tbuckley/cabot-search huggingface dataset:
Dipyridamole-Thallium Scintigraphy and Gated Radionuclide Angiography to Assess Cardiac Risk before Abdominal Aortic Surgery
Authors: Jean-Francois Baron, Olivier Mundler, Michele Bertrand, Eric Vicaut, Eric Barre, Gilles Godet, Charles Marc Samama, Pierre Coriat, Edouard Kieffer, Pierre Viars
Journal: New England Journal of Medicine (1994)

Because many patients with atherosclerotic disease of the abdominal aorta also have coronary artery disease, assessment of cardiac risk before abdominal aortic surgery has received much attention. Our prospective study was designed to identify predictors of cardiac risk in consecutive patients evaluated preoperatively with dipyridamole-thallium single-photon-emission computed tomography (SPECT) to assess myocardial perfusion and radionuclide angiography to measure left ventricular ejection fraction.Clinical and scintigraphic data were collected prospectively during hospitalization in 457 consecutive patients undergoing elective abdominal aortic surgery. Adverse cardiac outcomes were predicted with multivariate analyses.Eighty-six patients (19 percent) had one or more of the following postoperative complications: prolonged myocardial ischemia (61 patients), myocardial infarction (22), congestive heart failure (20), and severe ventricular tachyarrhythmia (2). Twenty patients died postoperatively (4.4 percent), half of them from cardiac causes. Information about myocardial perfusion obtained from dipyridamole-thallium SPECT did not accurately predict adverse cardiac outcomes. The best correlates of cardiac complications were definite clinical evidence of coronary artery disease (odds ratio, 2.6; 95 percent confidence interval, 1.6 to 4.3) and age greater than 65 years (odds ratio, 2.3; 95 percent confidence interval, 1.4 to 3.6). Measurement of the ejection fraction was useful only in the prediction of left ventricular failure. Age greater than 65 years was the only predictor of death (odds ratio, 26.4; 95 percent confidence interval, 3.5 to 200.0).The presence of definite clinical evidence of coronary artery disease and older age were the most important preoperative predictors of an adverse cardiac outcome after abdominal aortic surgery. These results suggest that the routine use of dipyridamole-thallium SPECT and radionuclide angiography for screening before abdominal aortic surgery may not be justified.
Bronchitis, Pneumonitis and Pneumonia in University of Wisconsin Students
Authors: Alfred S. Evans, Mary Brobst
Journal: New England Journal of Medicine (1961)

THE cause of acute infections of the lower respiratory tract has been a matter of considerable speculation, especially of that group called primary atypical pneumonia or viral pneumonia. The present report is concerned with 224 University of Wisconsin students admitted to the infirmary from 1953 through 1960 with evidence of bronchitis, pneumonitis or pneumonia. Detailed etiologic and clinical data are presented on 119 of this group who were intensively studied. The major clinical features of this syndrome were fever, cough, rales and usually x-ray evidence of infiltration.The association of the primary-atypical-pneumonia agent of Eaton, Meikeljohn and van Herick1 with . . .
Expression of the cancer-testis antigen FMR1NB on the surface of malignant cells.
Authors: T. Luetkens, Y. Cao, K. Bartels, S. Meyer, C. Bokemeyer, D. Atanackovic
Journal: Journal of Clinical Oncology (2010)

e13045 Background: Cancer-testis (CT) antigens represent ideal candidates for tumor-specific therapy due to their inherent immunogenicity and exceptional tissue restriction. Despite these advantageous properties the development of targeted therapeutics has been hampered by their predominantly intracellular localization. CT antigen FMR1NB might represent a promising exception due to its predicted transmembrane topology. Methods: We screened acute (AML) and chronic (CML) myeloid leukemia samples as well as healthy tissues for the expression of FMR1NB. Mammalian cell lines were transfected with FLAG- or GFP-tagged FMR1NB fusion constructs. We evaluated the subcellular localization of FMR1NB by fractionation and confocal microscopy. Epitopes of commercial anti-FMR1NB antibodies were characterized by ELISA using overlapping peptides. Results: FMR1NB mRNA was expressed in AML cell lines and patient samples and confirmed by western blot on the protein level. Specificity was confirmed by the lack of FMR1NB expression in healthy tissues. Confocal fluorescence microscopy of GFP chimeras in mammalian cell lines, immunofluorescence staining of AML cell lines, and subcellular fractionation strongly support a membraneous localization of FMR1NB including the plasmamembrane. In contrast to results of structural prediction software our characterization of epitopes recognized by polyclonal anti-FMR1NB antibodies and the subsequent immunostaining of intact transfected and native AML cells suggest an extracellular amino-terminus of FMR1NB. Flow cytometric analysis of AML and CML cell lines as well as AML patient samples and healthy donors further confirmed a strong and specific expression of FMR1NB on leukemia samples. Conclusions: FMR1NB mRNA is specifically expressed in AML cells and the resulting protein localizes to the membrane compartment including the plasma membrane. A putative extracellular domain of over 100aa length of the protein can be detected using FMR1NB-specific antibodies. The membrane localization of FMR1NB is a rare exception within the CT antigen family and our data suggest that it represents an ideal target for the diagnosis and therapy of myeloid leukemias. No significant financial relationships to disclose.
Case 35-1993
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Jerome O. Klein, Anthony R. Mattia
Journal: New England Journal of Medicine (1993)

Presentation of CaseA two-year-old boy was admitted to the hospital because of cervical lymphadenopathy and fever.He had been born to a 35-year-old woman by normal spontaneous vaginal delivery at 39 weeks (her third pregnancy). Because of thick meconium he spent 48 hours in an intensive care unit and required oxygen for 24 hours. Leukocytosis was found, and antibiotics were administered for two days. At the age of six weeks he was admitted to another hospital because of possible sepsis. Antibiotics were administered for 72 hours and were discontinued when all cultures were reported to be negative.At 12 . . .
Pharmacokinetics of a single 2-mg dose of everolimus in healthy Mexican volunteers.
Authors: J. A. Palma, M. Pereda, M. Lopez, T. Castro Sr., O. Hernandez, C. Trujillo, E. Nuñez
Journal: Journal of Clinical Oncology (2010)

e13157 Background: Everolimus is a derivative of rapamycin. It targets the mTOR (mammalian target of rapamycin), an intracellular serine-threonine kinase, which works as a central regulator of signal transduction cascades. mTOR regulates the synthesis of proteins involved in the development and progression of cancer. Everolimus acts directly on tumor cells by inhibiting their growth and proliferation and tumor angiogenesis. Objective: To evaluate oral pharmacokinetics (PK) of single-dose of everolimus in 12 male healthy Mexican volunteers. Methods: Twelve healthy volunteers were studied in order to determine PK parameters after a single oral dose of 2 mg of everolimus and values of Cmax, tmax, AUC, half-life time, clearance and apparent volume of distribution were obtained. Blood samples were drawn at 0.0 (pre-dose), 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0 and 120.0 hrs after drug administration. Results: PK results: The mean Cmaxwas 18.84 ng/mL at 0.67 hours (Tmax), and t1/2 was 45.74 hours. Conclusions: Everolimus is metabolized by cytochrome CYP3A4, and there is evidence that the Mexican mestizo population has a reduction of this cytochrome which could explain the high bioavailability of some drugs in Mexican patients. In the present study with a single dose of everolimus this does not seem to be the case, indeed, the results were comparable to a Caucasian (German) population (Kovarik et al, Pharmacotherapy 2002;22:154–159), in which was reported Cmax of 17.9 ng/mL at 0.5 hours (Tmax), and t1/2 of 31.5 hours. No substantial differences in PK were observed between Mexican population and German population. The results of Cmaxand AUC were similar and compatible with the Kovarik results with a single dose of 2 mg and as everolimus pK is lineal until 8 mg, these results can be extrapolated to higher doses. Everolimus is safe in 2 mg dose in Mexican healthy volunteers (no adverse events were reported during study). Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis
Progress in the Management of Hyperprolactinemia
Authors: Omar Serri
Journal: New England Journal of Medicine (1994)

Hyperprolactinemia is a frequent cause of amenorrhea, infertility, and galactorrhea in women and decreased libido and impotence in men. Most patients are young women, both because of the sensitivity of pituitary-gonadal function in women to inhibition by hyperprolactinemia and because its most common causes -- a prolactin-secreting pituitary adenoma (prolactinoma) and idiopathic hyperprolactinemia -- are more common in women. Other, less frequent causes are drugs, primary hypothyroidism, and non-prolactin-secreting hypothalamic or pituitary tumors that compress the pituitary stalk. Idiopathic hyperprolactinemia is diagnosed when the serum prolactin concentration is elevated with no demonstrable pituitary or hypothalamic lesions or any other recognized . . .
Abstract 782: Modulation of receptor tyrosine kinase signaling by cMET inhibitor, INC280, in cMETmut/amp gastric carcinoma cell line Hs746.T
Authors: Maria C. Pinzon-Ortiz, Xianhui Rong, Jinsheng Liang, Hui Qin Wang, Alan Huang, Robert Schlegel, Z. Alexander Cao
Journal: Cancer Research (2015)

Abstract Aberrant Receptor Tyrosine Kinase (RTK) activity is one of the hallmarks of cancer. The genetic alternations of ABL and EGFR are classical examples of RTK-dependent oncogenesis. Recent data suggest that non mutated RTK signaling can form feedback pathways to serve as resistant mechanism against targeted therapies. Here, we examined the regulation of RTK signaling by a potent cMET inhibitor, INC280 (enzymatic EC50 against c-MET = 0.13 nM), in a cMET-dependent human gastric tumor model Hs746.T. Hs746.T is a heavily cMET dependent cell line with both cMET amplication (12.9 copies) and mutation (G-T mutation at slice donor site to cause juxtamembrane domain deletion). This model is exquisitely sensitive to cMET inhibitor, INC280 in vitro (GI50 = 9 nM) and in vivo. The treatment of INC280 lead to significant inhibition of pcMET. Furthermore, the treatment of INC280 resulted in the suppression of pEGFR, though INC280 does not actively inhibit EGFR (enzymatic EC50 against EGFR &amp;gt; 10 microM). This result supports prior reports that cMET and EGFR can form physical complex, with cMET modulating EGFR activation. Consequently, INC280 inhibited downstream signaling nodes of pAKT, pS6RP, pMEK and pERK in Hs746.T. To examine the RTK signaling underlying possible treatment relapse, we treated Hs746.T cells chronically in vitro under increasing concentrations of INC280. After 8 weeks of treatment, Hs746.T-R cells were generated that grew at 600 nM of INC280. RTK signaling was examined in Hs746.T-R cells under treatment of INC280. As expected, cMET signaling was significantly curtailed in Hs746.T-R cells, as was pEGFR. Interestingly, pPDGFRb was elevated in Hs746.T-R, compared to the parental cell line. We hypothesize that the increased signaling through PDGFRb may serve as resistance mechanism to INC280 in Hs746.T-R cells. In summary, we have examined RTK signaling in the cMET-dependent Hs746.T cell line. Our finding supported the notion of RTK cross-talk between cMET and EGFR in this setting. Additionally, our data reveal that additional RTK signaling (PDGFRb) can be induced under chronic treatment of INC280 to possibly mediate resistance to cMET inhibition. Citation Format: Maria C. Pinzon-Ortiz, Xianhui Rong, Jinsheng Liang, Hui Qin Wang, Alan Huang, Robert Schlegel, Z. Alexander Cao. Modulation of receptor tyrosine kinase signaling by cMET inhibitor, INC280, in cMETmut/amp gastric carcinoma cell line Hs746.T. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 782. doi:10.1158/1538-7445.AM2015-782
Case 20-1999
Authors: Jane G. Schaller, John L. Niles, Lisa H. Lerner
Journal: New England Journal of Medicine (1999)

Presentation of CaseA 16-year-old girl was admitted to the hospital because of fever, rash, and severe ocular disease.The patient had been in good health until three months earlier, when small, painful, mildly pruritic vesicles appeared on her left thigh. She was given oral and topical medications, and the rash disappeared within a few days, leaving hyperpigmented scars. Thereafter, she had intermittent fever, fatigue, and anorexia, with a weight loss of 14 kg.Two weeks before admission, the patient's left ear began to drain. Several days before admission, painful intraoral lesions appeared. One day before admission, clarithromycin was prescribed . . .
Keeping patients out of hospital
Authors: N J Naftalin
Journal: BMJ (2000)

Papers p 279

Secondary care consumes a large proportion of the healthcare budget and the need to spend wisely is ever pressing. The prevailing political philosophy of the past few decades in Britain has meant that efficiency and effectiveness have become part of NHS vocabulary. Doctors have probably been better at adopting new practices than they have been at dropping outdated methods, but in both areas there is room for improvement. Moreover, government funding is unlikely to improve unless the profession can show not only its commitment to best practice but also its ability constantly to examine its procedures and implement improvements or abandonment when necessary. Clinical governance should nourish this process, but if success is to be achieved it will come from leadership, drive, and initiative from within the profession. The move to keep patients out of hospital is clearly part of the search for efficiency and effectiveness, but it is important to know what patients think of it and that clinical effectiveness is …
Human Macrophage Function in Cancer: Systemic and Local Changes Detected by an Assay for Fc Receptor Expression&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: J Rhodes, P Plowman, M Bishop, D Lipscomb
Journal: JNCI Journal of the National Cancer Institute (1981)

Journal Article Human Macrophage Function in Cancer: Systemic and Local Changes Detected by an Assay for Fc Receptor Expression Get access John Rhodes, John Rhodes Search for other works by this author on: Oxford Academic PubMed Google Scholar Piers Plowman, Piers Plowman Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael Bishop, Michael Bishop Search for other works by this author on: Oxford Academic PubMed Google Scholar David Lipscomb David Lipscomb Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 66, Issue 3, March 1981, Pages 423–429, https://doi.org/10.1093/jnci/66.3.423 Published: 01 March 1981 Article history Received: 26 July 1979 Revision received: 05 September 1980 Accepted: 15 September 1980 Published: 01 March 1981
P114 Can a Dedicated ‘Fast Track’ Sleep Service successfully establish Vocational Drivers on CPAP within four weeks of referral?
Authors: BAM Downie, G Olds, M Tomlinson, SD West
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> Sleepiness due to Obstructive Sleep Apnoea (OSA) can impair driving, and OSA has been implicated in road traffic accidents. DVLA guidelines state that those with “sleepiness sufficient to impair driving” should cease driving until they have been investigated and treated. This may have a significant effect on the ability of vocational drivers to earn a living. Fear of lengthy investigations and licence regulations may deter these patients from seeking treatment. We developed a dedicated service that aimed to diagnose OSA and successfully establish vocational drivers on CPAP within 4 weeks of referral. <h3>Methods</h3> The service was advertised to local GPs, encouraging identification of vocational drivers at point of referral. Patients were seen by a nurse specialist and underwent domiciliary sleep studies, returning the following day for results and CPAP therapy. Those who were not identified via GP referral were fast-tracked from first clinic appointment. Compliance and Epworth Sleepiness Score (ESS) were evaluated after one week of treatment on CPAP, or as soon as the patient could attend thereafter. <h3>Results</h3> Between September 2014 and July 2015, 29 drivers were referred; one failed to attend. Fifteen held a type 1 drivers’ licence and 13 a type 2 licence. At presentation, the mean age was 48 years (range 25–61), mean BMI was 34 (27–51) and mean ESS was 10 (0–21). Sleep studies showed a mean ODI of 30 (0–93), with moderate or severe OSA in 18 (64%). Twenty two patients were commenced on CPAP (79%). Seventeen patients attended for review on CPAP, a mean of 16 days after initiation. Mean ESS was 5.4 and mean CPAP usage was 5.3 h/night. Of these, six people were reviewed between six and eight days after CPAP initiation; their mean compliance was 6.2 h/night (4.1–8.3). Mean time from referral (or first clinic visit) to review on CPAP was 33 days. <h3>Conclusion</h3> A fast track service is practical and effective at diagnosing OSA and establishing vocational drivers on CPAP. There were some delays due to patient non-attendance or re-scheduling. It is vital that GPs are aware of the service and refer patients as vocational drivers.
Local control of the metastatic properties of prostate cancer cells: The role of Luteinizing Hormone-Releasing Hormone.
Authors: Patrizia Limonta, Roberta M. Moretti, Marcella Motta, Marina Montagnani Marelli
Journal: Cancer Research (2004)

3422  Carcinoma of the prostate represents the second leading cause of cancer-related deaths among men in Western countries. The tumor, which is usually androgen-dependent in its early stages, very often progresses to a condition of insensitivity to testicular steroids. This condition is characterized not only by a high rate of cell proliferation, but also by a strong metastatic behavior. Luteinizing Hormone-Releasing Hormone (LHRH), besides being the key regulator in the control of the reproductive functions, has been shown to be expressed in hormone-related tumors, to behave as an autocrine regulator of tumor growth. In particular, we have previously demonstrated that LHRH is produced by androgen-independent prostate cancer cells (DU 145) and it exerts a specific antiproliferative action on these cells, by interfering with the stimulatory activity of IGF-I. The present experiments have been performed to clarify whether LHRH might also be involved in the regulation of the metastatic behavior of androgen-independent prostate cancer cells and to possibly clarify its mechanism of action. To this purpose, in DU 145 cells, the effects of LHRH receptor activation (achieved by using a potent LHRH agonist, Leuprorelin) have been tested on: a) the migratory capacity; b) the invasive properties; c) alphavbeta3 integrin expression; d) the ability of IGF-I to promote cell motility. The results obtained demonstrate that: a) LHRH receptor activation significantly reduces the capacity of prostate cancer cells to migrate towards a chemotactic stimulus, when plated in the upper compartment of a Boyden’s chamber; b) the LHRH receptor agonist substantially decreases the ability of prostate cancer cells to invade a reconstituted basement membrane (Matrigel); LHRH receptor activation induces a significant decrease of the level of expression of alphavbeta3 integrin expression; d) the LHRH receptor agonist significantly counteracts the stimulatory effect of IGF-I on the migratory behavior of the cells as well as on alphavbeta3 integrin expression. These findings suggest that locally expressed LHRH may reduce the migratory and invasive behavior of androgen-independent prostate cancer cells, at least partially, by interfering with the pro-metastatic activity of IGF-I.
Thalidomide for the Treatment of Chronic Graft-versus-Host Disease
Authors: Georgia B. Vogelsang, Evan R. Farmer, Allan D. Hess, Viki Altamonte, William E. Beschorner, Douglas A. Jabs, Russell L. Corio, L. Stefon Levin, O. Michael Colvin, John R. Wingard, George W. Santos
Journal: New England Journal of Medicine (1992)

Allogeneic bone marrow transplantation is an accepted therapy for hematologic cancer, aplastic anemia, and inherited immunodeficiencies. Chronic graft-versus-host disease (GVHD) is the principal complication in patients surviving more than 100 days. Thalidomide has been shown experimentally to be effective in treating GVHD.
S81 Feasibility and uptake of enhanced smoking cessation services within ambulatory HIV care
Authors: C Kyriacou, N Stewart, A Melville, J Brown, K Edwards, R Lloyd, M Johnson, J Flint, A Rodger, M Lipman
Journal: Thorax (2015)

<h3>Background</h3> HIV infected individuals are at increased risk of smoking-related illness and smoking rates amongst populations with HIV are often significantly higher than the general population. Interventions that reduce the prevalence of smoking in this population are urgently required. <h3>Aims</h3> We sought to establish the impact of initiating regular smoking screening and advice by healthcare assistants (HCAs) or nurses as part of routine care appointments in a HIV ambulatory care service. <h3>Methods</h3> Individuals attending for ambulatory HIV care appointments were asked brief screening questions regarding cigarette smoking by Healthcare Assistants (HCAs) or nurses. This was completed whilst clinical observations were performed, allowing this intervention to be delivered as part of routine care. Those who were current smokers were given Very Brief Advice (VBA) regarding smoking cessation and offered referral to smoking cessation services. The number of referrals to smoking cessation services was compared to the six months prior to the introduction of the enhanced service. <h3>Results</h3> 1,031 individuals were screened between October 2014 and March 2015: 262 (25%) reported that they were current smokers. 248 (93%) of these smokers were provided with VBA and the opportunity of referral to smoking cessation services. Of these, 103 (38%) accepted referral compared to 6 referrals from the HIV outpatient service in the preceding 6 months. <h3>Conclusions</h3> An intervention to ask service users about smoking and provide smoking cessation advice can be undertaken as part of routine care in an ambulatory HIV care service and is effective in identifying smokers and increasing referrals to smoking cessation services. Further work will evaluate the impact of this intervention in HIV positive subjects.