tbuckley/cabot-search huggingface dataset:
Abstract 4231: A 3′-substituted 7-bromoindirubin induces apoptosis of human melanoma cells via inhibition of STAT3 and AKT signaling
Authors: Lucy Liu, Sangkil Nam, Jun Wu, Yan Wang, Leandros Skaltsounis, Richard Jove
Journal: Cancer Research (2011)

Abstract Small-molecule inhibitors of STAT3 or AKT signaling represent potential molecular-targeted cancer therapeutic agents. Here, we investigated the role of STAT3 and AKT signaling in growth inhibition of human melanoma cells by a 3′-substituted 7-bromoindirunin derivative (MLS2438). Effects of MLS2438 on cell viability, apoptosis and expression of signaling proteins were evaluated by MTS cell viability assay, Annexin V staining and immunobloting analysis respectively in human melanoma cells. SRC and AKT in vitro kinase assays were conducted using recombinant kinases, substrates and 33P-labeled ATP. Immunodeficient NOD/SCID/IL2Rgamma null (NSG) mice were used in the animal studies. We show that MLS2438 inhibits STAT3 and AKT signaling, and induces apoptosis of human melanoma cells. MLS2438 directly inhibits SRC and AKT kinase activity both in vitro and in intact cancer cells. Moreover, MLS2438-induced apoptosis of human melanoma cells is associated with reduced phosphorylation of SRC, JAK, STAT3 and AKT in both dose- and time-dependent manners. Consistent with inhibition of STAT3 and AKT signaling, the anti-apoptotic protein Mcl-1 and pro-proliferative protein c-Myc were down-regulated. In contrast to the decreased phosphorylation levels of SRC, JAK, STAT3 and AKT, phosphorylation levels of the MAPK (Erk1/2) signaling protein were not inhibited in cells treated with MLS2438. Importantly, MLS2438 suppressed tumor growth in vivo with low toxicity in an A2058 human melanoma xenograft mouse model. Our data demonstrate that MLS2438, a novel natural product derivative, induces apoptosis of human melanoma cells associated with inhibition of STAT3 and AKT signaling. Our findings support further development of MLS2438 as a potential small-molecule inhibitor that targets STAT3 and AKT signaling in tumor cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4231. doi:10.1158/1538-7445.AM2011-4231
THE AURAL MASSEUR IN THE MANHATTAN EYE AND EAR HOSPITAL.
Authors: CHEVALIER JACKSON
Journal: JAMA (1895)

The aural masseur described by me in theJournal of the American Medical Associationof May 11, 1895, had given me such good results in the treatment of defective hearing and tinnitus aurium, in cases of otitis media catarrhalis chronica, that I sent an instrument like my own, some six months ago to Dr. D. B. St. John Roosa for a thorough trial and opinion on its merits. He placed the instrument in the Manhattan Eye and Ear Hospital, where it was tested thoroughly in charge of Dr. Bretano Clemens who has sent me the following report: I submit to you some results of my observations of the use of your electro-pneumatic masseur in cases of tinnitus aurium. Of late years so many instruments have been brought to the notice of the profession for the relief of this distressing affliction, and the advantages of each have been so strongly maintained
Postirradiation Screening for Thyroid Nodules
Authors: Paul C. Royce
Journal: JAMA (1980)

<h3>To the Editor.—</h3> The letter by Refetoff et al (243:1131, 1980), commenting on our report of the "Value of Postirradiation Screening for Thyroid Nodules," addresses the following two issues: the study itself and the publicity given to the study by the media. We would like the opportunity to comment on both. First, our study is, despite their contention, unique. It is the only one in which irradiated and nonirradiated persons were examined concurrently by physicians who were unaware of the medical history of the examinees. This control is vital in clinical investigation where the end point is not always clear and the observers may be biased. Second, they allege that our examination was not "by any stretch of the imagination, a complete or even an optimal screening program." To this we can reply only that the procedures we followed were those recommended by the National Cancer Institute.<sup>1</sup>Our procedures
The Health and Developmental Status of Very Low—Birth-Weight Children at School Age
Authors: Marie C. McCormick
Journal: JAMA (1992)

To assess the effect of improved survival of increasingly premature infants by examining the outcomes at school age of a large group of children born at different birth weights.Inception cohort.Participants were selected from two previously studied multisite cohorts: very low-birth-weight (less than or equal to 1500 g) children referred to participating intensive care units and heavier birth-weight children drawn from a stratified random sample of births in geographically defined regions. Follow-up at 8 to 10 years of age was by a combination of telephone interview and home/clinic visits for 65.1% (1868) of those eligible.The presence or absence of 17 specific conditions, limitations in activities of daily living due to health, mental health (affective health, behavior problems), and, for a subset, IQ scores.Decreasing birth weight was associated with an increased morbidity for all measures except affective health; those with birth weights of 1500 g or less were more likely to experience multiple health problems. Maternal educational attainment did not influence the association of birth weight with morbidity except for IQ among children whose birth weight was above 1000 g, for which socioeconomic disadvantage worsened the status of all children irrespective of birth weight.Children born at lower birth weights experience increased morbidity at early school age. These results reinforce the importance of postdischarge, early intervention programs to reduce the risk of these later health problems.
Microscopic haematuria Role of renal biopsy is undervalued
Authors: P Topham, S Harper, J Feehally, F H Schroeder
Journal: BMJ (1994)

EDITOR, - Fritz H Schroder emphasises the central importance of cystoscopy in the investigation of microscopic haematuria, regarding renal biopsy as required in only a minority of patients.1 We have commented previously on the disadvantage of this approach, which is likely falsely to reassure some patients with glomerular disease, which may be progressive.2

Schroder relies on urinary red cell morphology to distinguish glomerular from non-glomerular haematuria and thus to direct the use of renal biopsy. Although both phase contrast microscopy and the alternative Coulter counter analysis of urinary red cells have been advocated enthusiastically, some authors have reported finding them unhelpful, particularly when the number of red cells is low3; the two techniques have not entered widely into British nephrological practice.4

We recently …
Nonbacterial Regional Lymphadenitis (Cat-Scratch Fever)
Authors: Lawrence J. Kunz
Journal: New England Journal of Medicine (1961)

SINCE the antigen employed in the intradermal test for nonbacterial regional lymphadenitis ("cat-scratch fever") is prepared from human tissue or exudate, the process of skin testing involves the danger of transmitting viral hepatitis to test subjects. Although such occurrences have not been reported, prudence suggests that the skin-test antigen be so prepared as to eliminate or minimize the risk of transmitting infectious virus. The following is a brief report of the activity of an intradermal test antigen treated by prolonged heating and of its stability on storage.Material and MethodsApproximately 18 ml. of pus obtained from an infected lymph . . .
Endocardial Ablation to Eliminate Epicardial Arrhythmia Substrate in Scar-Related Ventricular Tachycardia
Authors: Yuki Komatsu, Matthew Daly, Frédéric Sacher, Hubert Cochet, Arnaud Denis, Nicolas Derval, Laurence Jesel, Stephan Zellerhoff, Han S. Lim, Amir Jadidi, Isabelle Nault, Ashok Shah, Laurent Roten, Patrizio Pascale, Daniel Scherr, Valerie Aurillac-Lavignolle, Mélèze Hocini, Michel Haïssaguerre, Pierre Jaïs
Journal: Journal of the American College of Cardiology (2014)
The Merck Index of Chemicals and Drugs: An Encyclopedia for Chemists, Pharmacists, Physicians, and Members of Allied Professions
Authors: Walter Wolman
Journal: JAMA (1960)

After eight years this excellent reference book has appeared in its seventh edition. It serves as a single-volume encyclopedia of over 10,000 chemical entities for use by physicians, pharmacists, chemists, and members of other allied professions. It contains a cross-index of over 30,000 names. Over 3,400 structural formulas are included. Several sections among the many of interest to physicians are the cross-index of names, and those concerning radioactive isotopes used in medical therapy and diagnosis, first aid in poisoning, calories in foods, some biological units and their use, prescription notation, metric and U. S. systems of weights and measures, conversion formulas, and isotonic solutions. For each chemical entity, certain physical data are given along with a description of commercial use, information on medical use, brief statements on dosage, toxicity, and contraindications. Pertinent references are often included. This is a helpful reference book with which physicians might become acquainted as a
STABILITY OF THE DIASTOLIC WAVE-FREE PERIOD AFTER PHARAMOCOLOGICAL PROVOCATION, AND DURING HAEMODYNAMIC PERTURBATIONS: IMPLICATIONS FOR THE CLINICAL APPLICABILITY OF THE INSTANTANEOUS WAVE-FREE RATIO (IFR)
Authors: Sayan Sen, Sukhjinder Nijjer, Ricardo Petraco, Christopher Broyd, Nicholas Foin, Iqbal Malik, Ghada Mikhail, Rodney Foale, darrel francis, Alun Hughes, Jamil Mayet, Justin Davies
Journal: Journal of the American College of Cardiology (2012)
Particle‐Stabilized Emulsion Droplets for Gravity‐Mediated Targeting in the Posterior Segment of the Eye
Authors: Yoo C. Kim, Henry F. Edelhauser, Mark R. Prausnitz
Journal: Advanced Healthcare Materials (2014)

This study tests the hypothesis that high‐density particle‐stabilized emulsion droplets (PEDs) can be designed to use gravity to target specific locations in the eye via suprachoroidal space injection. PEDs contain a core of high‐density perfluorodecalin measuring ≤35 μm in diameter surrounded and stabilized by fluorescein‐tagged, polystyrene nanoparticles that simulate polymeric drug carriers. A hollow microneedle infuses PEDs into the suprachoroidal space of rabbit eyes in vivo, which are later dissected and imaged to quantify distribution of fluorescent nanoparticles within the suprachoroidal space. With cornea oriented upward, such that gravity should move PEDs toward the back of the eye, up to 50% of nanoparticles are in the most posterior quadrant near the macula immediately after injection and 5 d later. With cornea oriented downward, to promote PED movement toward the front of the eye, approximately 60% of injected nanoparticles are targeted to the most anterior quadrant of the posterior segment near ciliary body. Injection of approximately neutral‐density particles of the same size shows approximately equal distribution throughout the posterior segment. This study demonstrates for the first time that high‐density PEDs can be used to deliver nanoparticles to specific locations in the back of the eye, including targeted delivery to the macula.
Carcinoid Tumors of Gastrointestinal Tract: Outcomes According to Treatment Modality in Rectal Carcinoid Tumors
Authors: Dae Young Cheung, Hye Kang Kim, Hyun Jin Kim, Hyung Jun Cho, Jae Kwang Kim, Jin Il Kim, Joon Han Jeon, Seong Jin Lee, Soo-Heon Park
Journal: Annals of Oncology (2013)
ACE Inhibitor Use Is Associated With Hospitalization for Severe Hypoglycemia in Patients With Diabetes
Authors: Andrew D Morris, Douglas I Boyle, Alexander D McMahon, Hilary Pearce, Josie M.M Evans, Ray W Newton, Roland T Jung, Thomas M MacDonald
Journal: Diabetes Care (1997)

OBJECTIVE To evaluate the association between the use of ACE inhibitors and hospital admission for severe hypoglycemia and to explore the effects of potential confounding variables on this relationship. RESEARCH DESIGN AND METHODS The association between the use of ACE inhibitors and the incidence of hypoglycemia is controversial. A recent study reported that 14% of all hospital admissions for hypoglycemia might be attributable to ACE inhibitors. We performed a nested case-control study, using a cohort of 6,649 diabetic patients taking insulin or oral antidiabetic drugs, on the Diabetes Audit and Research in Tayside, Scotland (DARTS) database. From 1 January 1993 to 30 April 1994, we identified 64 patients who had been admitted to Tayside hospitals with hypoglycemia and selected 440 control patients from the same cohort. RESULTS Hypoglycemia was associated with the use of ACE inhibitors (odds ratio [OR] 3.2, 95% CI 1.2–8.3, P = 0.023), whereas use of β-blockers and calcium antagonists was not associated with an increased risk of hospitalization for hypoglycemia with ORs of 0.9 (95% CI 0.3–3.3) and 1.7 (95% CI 0.2–2.1), respectively. There were significant differences between case and control patients in type of diabetes treatment, diabetes duration, place of routine diabetes care, and congestive cardiac failure. These differences did not confound the relationship between ACE inhibitors and hypoglycemia (adjusted OR 4.3, 95% CI 1.2–16.0). CONCLUSIONS The results show that the association between ACE inhibitor therapy and hospital admission for severe hypoglycemia is not explained by these confounding factors. Although ACE inhibitors have distinct advantages over other antihypertensive drugs in diabetes, the risk of hypoglycemia should be considered.
Exposure to acetamide-based compounds is a risk factor of acute hepatic inflammation
Authors: T.-J. Hsu, P.-Y. Chu, V. R. M. Chandrasekaran, Y.-H. Li, S. Periasamy, M.-Y. Liu
Journal: Gut (2011)

<h3>Introduction</h3> Acetamide-based compounds widely used in industries and their toxic effect have not been studied. Thioacetamide (TAA) is widely used in industry and is known to be a hepatotoxicants in experimental animals. However, the mechanism underlying TAA-induced acute inflammation is still unclear. The authors investigated the mechanisms and the involvement of main TAA metabolites in acute hepatic inflammation induced by TAA-in rats. <h3>Methods</h3> Acute hepatic inflammation was induced by TAA (0, 10, 30 and 100 mg/kg, intraperitoneally), while the inflammatory indicators including cytokines and nitric oxide were determined 0, 1, 3, 6 and 12 h after TAA administration. Hepatic pro-inflammatory cytokines were measured quantitatively using ELISA. SKF525A (cytochrome P450 2E1 (CYP 2E1) inhibitor) were used to examine the role of cytochrome in TAA-induced acute hepatic inflammation. In addition, TAA-S-oxide and acetamide were also used to examine the involvement of TAA metabolites in the early stage of TAA-induced hepatic inflammation. <h3>Results</h3> TAA increased, within 6 h, hepatic tumour necrosis factor-aproduction, interleukin 1b, nitrite levels, inducible nitric oxide synthase expression and myeloperoxidase activity. CYP 2E1 inhibitors showed significant inhibition of tumour necrosis factor α, interleukin 1β, nitrite, and myeloperoxidase activity after TAA treatment. In addition, acetamide, but not TAA-S-oxide, increased myeloperoxidase activity and all tested proinflammatory mediators generation. <h3>Conclusion</h3> The authors conclude that acetamide-associated neutrophil activation is involved, at least partially, in TAA-induced hepatic inflammation. Further, exposure to acetamide-based compounds may be a risk factor of acute hepatic inflammation.
Brief Psychotherapy with Children: Process of Therapy
Authors: ALAN J. ROSENTHAL, SAUL V. LEVINE
Journal: American Journal of Psychiatry (1971)

Brief psychotherapy with children has not achieved the same acceptance as this treatment modality with adults. The authors conducted a project, reported previously, in which they compared treatment outcome following brief (eight-visit maximum) psychotherapy with that of longer-term treatment; a one-year follow-up had shown similar results following both forms of treatment. In this paper the therapeutic techniques are analyzed and the content of brief psychotherapy with children is detailed.
Mid term effects of pulmonary thromboendarterectomy on clinical and cardiopulmonary function status
Authors: M C Zoia
Journal: Thorax (2002)

Chronic thromboembolic pulmonary hypertension (CTEPH) can be successfully treated surgically by pulmonary thromboendarterectomy (PTE) but there are few data on mid-term cardiopulmonary function, particularly on exertion, and clinical benefits following pulmonary PTE.A 2 year follow up study was undertaken of clinical status, haemodynamic and lung function indices, gas exchange, and exercise tolerance in 38 patients of mean (SD) age 50 (15) years who had undergone PTE.In-hospital mortality was about 10%. Before PTE all the patients were severely impaired (NYHA classes III-IV). There was no time difference in the improvement in the parameters: nearly all the improvement in cardiac output, gas exchange, and clinical status was achieved in the first 3 months as a result of the relief of pulmonary obstruction. At 3 months the percentage of patients with normal cardiac output and PaO(2) and of those with reduced clinical impairment increased to 97%, 59%, and 87%, respectively, without any further change. Only mean pulmonary artery pressure (mPAP), carbon monoxide transfer factor (TLCO), and exercise tolerance improved gradually during the second year, probably due to the recovery of the damaged small vessels. TLCO was overestimated before PTE but afterwards the trend was similar to that of mPAP.At mid term only a few patients did not have a satisfactory recovery because of lack of operative success, hypertension relapse, or the effect of preoperative hypertension on vessels in non-obstructed segments. Most of the patients, even the more compromised ones, had excellent long lasting results.
Routine Endoscopic and Radiological Examination of the Duodenum: Analysis of Diagnostic Value and Influence of Duodenoscopy Upon the Choice of Treatment
Authors: O. Jensen, E. Kristensen
Journal: Endoscopy (1974)

The introduction of fibreoptic duodenoscopy has increased the possibilities of diagnosing duodenal diseases, among which duodenal ulcer is the most common. However, there have been no studies on the influence of duodenoscopy upon the choice between medical and surgical treatment of duodenal ulcer. A retrospective comparative analysis of 331 endoscopic and appurtenant radiographic examinations of the duodenum at an interval of up to 2 weeks was performed. The difficulty of diagnosing an ulcer in a deformed duodenal bulb proved to be of the same order in endoscopy and radiography. A discrepancy between endoscopic and radiographic demonstration of duodenal ulcer or its sequelae was found in 27% of the cases in which one of the diagnostic procedure gave evidence of ulcer, suspicion of ulcer, deformation, or stenosis (Table 3). The absolute diagnostic value of the two methods could not be assessed, lacking possibilities of finally confirming the diagnoses. Endoscopy appears to posses a higher degree of diagnostic accuracy than radiography. However, the greatest diagnostic accuracy was obtained by a combination of both procedures. Twenty-seven patients underwent operation for duodenal ulcer. Supplementing the radiological examination of the duodenum by duodenoscopy proved to have had no influence upon the choice between surgical and medical treatment. As medical treatment of duodenal ulcer is directed at the dyspepsia, and as the incidence of malignant lesions in the duodenum is low, routine endoscopic follow-up control of duodenal ulcers was not found to be indicated. Prospective endoscopic evaluations of the course of duodenal ulcer may perhaps alter the criteria for choosing between medical and surgical treatment. On the basis of the present study the introduction of routine endoscopic examination of the duodenum cannot be recommended as yet.
Subtle Immunologic Abnormalities in Four Boys with Subacute Sclerosing Panencephalitis
Authors: Kenneth L. Gerson, Robert H. A. Haslam
Journal: New England Journal of Medicine (1971)

Abstract Four boys with subacute sclerosing panencephalitis did not express delayed responses to six common skin-test antigens. Skin allografts were rejected more slowly than normal, and contact se...
Pemphigus associated with giant lymph node hyperplasia.
Authors: J Redon, G Sorni, A Gonzalez-Molina, M Caballero, J Baguena
Journal: BMJ (1983)

Total and differential white cell counts were normal, as were numbers of B and T cells.There was possibly, however, a slight hypogammaglobulinaemia, concentrations of IgM (36 IU/ml), IgG (45 IU/ml), and IgD (13 IU/ml) being at the lower limits of normal.Concurrent chest infections probably also had a debilitating effect.Case 2 was a nurse who had been doing night duty on the same ward as case 1. Fourteen days after cryptosporidiosis had been diagnosed in case 1 she presented with abdominal cramps and watery diarrhoea.No entero- pathogenic bacteria or viruses were detected but Cryptosporidium oocysts (1OX 106/1) were seen in the first faecal sample, taken on day 2 of her illness.Stools quickly returned to normal but diarrhoea recurred on day 7 and oocysts were detected.Excretion of oocysts reached a peak on day 9 (10 x I0O/1) but recovery was rapid and only low numbers ( >106/1) were detected on days 11-18.
Test Strips for Blood Glucose Monitors Are Not Always Accurate
Authors: Richard J. Melker
Journal: Diabetes Care (2003)

Self-monitoring of blood glucose is essential for managing diabetes. Over 30 different blood glucose monitors cleared by the U.S. Food and Drug Administration (FDA) are available to consumers. The FDA relies solely on data provided by manufacturers for clearance. Few physicians or diabetic patients are aware that blood glucose monitor test strips that are exposed to humidity and/or excessive temperature give falsely elevated results. Manufacturers know this, and the information they provide to patients obfuscates the problem; furthermore, the FDA does not require the reporting of environmental effects on accuracy.

On more than one occasion, I administered excessive insulin based on results from the last few test strips from vials of 50 that had …
ABC of clinical electrocardiography: Introduction. II---Basic terminology
Authors: S. Meek
Journal: BMJ (2002)

This article explains the genesis of and normal values for the individual components of the wave forms that are seen in an electrocardiogram. To recognise electrocardiographic abnormalities the range of normal wave patterns must be understood.



Complex showing P wave highlighted



The sinoatrial node lies high in the wall of the right atrium and initiates atrial depolarisation, producing the P wave on the electrocardiogram. Although the atria are anatomically two distinct chambers, electrically they act almost as one. They have relatively little muscle and generate a single, small P wave. P wave amplitude rarely exceeds two and a half small squares (0.25 mV). The duration of the P wave should not exceed three small squares (0.12 s).



Atrial depolarisation gives rise to the P wave



The wave of depolarisation is directed inferiorly and towards the left, and thus the P wave tends to be upright in leads I and II and inverted in lead aVR. Sinus P waves are usually most prominently seen in leads II and V1. A negative P wave in lead I may be due to incorrect recording of the electrocardiogram (that is, with transposition of the left and right arm electrodes), dextrocardia, or abnormal atrial rhythms.



P waves are usually more obvious in lead II than in lead I



The P wave in V1 is often biphasic. Early right atrial forces are directed anteriorly, giving rise to an initial positive deflection; these are followed by left atrial forces travelling posteriorly, producing a later negative deflection. A large negative deflection (area of more than one small square) suggests left atrial enlargement.

#### Characteristics of the P wave



Normal duration of PR interval is 0.12-0.20 s …