tbuckley/cabot-search huggingface dataset:
THE ASSOCIATION BETWEEN VON WILLEBRAND FACTOR, CORONARY PLAQUE BURDEN ON INTRAVASCULAR ULTRASOUND AND CARDIOVASCULAR OUTCOME IN PATIENTS UNDERGOING CORONARY ANGIOGRAPHY
Authors: Jin M. Cheng, Michelle Sonneveld, Rohit Oemrawsingh, Moniek De Maat, Isabella Kardys, Hector Garcia Garcia, Robert van Geuns, Patrick Serruys, Eric Boersma, Martijn Akkerhuis, Frank Leebeek
Journal: Journal of the American College of Cardiology (2014)
Recent advances: Ophthalmology
Authors: A. R Fielder, C. Bentley, M. J Moseley
Journal: BMJ (1999)

When pondering recent advances in any clinical discipline there is a tendency to focus on new techniques, drugs, surgical instruments, and at the most fundamental level, on molecular biology. This article is no exception, as progress in all these spheres is essential if headway is to be made. But we are all also aware that new surgical tools quite soon become tarnished, replaced, and even forgotten. We have therefore included topics where the “advance” has served to highlight how little we know rather than how much progress has been made. We hope these finding will soon affect clinical practice. 


Summary points


Several new topical drugs have been developed for open angle glaucoma which can be used alone or in combination


Outcome of glaucoma surgery can be improved in high risk patients by topically applied antimetabolites


Endoscopic devices permit direct visualisation for many intraocular and extraocular surgical procedures


Early exposure to light is not a factor in the development of retinopathy of prematurity


Effectiveness of the standard treatment of amblyopia has been called into question


Many visually impaired elderly people in the community are unidentified and do not get treatment or support


Guidelines are available on breaking the news of a child’s visual impairment to parents








Methods
This review is not systematic but a pot pourri of topics identified with the rationale stated in the introduction in mind. Although we did not do a detailed critical appraisal of all cited publications, most of the reported findings remain uncontroversial. Where this is not so, we refer to any ongoing debate.
Abstract 696: Development of selective CDK8 inhibitors for colorectal cancer and mantle cell lymphoma treatment.
Authors: Tomasz Rzymski, Adrian Zarebski, Renata Windak, Karolina Krawczynska, Ewa Trebacz, Agnieszka Dreas, Katarzyna Kucwaj, Karolina Osowska, Marek Cholody, Paulina Szczepanska, Jakub Woyciechowski, Radosław Obuchowicz, Magdalena Salwińska, Joanna Fogt, Malgorzata Zurawska, Arkadiusz Białas, Katarzyna Wiklik, Mariusz Milik, Angelo Sanzone, Adam Radzimierski, Krzysztof Brzózka
Journal: Cancer Research (2013)

Abstract CDK8 is a kinase component of the mediator complex which functions as a bridge between a basal transcriptional machinery and specific transcription factors. CDK8 is amplified and differentially expressed in colorectal cancer and in certain hematological malignancies such as mantle cell lymphomas. Cells that express elevated CDK8 levels are highly dependent on its expression for proliferation. Here we report development of first-in-class selective inhibitors CDK8. Compounds from the SEL120 series have binding affinities towards CDK8 in the low nM range. Results from the kinome panel indicated that selectivity of SEL120 compounds was comparable with some of the most selective clinical kinase inhibitors. SEL120 compounds reduced viability of mantle cell lymphoma and colorectal cancer cell lines, with particularly good activity in cell lines overexpressing CDK8 and with G13D mutation in KRAS. Slightly lower sensitivity was observed for cells with mutated P53 and other mutations in KRAS/BRAF pathway. In contrast to pan-CDK inhibitors with main target activity on CDK9, treatment with SEL120 compounds did not repress phosphorylation of PolII and did not cause global transcriptional shutdown. Selective inhibition of CDK8 was sufficient to inhibit both paracrine and autocrine activities of cancer cells and stimulated normal cells. Production of proinflammatory cytokines, such as IL6 was repressed by SEL120 compounds in normal and cancer cells stimulated by sub-optimal doses of chemotherapeutics. SEL120 also reduced both murine and human IL6 in blood of mice bearing human xenograft models. Oral administration of SEL120 revealed favorable pharmacokinetics profile and strong, dose dependent potency in colon cancer mouse xenograft models. Presented data validate inhibition of CDK8 as a promising strategy for anticancer treatment, particularly for CRC and mantle cell lymphomas resistant to current treatments. Citation Format: Tomasz Rzymski, Adrian Zarebski, Renata Windak, Karolina Krawczynska, Ewa Trebacz, Agnieszka Dreas, Katarzyna Kucwaj, Karolina Osowska, Marek Cholody, Paulina Szczepanska, Jakub Woyciechowski, Radosław Obuchowicz, Magdalena Salwińska, Joanna Fogt, Malgorzata Zurawska, Arkadiusz Białas, Katarzyna Wiklik, Mariusz Milik, Angelo Sanzone, Adam Radzimierski, Krzysztof Brzózka. Development of selective CDK8 inhibitors for colorectal cancer and mantle cell lymphoma treatment. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 696. doi:10.1158/1538-7445.AM2013-696
Serum pyridoxal in patients with gastric pathology.
Authors: C R Sanderson, R E Davis
Journal: Gut (1976)

Fasting serum pyridoxal was assayed by an automated microbiological system in 60 patients investigated for dyspepsia, patients with active peptic ulceration being excluded from the study. Gastritis was present in 30 patients, gastric carcinoma in 16, six patients had benign polyps, and, in eight patients, radiology, endoscopy, and biopsy failed to shown any abnormality. Of the 52 patients with gastric pathology, 44 had a low serum pyridoxal.
Variation of Plasma Electrolyte and Total Protein Levels in the Individual
Authors: J. K. Fawcett, V. Wynn
Journal: BMJ (1956)

An attempt has been made to sift some of the clinical experience from 155 consecutive cases of persistent ductus arteriosus.The results of surgery in 138 of these cases are presented briefly, together with the management of the 17 not submitted to operation.Experience is dis- cussed and present policies are outlined in dealing with this abnormality in children and adults and when it is complicated by pulmonary hypertension and bacterial endarteritis.We thank our colleagues in the cardio-surgical unit for permis- sion to present this work.The operations were performed by Mr. Douglas Robb and one of us (R. N.).
Changes in Association between Previous Therapeutic Abortion and Preterm Birth in Scotland, 1980 to 2008: A Historical Cohort Study
Authors: Clare Oliver-Williams, Michael Fleming, Kirsten Monteath, Angela M. Wood, Gordon C. S. Smith
Journal: PLoS Medicine (2013)

Background Numerous studies have demonstrated that therapeutic termination of pregnancy (abortion) is associated with an increased risk of subsequent preterm birth. However, the literature is inconsistent, and methods of abortion have changed dramatically over the last 30 years. We hypothesized that the association between previous abortion and the risk of preterm first birth changed in Scotland between 1 January 1980 and 31 December 2008. Methods and Findings We studied linked Scottish national databases of births and perinatal deaths. We analysed the risk of preterm birth in relation to the number of previous abortions in 732,719 first births (≥24 wk), adjusting for maternal characteristics. The risk (adjusted odds ratio [95% CI]) of preterm birth was modelled using logistic regression, and associations were expressed for a one-unit increase in the number of previous abortions. Previous abortion was associated with an increased risk of preterm birth (1.12 [1.09–1.16]). When analysed by year of delivery, the association was strongest in 1980–1983 (1.32 [1.21–1.43]), progressively declined between 1984 and 1999, and was no longer apparent in 2000–2003 (0.98 [0.91–1.05]) or 2004–2008 (1.02 [0.95–1.09]). A statistical test for interaction between previous abortion and year was highly statistically significant (p<0.001). Analysis of data for abortions among nulliparous women in Scotland 1992–2008 demonstrated that the proportion that were surgical without use of cervical pre-treatment decreased from 31% to 0.4%, and that the proportion of medical abortions increased from 18% to 68%. Conclusions Previous abortion was a risk factor for spontaneous preterm birth in Scotland in the 1980s and 1990s, but the association progressively weakened and disappeared altogether by 2000. These changes were paralleled by increasing use of medical abortion and cervical pre-treatment prior to surgical abortion. Although it is plausible that the two trends were related, we could not test this directly as the data on the method of prior abortions were not linked to individuals in the cohort. However, we speculate that modernising abortion methods may be an effective long-term strategy to reduce global rates of preterm birth. Please see later in the article for the Editors' Summary
Handbook of Practical Urology
Authors: Bernard R. Sears
Journal: JAMA (1965)

Experience shows that the first lessons learned are the ones that take deepest root. Consequently, this book for house officers has immense possibilities. Dr. Hirschhorn designed his text as an illustrated "practical working manual of selected material." House officers will find this book so useful that inevitably they will demand new editions of greater scope: more topics and more detail. Here are some examples. The section on emergencies should have a chapter on septicemia and septic shock, one of the gravest of urologicemergencies. The discussion of nephrostomy drainage should consider the different requirements of temporary versus permanent drainage, a large tube being important for the latter since the fistula sometimes contracts. What size tubes are recommended? How long before a stable fistula forms around the tube so that it can be safely changed? Similarly, "when the bladder has a small laceration," urethral catheter drainage can suffice and one should "follow
Climate change could stretch health systems to breaking point, European Commission says
Authors: R. Watson
Journal: BMJ (2009)

The European Commission warned this week that although climate change may not create many new or unknown health threats, it might increase demands on health systems to such an extent that their capacities would be unable to handle the extra pressure.

In an 18 page policy paper that emphasises the need for the health sector to prepare for climate change, the commission notes, “It may also interfere with their ability to cope with demand by undermining infrastructures, technology, and the availability of the workforce.”

Climate change, it says, will affect human health …
627. Adenoviral-Mediated Systemic Transduction of the Angiotensin II (Ang II) Type 2 Receptor (AT2R) Enhances the Hypotensive Action of Losartan
Authors: Hongwei Li, Yongxin Gao, Justin Grobe, Mohan Raizada, Michael Katovich, Colin Sumners
Journal: Molecular Therapy (2005)

The Ang II type 1 receptor antagonist losartan (LOS) is an effective and specific antihypertensive agent. It has been suggested that a greater beneficial action of LOS may be obtained by co-stimulation of AT2R, which appear to mediate vasodilatory and blood pressure (BP) lowering effects of Ang II. Our overall objective in the present study was to investigate whether systemic over expression of AT2R can enhance the antihypertensive action of LOS in an Angiotensin II-dependent model of high blood pressure. For this study we constructed an adenoviral vector (Ad-CMV-AT2R-EGFP) containing AT2R genomic DNA with two introns and the encoding region. This vector was highly efficient at transducing AT2R in C2C12 myoblasts in vitro, and in liver, heart, kidney and adrenal 3 days following intracardiac injection in vivo. For the experimental protocol, 16 Sprague Dawley rats were infused s.c. via osmotic minipumps with Ang II (200 ng|[bull]|kg|[minus]|1|[bull]|min|[minus]|1) for 3 weeks to produce hypertension. Following this, rats were injected intracardially with either 2.5|[times]|1010 nfectious units of Ad-CMV-AT2R-EGFP or Ad-CMV-EGFP (8 rats/group). At 3 days post viral injections, measurement of mean basal BP via an arterial catheter revealed no differences between the AT2R- (157.9 +/- 6.01 mmHg) and EGFP-treated (150.8 +/-11.11 mmHg) groups. Likewise, basal heart rate was no different between the AT2R and EGFP-treated animals (387.78+/- 49.10 and 349+/-49.36 BPM, respectively). However, the fall in BP produced by LOS (1 mg/kg, i.v.) was significantly greater in the AT2R-treated animals (29.53 +/- 5.94 mmHg) than in the control (EGFP) group (8.9+/-3.97 mmHg), p<0.05. Rats were euthanized immediately following the experiments, and expression analyses revealed the presence of AT2R transcript within the heart and liver of each of AT2R-treated animal. These data indicate that systemic over expression of AT2R is associated with increased anti-hypertensive actions of LOS, and suggest that AT2R over expression may be beneficial in patients treated with AT1R antagonists to lower BP.
Mortality Following Ventricular Arrhythmia Suppression by Encainide, Flecainide, and Moricizine After Myocardial Infarction
Authors: Andrew E. Epstein
Journal: JAMA (1993)

To test the hypothesis that in survivors of myocardial infarction, the suppression of ventricular premature depolarizations improves survival free of cardiac arrest and arrhythmic death.International, prospective, multicenter, randomized, placebo-controlled trial.University and community hospitals.A total of 3549 patients with myocardial infarction and left ventricular dysfunction.Administration of encainide, flecainide, moricizine, or placebo to suppress ventricular premature depolarizations.Overall survival and survival free of cardiac arrest or arrhythmic death were compared in patients randomized to long-term, active antiarrhythmic drug therapy vs corresponding placebo, using the stratified log rank statistic.At 1 year from the time of randomization to blinded therapy, 95% of placebo-treated patients vs 90% of active drug-treated patients remained alive (P = .0006). Similarly, at 1 year, 96% of placebo-treated patients vs 93% of active drug-treated patients remained free of cardiac arrest or arrhythmic death (P = .003).The suppression of asymptomatic or mildly symptomatic ventricular arrhythmias after myocardial infarction does not improve survival and can increase mortality. Treatment strategies designed solely to suppress these arrhythmias should no longer be followed.
Regional myocardial perfusion and glucose metabolism in experimental left bundle branch block.
Authors: S Ono, R Nohara, H Kambara, K Okuda, C Kawai
Journal: Circulation (1992)

Several authors have reported cases in which 201Tl scintigraphy demonstrated perfusion abnormality in the septum of patients with left bundle branch block (LBBB) and normal coronary arteriogram. The mechanism of this abnormality, however, remains to be clarified.To determine whether LBBB itself induces abnormal myocardial perfusion and ischemia and to elucidate its mechanism, we used an in vivo animal model. LBBB was induced by right ventricular pacing in 17 open-chest dogs. We examined myocardial perfusion and glucose uptake using 201Tl and 18F-labeled 2-fluoro-2-deoxy-D-glucose. 201Tl activity in the septum was reduced to 74.7 +/- 14.5% of its maximal activity, and mean activity was 86.5 +/- 5.3% in the free wall (p less than 0.05). 18F activity in the septum was also reduced compared with that in the free wall (67.4 +/- 12.1% versus 88.0 +/- 5.2%, p less than 0.05). Regional myocardial blood flow was significantly reduced in the septum compared with the free wall, averaging 0.53 +/- 0.18 ml/min/g versus 0.84 +/- 0.14 ml/min/g, respectively (p less than 0.01). Systolic thickening in the septum was reduced from 1.36 +/- 0.20 to 0.98 +/- 0.04 (p less than 0.01) after the induction of LBBB, and the intramyocardial pressure in the septum in diastolic phase, in which the major flow of left anterior descending coronary artery (LAD) exists, increased from 26.6 +/- 10.5 to 57.8 +/- 22.2 mm Hg (p less than 0.02). Mean aortic pressure, LAD flow, and lactate extraction rate showed no significant change.LBBB itself may reduce myocardial perfusion and glucose uptake in the septum because of impaired systolic thickening and augmented intramyocardial pressure in the septum; however, this is not necessarily related to septal ischemia.
On the Indications for the use of the Kreuznach Waters in Strumous Disease
Authors: None Heusner
Journal: BMJ (1888)

7~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ degeneration of the heart in a large percentage of cases of diabetes.If we read such statements by the side of the anatomical records which I have mentioned, it will be seen that they have to be taken for what they are worth; for neither fatty metamor- phosis nor infiltration of fat has been at all commonly met with post mortem.On the other hand, such observations have a clinical value, since, as far as symptoms are concerned, fatty degeneration, infiltration of fat, brown atrophy, dilatation, and other anatomical lesions of the heart may show at times the same clinical aspect, namely, that of cardiac asthenia, which latter appears to me due to the claims made upon the heart by the diabetic change of metabolism.Compensation under these circumstances must always be temporary, more especially where the nutrition of the system in general suffers at an early period, and where the formation of urea and sugar exceeds that limit within which well-nourished kidneys and a well-nourished heart are able to eliminate these substances.As far as treatment is concerned, it appears from the foregoin that everything should be avoided that may impair the action of the heart and kidneys; for we know that organs which are in a state of hyperactivity easily become diseased.I may here refer to the frequent occurrence of valvular disease in nephritis, and of nephritis in diabetes.The latter I have found recorded in 30 out of 66 cases contained in the records of the Pathological Insti- tute of Berlin.Stokvis has forcibly drawn attention to the same point in his able paper on diabetes read before the late Medical Congress at Wiesbaden, while I have seen nephritis in 64 out of 380 cases, although not frequently in the form of granular con- tracted kidney.The principle of sparing the suffering organs as much as pos- sible has, in my opinion, to be carried out particularly as regards diet.In many cases a rigid nitrogenous diet cannot be enforced. 1have, on this account, during the last few years, frequently added milk to the diabetic diet, and can fully corroborate the favourable testimony which Hoffmann gave on this point before the late Medical Congress.
AAV Vectors Avoid Inflammatory Signals Necessary to Render Transduced Hepatocyte Targets for Destructive T Cells
Authors: Suryanarayan Somanathan, Ekaterina Breous, Peter Bell, James M Wilson
Journal: Molecular Therapy (2010)

Studies in mice indicate that gene transfer to liver with vectors based on adeno-associated viruses (AAVs) is characterized by immunological tolerance to antigenic transgene products. Mechanisms to explain host nonresponsiveness have focused on aberrant T-cell responses. We propose a distinct mechanism for conferring tolerance to AAV-transduced hepatocytes that relates to diminished sensitivity of the target organ to T cell-mediated effects. T cells to beta-galactosidase (beta-gal) were adoptively transferred into RAG(-/-) mice expressing beta-gal in hepatocytes due to prior administration of either Ad or AAV vectors. Adoptive transfer was associated with extinction of LacZ expression in Ad-LacZ-transduced RAG(-/-) mice and had no effect on liver LacZ expression in AAV-LacZ-transduced RAG(-/-) mice. Systemic administration of TLR ligands lipopolysaccharide (LPS) and CpG at the time of adoptive transfer did lead to extinction of LacZ expression. Systemic TLR ligands were associated with upregulation of major histocompatibility complex (MHC) class I and the cell adhesion molecules ICAM and VCAM as was seen with Ad-LacZ alone. These data indicate that AAV transduction lacks the inflammatory signals necessary to render hepatocyte targets for cytotoxic T lymphocytes (CTLs). Underlying liver pathology may confound vector performance and should be considered in the design of clinical trials.
Therapy of Peptic Ulcer
Authors: Jon I. Isenberg
Journal: JAMA (1975)

THE PURPOSE of this article is to serve as a guide to the management of gastric or duodenal ulcer. Therapy is directed at four aspects of ulcer disease: (1) relief of ulcer pain, (2) hastening of ulcer healing, (3) prevention of complications, and (4) decrease or elimination of recurrences. The available treatment consists mainly of antacids and anticholinergic drugs. Regrettably, there are still many unanswered questions regarding the efficacy of these drugs in ulcer therapy.<sup>1,2</sup> <h3>ANTACIDS</h3> Antacids have been in use for acidpeptic disease since the first century AD. The rationale for their use includes the following: (1) Ulcer does not occur in the absence of gastric acid. This has been referred to as Schwartz's dictum: "no acid—no ulcer." (2) Peptic activity decreases as gastric acidity decreases. (3) Experimental ulcer formation is inhibited by antacids. (4) Acid-reducing operations usually cure ulcer. Recent studies with antacids have disclosed certain important
Screening for Syphilis Infection in Pregnant Women: Evidence for the U.S. Preventive Services Task Force Reaffirmation Recommendation Statement
Authors: Tracy Wolff, Erica Shelton, Cecili Sessions, Therese Miller
Journal: Annals of Internal Medicine (2009)

Background: In 2004, the U.S. Preventive Services Task Force strongly recommended that clinicians screen all pregnant women for syphilis infection. Purpose: To update the evidence on screening pregnant women for syphilis infection. Data Sources: MEDLINE searches from 1 January 2003 through 31 July 2008, recent systematic reviews, reference lists of retrieved articles, and expert suggestions. Study Selection: English-language studies were selected to answer the following 2 questions: Does screening for syphilis in pregnancy reduce the prevalence of congenital syphilis in neonates? Are there harms of screening for syphilis or harms of treatment with penicillin in pregnancy to women or neonates? Randomized, controlled trials; meta-analyses; systematic reviews; cohort studies; and ecologic studies were selected for the potential benefits question. Randomized, controlled trials; meta-analyses; systematic reviews; cohort studies; case–control studies; and large case series were selected for the potential harms question. Data Extraction: Information on the study design, selection criteria, demographic characteristics, and clinical outcomes was extracted from each study. Data Synthesis: One study on benefits evaluated the effect before and after the implementation of a universal syphilis screening program for pregnant women and found reductions in rates of congenital syphilis. Two studies on screening accuracy for syphilis reported false-positive rates of less than 1%. One study that used a large insurance claims database reported an incidence of anaphylaxis after oral penicillin of 0.1 per 10 000 dispensings. In a study from Hungary, oral penicillin in pregnancy was not associated with orofacial clefts. Limitations: This was a targeted literature search and could have missed small studies on the benefits and harms of screening for syphilis in pregnancy. We did not review evidence on interventions to improve rates of prenatal screening. Conclusion: New evidence from a study of universal screening supports previous evidence on the effectiveness of screening for syphilis in pregnancy to prevent congenital syphilis. Harms include testing and follow-up for false-positive test results and adverse effects from penicillin treatment.