tbuckley/cabot-search huggingface dataset:
False Glucose Values With Use of Oxazepam
Authors: Joseph D. Teller
Journal: JAMA (1972)

<h3>To the Editor.—</h3> Zileli et al (215:1986, 1971) cautioned against the possibility of falsely high blood glucose values in persons taking oxazepam (Serapax), since a comatose patient who had attempted suicide by ingesting the drug reportedly had a blood glucose level of 1,680 mg/100 ml. Frings (217:1244, 1971) later reported that pure oxazepam gave no in vitro glucose reaction, whereas a 30-mg capsule of oxazepam (Serax) had an apparent glucose content of 50 mg. He concluded that it was the capsule "filler" that reacted, and pointed out that it was highly unlikely that it would affect the blood glucose. Recently, Spiegel and Enthoven (220:1499, 1972) confirmed Zileli's results with capsules and tablets of oxazepam, and corroborated Frings' findings in detecting no glucose-like reaction with the pure drug by using five different methods including glucose oxidase (glucostat) and hexokinase (glucostrate). They suggested the strong possibility of lactose as the "filler," but
UK response to global HIV epidemic is condemned for lack of coordination
Authors: Zosia Kmietowicz
Journal: BMJ (2005)

The UK government has responded too slowly to the worldwide epidemic of HIV and AIDS and with too little control over how the money it donates is spent, says a highly critical report from the public spending watchdog.

Although the United Kingdom is the second biggest donor to HIV and AIDS programmes, after the United States, the money it donates through the Department for International Development is not always used in the best possible way, says the House of Commons Public Accounts Committee.

The report criticises the department for its delayed response to tackling HIV and AIDS, although it …
Melanoma Incidence and Mortality Among US Whites, 1969-1999
Authors: A. C. Geller
Journal: JAMA (2002)

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A8.11 Rankl Expression is Lower on T and B Lymphocytes and Rankl<sup>+</sup>Cells Tend to Accumulate in Circulation of Rheumatoid Arthritis Patients Treated with TNF Blockers
Authors: IP Perpétuo, R Marques, C Ponte, H Canhão, JE Fonseca
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background and Objectives</h3> Rheumatoid arthritis (RA) is characterised by bone resorption and joint destruction. The receptor activator of NF-kB ligand (RANKL) plays a major role in bone loss because it is responsible for osteoclast differentiation and it is known that hyperactive immune system cells express surface RANKL. Several therapies commonly used for RA treatment have been shown to stop RA joint destruction. One of the hypothetical mechanisms explaining this effect could be an interference with the RANKL system. The aim of this work was to assess the effects of RA therapies in RANKL surface expression in different leukocyte populations by flow cytometry. <h3>Methods</h3> Forty-nine patients diagnosed with RA were recruited for this study. Seventeen patients were naïve to any therapy, 14 were under methotrexate (MTX) – 8 of them at baseline of treatment with TNF blockers – and 18 patients were treated with TNF blockers. Blood was collected and total leukocytes were used for flow cytometry staining with anti human-CD66b for neutrophils, CD3 for T lymphocytes, CD19 for B lymphocytes and RANKL. <h3>Results</h3> There were no differences regarding gender distribution, age, disease activity, C-reactive protein (CRP) levels or erythrocyte sedimentation rate (ESR). Patients treated with MTX or TNF blockers have reduced RANKL expression in neutrophils, T and B lymphocytes (p = 0.0027, p = 0.0003 and p = 0.0032, respectively) when compared to untreated patients. However the number of circulating RANKL<sup>+</sup> T and B lymphocytes was increased in patients treated with TNF blockers when compared to naïve patients (p = 0.0070 and p = 0.0183 respectively). No differences were found between groups regarding circulating number of leukocytes. We found no correlation of the studied parameters with CRP, ESR or DAS28. <h3>Conclusions</h3> RANKL surface expression on T and B lymphocytes decreases and RANKL<sup>+</sup> cells tend to accumulate in the circulation of patients treated with TNF blockers. The reasons for this effect are not clear but might be related to disturbances induced by TNF blockage in gene expression, cell activation and migration.
Abstract P2-09-39: Multi-Gene Predictors Developed from Breast Cancer Cell Lines To Predict Response to Chemotherapy: A Validation Study on US Oncology Study 02-103
Authors: K Shen, L Pusztai, Y Qi, WF Symmans, N Song, SD Rice, MJ Gabrin, JA O'Shaughnessy, FA. Holmes
Journal: Cancer Research (2010)

Abstract PURPOSE: Multi-gene predictors (MGPs) of response to multidrug chemotherapy regimens were developed using an in vitro chemoresponse assay in which cell lines were exposed to chemotherapy. The goal of this study was to assess the predictive value of these MGPs using clinical breast cancer patient gene expression data from a clinical trial. METHOD: US Oncology 02-103 was a phase II trial in which women with stage II/III breast cancer were treated with neoadjuvant chemotherapy consisting of four cycles of fluorouracil/epirubicin/cyclophosphamide (FEC) followed by four cycles of docetaxel/capecitabine (TX). Most HER-2 positive patients also received trastuzumab. MGPs of FEC, TX and TFEC (docetaxel/fluorouracil/epirubicin/cyclophosphamide) sensitivity were developed using in vitro assay results from breast cancer cell lines exposed to these drug combinations and publicly-available gene expression data for the same cell lines. MGPs were not developed for trastuzumab treatment. Area under the receiver-operator curve (AUC) was used to evaluate the performance of the three MGPs’ to predict patient pathologic complete response (pCR). Patients who did or did not receive trastuzumab were evaluated separately. Validation was performed blindly and the predictors were applied without knowledge of patient clinical outcome. RESULTS: Eighty-six patients had genomic data available and were included in this analysis. The predictive performance of the FEC, TX and TFEC MGPs were AUCs of 0.72, 0.69, and 0.73, respectively, in the patients who received FEC-TX chemotherapy without trastuzumab (n=61). Within this group, higher AUCs were observed in ER-negative patients compared to ER-positive patients (0.69, 0.72, 0.74 vs. 0.64, 0.54, 0.62, respectively). The prediction accuracies were low (AUCs = 0.43, 0.56 and 0.43) for patients who received trastuzumab together with chemotherapy (n=25) as expected, indicating that the MGPs may have the potential to be regimen-specific. CONCLUSION: Cell line-derived MGPs of multidrug chemotherapy regimens showed promising performance in this blinded validation study, particularly among patients with ER-negative breast cancers. Further clinical data are needed to confirm this finding. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-09-39.
An LRP5 Receptor with Internal Deletion in Hyperparathyroid Tumors with Implications for Deregulated WNT/β-Catenin Signaling
Authors: Peyman Björklund, Göran Åkerström, Gunnar Westin
Journal: PLoS Medicine (2007)

Background Hyperparathyroidism (HPT) is a common endocrine disorder with incompletely understood etiology, characterized by enlarged hyperactive parathyroid glands and increased serum concentrations of parathyroid hormone and ionized calcium. We have recently reported activation of the Wnt signaling pathway by accumulation of β-catenin in all analyzed parathyroid tumors from patients with primary HPT (pHPT) and in hyperplastic parathyroid glands from patients with uremia secondary to HPT (sHPT). Mechanisms that may account for this activation have not been identified, except for a few cases of β-catenin (CTNNB1) stabilizing mutation in pHPT tumors. Methods and Findings Reverse transcription PCR and Western blot analysis showed expression of an aberrantly spliced internally truncated WNT coreceptor low-density lipoprotein receptor–related protein 5 (LRP5) in 32 out of 37 pHPT tumors (86%) and 20 out of 20 sHPT tumors (100%). Stabilizing mutation of CTNNB1 and expression of the internally truncated LRP5 receptor was mutually exclusive. Expression of the truncated LRP5 receptor was required to maintain the nonphosphorylated active β-catenin level, transcription activity of β-catenin, MYC expression, parathyroid cell growth in vitro, and parathyroid tumor growth in a xenograft severe combined immunodeficiency (SCID) mouse model. WNT3 ligand and the internally truncated LRP5 receptor strongly activated transcription, and the internally truncated LRP5 receptor was insensitive to inhibition by DKK1. Conclusions The internally truncated LRP5 receptor is strongly implicated in deregulated activation of the WNT/β-catenin signaling pathway in hyperparathyroid tumors, and presents a potential target for therapeutic intervention.
Aflatoxin inhalation and alveolar cell carcinoma.
Authors: I Dvorackova
Journal: BMJ (1976)

have reported values of 25-hydroxycholecalciferol of over 749 nmol/l (300 ng/ml) in vitamin D intoxication, and the value in the present case was even greater.It is not clear how much calciferol was being ingested, but the lack of response of the hypercalcaemia to treatment with prednisolone could have been due to consumption of a very high dose.
Estimation of Creatinine Clearance
Authors: MICHAEL D. ROBSON
Journal: Annals of Internal Medicine (1975)

Comments1 January 1975Estimation of Creatinine ClearanceMICHAEL D. ROBSON, M.R.C.P.MICHAEL D. ROBSON, M.R.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-82-1-125_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: A simple method of estimating creatinine clearance from the serum creatinine would be very useful in planning the dosage of certain drugs when renal function is impaired. Since urine collection in seriously ill patients is often impractical, a number of formulas have been proposed that are either cumbersome (1) or require the use of a computer (2).Because a serum creatinine of 10 mg/100 ml in a patient weighing 50 kg represents a much more serious degree of renal failure than the same level of creatinine in a patient weighing 80 kg, an attempt was made to...References1. JELLIFFE R: Creatinine clearance: bedside estimate (letter). Ann Intern Med 79:604, 1973 LinkGoogle Scholar2. JELLIFFEJELLIFFE RS: A computer program for estimation of creatinine clearance from unstable serum creatinine levels, age, sex, and weight. Mathematical Bioscience 14:17-24, 1972 CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Chief, Nephrology Unit Jaffa Hospital Tel Aviv, Israel PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 January 1975Volume 82, Issue 1Page: 124-124KeywordsComputersCreatinineDrugsRenal failureUrine ePublished: 1 December 2008 Issue Published: 1 January 1975 PDF downloadLoading ...
Abstract 4699: A siRNA high-throughput screening identified Wee1 as determinant of Chk1 inhibitor sensitivity
Authors: Laura Carrassa, Rosaria Chilà, Monica Lupi, Francesca Ricci, Marco Mazzoletti, Cinzia Celenza, Massimo Broggini, Giovanna Damia
Journal: Cancer Research (2012)

Abstract Targeting Chk1 protein kinase is a valid anti cancer strategy to enhance the cytotoxic effects of radio and chemotherapy. Recent evidence disclosed a role of Chk1 in unperturbed cell proliferation and survival, implying that Chk1 inhibitors could also be effective as single agents in tumors with a specific genetic background. The effect of Chk1 inhibition on a wide panel of cancer cell lines has been herein conducted by using a specific and selective Chk1 inhibitor PF-00477736. The results showed that 2 cancer cell lines out of 16 analyzed (the ovarian cancer cell line OVCA-432 and the breast cancer cell line SK-BR3) were very sensitive to PF-00477736 treatment. To identify genes in synthetic lethality with Chk1, which may justify the sensitivity to Chk1 inhibitor of some cancer cell lines, a high-throughput screening using a siRNA library directed against 719 human protein kinases, in combination with either scramble or Chk1 siRNA, was undertaken. The ovarian cancer cell line OVCAR-5, resistant to Chk1 inhibition, was used to perform the screening. After 2 independent screenings and the validation procedure using specific esiRNAs, and the three siRNAs of each target (used in the screening as a pool), the Wee1 tyrosine kinase was identified as the most significant gene in synthetic lethality with Chk1. Treatment with both PF-00477736 and a Wee1 inhibitor (MK-1775) confirmed the remarkable synergistic effect in various human cancer cell lines (breast, ovarian, colon, prostate). Same results have been obtained with AZD-7762 Chk1 inhibitor. Isogenic cellular systems differing only for the status of p53 (the colon carcinoma cancer cell lines HCT-116 p53 +/+ and p53 -/- and the ovarian cancer cell lines A2780 and A2780/E6) showed a comparable and strong synergistic effect of the combined treatment. Interestingly, in the normal fetal human lung cell line MRC-5 the effect of the combined treatment was additive. Time lapse experiments and an evaluation of the ability of cells to form colonies, suggested that cells treated with the two inhibitors almost completely lost the ability to proliferate and failed to perform a proper cell division. A detailed molecular analysis showed that the combined treatment causes cells to undergo premature mitosis before the end of DNA replication and with damaged DNA, leading to a massive cell death by apoptosis. Taken together these preclinical data address a new promising combined targeted anticancer strategy that deserves clinical investigation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4699. doi:1538-7445.AM2012-4699
Combined Care of the Rheumatic Patient
Authors: D V Doyle
Journal: Annals of the Rheumatic Diseases (1985)

patients, one to five years in five patients, six to 10 years in eight patients, and more than 10 years in four patients.During the experiment only two patients described improvement with therapy.Four- teen of the patients (70%) stopped therapy due to lack of response.Of these, eight did not even complete one month of therapy.Seven patients (35%) described side effects (Table 1) consisting of: palpitations in two patients, abdominal discomfort in two patients, dryness of mouth, nervousness, and loss of balance, each in one patient.Of the two patients that reported improvement of symptoms with therapy, one omitted therapy due to adverse effects and one continued therapy for more than three months.
P406Adaptive changes of rat heart mitochondrial respiration: response of remote ischemic preconditioning
Authors: I Kancirova, M Jasova, M Murarikova, S Carnicka, Z Sumbalova, O Ulicna, O Vancova, I Waczulikova, A Ziegelhoffer, M Ferko
Journal: Cardiovascular Research (2014)

Introduction: Myocardium heavily depends on the oxidative generation of energy that requires involvement of functional mitochondria. These organelles were recently shown to participate also in the mechanisms of cardioprotection induced by ischemic preconditioning. Based on the previous findings of increased myocardial resistance to ischemia, it could be assumed that mitochondria and functional alterations in the respiratory chain might also be involved in the mechanisms of remote ischemic preconditioning (RIP). In RIP, the increased cardiac resistance to ischemia is achieved by brief episodes of ischemia with subsequent reperfusion performed in distant organs or places. Hence, on the contrary to ischemic preconditioning, a direct restriction of oxygen supply to cardiac mitochondria is missing. The aim of this pilot study was to reveal whether, and in what way are cardiac mitochondria and respiratory chain involved in the mechanism of cardioprotection. Methods: For this purpose, 13-week-old male Wistar rats were divided into 2 groups: control group without RIP (n=21) and the group with RIP (n=21). Protocol of RIP consisted of 3 cycles of ischemia and reperfusion, 5 min of duration each. Not-preconditioned and preconditioned hearts were subjected to the testing of ischemia-reperfusion injury (T-IRI): 30 minute ischemia followed by 40 minutes of reperfusion according to Langendorff. Parameters of oxidative phosphorylation (OXPHOS) in the isolated cardiac mitochondria were determined by the method of high resolution respirometry using Oxygraph-2k (Oroboros Instruments, Austria). Results: Mitochondrial respiration was stimulated by ADP (state III) using glutamate+malate and malate+octanoylcarnitine as substrates. After ischemic phase of T-IRI the hearts without RIP exhibited a decrease by 26.7% whereas the hearts with RIP showed an increase by 40.4% in the rate of O2-consumption in comparison with the hearts in baseline preischemic phase of T-IRI. Reperfusion phase of T-IRI was characterized by a decrease in state III respiration in the group of hearts without RIP (65.9 %) and with RIP (35.6%). Interestingly, a decrease in O2-consumption induced by reperfusion was less pronounced when malate+octanoylcarnitine as a substrate was used instead of glutamate+malate. Conclusion: Our results revealed that the positive effect of remote preconditioning i.e., the increased or better preserved state III O2 consumption, became manifested only during the ischemic and reperfusion phase of T-IRI. Grants: VEGA 2/0101/12, APVV 0102-11, KEGA 003 UK-4/2012.
Bortezomib Added to Daunorubicin and Cytarabine During Induction Therapy and to Intermediate-Dose Cytarabine for Consolidation in Patients With Previously Untreated Acute Myeloid Leukemia Age 60 to 75 Years: CALGB (Alliance) Study 10502
Authors: Eyal C. Attar, Jeffrey L. Johnson, Philip C. Amrein, Gerard Lozanski, Martha Wadleigh, Daniel J. DeAngelo, Jonathan E. Kolitz, Bayard L. Powell, Peter Voorhees, Eunice S. Wang, William Blum, Richard M. Stone, Guido Marcucci, Clara D. Bloomfield, Barry Moser, Richard A. Larson
Journal: Journal of Clinical Oncology (2012)

Purpose The purpose of this study was to determine remission induction frequency when bortezomib was combined with daunorubicin and cytarabine in previously untreated older adults with acute myeloid leukemia (AML) and safety of bortezomib in combination with consolidation chemotherapy consisting of intermediate-dose cytarabine (Int-DAC). Patients and Methods Ninety-five adults (age 60 to 75 years; median, 67 years) with previously untreated AML (including therapy-related and previous myelodysplastic syndrome) received bortezomib 1.3 mg/m 2 intravenously (IV) on days 1, 4, 8, and 11 with daunorubicin 60 mg/m 2 on days 1 through 3 and cytarabine 100 mg/m 2 by continuous IV infusion on days 1 through 7. Patients who achieved complete remission (CR) received up to two courses of consolidation chemotherapy with cytarabine 2 gm/m 2 on days 1 through 5 with bortezomib. Three cohorts with escalating dose levels of bortezomib were tested (0.7, 1.0, and 1.3 mg/m 2 ). Dose-limiting toxicities were assessed during the first cycle of consolidation. The relationship between cell surface expression of CD74 and clinical outcome was assessed. Results Frequency of CR was 65% (62 of 95), and 4% of patients (four of 95) achieved CR with incomplete platelet recovery (CRp). Eleven patients developed grade 3 sensory neuropathy. Bortezomib plus Int-DAC proved tolerable at the highest dose tested. Lower CD74 expression was associated with CR/CRp (P = .04) but not with disease-free or overall survival. Conclusion The addition of bortezomib to standard 3 + 7 daunorubicin and cytarabine induction chemotherapy for AML resulted in an encouraging remission rate. The maximum tested dose of bortezomib administered in combination with Int-DAC for remission consolidation was 1.3 mg/m 2 and proved tolerable. Further testing of this regimen is planned.
Oncogene Addiction versus Oncogene Amnesia: Perhaps More than Just a Bad Habit?
Authors: Dean W. Felsher
Journal: Cancer Research (2008)

Abstract Cancer is a multistep process whereby genetic events that result in the activation of proto-oncogenes or the inactivation of tumor suppressor genes usurp physiologic programs mandating relentless proliferation and growth. Experimental evidence surprisingly illustrates that the inactivation of even a single oncogene can be sufficient to induce sustained tumor regression. These observations suggest the hypothesis that tumors become irrevocably addicted to the oncogenes that initiated tumorigenesis. The proposed explanation for this phenomenon is that activated oncogenes result in a signaling state in which the sudden abatement of oncogene activity balances towards proliferative arrest and apoptosis. Indeed, substantial evidence supports this hypothesis. Here, we propose an alternative, although not necessarily mutually exclusive, explanation for how oncogenes initiate and sustain tumorigenesis. We suggest that oncogene activation initiates tumorigenesis precisely because it directly overrides physiologic programs inducing a state of cellular amnesia, not only inducing relentless cellular proliferation, but also bypassing checkpoint mechanisms that are essential for cellular mortality, self-renewal, and genomic integrity. Because no single oncogenic lesion is sufficient to overcome all of these physiologic barriers, oncogenes are restrained from inducing tumorigenesis. Correspondingly, in a tumor that has acquired the complete complement of oncogenic lesions required to overcome all of these safety mechanisms, the inactivation of a single oncogene can restore some of these pathways resulting in proliferative arrest, differentiation, cellular senescence, and/or apoptosis. Thus, oncogenes induce cancer because they induce a cellular state of enforced oncogenic amnesia in which, only upon oncogene inactivation, the tumor becomes aware of its transgression. [Cancer Res 2008;68(9):3081–6]
OUTCOMES FOLLOWING TRANSCATHETER AORTIC VALVE IMPLANTATION COMPARING EDWARDS SAPIEN&amp;trade; WITH MEDTRONIC COREVALVE REVALVING SYSTEM&amp;reg; DEVICES: RESULTS FROM THE MILAN REGISTRY
Authors: Gill Louise Buchanan, Alaide Chieffo, Matteo Montorfano, Francesco Maisano, Azeem Latib, Filippo Figini, Micaela Cioni, Santo Ferrarello, Remo Daniel Covello, Annalisa Franco, Chiara Gerli, Pietro Spagnolo, Antonio Grimaldi, Giovanni La Canna, Mauro Carlino, Ottavio Alfieri, Antonio Colombo
Journal: Journal of the American College of Cardiology (2012)