tbuckley/cabot-search huggingface dataset:
Heparan sulfate proteoglycans: heavy hitters in the angiogenesis arena
Authors: Renato V. Iozzo, James D. San Antonio
Journal: Journal of Clinical Investigation (2001)

Without new blood vessels, neoplasms cannot expand beyond a few millimeters, the point at which the diffusion of nutrients and the disposal of waste products become rate-limiting. Regulation of angiogenesis thus must be controlled at multiple levels. For instance, the VEGF family of heparin-binding proteins and their primary receptors, VEGFR-1 and VEGFR-2 (KDR), products of the flt-1 and the flk-1 gene, respectively, are required for angioblast differentiation and vasculogenesis, and specific VEGF isoforms play distinct roles in promoting endothelial growth and migration during angiogenesis. In addition, angiogenesis is profoundly affected by several members of the FGF family and their four receptors, and indeed, supplementing the media of endothelial cell cultures with basic FGF (FGF2) and heparin is now well established as a means to obtain optimal growth, migration, and capillary morphogenesis. In addition to producing proangiogenic factors, tumor cells also directly or indirectly generate negative angiogenic stimuli. The ultimate growth rate of the tumors is thus a fine balance between positive and negative angiogenic cues.
General practitioner obstetrics in the Northern region in 1983.
Authors: G N Marsh, H A Cashman, I T Russell
Journal: BMJ (1985)

In late 1983 a four page questionnaire on general practitioner obstetrics was sent to a 50% random sample of general practitioners in the Northern region of England; 84% responded. Half of them said that they had access to general practitioner facilities for delivery, and half of these used them. A quarter of all respondents had provided intranatal care previously but had given it up, most of them during the late 1970s. Younger general practitioners were more highly qualified in obstetrics than older ones but did not do more intranatal work. Isolated general practitioner maternity units were much more likely to be used than those that were alongside consultant units or integrated with them. Ninety per cent of respondents provided antenatal care, 77% of these at special clinics and 88% with midwives in attendance. Teamwork, however, was not well developed. Increasing general practitioner participation in obstetric care seems feasible but depends heavily on more appropriate training and intranatal facilities being provided for general practitioners in association with specialist units.
Essentials of Toxicology
Authors: Jay M. Arena
Journal: JAMA (1968)

This basic science text presents the various biological and chemical factors that are involved when chemicals produce harmful effects on biological cells, systems, or whole animals. Dr. Loomis draws upon his experience as a practicing toxicologist and professor of pharmacology to identify and describe the causes and mechanisms in chemical-induced toxicity. He discusses, among other topics, mechanisms in the translocation of chemicals within the biological specimen; biotransformation mechanisms which alter structure, pharmacological action, and toxicity; factors responsible for nonselective as well as selective action of chemicals on various biological specimens; genetic and immunologic mechanisms involved in toxicity; the merits and deficiencies of the use of statistics in evaluating of harmful effects of chemicals. <i>Essentials of Toxicology</i>is a valuable general source of information on the modern concepts of toxicity from chemicals.
How many whole time equivalents rather than heads in the NHS?
Authors: Anthea J Sherwood
Journal: BMJ (2006)

How much will Herceptin really cost? Balancing local and national priorities is not newEditor-Herceptin for early stage breast cancer is a cost effective treatment, and it is right that the NHS should make it available.The challenge of funding new treatments and balancing local and national priorities is one the NHS has faced since its inception. 1 The process the National Institute for Health and Clinical Excellence (NICE) follows for evaluating new medicines is the most rigorous anywhere in the world, and local NHS organisations can have confidence that implementing our recommendations is an effective use of their resources.NICE's independent advisory committees do not rubber stamp decisions.They make them based on an objective and impartial interpretation of the evidence.Those who suggest otherwise should come forward with their evidence for doing so.It is wrong to suggest that a single recommendation from NICE will necessarily cause other services to be reduced and that these decisions are made by clinicians only.Many demands are made on available funds in any hospital at any one time and it is the responsibility of local NHS management, working with their clinical teams, to make the best use of these resources.This difficult job is made easier by NICE guidance and the support tools we offer, such as our commissioning guides and our forthcoming advice on shifting spending from less to more effective treatments.
Experiences with Policing among People Who Inject Drugs in Bangkok, Thailand: A Qualitative Study
Authors: Kanna Hayashi, Will Small, Joanne Csete, Sattara Hattirat, Thomas Kerr
Journal: PLoS Medicine (2013)

Background Despite Thailand's commitment to treating people who use drugs as “patients” not “criminals,” Thai authorities continue to emphasize criminal law enforcement for drug control. In 2003, Thailand's drug war received international criticism due to extensive human rights violations. However, few studies have since investigated the impact of policing on drug-using populations. Therefore, we sought to examine experiences with policing among people who inject drugs (PWID) in Bangkok, Thailand, between 2008 and 2012. Methods and Findings Between July 2011 and June 2012, semi-structured, in-depth interviews were conducted with 42 community-recruited PWID participating in the Mitsampan Community Research Project in Bangkok. Interviews explored PWID's encounters with police during the past three years. Audio-recorded interviews were transcribed verbatim, and a thematic analysis was conducted to document the character of PWID's experiences with police. Respondents indicated that policing activities had noticeably intensified since rapid urine toxicology screening became available to police. Respondents reported various forms of police misconduct, including false accusations, coercion of confessions, excessive use of force, and extortion of money. However, respondents were reluctant to report misconduct to the authorities in the face of social and structural barriers to seeking justice. Respondents' strategies to avoid police impeded access to health care and facilitated transitions towards the misuse of prescribed pharmaceuticals. The study's limitations relate to the transferability of the findings, including the potential biases associated with the small convenience sample. Conclusions This study suggests that policing in Bangkok has involved injustices, human rights abuses, and corruption, and policing practices in this setting appeared to have increased PWID's vulnerability to poor health through various pathways. Novel to this study are findings pertaining to the use of urine drug testing by police, which highlight the potential for widespread abuse of this emerging technology. These findings raise concern about ongoing policing practices in this setting. Please see later in the article for the Editors' Summary
Limitation of myocardial infarct size in the rabbit by ischaemic preconditioning is abolished by sodium 5-hydroxydecanoate
Authors: E. J Hide, C. Thiemermann
Journal: Cardiovascular Research (1996)

Objective: To investigate the effect of the ATP-sensitive potassium (KATP) channel inhibitor sodium 5-hydroxydecanoate (5-HD) on the reduction in myocardial infarct size afforded by ischaemic preconditioning in the sodium pentobarbitone anaesthetised rabbit. Methods: New Zealand white rabbits were anaesthetised with sodium pentobarbitone and subjected to 60 min occlusion of the first antero-lateral branch of the left coronary artery (LAL) followed by 120 min reperfusion. Ischaemic preconditioning was achieved by a single episode of 5 min LAL occlusion followed by 15 min reperfusion prior to the 60 min occlusion. 5-HD (5 mg kg−1), an ischaemia selective KATP channel inhibitor, was administered into the left ventricle as a bolus injection 10 min prior to the onset of ischaemic preconditioning. Injection of Evans blue dye was used to determine the area of the left ventricle at risk and infarct size was determined by incubation of the area at risk with nitro-blue tetrazolium. Results: There were no significant differences between groups in haemodynamics or area at risk. Ischaemic preconditioning resulted in a significant reduction in infarct size (27 ± 8%) when compared to control animals (55 ± 3%; P < 0.05). Pretreatment of animals with 5-HD completely abolished the cardioprotection seen with ischaemic preconditioning (50 ± 6%). Conclusion: These results support the hypothesis that the cardioprotection afforded by ischaemic preconditioning in the pentabarbitone anaesthetised rabbit is dependent on the opening of KATP channels.
Burn Information Exchange
Authors: Burton A. Waisbren
Journal: JAMA (1976)

The article by Feller et al of the National Burn Information Exchange (NBIE) is an important contribution to burn literature (p 1943). It clearly demonstrates that the current problem in burn therapy is to determine why some burn centers are achieving results that are so much better than those achieved by others. The article also sets a standard by which hospitals admitting large numbers of burn patients can rate themselves. The surprising differences demonstrated among ten of the leading burn centers in this country is that in three of them, a patient with a 41% combined second- and third-degree burn will have a chance of death over 50%, while in three other burn centers, presumably the same patient would have to have a burn of 64% to have the same chance of death. The NBIE is actively pursuing the reasons for this wide discrepancy in the results of therapy at
Winning counterterrorism's version of Pascal's wager, but struggling to open the purse
Authors: Brian J. Gibbs
Journal: Behavioral and Brain Sciences (2014)

Abstract Lankford's essential empirical argument, which is based on evidence such as psychological autopsies, is that suicide attacks are caused by suicidality. By operationalizing this causal claim in a hypothetical experiment, I show the claim to be provable, and I contend that its truth is supported by Lankford's data. However, I question his ensuing arguments about beauty and goodness, and thereby the practical value of his work in counterterrorist propaganda.
Abstract P94: Impact of Percutaneous Coronary Intervention and Mild Hypothermia Therapy for Patients With Out-of-hospital Cardiac Arrest of Acute Coronary Syndrome From Multicenter Hypothermia Registry in Japan
Authors: Shinichi Shirai, Tatsuki Doijiri, Ken Nagao, Naohiro Yonemoto, Hiroyuki Yokoyama, Hiroshi Nonogi
Journal: Circulation (2009)
A prospective, randomized controlled trial of transjugular intrahepatic portosystemic shunt versus cyanoacrylate injection in the prevention of gastric variceal rebleeding
Authors: G.-H. Lo, H.-L. Liang, W.-C. Chen, M.-H. Chen, K.-H. Lai, P.-I. Hsu, C.-K. Lin, H.-H. Chan, H.-B. Pan
Journal: Endoscopy (2007)

See also: Commentaire de travail de G.-H. Lo et al., pp. 679Endoscopy 2007; 39(08): 844-844DOI: 10.1055/s-0032-1306965
Myocardial function in normal and spontaneously hypertensive rats during reperfusion after a period of global ischaemia
Authors: L H E H SNOECKX, G J VAN DER VUSSE, W A COUMANS, P H M WILLEMSEN, T VAN DER NAGEL, R S RENEMAN
Journal: Cardiovascular Research (1986)

Isolated working hearts of 16 month old spontaneously hypertensive rats (SHR, n = 8) and age matched Wistar-Kyoto (WKY, n = 8) rats were exposed to 30 min global normothermic ischaemia followed by 60 min reperfusion. The hearts were routinely perfused at an afterload level of 13.3 kPa and a preload level of 1.0 kPa. The control values of left ventricular pressure, its maximal positive first derivative (dP1v/dtmax), coronary flow per gram heart tissue, and release of lactate and enzymes such as lactate dehydrogenase and aspartate aminotransferase were comparable in both groups. WKY rat hearts ejected almost twice as much perfusate per gram heart weight as the SHR hearts. In pressure-flow curves, obtained during the control period in SHR hearts, cardiac output was independent of changes in afterload, varying between 10.7 and 18.7 kPa. In contrast, in WKY rat hearts increases in afterload resulted in a progressive decrease in cardiac output. Reperfusion of the SHR hearts after 30 min of global normothermic ischaemia resulted in a poor recovery of cardiac output (13% of the control values) and dP1v/dtmax (32%) compared with the values in the WKY rat hearts (66% and 91% of the control values respectively). Reactive hyperaemia was prominent in the WKY rat hearts but completely absent in the SHR hearts. During one hour reperfusion, SHR hearts lost 3.5 times more lactate dehydrogenase and 2.5 times more aspartate aminotransferase than the WKY rat hearts. Pressure-flow curves, obtained during the reperfusion period, showed modest recovery of myocardial function of the WKY rat hearts at the lowest afterload level tested but completely depressed myocardial function of the SHR hearts at all afterload levels. Heart tissue contents of adenosine triphosphate and creatine phosphate after one hour of reperfusion were lower in the SHR than in the WKY rats, but compared with native values a comparable percentage decrease was seen in both groups of rats.
Cell‐mediated immune‐pancytopenia complicating primary sjögren's syndrome
Authors: Takeshi Seki, Kendo Kiyosawa, Satoshi Monno, Yasuharu Imai, Kenichi Furukawa, Shigeyuki Kumazawa, Masao Ota, Hiroshi Saito, Seiichi Furuta, Tatsutoshi Nakahata
Journal: American Journal of Hematology (1993)

Abstract A 64‐year‐old woman with mild bilateral parotid gland swelling and bilateral lower extremity purpura was admitted for evaluation of xerostomia and pancytopenia. The patient had an increased erythrocyte sedimentation rate, pancytopenia, and positive tests for antibodies to nuclear antigen, SS‐A, and SS‐B. Impaired cell‐mediated immunity was also present. Bone marrow aspiration showed a hypoplastic marrow with an increased percentage of lymphocytes. A positive Schirmer's test and keratoconjunctivitis were also noted. A diagnosis of primary Sjögren's syndrome was made by sialography and histological salivary gland findings. Therapy with prednisolone improved the pancytopenia. Addition of the patient's peripheral blood mononuclear cells to cultures of bone marrow mononuclear cells derived from a healthy volunteer dose dependently inhibited colony formation, including mixed hemopoietic colonies. On the other hand, addition of the patient's serum failed to inhibit colony formation by normal bone marrow mononuclear cells. These results suggested that one of the causes of pancytopenia in primary Sjögren's syndrome might be mediated by the inhibition of mononuclear cells to the hemopoietic progenitors.
Induction of ovulation after GnRH antagonists
Authors: R. Ron-El
Journal: Human Reproduction Update (2000)

The gonadotrophin-releasing hormone (GnRH) antagonist binds competitively to the receptors and thereby prevents endogenous GnRH from exerting its stimulatory effect on the pituitary cells. This causes suppression of gonadotrophin secretion which occurs immediately after administration of the antagonist. When using GnRH antagonist in controlled ovarian stimulation, ovulation or maturation of the oocyte can, therefore, be induced by a variety of drugs, e.g. native GnRH, recombinant LH or short-acting GnRH agonists. Short-acting GnRH agonists were recommended for triggering ovulation in cases with a high risk of developing ovarian hyperstimulation syndrome (OHSS). Since it is evident that GnRH is required to initiate the LH surge and the oestradiol rise, a single administration of GnRH antagonist during the late follicular phase delays the LH surge. Studies showed that a single s.c. administration of 3 or 5 mg of Cetrorelix in the late follicular stage was sufficient to prevent the LH surge for 6--17 days. This phenomenon can be used in high responder patients who are prone to OHSS. The question whether this delay has any effect on oocyte quality and maturation still remains unanswered. Overall, there are four uses for GnRH antagonist: (i) using short-acting GnRH agonists for triggering ovulation in cases in which the GnRH antagonist is part of the protocol for ovarian stimulation. Recombinant LH and native LHRH could also be used as triggers of LH surge; (ii) delaying the LH surge in cases prone to OHSS by treatment with GnRH antagonist; (iii) to administer GnRH antagonist during the luteal phase to decrease the activity of corpora lutea; (iv) in polycystic ovarian disease with elevated LH the LH/FSH ratio can be corrected with the injection of GnRH antagonist prior to and during ovarian stimulation.
IPRONIAZID CHEMOTHERAPY IN MELANCHOLIA
Authors: THEODORE R. ROBIE
Journal: American Journal of Psychiatry (1958)

1. Chemotherapeutic remission of melancholia can now be accomplished, in a majority of cases, without resort to ECT, by carefully supervised administration of Marsilid, Roche iproniazid (1-isonicotinyl, 2-isopropylhydrazine phosphate). 2. However, until methods are discovered for accelerating Marsilid's effectiveness in the first few days of treatment, the aggressively suicidal case must still be given ECT, which assures most immediate remission of depression. Each case must be carefully evaluated when first seen. 3. This chemical, introduced 6 years ago for the treatment of tuberculosis, is now found to possess much wider scope in medicine including therapeutic efficacy in some apathetic and withdrawn, seclusive types. 4. A major factor in the effectiveness of this chemical in accomplishing psychic energization is the prevention of inactivation of the brain-stored powerful hormone serotonin, by its amine oxidase inhibitor action, but other equally powerful chemical Interactions may be simultaneously involved. 5. The powerful chemical forces released may Induce serious complications unless the physician psychiatrist is constantly alert to the need for frequent alteration of dosage as indicated by his physical findings. 6. Excellent antidotes for certain complications are available. 7. A by-product of major significance is the enhancement of psychotherapy through increased spontaneity, improved sense of well being and resulting betterment of rapport.
Emergency doctors call for more patients to be diverted from A&E to general practice
Authors: I. Torjesen
Journal: BMJ (2013)

Too many patients are seeing emergency departments as an alternative to primary care and need to be diverted back to GP services, the College of Emergency Medicine has told a government review into urgent and emergency care.

In a written submission to the review of urgent and emergency care services being led by the NHS’s medical director, Bruce Keogh,1 the college said that too many patients were turning up at emergency departments when they did not need to be there and could be treated more cost efficiently by other services.2

Between 2011-2012 and 2012-2013 the number of people attending emergency departments rose by 250 000, and the college attributes much of this rise to increasing patient expectations and …
High Residual Platelet Reactivity After Clopidogrel Loading and Long-term Cardiovascular Events Among Patients With Acute Coronary Syndromes Undergoing PCI
Authors: Guido Parodi, Rossella Marcucci, Renato Valenti, Anna Maria Gori, Angela Migliorini, Betti Giusti, Piergiovanni Buonamici, Gian Franco Gensini, Rosanna Abbate, David Antoniucci
Journal: JAMA (2011)

High residual platelet reactivity (HRPR) in patients receiving clopidogrel has been associated with high risk of ischemic events after percutaneous coronary intervention (PCI).To test the hypothesis that HRPR after clopidogrel loading is an independent prognostic marker of risk of long-term thrombotic events in patients with acute coronary syndromes (ACS) undergoing an invasive procedure and antithrombotic treatment adjusted according to the results of platelet function tests.Prospective, observational, referral center cohort study of 1789 consecutive patients with ACS undergoing PCI from April 2005 to April 2009 at the Division of Cardiology of Careggi Hospital, Florence, Italy, in whom platelet reactivity was prospectively assessed by light transmittance aggregometry.All patients received 325 mg of aspirin and a loading dose of 600 mg of clopidogrel followed by a maintenance dosage of 325 mg/d of aspirin and 75 mg/d of clopidogrel for at least 6 months. Patients with HRPR as assessed by adenosine diphosphate test (≥70% platelet aggregation) received an increased dose of clopidogrel (150-300 mg/d) or switched to ticlopidine (500-1000 mg/d) under adenosine diphosphate test guidance.The primary end point was a composite of cardiac death, myocardial infarction, any urgent coronary revascularization, and stroke at 2-year follow-up. Secondary end points were stent thrombosis and each component of the primary end point.The primary end point event rate was 14.6% (36/247) in patients with HRPR and 8.7% (132/1525) in patients with low residual platelet reactivity (absolute risk increase, 5.9%; 95% CI, 1.6%-11.1%; P = .003). Stent thrombosis was higher in the HRPR group compared with the low residual platelet reactivity group (6.1% [15/247] vs 2.9% [44/1525]; absolute risk increase, 3.2%; 95% CI, 0.4%-6.7%; P = .01). By multivariable analysis, HRPR was independently associated with the primary end point (hazard ratio, 1.49; 95% CI, 1.08-2.05; P = .02) and with cardiac mortality (hazard ratio, 1.81; 95% CI, 1.18-2.76; P = .006).Among patients receiving platelet reactivity-guided antithrombotic medication after PCI, HRPR status was significantly associated with increased risk of ischemic events at short- and long-term follow-up.clinicaltrials.gov Identifier: NCT01231035.
Alterations of the PPP2R1B gene located at 11q23 in human colorectal cancers
Authors: Y Takagi
Journal: Gut (2000)

In 1998 the PPP2R1B gene encoding the A subunit of the serine/threonine protein phosphatase was identified as a putative tumour suppressor gene in lung and colon cancer in the chromosome region 11q22-24. The aim of the present study was to determine the type of alterations in primary rectal cancers as well as colon cancers and the correlation between these alterations and clinicopathological data.Mutation analyses of the PPP2R1B gene sequence encoding the binding sites of the catalytic C subunit (Huntington elongation A subunit TOR (HEAT) repeats 11-15) and partial binding sites of the regulatory B subunit were carried out on cDNA samples from 30 primary colorectal cancer specimens and corresponding normal tissues using a combination of the polymerase chain reaction and subsequent direct DNA sequencing.Five missense mutations producing amino acid substitutions were detected in the four colon cancer cases (13.3%; four of 30 colorectal cancers): (15)glycine (GGT) to alanine (GCT) and (499)leucine (TTA) to isoleucine (ATA) in the same case, and (498)valine (GTG) to glutamic acid (GAG), (500)valine (GTA) to glycine (GGA), and (365)serine (TCT) to proline (CCT). Of these five mutations, three (60%) were located in HEAT repeat 13 and four (80%) showed T to other nucleotide substitutions. In addition, a normal polymorphism, (478)leucine, was found. No correlation was found between these mutations and clinicopathological data.Our results suggest that the PPP2R1B gene is one of the true targets at 11q23, and its inactivation is involved in the development of all types of colorectal cancers.