tbuckley/cabot-search huggingface dataset:
Abstract B43: Alisertib (MLN8237), an Aurora Kinase A inhibitor, enhances Docetaxel-induced cell death in Upper Gastrointestinal Adenocarcinoma cells
Authors: Vikas Sehdev, Frank Revetta, Abbes Belkhiri, Jeffrey Ecsedy, Alexander Zaika, Wael El-Rifai
Journal: Clinical Cancer Research (2012)

Abstract Upper gastrointestinal adenocarcinomas (UGCs) respond poorly to current chemotherapeutic regimes. We and others have previously reported frequent AURKA gene amplification and mRNA and protein overexpression in UGCs. It has been shown that AURKA can induce chemotherapeutic resistance and regulate several key signaling pathways in cancer cells, suggesting its role as a central node in cancer cell signaling. The DCF (docetaxel, cisplatin and 5-FU) regimen is the most promising chemotherapeutic regimen against UGC. However, AURKA overexpression can mediate resistance to both Taxol and cisplatin. These findings provide a credible rationale for targeting AURKA. In this study we have reported therapeutic response of the recently developed AURKA selective inhibitor MLN8237 as a single agent and in combination with docetaxel. Our findings provide a foundation for a promising new approach of future targeted therapy in UGCs. Using AGS, FLO-1 and OE33 UGC cell lines, with constitutive AURKA overexpression and variable-p53 status, we observed inhibition of cancer cell survival with 0.5μM MLN8237 (p&amp;lt;0.05) alone. This effect was significantly enhanced in combination with 1.0nM docetaxel (p&amp;lt;0.001). Cell cycle analyses after 48hr of treatment with MLN8237 demonstrated a significant increase in the percentage of polyploidy for AGS and OE33 UGC cells (p&amp;lt;0.01) which was further enhanced by docetaxel (p&amp;lt;0.001). Additionally, an increase in the percentage of cells in the sub-G1-phase at 24hrs and 48hrs was observed with MLN8237 in FLO-1 (p&amp;lt;0.01) cells which was significantly enhanced with MLN8237 and docetaxel combination (p&amp;lt;0.001). Western blot analysis demonstrated higher induction of cleaved caspase 3 and cleaved PARP with the combined treatment, as compared to a single agent treatment. Using xenograft models, we demonstrated an enhanced anti-tumor role for the MLN8237 and docetaxel combination, as compared to single agent treatments (p&amp;lt;0.001). In conclusion, this study demonstrates that MLN8237, combined with docetaxel, can mediate a better therapeutic outcome in UGCs.
CHOLECYSTOGRAPHY IN DIABETES MELLITUS
Authors: M. K. TEDSTROM
Journal: JAMA (1926)

Gallbladder and bile duct disease has long been recognized as a cause for pancreatitis. Judd<sup>1</sup>says, "Cholecystitis is nearly always associated with a certain grade of hepatitis or pancreatitis, or both," and Deaver and Sweet<sup>2</sup>say, "The most frequent forerunner of disease of the pancreas is some affection of the gallbladder or the bile passages which is frequently but not always associated with calculi." Mayo-Robson believes that there is evidence of chronic pancreatitis in 60 per cent of patients in whom operation has shown the presence of stone in the common bile duct. This being a common observation of surgeons, the association of chcolecystitis and diabetes mellitus has been sought. From a statistical standpoint, there are those who could find no relationship between the incidence of biliary tract diseases and diabetes,<sup>3</sup>while others are convinced that there is such a relationship.<sup>4</sup> It seemed, therefore, worth while
A Genetic Association Study of Serum Acute-Phase C-Reactive Protein Levels in Rheumatoid Arthritis: Implications for Clinical Interpretation
Authors: Benjamin Rhodes, Marilyn E. Merriman, Andrew Harrison, Michael J. Nissen, Malcolm Smith, Lisa Stamp, Sophia Steer, Tony R. Merriman, Timothy J. Vyse
Journal: PLoS Medicine (2010)

A genetic association study by Timothy Vyse and colleagues suggests that there is a significant association between CRP variants and acute-phase serum CRP concentrations in patients with rheumatoid arthritis, including those with chronic inflammation.
Coronary angioplasty in cardiac transplant patients. Results of a multicenter study.
Authors: A A Halle, R F Wilson, E K Massin, R C Bourge, M L Stadius, M R Johnson, R B Wray, J B Young, R A Davies, G D Walford
Journal: Circulation (1992)

BACKGROUND Accelerated allograft atherosclerosis is the main cause of death of cardiac transplant recipients after the first year after transplantation. Because no medical therapy is known to prevent or retard graft atherosclerosis and transplantation is associated with a shortened allograft survival, alternative, palliative therapy with percutaneous transluminal coronary angioplasty (PTCA) has been attempted. Because no single medical center has performed angioplasty in a large number of cardiac transplant recipients, representatives of 11 medical centers retrospectively analyzed their complete experience of coronary angioplasty in cardiac transplant patients to determine the safety, efficacy, limitations, and long-term outcome of angioplasty in allograft coronary vascular disease. METHODS AND RESULTS Thirty-five patients underwent 51 angioplasty procedures for 95 lesions 46 +/- 5 months (mean +/- SEM) after transplantation. The primary indications for angioplasty included angiographic coronary disease in 22 cases (43%) and noninvasive evidence of ischemia in 18 procedures (35%). Angiographic success, defined as less than or equal to 50% post-PTCA stenosis, occurred in 88 of 95 lesions (93%). Mean pre-PTCA stenosis was 83 +/- 1.1%; mean post-PTCA stenosis was 29 +/- 2.1% (p less than 0.0001). Periprocedural complications included myocardial infarction and late in-hospital death in one patient and three groin hematomas. Twenty-three of the 35 patients (66%) had no major adverse outcome such as death, retransplantation, or myocardial infarction at 13 +/- 3 months after angioplasty. Four patients died less than 6 months after angioplasty, and four died more than 6 months after angioplasty (range, 6-23 months). Two patients had retransplantation 2 months after PTCA, and one patients had retransplantation 18 months after angioplasty. CONCLUSIONS Coronary angioplasty may be applied in selected cardiac transplant recipients with comparable success and complication rates to routine angioplasty. Whether angioplasty prolongs allografts survival remains to be determined by a prospective, controlled trial.
Effects of ischemia and hypercarbic acidosis on myocyte calcium transients, contraction, and pHi in perfused rabbit hearts.
Authors: R Mohabir, H C Lee, R W Kurz, W T Clusin
Journal: Circulation Research (1991)

The time courses of changes in pHi and cytosolic calcium were compared in isolated perfused rabbit hearts with the use of the calcium-sensitive fluorescent indicator indo-1 and the pH indicator 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF). Cell-permeant forms of these indicators were loaded into myocytes by arterial infusion or by direct infusion into the extravascular space. Indo-1 fluorescence was recorded from the epicardial surface of the left ventricle at an excitation wavelength of 360 nm and emission wavelengths of 400 and 550 nm. BCECF fluorescence was recorded at an excitation wavelength of 490 nm and an emission wavelength of 530 nm. Calibration procedures were developed for each indicator that allowed [Ca2+]i and pHi to be quantified during ischemia. Global ischemia decreased contractility and caused a rapid increase in both the systolic and end-diastolic levels of the calcium transients. Ninety seconds of ischemia increased peak systolic [Ca2+]i from 609 +/- 29 to 1,341 +/- 159 nM, while end-diastolic [Ca2+]i increased from 315 +/- 25 to 553 +/- 52 nM. The observed increase in diastolic [Ca2+]i, was shown not to arise from indo-1-loaded endothelial cells. The initial increase in [Ca2+]i was followed by a gradual decline and then a secondary rise occurring between 5 and 15 minutes of ischemia. In contrast, ischemia caused a monotonic decrease in pHi from a baseline of 7.03 +/- 0.06 to 6.83 +/- 0.02 after 2 minutes, 6.32 +/- 0.1 after 10 minutes, and 6.11 +/- 0.04 after 15 minutes. Perfusion of hearts with acidified (hypercarbic) saline increased the systolic and diastolic levels of the calcium transients, but only when pHi fell below a threshold value, which was more acidic than values achieved during the first 2 minutes of ischemia (6.83 +/- 0.03). Lesser degrees of acidification caused a decrease in contractility but did not affect the calcium transients. Effects of pHi on the calcium transients were not due to altered calcium sensitivity of indo-1. These results suggest that cytosolic acidification may contribute to the increase in [Ca2+]i during the first 15 minutes of global ischemia, but the [Ca2+]i increase during the first 2 minutes is mediated by other factors.
Mental health should be measured by same instrument in different ethnic populations
Authors: S. Ebrahim
Journal: BMJ (1997)

Prescribing antidepressants in general practiceWhat is an effective dose?Editor-What should be the advised dosage of a tricyclic antidepressant for major depression?In his editorial Tony Kendrick quotes a recommended dose of a typical tricyclic antidepressant, amitriptyline, as 125 mg daily. 1 This dosage is at the higher end of the range of dosages quoted for all tricyclic antidepressants in the British National Formulary.If followed it would have major implications for the prescribing habits of general practitioners.The recommended dosage for amitriptyline for major depression is quoted from a consensus statement published in the BMJ in 1992. 2 The source of this recommendation is a double blind placebo controlled trial of amitriptyline among depressed patients in general practice. 3 In this trial patients given the active drug received amitriptyline 75 mg daily by the end of the first week, amitriptyline 100 mg during the second week, and amitriptyline 125-175 mg, depending on improvement, during the remaining four weeks of the study.The median dose of amitriptyline given over the six week study period was 125 mg.It is the median tolerated dose.Figure 1 in the paper by Hollyman et al clearly shows a response to treatment in the first two weeks, when the lower dose of amitriptyline was given. 3 Kendrick discusses the results of several investigations into the effectiveness of antidepressants at different dosages.Similar investigations have been used to develop the dose range of every prescribable antidepressantfor example, Kerihuel and Dreyfus reviewed 34 randomised clinical trials of lofepramine. 4 In the papers reviewed the concentration of lofepramine giving a clinical response ranged from 105 mg to 210 mg, which is equivalent to 75-150 mg amitriptyline.The principle that more severe cases of major depression require higher doses of antidepressants is also valid.It also holds true for newer selective serotonin reuptake inhibitors.For example, a study of prescribing patterns across 23 381 prescriptions shows that a prescription for higher than the initial dose was required in 6.8% of patients taking fluoxetine, 21.1% of patients taking paroxetine, and 51% of patients taking sertraline. 5
Common acute lymphoblastic leukemia antigen expressed on leukemia and melanoma cell lines has neutral endopeptidase activity.
Authors: C V Jongeneel, E J Quackenbush, P Ronco, P Verroust, S Carrel, M Letarte
Journal: Journal of Clinical Investigation (1989)

We have previously reported that the amino acid sequence of the common acute lymphoblastic leukemia antigen (CALLA, CD10) translated from a normal human kidney cDNA clone is identical to that of neutral endopeptidase (NEP, EC 3.4.24.11). In this study, we show that by flow cytometry, a monoclonal antibody (135A3) produced against rabbit NEP reacted selectively with leukemia and melanoma cell lines expressing CALLA on their surface. A glycoprotein of apparent Mr 100,000 was immunoprecipitated from surface labeled NALM-1 leukemia or Mel-1477 melanoma cells with monoclonal antibodies to NEP (135A3) or CALLA (44C10). mRNAs hybridizing to a NEP-specific probe were present in CALLA+ leukemia and melanoma cell lines, but absent from CALLA- lines. NEP enzymatic activity was detected on intact cells from CALLA+ lines, but not CALLA- lines. The activity was blocked by two selective inhibitors of NEP, thiorphan and phosphoramidon. CALLA antigen purified from the NALM-6 leukemic cell line by affinity to 44C10-IgG Sepharose retained a peptidase activity that was completely blocked by thiorphan and phosphoramidon. Thus the CALLA antigen present at the surface of leukemia and melanoma cell lines is an enzymatically active neutral endopeptidase.
Implementation of the Quality Oncology Practice Initiative at a University Comprehensive Cancer Center
Authors: Douglas W. Blayney, Kristen McNiff, David Hanauer, Gretchen Miela, Denise Markstrom, Michael Neuss
Journal: Journal of Clinical Oncology (2009)

The Quality Oncology Practice Initiative (QOPI) is a voluntary program developed by the American Society of Clinical Oncology (ASCO) to aid oncology practices in quality self-assessment. Few academic cancer centers have been QOPI participants.We implemented the QOPI process at the University of Michigan Comprehensive Cancer Center, a large, hospital-based academic cancer center, and report our experience with five rounds of data collection. Patient medical records were selected using QOPI-specified procedures and abstracted locally; results were entered into an ASCO-maintained database and analyzed.Abstractors who were not directly involved with patient care required an average of 62.3 minutes per medical record (4.7 minutes per data element) to abstract data. We found that compliance with quality measures was uniformly high when measures were structured into our electronic medical record. Results from other measures, including those measuring chemotherapy administration in the last 2 weeks of life, were initially markedly different from those reported by other QOPI participants. Our practice changed toward the QOPI national practice norm after a presentation of the results at a faculty research conference. We found that other measures were consistently greater than 90%, including disease-specific diagnosis and treatment measures.Measuring and showing performance data to physicians was sufficient to change some aspects of physician behavior. Improvement in other measures requires structural practice changes. QOPI, an oncologist-developed system, can be adapted for use in practice improvement at an academic medical center.
Risedronate induced BOOP complicated with sarcoidosis
Authors: T Arai
Journal: Thorax (2005)

Bisphosphonates are synthetic compounds that are taken up preferentially by skeletal tissue and suppress osteoclast mediated bone resorption. They are being used increasingly in the treatment of osteoporosis.1 Bronchoconstriction caused by bisphosphonates has been described2 but drug induced pneumonitis has not previously been reported.3 This is the first report of interstitial pneumonia induced by the bisphosphonate risedronate.

A woman developed an intramuscular mass in her right arm at the age of 51 years. Sarcoidosis was diagnosed by non-necrotising epithelioid granulomas in the resected specimen of the mass, bilateral hilar lymphadenopathy on the chest radiograph, a negative reaction to tuberculin test, and an increase in the serum angiotensin converting enzyme (ACE) level to 27.9 U/ml. She had pain in her right …
The Sedimentation Rate
Authors: Cynthia S. Hardison
Journal: JAMA (1968)

The sedimentation rate measures the rate of fall of erythrocytes in the plasma. The rate is accelerated when alterations in plasma protein fractions cause rouleau formation or aggregation of red blood cells due to change in physicochemical properties of plasma and erythrocyte surfaces. These aggregates fall faster than isolated erythrocytes because there is less total surface exposed to surrounding plasma. <h3>Methods</h3> Textbooks of clinical pathology contain details of the various methods of determining sedimentation rate and the normal values for each method. Disposable tubes are available, and a micromethod is useful for determining the sedimentation rate in infants. The Westergren and Wintrobe methods are most commonly used. Correction for anemia is regarded as inaccurate and is not commonly performed. Since the test is only roughly quantitative, minor variations from the normal values ought to be disregarded. Rates tend to be higher in children, in the elderly, and in adult women.
New quinolone generation active over wide spectrum
Authors: Donald E. Riesenberg
Journal: JAMA (1986)

They are related to nalidixic acid, have a very broad spectrum of activity, and may be useful in a wide range of deep-seated infections—orally. They are known as the second generation quinolones. However, this exciting group of at least 12 new compounds is not yet clinically available. Scientists attending the Interscience Conference on Antimicrobial Agents and Chemotherapy in Minneapolis had the opportunity to hear nearly 100 presentations concerning the newer quinolones. The parent compound, nalidixic acid, is effective in treating urinary tract infections, but controversy has existed for years over whether resistant organisms emerge rapidly during therapy (<i>JAMA</i>1976;236:1857-1860). According to Jerome Boscia, MD, associate professor of medicine, Medical College of Pennsylvania, Philadelphia, it also has been difficult to achieve adequate blood levels of nalidixic acid and other older quinolones. "They were great for urinary tract infections, but they really didn't give good serum levels," says Boscia. Initial reports, from in
Cysteamine Therapy for Children with Nephropathic Cystinosis
Authors: William A. Gahl, George F. Reed, Jess G. Thoene, Joseph D. Schulman, William B. Rizzo, Adam J. Jonas, Daniel W. Denman, James J. Schlesselman, Brian J. Corden, Jerry A. Schneider
Journal: New England Journal of Medicine (1987)

We treated 93 children with nephropathic cystinosis with oral cysteamine (mean dose, 51.3 mg per kilogram of body weight per day) for up to 73 months. This agent is known to be effective in depleting cells of cystine. In our study, the mean cystine depletion from leukocytes was 82 percent. A historical control group of 55 children received either ascorbic acid (27 children) or placebo (28). At age six, 2 of 17 controls had a serum creatinine level less than 1.0 mg per deciliter, as compared with 17 of 27 patients treated with cysteamine for at least one year (odds ratio, 12.8; 95 percent confidence interval, 2.1 to 33.9). At the end of the study, creatinine clearance was higher in the cysteamine group than in the control group (38.5 vs. 29.7 ml per minute per 1.73 m2; 95 percent confidence limits on the difference, 1.8 and 15.8), even though the cysteamine group was on average 1.4 years older than the control group. Cysteamine also improved growth; those in the cysteamine group between two and three years of age grew at 93 percent of the normal velocity, as compared with 54 percent in the control group. Fourteen percent of the patients could not tolerate the taste and smell of cysteamine. Concurrent controls treated in a blinded fashion with a placebo were not included in this study. With this limitation in mind, we conclude that oral cysteamine, by depleting cells of cystine, helps maintain renal glomerular function, improves growth, and constitutes the current treatment of choice for nephropathic cystinosis. (N Engl J Med 1987; 316:971–7.)
Determination of pH or lactate in fetal scalp blood in management of intrapartum fetal distress: randomised controlled multicentre trial
Authors: E Wiberg-Itzel, C Lipponer, M Norman, A Herbst, D Prebensen, A Hansson, A-L Bryngelsson, M Christoffersson, M Sennström, U-B Wennerholm, L Nordström
Journal: BMJ (2008)

<b>Objective</b> To examine the effectiveness of pH analysis of fetal scalp blood compared with lactate analysis in identifying hypoxia in labour to prevent acidaemia at birth. <b>Design</b> Randomised controlled multicentre trial. <b>Setting</b> Labour wards. <b>Participants</b> Women with a singleton pregnancy, cephalic presentation, gestational age ≥34 weeks, and clinical indication for fetal scalp blood sampling. <b>Interventions</b> Standard pH analysis (n=1496) or lactate analysis (n=1496) with an electrochemical microvolume (5 μl) test strip device. The cut-off levels for intervention were pH &lt;7.21 and lactate &gt;4.8 mmol/l, respectively. <b>Main outcome measure</b> Metabolic acidaemia (pH &lt;7.05 and base deficit &gt;12 mmol/l) or pH &lt;7.00 in cord artery blood. <b>Results</b> Metabolic acidaemia occurred in 3.2% in the lactate group and in 3.6% in the pH group (relative risk 0.91, 95% confidence interval 0.61 to 1.36). pH &lt;7.00 occurred in 1.5% in the lactate group and in 1.8% in the pH group (0.84, 0.47 to 1.50). There was no significant difference in Apgar scores &lt;7 at 5 minutes (1.15, 0.76 to 1.75) or operative deliveries for fetal distress (1.02, 0.93 to 1.11). <b>Conclusion</b> There were no significant differences in rate of acidaemia at birth after use of lactate analysis or pH analysis of fetal scalp blood samples to determine hypoxia during labour. <b>Trial registration</b> ISRCT No 1606064.
Randomized Trial in Advanced Ovarian Cancer Comparing Cisplatin and Carboplatin
Authors: C. Mangioni, G. Bolis, S. Pecorelli, K. Bragman, A. Epis, G. Favalli, A. Gambino, F. Landoni, M. Presti, W. Torri, L. Vassena, F. Zanaboni, S. Marsoni
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Randomized Trial in Advanced Ovarian Cancer Comparing Cisplatin and Carboplatin Get access C. Mangioni, C. Mangioni Clinica Ostetrico-Ginecologica, Ospedale S. GerardoMilan, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar G. Bolis, G. Bolis III Clinica Ostetrico-Ginecologica), Università di MilanoMilan, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar S. Pecorelli, S. Pecorelli Clinica Ostetrico-Ginecologica, Università di BresciaBrescia, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar K. Bragman, K. Bragman Pharmaceutical Research and DevelopmentBristol-Myers, Brussels, Belgium Search for other works by this author on: Oxford Academic PubMed Google Scholar A. Epis, A. Epis Clinica Ostetrico-Ginecologica, Ospedale S. GerardoMilan, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar G. Favalli, G. Favalli Clinica Ostetrico-Ginecologica, Università di BresciaBrescia, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar A. Gambino, A. Gambino Clinica Ostetrico-Ginecologica, Università di BresciaBrescia, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar F. Landoni, F. Landoni Clinica Ostetrico-Ginecologica, Ospedale S. GerardoMilan, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar M. Presti, M. Presti III Clinica Ostetrico-Ginecologica), Università di MilanoMilan, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar W. Torri, W. Torri Istituto di Ricerche Farmacologiche Mario NegriMilan, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar ... Show more L. Vassena, L. Vassena Clinica Ostetrico-Ginecologica, Ospedale S. GerardoMilan, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar F. Zanaboni, F. Zanaboni III Clinica Ostetrico-Ginecologica), Università di MilanoMilan, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar S. Marsoni S. Marsoni * Istituto di Ricerche Farmacologiche Mario NegriMilan, Italy *Correspondence to: Dr. S. Marsoni, Istituto M. Negri, Via Eritrea 62, Milan 20157, Italy. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 19, 4 October 1989, Pages 1464–1471, https://doi.org/10.1093/jnci/81.19.1464 Published: 04 October 1989 Article history Received: 21 March 1989 Revision received: 10 July 1989 Accepted: 11 July 1989 Published: 04 October 1989