enriched in specific Gene Ontology categories and show a distinct mRNA expression pattern, suggesting that there is a core promoter code in Drosophila . Conclusion Drosophila and human promoters use different DNA sequences to regulate gene expression, supporting the idea that evolution occurs by the modulation of gene regulation.
Vascular Adhesion Protein-1 Enhances Tumor Growth by Supporting Recruitment of Gr-1+CD11b+ Myeloid Cells into Tumors
Authors: Fumiko Marttila-Ichihara, Kaisa Auvinen, Kati Elima, Sirpa Jalkanen, Marko Salmi
Journal: Cancer Research (2009)

Cancer growth is regulated by several nonmalignant cell types, such as leukocytes and endothelial cells, which reside in the stroma of the tumor. Vascular adhesion protein-1 (VAP-1) is an amine oxidase enzyme that is expressed on the surface of endothelial cells. It supports leukocyte traffic into inflamed tissues, but nothing is known about its possible role in cancer biology in vivo. Here, we report that B16 melanoma and EL-4 lymphoma remain smaller in VAP-1-deficient mice than in wild-type controls. We found an unexpected defect in tumor angiogenesis in the absence of VAP-1. VAP-1 also selectively enhanced the recruitment of Gr-1+CD11b+ myeloid cells into the tumors. Generation of mice expressing enzymatically inactive VAP-1 showed that the oxidase activity of VAP-1 was necessary to support neoangiogenesis, myeloid cell recruitment, and tumor growth in vivo. These data describe VAP-1 as the first adhesion molecule known to be involved in the recruitment of Gr-1+CD11b+ myeloid cells into tumors. They also suggest that VAP-1 is a potential new tool for immunotherapy of tumors that could be exploited to reduce tumor burden by controlling the traffic of Gr-1+CD11b+ myeloid cells.
Quantitative contribution of systemic vascular autoregulation in acute hypertension in conscious dogs.
Authors: P J Metting, K A Kostrzewski, P M Stein, B A Stoos, S L Britton
Journal: Journal of Clinical Investigation (1989)

Experiments were performed in nine conscious dogs to quantitate the contribution of systemic vascular autoregulation to the increases in total peripheral resistance (TPR) and mean arterial pressure (MAP) produced by angiotensin II (ANG II), arginine vasopressin (AVP), and norepinephrine (NE). We hypothesized that if autoregulatory vasoconstriction is significant, then the increase in TPR produced by vasoconstrictor infusion will be greater when MAP is controlled at hypertensive values than when the increase in pressure is prevented by controlling MAP at the animal's normotensive value. Each drug was infused at a dose sufficient to increase MAP by 50%. Then, a constant rate of vasoconstrictor infusion was maintained while MAP was controlled at hypertensive or normotensive levels for 15-min periods using a gravity reservoir connected to the left common carotid artery. During AVP infusion, TPR was significantly greater when MAP was controlled at hypertensive than at normotensive values. This autoregulatory-mediated vasoconstriction accounted for approximately three-fourths of the increase in MAP produced by AVP. No significant autoregulatory component was identified for the increases in TPR and MAP produced by ANG II or NE. We conclude that systemic vascular autoregulation is a powerful physiological property that contributes to the hemodynamic response to pressor doses of AVP.
Aktinik keratoz tedavisinde 6 ay süreyle haftada 1 kez %5 imiquimod krem ile plasebo-kontrollü, çift-kör, randomize, pilot çalışma
Authors: Joshua A. Zeichner, Dana W. K. Stern, Annemarie Uliasz, Sarit Itenberg, Mark Lebwohl
Journal: Journal of the American Academy of Dermatology (2009)
Development of a radiographic index to assess the tarsal involvement in patients with spondyloarthropathies
Authors: C Pacheco-Tena
Journal: Annals of the Rheumatic Diseases (2002)

To develop and test an index to evaluate the radiographic changes that occur in the tarsus and adjacent areas of the foot in patients with spondyloarthropathies (SpA).The spondyloarthropathy tarsal radiographic index (SpA-TRI) was developed in three consecutive steps: (a) detection of descriptors after reviewing 70 radiographic files; (b) descriptor gradation and subsequent modifications performed by a consensus committee, and (c) interobserver variability assessed by three blinded and independent observers on 272 radiographs: anteroposterior 118, lateral 90, oblique 64 from 121 patients with SpA, and intraobserver variability on 75 radiographs from 25 patients with SpA. Statistical analysis included percentage of agreement and kappa test. SpA-TRI score ranges from 0 to 4 (0=normal; 1=osteopenia or suspicious findings; 2=definite joint space narrowing, bony erosion(s), periosteal whiskering, or enthesophyte(s) in the plantar fascia or Achilleal tendon attachments; 3=para-articular enthesophyte(s); 4=bony ankylosis (joint space fusion or complete bridging)).Complete agreement for every evaluation was >40%, and discordance >1 grade was <15%. The kappa scores among the three observers were acceptable for all the single projections: oblique (0.52, 0.36, 0.35), lateral (0.50, 0.42, 0.56), and anteroposterior (0.40, 0.41, 0.21) views. The combination of lateral and oblique views achieved the highest concordance rates (0.72, 0.33, 0.66), surpassing that of the three projections altogether (0.34, 0.58, 0.37). In every case the concordance was comparable with that of sacroiliac joints (0.47, 0.41, 0.34); intraobserver concordance showed a similar trend.The SpA-TRI is an index that includes the most prominent features of tarsal disease and adjacent areas of the foot in SpA and grades them accordingly, it has an adequate reproducibility, and is suitable for use with two or more projections, preferably the combination of oblique and lateral.
Acute Toxicity and Quality of Life After Dose-Intensified Salvage Radiation Therapy for Biochemically Recurrent Prostate Cancer After Prostatectomy: First Results of the Randomized Trial SAKK 09/10
Authors: Pirus Ghadjar, Stefanie Hayoz, Jürg Bernhard, Daniel R. Zwahlen, Tobias Hölscher, Philipp Gut, Matthias Guckenberger, Guido Hildebrandt, Arndt-Christian Müller, Ludwig Plasswilm, Alexandros Papachristofilou, Lukas Stalder, Christine Biaggi-Rudolf, Marcin Sumila, Helmut Kranzbühler, Yousef Najafi, Piet Ost, Ngwa C. Azinwi, Christiane Reuter, Stephan Bodis, Khanfir Kaouthar, Peter Wust, George N. Thalmann, Daniel M. Aebersold
Journal: Journal of Clinical Oncology (2015)

Patients with biochemical failure (BF) after radical prostatectomy may benefit from dose-intensified salvage radiation therapy (SRT) of the prostate bed. We performed a randomized phase III trial assessing dose intensification.Patients with BF but without evidence of macroscopic disease were randomly assigned to either 64 or 70 Gy. Three-dimensional conformal radiation therapy or intensity-modulated radiation therapy/rotational techniques were used. The primary end point was freedom from BF. Secondary end points were acute toxicity according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0) and quality of life (QoL) according to the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires C30 and PR25.Three hundred fifty patients were enrolled between February 2011 and April 2014. Three patients withdrew informed consent, and three patients were not eligible, resulting in 344 patients age 48 to 75 years in the safety population. Thirty patients (8.7%) had grade 2 and two patients (0.6%) had grade 3 genitourinary (GU) baseline symptoms. Acute grade 2 and 3 GU toxicity was observed in 22 patients (13.0%) and one patient (0.6%), respectively, with 64 Gy and in 29 patients (16.6%) and three patients (1.7%), respectively, with 70 Gy (P = .2). Baseline grade 2 GI toxicity was observed in one patient (0.6%). Acute grade 2 and 3 GI toxicity was observed in 27 patients (16.0%) and one patient (0.6%), respectively, with 64 Gy, and in 27 patients (15.4%) and four patients (2.3%), respectively, with 70 Gy (P = .8). Changes in early QoL were minor. Patients receiving 70 Gy reported a more pronounced and clinically relevant worsening in urinary symptoms (mean difference in change score between arms, 3.6; P = .02).Dose-intensified SRT was associated with low rates of acute grade 2 and 3 GU and GI toxicity. The impact of dose-intensified SRT on QoL was minor, except for a significantly greater worsening in urinary symptoms.
Cholinergic stimulation blocks endothelial cell activation and leukocyte recruitment during inflammation
Authors: Rubina W. Saeed, Santosh Varma, Tina Peng-Nemeroff, Barbara Sherry, David Balakhaneh, Jared Huston, Kevin J. Tracey, Yousef Al-Abed, Christine N. Metz
Journal: The Journal of Experimental Medicine (2005)

Endothelial cell activation plays a critical role in regulating leukocyte recruitment during inflammation and infection. Based on recent studies showing that acetylcholine and other cholinergic mediators suppress the production of proinflammatory cytokines via the α7 nicotinic acetylcholine receptor (α7 nAChR) expressed by macrophages and our observations that human microvascular endothelial cells express the α7 nAChR, we examined the effect of cholinergic stimulation on endothelial cell activation in vitro and in vivo. Using the Shwartzman reaction, we observed that nicotine (2 mg/kg) and the novel cholinergic agent CAP55 (12 mg/kg) inhibit endothelial cell adhesion molecule expression. Using endothelial cell cultures, we observed the direct inhibitory effects of acetylcholine and cholinergic agents on tumor necrosis factor (TNF)-induced endothelial cell activation. Mecamylamine, an nAChR antagonist, reversed the inhibition of endothelial cell activation by both cholinergic agonists, confirming the antiinflammatory role of the nAChR cholinergic pathway. In vitro mechanistic studies revealed that nicotine blocked TNF-induced nuclear factor–κB nuclear entry in an inhibitor κB (IκB)α- and IκBε-dependent manner. Finally, with the carrageenan air pouch model, both vagus nerve stimulation and cholinergic agonists significantly blocked leukocyte migration in vivo. These findings identify the endothelium, a key regulator of leukocyte trafficking during inflammation, as a target of anti-inflammatory cholinergic mediators.
Endogenous testosterone attenuates neointima formation after moderate coronary balloon injury in male swine
Authors: D. L. Tharp, I. Masseau, J. Ivey, V. K. Ganjam, D. K. Bowles
Journal: Cardiovascular Research (2009)

Previous studies from our laboratory have demonstrated that testosterone increases coronary smooth muscle protein kinase C delta (PKCδ) both in vivo and in vitro and inhibits coronary smooth muscle proliferation by inducing G0/G1 cell cycle arrest in a PKCδ-dependent manner. The purpose of the present study was to determine whether endogenous testosterone limits coronary neointima (NI) formation in a porcine model of post-angioplasty restenosis. Sexually mature, male Yucatan miniature swine were either left intact (IM), castrated (CM), or castrated with testosterone replacement (CMT; Androgel, 10 mg/day). Angioplasty was performed in both the left anterior descending and left circumflex coronary arteries with balloon catheter overinflation to induce either moderate (1.25–1.3x diameter; 3 × 30 s) or severe (1.4x diameter; 3 × 30 s) injury, and animals were allowed to recover for either 10 or 28 days. Injured coronary sections were dissected, fixed, stained (Verheoff-Van Gieson, Ki67, PKCδ, p27), and analysed. Vessels without internal elastic laminal rupture were excluded. Following moderate injury, intimal area, intima-to-media ratio (I/M), and I/M normalized to rupture index (RI) were increased in CM compared with IM and CMT. RI, medial area, and intimal/medial thickness (IMT) were not different between groups. NI formation was inversely related to serum testosterone concentration. Conversely, following severe injury, there were no significant differences between the groups. Testosterone inhibited proliferation and stimulated PKCδ and p27kip1 expression during NI formation (10 days post-injury). These findings demonstrate that endogenous testosterone limits coronary NI formation in male swine and provides support for a protective role for testosterone in coronary vasculoproliferative diseases, such as restenosis and atherosclerosis.
An Immunologic Evaluation of Hemophiliac Patients and Their Wives
Authors: RICHARD D. deSHAZO
Journal: Annals of Internal Medicine (1983)

Recently, hemophiliac patients receiving factor VIII concentrate therapy have developed the acquired immunodeficiency syndrome. Because abnormalities of cell-mediated immunity are found in this syndrome, we evaluated the peripheral blood immunologic status of 24 patients with classic hemophilia and 5 patients with factor IX deficiency. Both groups had decreased percentages and numbers of helper-inducer lymphocytes (OKT4 + ) and increased percentages of suppressor-cytotoxic T- lymphocytes (OKT8 + ) which resulted in depressed OKT4/T8 ratios. Abnormalities of the T-lymphocyte subpopulation were most severe in 7 patients with factor VIII deficiency with lymphadenopathy who also had increased Ia+ cells and profoundly suppressed lymphocyte mitogenic responses. No correlation was found between OKT4/OKT8 ratios or lymphocyte responses to mitogen and the amount of factor VIII concentrate used per year. Evaluation of five wives of factor-VIII-deficient patients who had abnormal OKT4/ OKT8 ratios showed decreased percentages of OKT4 cells, but normal lymphocyte mitogenic responses. Serum levels of IgG were elevated in factor-VIII-deficient patients but not their wives or factor-IX-deficient patients. We conclude that T-lymphocyte subpopulation abnormalities and lymphocyte mitogenic responses are depressed in asymptomatic hemophiliac patients receiving either factor VIII or factor IX concentrates. These abnormalities are most severe in otherwise asymptomatic hemophiliac patients who have developed lymphadenopathy.
The role of hospital volume in coronary artery bypass grafting: is more always better?11&gt;Presented, in part, at the Annual Meeting of the American Heart Association in New Orleans, Louisiana, on November 13, 2000.
Authors: Brahmajee K Nallamothu, Sanjay Saint, Scott D Ramsey, Timothy P Hofer, Sandeep Vijan, Kim A Eagle
Journal: Journal of the American College of Cardiology (2001)
Controlled inpatient study of tienilic acid in treatment of gout and hypertension.
Authors: J A Reardon, J T Scott
Journal: Annals of the Rheumatic Diseases (1980)

Under inpatient controlled conditions 4 patients with gout and hypertension were treated with varying doses of tienilic acid, a new uricosuric diuretic. Plasma urate levels were reduced by an average of 50% in association with significantly increased urinary urate excretion. A twice-daily regimen was considerably more effective than a single morning dosage in reduction of plasma urate, though both regimens were equally effective in antihypertensive potency. The single daily regimen produced greater diurnal fluctuations in plasma urate and was more frequently associated with the development of acute gout attacks.