tbuckley/cabot-search huggingface dataset:
A man with acute venous thromboembolism and thrombocytopenia
Authors: M. Mohamed, R. Hayes, T. Mosetlhi
Journal: BMJ (2014)

A 64 year old man presented to the emergency department with shortness of breath and pleuritic chest pain of 12 hours’ duration. Eight days earlier he had undergone radical prostatectomy for early stage prostatic cancer. He had been given tramadol for analgesia and unfractionated heparin (5000 units subcutaneously) twice a day for four days for postoperative thromboprophylaxis. His full blood counts and biochemical parameters were within normal limits and he was discharged home on the fourth day after surgery with no complications. 

His medical history and family history were unremarkable. On examination his respiratory rate was 25 breaths/min, heart rate was 100 beats/min, blood pressure was 130/88 mm Hg, and oxygen saturation in room air was low (90%). Cardiac, respiratory, abdominal, and neurological examinations were normal. His left leg and thigh were swollen but non-tender. There were no bleeding manifestations or evidence of active infection at that time. Chest radiography and electrocardiography were unremarkable. 

However, axial computed tomography pulmonary angiography showed extensive thromboemboli in the right and left main pulmonary arteries extending more distally and associated with bilateral wedge shaped pulmonary infarcts (fig 1⇓). Doppler ultrasound showed thrombosis in the left popliteal vein extending up to the common femoral vein. Full blood counts showed low platelets (34×109/L), normal haemoglobin, and normal numbers of white cells. Blood film examination was unremarkable. His coagulation assays, renal parameters, and liver function tests were within normal limits.



Fig 1 Axial computed tomography pulmonary angiogram showing extensive thromboemboli in the right and left main pulmonary arteries (yellow arrows) extending more distally and associated with bilateral wedge shaped pulmonary infarcts (blue arrowheads)





### 1 What is the most likely diagnosis in this patient?

#### Short answer

Heparin …
Letter by Roguin and Musallam Regarding Article, “Stent Thrombosis With Ticagrelor Versus Clopidogrel in Patients With Acute Coronary Syndromes: An Analysis From the Prospective, Randomized PLATO Trial”
Authors: Ariel Roguin, Anees Musallam
Journal: Circulation (2014)

We read with interest the article by Steg et al 1 on stent thrombosis in the Platelet Inhibition and Patient Outcomes (PLATO) trial.We have several comments.In the original New England Journal of Medicine publication of the PLATO trial, Wallentin et al 2 reported that among patients who received a stent during the study (n=11 289), the rate of definite stent thrombosis was lower in the ticagrelor group than in the clopidogrel group (1.3% versus 1.9%; P=0.009).The clinical question that should be asked is whether the stent thrombosis rate in patients with acute coronary syndrome receiving a new stent is lower with the new antiplatelet medication.Therefore, in our opinion, all the patients with stents implanted in the past (n=1404) should not be included because they introduce bias, they dilute the rate of thrombosis, and they are clinically less relevant.When reporting the timing of stent thrombosis, Steg et al 1 correctly took only the 9885 patients in whom a new stent was implanted during the trial.This number is different from that in the original publication.For the same number of patients with stent thrombosis, the rate will be lower if it is calculated with a higher denominator.If the authors took only those with new stents (lower denominator), then the rate of thrombosis in the trial would have been higher.Compliance with the antiplatelet medication is of major importance, especially in a discussion about stent thrombosis.Of note, among those who had thrombosis, 43% in the clopidogrel arm and 31% in the ticagrelor arm were not on their medications.This is at least problematic because 1 in 3 patients was not on the study medication.This makes definitive conclusions harder to obtain.Lastly, in the PLATO trial, stent thrombosis was identified from adjudication forms for events identified as death, myocardial infarction, severe recurrent ischemia, and recurrent ischemia.However, the Academic Research Consortium definition of stent thrombosis takes into account not only myocardial infarction and death but also angiographic stent thrombosis, but this information was not available for a large number of participants in the PLATO trial.On the basis of previous pharmacological studies, we believe that ticagrelor indeed should have and has a lower stent thrombosis rate.The article by Steg et al adds important information in this area.
SOME UNUSUAL FEATURES OF APPENDICITIS AND THEIR TREATMENT.
Authors: ERNEST LaPLACE
Journal: JAMA (1901)

The protean character of various forms of pathological conditions, grouped under the head of appendicitis, offers the surgeon an unusual and often unforeseen group of clinical, as well as pathological, manifestations. The varying size and anatomic appearance of the appendix, the various movements through which it passes in peristaltic action, the various directions in which it might permanently locate itself, from the adhesions it is likely to make during the course of a surrounding inflammation, make the possible resulting pathological lesions almost numberless. Should a case be submitted to operation a very short time after the initial symptoms present themselves, the purpose of this paper would be eliminated, for nothing would be found but a displaced appendix adherent to the colon, ileum or retroperitoneum. Possibly when an anomaly takes place, an adhesion to surrounding organs might be found, and the operation or cure of the condition would consist simply in
Mucosal but not peripheral FOXP3+ regulatory T cells are highly increased in untreated HIV infection and normalize after suppressive HAART
Authors: Hans-Jörg Epple, Christoph Loddenkemper, Desirée Kunkel, Hanno Tröger, Jochen Maul, Verena Moos, Erika Berg, Reiner Ullrich, Jörg-Dieter Schulzke, Harald Stein, Rainer Duchmann, Martin Zeitz, Thomas Schneider
Journal: Blood (2006)
Outcomes of pregnancy in insulin dependent diabetic women: results of a five year population cohort study
Authors: I F Casson, C A Clarke, C V Howard, O McKendrick, S Pennycook, P O D Pharoah, M J Platt, M Stanisstreet, D van Velszen, S Walkinshaw
Journal: BMJ (1997)

<h3>Abstract</h3> <b>Objective:</b> To monitor pregnancies in women with pre-existent insulin dependent diabetes for pregnancy loss, congenital malformations, and fetal growth in a geographically defined area of north west England. <b>Design:</b> Population cohort study. <b>Setting:</b> 10 maternity units in Cheshire, Lancashire, and Merseyside which had no regional guidelines for the management of pregnancy in diabetic women. <b>Subjects:</b> 462 pregnancies in 355 women with insulin dependent diabetes from the 10 centres over five years (1990-4 inclusive). <b>Main outcome measures:</b> Numbers and rates of miscarriages, stillbirths, and neonatal and postneonatal deaths; prevalence of congenital malformations; birth weight in relation to gestational age. <b>Results:</b> Among 462 pregnancies, 351 (76%) resulted in a liveborn infant, 78 (17%) aborted spontaneously, nine (2%) resulted in stillbirth, and 24 (5%) were terminated. Of the terminations, nine were for congenital malformation. The stillbirth rate was 25.0/1000 total births (95% confidence interval 8.9 to 41.1) compared with a population rate of 5.0/1000, and infant mortality was 19.9/1000 live births (5.3 to 34.6) compared with 6.8/1000. The prevalence of congenital malformations was 94.0/1000 live births (63.5 to 124.5) compared with 9.7/1000 in the general population. When corrected for gestational age, mean birth weight in the sample was 1.3 standard deviations greater than that of infants of non-diabetic mothers. Infants with congenital malformations weighed less than those without. <b>Conclusion:</b> In an unselected population the infants of women with pre-existent insulin dependent diabetes mellitus have a 10-fold greater risk of a congenital malformation and a fivefold greater risk of being stillborn than infants in the general population. Further improvements in the management of pregnancy in diabetic women are needed if target of the St Vincent declaration of 1989 is to be met. <h3>Key messages</h3> Infants of women with established insulin dependent diabetes mellitus have 10 times the population risk of congenital malformations and five times the stillbirth rate Excess mortality among infants of women with pre-existent insulin dependent diabetes mellitus is predominantly due to congenital malformations The birth prevalence of congenital malformations can be reduced by good periconceptional glycaemic control, but the challenge remains to implement this on a population basis Macrosomia remains a problem among infants of women with established insulin dependent diabetes mellitus
Elevated phosphorylase kinase activity in psoriatic epidermis: correlation with increased phosphorylation and psoriatic activity
Authors: M.C.Y. HENG, M.K. SONG, M.K. HENG
Journal: British Journal of Dermatology (1994)

To determine whether abnormal activity of a calmodulin-containing enzyme which catalyses phosphorylation reactions may play a pathogenetic role in psoriasis, the presence and activity of phosphorylase kinase (PK) in human epidermis were determined in patients with untreated/active psoriasis (n = 10), treated/resolving psoriasis (n = 10), and non-psoriatic controls (n = 10). Biopsies were taken from involved and uninvolved skin for PK, organic phosphorus, and inorganic phosphate estimation, and light and electron microscopy. The enzyme was present in involved and uninvolved skin of every patient in the study. PK activity (units/mg protein) was significantly higher in active psoriasis than in resolving psoriasis and controls. PK activity correlated directly with organic phosphorus levels, and inversely with the extent of cellular glycogenolysis measured by the depletion of glycogen granules within the keratinocytes. The study demonstrates that PK is present in both psoriatic and normal epidermis, with significantly higher levels in active psoriasis. Furthermore, higher levels of PK activity, glycogenolysis and phosphorylation are associated with increased clinical psoriatic activity. We conclude that PK, a calmodulin-containing enzyme, is involved in regulating calcium-dependent phosphorylation events in human epidermis, and disturbance of its activity may play a key role in the clinical manifestations of psoriasis.
Health authority employing HIV positive dentist wins anonymity
Authors: C. Dyer
Journal: BMJ (2002)

An English health authority that has not contacted former patients of an HIV positive dentist nearly a year after it learned of his HIV status won an appeal court ruling last week barring the media from identifying it.

No decision has yet been taken on whether to get in touch with patients of the dentist, who has now developed AIDS and offer them HIV testing. Official guidelines under which patients of HIV positive health workers who perform invasive procedures are contacted and offered counselling and testing are about to be superseded by new guidance, but not until mid-March at the earliest.

Three appeal court judges, headed by the master of the rolls, Lord Phillips, set aside a ban on identifying the man's specialty but overturned a High Court ruling allowing the Mail on …
Abstract 1718: Favorable clinical outcomes of pemetrexed treatment in anaplastic lymphoma kinase positive non-small-cell lung cancer patients were associated with low expression of thymidylate synthase in tumor
Authors: Ha Yeon Lee, Hee Kyung Ahn, Ji Yun Jeong, Mi Jung Kwon, Jung-Ho Han, Jong-Mu Sun, Jin Seok Ahn, Keunchil Park, Joo-Young Cha, Yeoung-Mi Cho, Yoon-La Choi, Myung-Ju Ahn
Journal: Cancer Research (2012)

Abstract Introduction The purpose of this study was to investigate the clinical characteristics and treatment outcomes of patients with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) to conventional chemotherapy in the pre-ALK inhibitor era Patients and Methods We retrospectively screened 381 consecutive NSCLC patients without known epidermal growth factor receptor (EGFR) or KRAS mutation who were diagnosed between 2007 and 2008 at a single center, and identified ALK rearrangements by fluorescence in situ hybridization Additional 44 ALK-positive patients from other period were included for the analysis of clinical outcomes Results Of the 381 tumors screened, four were excluded because the samples were unevaluable Twenty-one (5 6%) showed ALK rearrangements, with twenty adenocarcinomas and one pleomorphic carcinoma Of the entire 65 ALK-positive patients, 32 patients received pemetrexed as a second- or further-line therapy, in whom response rate was 34 4% (11/32) and median progression-free survival (PFS) was 4 0 months Among these 31 patients, 20 specimens were available for thymidylate synthase (TS) expression analysis Low expression of TS were found in 80% (16/20), with a trend toward longer PFS than TS-positive patients (median PFS 4 0 vs 1 0 months, P = 0 095) Conclusions The prevalence of ALK rearrangement was 5 6% among EGFR and/or KRAS wild-type/unknown NSCLC population Low TS protein expression might be associated with better clinical outcomes in ALK-positive NSCLC patients after pemetrexed given as a second- or further-line therapy 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 1718. doi:1538-7445.AM2012-1718
Inhibition of internal ribosomal entry site-directed translation of HCV by recombinant IFN-α correlates with a reduced La protein
Authors: Takeo Shimazaki, Masao Honda, Shuichi Kaneko, Kenichi Kobayashi
Journal: Hepatology (2002)

Translation of the hepatitis C virus (HCV) polyprotein is mediated by an internal ribosome entry site (IRES) that is located within the 5'-nontranslated region (5'NTR). We investigated the effect of interferon alfa (IFN-alpha) on the IRES-directed translation of HCV, using two stably transformed cell lines, RCF-1 and RCF-26, of Huh7 cells derived from human hepatocellular carcinoma that express dicistronic reporter proteins, Renilla luciferase (RL) and firefly luciferase (FL), separated by HCV-IRES. After the administration of IFN-alpha or poly(I)-poly(C), HCV-IRES-directed translation was inhibited in a dose-dependent manner. The relative HCV-IRES activity (F/L) decreased to 60% at 5,000 IU/mL of IFN-alpha and 45% at 40 microg/mL of poly(I)-poly(C). Thus, IFN-alpha or poly(I)-poly(C) inhibited HCV-IRES-directed translation more efficiently than a cellular cap-dependent translation. 2',5'-oligoadenylate synthetase (2',5'AS) protein level in cells analyzed significantly increased after the administration of IFN-alpha, but not upon poly(I)-poly(C). Overexpression of double-stranded RNA-activated protein kinase (PKR) gene did not mimic the selective inhibition of HCV-IRES-directed translation in the transformant cells, suggesting that neither the 2',5'AS nor the PKR system are involved in this selective inhibition. Interestingly, the expression of the autoantigen, La, which has been reported to enhance HCV-IRES-directed translation, was significantly reduced after the administration of IFN-alpha and poly(I)-poly(C) in a dose-dependent manner. Transient expression of La protein completely restored the selective inhibition of HCV-IRES-directed translation by IFN-alpha and poly(I)-poly(C). These findings suggested a new antiviral mechanism induced by IFN-alpha in that IFN-alpha or poly(I)-poly(C) selectively inhibited HCV-IRES-directed translation compared with the eukaryotic cap-dependent translation through the reduction of La protein.
Natural history and classification of occlusive thromboaortopathy (Takayasu's disease).
Authors: K Ishikawa
Journal: Circulation (1978)

Fifty-four Japanese patients with occlusive thromboaortopathy (OTAP), including four males, were classified according to evidence of complications attributed to OTAP at the time when the diagnosis was established: Group I, uncomplicated OTAP with or without the involvement of the pulmonary artery. Group II, mono-complicated OTAP: presence of a single complication together with uncomplicated OTAP. Group II was subdivided according to severity into group IIa - mild or moderate form, and group IIb - severe form. Group III, multi-complicated OTAP with two or more complications as well as uncomplicated OTAP. The five-year survival rate after established diagnosis was 83.1%. Seven patients died of OTAP within five years, but all had belonged to group IIb or III.
Immunogenetics and the design of Plasmodium falciparum vaccines for use in malaria-endemic populations
Authors: Magdalena Plebanski, Owen Proudfoot, Dodie Pouniotis, Ross L. Coppel, Vasso Apostolopoulos, Graham Flannery
Journal: Journal of Clinical Investigation (2002)

There are about 500,000,000 cases of clinical malaria of varying severity per year. Some 2 million deaths per year result, almost all of which occur in children living in sub-Saharan Africa and are due to Plasmodium falciparum infection (1). Optimism stemming from the development of vaccines that show some protection against malaria in animals and in malaria-naive humans challenged with laboratory strains of P. falciparum has been dampened by their failure to provide significant, long-lasting protection to individuals living in regions where the disease is endemic. One consequence of the great number of deaths in young children is that malaria has exerted an almost unparalleled selective pressure on humans, leading to the appearance of gene polymorphisms at high frequency, including some for lethal hemoglobinopathies (2). Polymorphic forms of a number of host genes involved in immunity have been associated with protection or susceptibility to malaria. These are likely to predispose populations to unique immune response patterns to vaccines, which may enhance or interfere with their efficacy. Here, we consider some recent findings on host diversity, particularly of gene products involved in immunity. We then discuss the results from recent human vaccine trials, as well as potential strategies to optimize vaccines for use in malaria-endemic areas.

Immunity to malaria is quite complex and still not completely understood. The cellular arm of the immune system is considered more important in controlling liver-stage infections, although antibodies contribute to protection; humoral immune mechanisms may be more important in controlling the blood stages. The role of other immune system components is not as well defined, but an involvement in resistance to malaria is often inferred where a particular polymorphism is common in individuals living in malaria-endemic areas. Genes that have come under specific scrutiny include those for components of the innate and acquired immune systems: mannose-binding protein (MBP), inducible nitric oxide synthase (iNOS), Fc receptors, cytokines and cytokine receptors, and the class I and class II MHC molecules.
Trusts need not wait for NICE appraisal in planning for new drugs, NHS centre says
Authors: C. White
Journal: BMJ (2010)

Primary care trusts and specialist commissioners in England should plan ahead for newly licensed drugs, irrespective of whether the National Institute for Health and Clinical Excellence (NICE) has evaluated their cost and clinical effectiveness, says the NHS National Prescribing Centre.

In the first of its Tough Decisions newsletters, designed to improve local decision making on the funding and commissioning of drugs, the centre lists several new drugs that it thinks patients and doctors are likely to want. These include two oral treatments for multiple sclerosis, cladribine and fingolimod, and two drugs for chronic obstructive pulmonary …
THE TREATMENT OF ACUTE GONORRHEA WITH ANTISEPTICS IN GELATIN
Authors: RUSSELL D. HERROLD
Journal: JAMA (1927)

Acute gonorrhea is a generalized inflammation of the mucous membrane of the anterior urethra resulting from the presence of gonococci and the toxic products. The degree of the extension to the posterior urethra or deep into the submucous tissues of the anterior urethra varies directly with the successful control during the early stages of the infection. Various percentages of the extension into the posterior urethra are given by different authors, but it is stated in many text-books on gonorrhea that as high as 75 per cent become posterior. It is doubtful whether such a high proportion become posterior in the present experience of urologists, but in our observations previous to the use of the present method, it seemed highly frequent. It is generally realized that the organotropic index of a drug must be considered as well as the gonococcidal index in determining the fitness of the drug for local treatment.
Magnetic-Resonance-Based Electrical Properties Tomography: A Review
Authors: None Xiaotong Zhang, None Jiaen Liu, None Bin He
Journal: IEEE Reviews in Biomedical Engineering (2014)

Frequency-dependent electrical properties (EPs; conductivity and permittivity) of biological tissues provide important diagnostic information (e.g., tumor characterization), and also play an important role in quantifying radiofrequency (RF) coil induced specific absorption rate (SAR), which is a major safety concern in high- and ultrahigh-field magnetic resonance imaging (MRI) applications. Cross-sectional imaging of EPs has been pursued for decades. Recently introduced electrical properties tomography (EPT) approaches utilize the measurable RF magnetic field induced by the RF coil in an MRI system to quantitatively reconstruct the EP distribution in vivo and noninvasively with a spatial resolution of a few millimeters or less. This paper reviews the EPT approach from its basic theory in electromagnetism to the state-of-the-art research outcomes. Emphasizing on the imaging reconstruction methods rather than experimentation techniques, we review the developed imaging algorithms, validation results in physical phantoms and biological tissues, as well as their applications in in vivo tumor detection and subject-specific SAR prediction. Challenges for future research are also discussed.
Cell adhesion induces p27Kip1-associated cell-cycle arrest through down-regulation of the SCFSkp2 ubiquitin ligase pathway in mantle-cell and other non-Hodgkin B-cell lymphomas
Authors: Tint Lwin, Lori A. Hazlehurst, Sophie Dessureault, Raymond Lai, Wenlong Bai, Eduardo Sotomayor, Lynn C. Moscinski, William S. Dalton, Jianguo Tao
Journal: Blood (2007)
Hydronephrosis in Infants and Children
Authors: Aurelio C. Uson
Journal: JAMA (1968)

From 1935 through 1965, 91 pyeloplasties and 45 nephrectomies were performed upon 126 infants or children with hydronephroses. In 27, nephrostomy was done before nephrectomy or pyeloplasty. Several children underwent unilateral nephrectomy and pyeloplasty on the opposite kidney; a few had bilateral pyeloplasties. Of the 126 children who underwent surgery for hydronephrosis, a total of 184 surgical procedures was necessary to excise or correct the hydronephrosis, as well as concomitant urological anomalies. "Splinting" catheters and nephrostomy or pyelostomy drainage tubes were used in almost all our pyeloplasties. The results of pyeloplasty have been good in children with grade 1 (mild) and grade 2 (moderate) hydronephrosis, and only fair in those with grade 3 (severe) hydronephrosis. Complications and failures occurred principally from 1935 to 1945. No surgical deaths, after pyeloplasty, ensued in the entire series.