tbuckley/cabot-search huggingface dataset:
Montelukast and Theophylline: No Use or Some Use in Persistent Asthma?
Authors: Charles G. Irvin, David A. Kaminsky, Nicholas R. Anthonisen, Mario Castro, Nicola A. Hanania, Janet T. Holbrook, John J. Lima, Robert A. Wise
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

The recent study by the American Lung Association Asthma Clinical Research Centers suggests that prescribing montelukast or theophylline for symptomatic patients with asthma, irrespective of existing treatment, confers little further benefit (1). However, before extrapolating their findings into everyday clinical practice it is important to consider several points regarding the validity of the study. First, between 21 and 26% of randomized patients were not using regular inhaled corticosteroids, while the vast majority of these alarmingly appeared to be maintained on long-acting 2-agonists as monotherapy. Second, since the mean prebronchodilator FEV1 in the symptomatic patients with asthma enrolled was between 78 and 80% predicted, it would appear reasonable to consider that inhaled corticosteroids—a fundamental component in all but the mildest of asthma—should have been instituted in “real life” before consideration of montelukast or theophylline. Third, at the end of the 24-week study, as many as 40% of individuals failed to adhere to randomized treatment. Fourth, the spectrum of asthma severity appears to have varied considerably in the study, presumably with patients with an FEV1 of 50% of predicted up to normal values. Moreover, while some patients were receiving no treatment prior to study entry, up to 40%were receiving combined inhaled corticosteroid and long-acting 2-agonist preparations. Finally, the authors failed to evaluate effects on underlying airway inflammation or airway hyperresponsiveness, which are undoubtedly integral pathophysiological components of the underlying syndrome of asthma. In view of shortcomings such as inappropriate maintenance therapy during the study, patient heterogeneity, and failure to evaluate inflammatory biomarkers, it may be understandable that the authors failed to demonstrate any benefit with the addition of montelukast or theophylline. Moreover, these factors may also explain why the current findings appear to contradict those of others, in terms of beneficial effects of add-on montelukast in the correct clinical setting across a spectrum of asthma phenotypes (2).
Younger Age of Presentation and Extraosseous Tumour in IgD Myelomatosis
Authors: J. R. Hobbs, A. A. Corbett
Journal: BMJ (1969)

A study of 14 personal patients and 16 others in the literature shows that (1) IgD myelomatosis often presents at a significantly younger age than other forms of myelomatosis, and (2) during life extraosseous tumour can be detected in about two-thirds of these patients. The IgD form represents 1·5% of myelomatosis and shows an increased incidence of osteolytic lesions, hypercalcaemia, and renal failure, together with heavy Bence Jones proteinuria (90% type L). Like only Bence Jones myelomatosis, the IgD form seems to behave clinically in a more vicious manner.
Number of alcohol related admissions in England has doubled in 12 years
Authors: Susan Mayor
Journal: BMJ (2008)

The number of admissions to hospitals in England for reasons specifically to do with alcohol has more than doubled over the past 12 years, warns a new report. The statistics also show a big increase in the number of prescriptions for drugs to treat alcohol dependency.

The figures show that the number of NHS hospital admissions resulting in a primary or secondary diagnosis that was related specifically to alcohol consumption rose from 93 459 in 1995-6 to 207 788 in 2006-7. Half of these were admissions for conditions with a primary diagnosis related to alcohol, most commonly mental and behavioural disorders resulting from alcohol consumption. The second most common cause of admission was alcoholic liver disease, which accounted for nearly 15 000 hospital admissions in 2006-7. Toxic effects of alcohol accounted …
Long-term efficacy and safety of adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B
Authors: Patrick Marcellin, Ting-Tsung Chang, Seng G. Lee Lim, William Sievert, Myron Tong, Sarah Arterburn, Katyna Borroto-Esoda, David Frederick, Franck Rousseau
Journal: Hepatology (2008)

Abstract Treatment of 171 patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) with adefovir dipivoxil (ADV) 10 mg over 48 weeks resulted in significant histological, virological, serological, and biochemical improvement compared with placebo. The long-term efficacy and safety of ADV in a subset of these patients was investigated for up to 5 years. Sixty-five patients given ADV 10 mg in year 1 elected to continue in a long-term safety and efficacy study (LTSES). At enrollment, the 65 LTSES patients were a median 34 years old, 83% male, 74% Asian, 23% Caucasian, median baseline serum hepatitis B virus (HBV) DNA 8.45 log10 copies/mL, and median baseline alanine aminotransferase (ALT) 2.0 × upper limit of normal. At 5 years on study, the median changes from baseline in serum HBV DNA and ALT for the 41 patients still on ADV were 4.05 log10 copies/mL and −50 U/L, respectively. HBeAg loss and seroconversion were observed in 58% and 48% of patients by end of study, respectively. Fifteen patients had baseline and end of follow-up liver biopsies; improvements in necroinflammation and fibrosis were seen in 67% and 60% of these patients, respectively. Adefovir resistance mutations A181V or N236T developed in 13 LTSES patients; the first observation was at study week 195. There were no serious adverse events related to ADV. Conclusion: Treatment with ADV beyond 48 weeks was well tolerated and produced long-term virological, biochemical, serological, and histological improvement. (Hepatology 2008;48:750–758.)
News of Risk as a Potential Stressor
Authors: Mardi Horowitz
Journal: JAMA (1985)

Medicine now takes aim at prevention of disease by early recognition of risk factors. While increased knowledge of dispositions to disorder may permit early intervention, it surely facilitates early diagnosis. Yet even these advances in knwoledge carry potential hazards for the patient. Informing a person that he is at higher than usual risk for serious illness, or perhaps premature death, may set loose a train of thought and emotions that could, in some, culminate in a stress response syndrome. Serious news of risk is incongruent with the current world view of an individual. Many persons regard themselves as invulnerable to illness and death, believing that such events only strike others. This usually unconscious and self-benevolent form of denial may be shattered when a physician informs a patient, on routine physical examination, that his or her blood pressure is dangerously elevated, that a painless mass may be cancerous, or that a
Phase I Trial of Cyclophosphamide as an Immune Modulator for Optimizing Oncolytic Reovirus Delivery to Solid Tumors
Authors: Victoria Roulstone, Khurum Khan, Hardev S. Pandha, Sarah Rudman, Matt Coffey, George M. Gill, Alan A. Melcher, Richard Vile, Kevin J. Harrington, Johann de Bono, James Spicer
Journal: Clinical Cancer Research (2014)

Reovirus is a wild-type oncolytic virus that is ubiquitous in the environment; most patients are therefore preimmune. Therapeutic administration leads to an increase in neutralizing antireovirus antibody (NARA) titer. We hypothesized that if NARA limited reovirus antitumor activity, the effect might be attenuated by coadministration of cyclophosphamide.In a phase I study, patients with advanced cancer received cyclophosphamide 3 days before intravenous reovirus serotype 3 Dearing (RT3D). The primary objective was to reduce the resulting rise in NARA titer. Cyclophosphamide dose was escalated from 25-1,000 mg/m(2) through nine cohorts; we aimed to define a well-tolerated immunomodulatory dose.The combination was well tolerated in 36 patients, with grade 3/4 toxicities only seen at or above the maximum tolerated dose of cyclophosphamide, which was 800 mg/m(2) combined with reovirus. Immunosuppressive effect, defined as maintaining NARA titer rise below a predefined threshold, was observed in only one patient. Furthermore, despite expected myelosuppression seen at higher cyclophosphamide doses, no changes in T-cell subsets, including Tregs, occurred with dose escalation. Viable virus was detected in association with peripheral blood mononuclear cells (PBMC) from 14% of patients 10 days after the last RT3D injection, despite high plasma NARA titer, demonstrating a potential mechanism for prolonged evasion of neutralization by reovirus.Coadministration of cyclophosphamide with reovirus is safe, but does not attenuate host antiviral responses. Alternative immunomodulation approaches should be explored, but association with PBMCs may allow reovirus to persist and evade even high levels of neutralizing antibodies.
A POCKET STERILIZER AND INSTRUMENT CASE.
Authors: W. P. HERRICK
Journal: JAMA (1903)

The object in devising this case was to do for minor and emergency surgery what the compressed tablet has done for minor and emergency medicine. When closed and packed the case measures 7×3, ½×1½ inches or 17.5×8.5×4 cm., thus being easily portable in the breast pocket or emergency bag. A telescope cover (see cut) gives an extra sterilized tray for instruments after boiling. The box itself being the boiling tray, both of these are manipulated, when hot, by the handles, the boiling tray by holes in its upper edge on either end, the cover by its edges, and the instrument tray proper by its wire handles. Thus we have a sterile field, with three trays, produced in one boiling. As an instrument case, the instruments are packed in the instrument tray, held in place to prevent rattling or damage by spring crossbars caught in
Delivery by caesarean section
Authors: Ashis Banerjee, James Hollinshead, Edward Williams, Horng Yen Wee, Swee Chong Quek, Stephen Michael Kinsella, Dominique Nuala Lucas, Neville p.N. Robinson, Steve S.M. Yentis, Anita Holdcroft, Anne A.E. May, Michael Wee, Malcolm Griffiths, Bharati Sharma, A. Aguillera, Patricia Barlow, Serge Rozenberg, Vincent Richman, Peter Od D Pharoah, Mary Jane Platt, Ian I.Z. Mackenzie, Derek D.J. Tuffnell, Kimberly Wilkinson, Nicola Beresford, Richard M. Smith
Journal: BMJ (2001)
Is therapeutic ultrasound effective in treating soft tissue lesions?
Authors: A Binder, G Hodge, A M Greenwood, B L Hazleman, D P Page Thomas
Journal: BMJ (1985)

Of 76 patients with lateral epicondylitis, 38 were randomly allocated to receive ultrasound treatment and 38 placebo. All 76 were given 12 treatments each over four to six weeks. The conditions of 24 patients (63%) treated with ultrasound and 11 (29%) given placebo improved, the difference being significant at the 1% level. Improvement in particular clinical variables (pain score, weight lifting, grip strength) also showed an advantage for the patients given ultrasound treatment. A simple underwater radiation balance showed considerable fluctuation in ultrasonic output, and frequent checks of output were shown to be necessary. Ultrasound enhances recovery in most patients with lateral epicondylitis.
New Antagonists Excite an Old Histamine Prospector
Authors: Charles F. Code
Journal: New England Journal of Medicine (1974)

IN 1972 Black and his associates1 introduced burimamide, the first histamine H2*-receptor antagonist. Ever since, gastroenterologists have been excited by the prospect that this substance might provide the universal inhibitor of gastric secretion that they have sought, for so long, to control gastric secretion in patients with peptic-ulcer disease. The recent development of metiamide, a more potent member of the same family of drugs, by the same workers,2 has further heightened expectations — and justifiably so. Preliminary studies are encouraging.3 But we should step back to put these developments into perspective, at least as I see them from . . .
Cdk5rap1-Mediated 2-Methylthio Modification of Mitochondrial tRNAs Governs Protein Translation and Contributes to Myopathy in Mice and Humans
Authors: Fan-Yan Wei, Bo Zhou, Takeo Suzuki, Keishi Miyata, Yoshihiro Ujihara, Haruki Horiguchi, Nozomu Takahashi, Peiyu Xie, Hiroyuki Michiue, Atsushi Fujimura, Taku Kaitsuka, Hideki Matsui, Yasutoshi Koga, Satoshi Mohri, Tsutomu Suzuki, Yuichi Oike, Kazuhito Tomizawa
Journal: Cell Metabolism (2015)
Why Does Uremia in Heroin Abusers Occur Predominantly Among Blacks?
Authors: Eli A. Friedman
Journal: JAMA (1983)

Racial differences in the incidence and cause of renal failure have been reported in South Africa, where analgesic nephropathy is preponderantly a disease of whites and hypertensive kidney damage is observed mainly in blacks.<sup>1</sup>In the United States, analysis of expenditures by the federal end-stage renal disease (ESRD) program bears out the clinical impression held by urban nephrologists that renal failure is more prevalent in blacks than in whites. Of 61,184 patients entered into federally funded dialysis programs between July 1973 and March 1982, the proportion of blacks was 28.1%, which far exceeded their representation of 11% in the total population.<sup>2</sup> Sickle cell hemoglobinopathy causing renal papillary necrosis and hematuria in carriers of the trait and membranoproliferative glomerulonephritis, sometimes progressing to uremia, in those with sickle cell disease affords a clear example of a nephropathy transmitted genetically in blacks.<sup>3</sup>Hypertensive cardiorenal syndromes and strokes are common in
Abstract 2316: Therapeutic targeting of novel human stem cell and cancer associated glycans
Authors: Mary R. Saunders, Hyun Joo An, David J. Olivos, Yoshiko Maeda, Ryan G. Lim, Carlito B. Lebrilla, Kit S. Lam
Journal: Cancer Research (2011)

Abstract Host and tumor surface glycans are important in regulating pivotal pathophysiological events during the development of cancer and tumor progression. Changes in glycosylation allow tumorigenic cells to seize control over developmental processes which allow cells to proliferate, invade, promote angiogenesis, and metastasize. Malignant transformation is accompanied by the expression of oncofetal antigens which are expressed on embryonic cells, tumor cells, and a few adult cells. Glycans common to human embryonic stem cells and cancer cells can be targeted using combinatorial chemistry. Several peptidomimetic ligands have been discovered using One Bead One Compound (OBOC) and One Bead Two Compound (OB2C) methods. These cell adhering ligands possess the potential to target tumorigenic cells and mediate intracellular signaling events by binding to high mannose glycans expressed on the surface of Jurkat, TK6, Her2 expressing MCF7, chemoresistant MCF7, HeLa, and SiHa cell lines. Three lead linear peptides with alternating natural and unnatural amino acids have been investigated for their in vivo targeting potential in the lymphoid leukemia, breast, and cervical cancer mouse xenograph models. In vitro and in vivo stem and cancer cell experiments, which demonstrate genetically altered glycan function, are currently being investigated for their anticancer potential. These novel agents may be used alone or in combination with chemoradiation and anti-angiogenesis strategies for treating cancer. 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 2316. doi:10.1158/1538-7445.AM2011-2316
In vitro/in vivo biorecognition of lectin-immobilized fluorescent nanospheres for human colorectal cancer cells
Authors: Shinji Sakuma, Takanori Yano, Yoshie Masaoka, Makoto Kataoka, None Ken-ichiro Hiwatari, Hiroyuki Tachikawa, Yoshikazu Shoji, Ryoji Kimura, Huaiyu Ma, Zhijian Yang, Li Tang, Robert M. Hoffman, Shinji Yamashita
Journal: Journal of Controlled Release (2008)
A Phase I Weekly Dosing Study of Brentuximab Vedotin in Patients with Relapsed/Refractory CD30-Positive Hematologic Malignancies
Authors: Michelle A. Fanale, Andres Forero-Torres, Joseph D. Rosenblatt, Ranjana H. Advani, Anna R. Franklin, Dana A. Kennedy, Tae H. Han, Eric L. Sievers, Nancy L. Bartlett
Journal: Clinical Cancer Research (2011)

The antibody-drug conjugate (ADC) brentuximab vedotin comprises a CD30-directed antibody covalently attached to the potent antimicrotubule agent monomethyl auristatin E (MMAE) via a protease-cleavable linker. This study explored the safety, maximum-tolerated dose (MTD), and activity of weekly dosing of brentuximab vedotin in patients with relapsed or refractory CD30-positive hematologic malignancies.In this phase I dose-escalation study, brentuximab vedotin was administered intravenously on Days 1, 8, and 15, of each 28-day cycle at doses ranging from 0.4 to 1.4 mg/kg. Forty-four patients were enrolled: 38 with Hodgkin lymphoma, five with systemic anaplastic large cell lymphoma, and one with peripheral T-cell lymphoma not otherwise specified. Doses were escalated in increments of 0.2 mg/kg until dose-limiting toxicity (DLT) was observed. Patients were monitored for antitherapeutic antibodies and pharmacokinetic parameters. Antitumor assessments were carried out every two cycles.The MTD was 1.2 mg/kg. The most common adverse events were peripheral sensory neuropathy, fatigue, nausea, diarrhea, arthralgia, and pyrexia; and the majority of events were mild to moderate in severity. Tumor regression occurred in 85% of patients and the overall objective response rate was 59% (n = 24), with 34% (n = 14) complete remissions. The median duration of response was not reached at a median follow-up of 45 weeks on study.Weekly administration of brentuximab vedotin resulted in tumor regression and durable remissions in patients with CD30-positive malignancies. This ADC was associated with manageable toxicity, including peripheral neuropathy. Further study in CD30-positive malignancies is warranted.
Free personal care in Scotland may have to end, amid public spending pressure
Authors: B. Christie
Journal: BMJ (2009)

Free public services such as personal care for elderly people may have to be reconsidered in Scotland as public spending comes under pressure, an influential report has warned.

Audit Scotland calculates that if current spending levels continue, Scotland will overspend its budget by between £1.2bn (€1.3bn; $2bn) and £2.9bn by 2013-14. The 2% efficiency savings target set by the Scottish government will not be enough to fill this gap.

The Scottish budget, which mostly comes in a block grant from the UK parliament, could be cut by between 7% and 13% …
<i>Matrilysin</i>(<i>MMP-7</i>) Is a Novel Broadly Expressed Tumor Antigen Recognized by Antigen-Specific T Cells
Authors: Yuko Yokoyama, Frank Grünebach, Susanne M. Schmidt, Annkristin Heine, Maik Häntschel, Stefan Stevanovic, Hans-Georg Rammensee, Peter Brossart
Journal: Clinical Cancer Research (2008)

A prerequisite for the development of vaccination strategies is the identification and characterization of relevant tumor-associated antigen. Using microarray and reverse transcription-PCR analysis, we found matrix metalloproteinase (MMP)-7 to be extensively up-regulated in renal cell carcinomas and expressed in a broad variety of malignant cells. MMP-7 can promote cancer invasion and angiogenesis by proteolytic cleavage of extracellular matrix and basement membrane proteins, thus making it a promising target in the context of immunotherapies.To analyze the possible use of MMP-7 as a tumor-associated antigen, specific CTLs were induced using monocyte-derived dendritic cells electroporated with MMP-7-mRNA. In addition, to better characterize the fine specificity of these CTLs, MMP-7 MHC class I ligands were isolated and characterized in renal cell carcinoma tissue, which overexpressed MMP-7, by mass spectrometry-based peptide sequencing. Using this approach, we identified a novel HLA-A3-binding antigenic MMP-7 peptide. CTLs generated from healthy donors by in vitro priming with dendritic cells, pulsed with the novel peptide, were used as effectors in (51)Cr-release assays.The induced CTLs elicited an antigen-specific and HLA-restricted cytolytic activity against tumor cells endogenously expressing the MMP-7 protein. Furthermore, we were able to induce MMP-7-specific CTLs using peripheral blood mononuclear cells from a patient with acute lymphoblastic leukemia capable of recognizing the autologous leukemic blasts while sparing nonmalignant cells.Our study describes the identification of a novel broadly expressed T-cell epitope derived from the MMP-7 protein that represents an interesting candidate to be applied in immunotherapies of human malignancies targeting both tumor cells and neovascularization.
Down-regulation of Platelet-Derived Growth Factor-D Inhibits Cell Growth and Angiogenesis through Inactivation of Notch-1 and Nuclear Factor-κB Signaling
Authors: Zhiwei Wang, Dejuan Kong, Sanjeev Banerjee, Yiwei Li, N. Volkan Adsay, James Abbruzzese, Fazlul H. Sarkar
Journal: Cancer Research (2007)

Abstract Platelet-derived growth factor-D (PDGF-D) signaling plays critical roles in the pathogenesis and progression of human malignancies; however, the precise mechanism by which PDGF-D causes tumor cell invasion and angiogenesis remain unclear. Because Notch-1, nuclear factor-κB (NF-κB), vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMP) are critically involved in the processes of tumor cell invasion and metastasis, we investigated whether PDGF-D down-regulation could be mechanistically associated with the down-regulation of Notch-1, NF-κB, VEGF, and MMP-9, resulting in the inhibition of tumor cell invasion and angiogenesis. Our data showed that down-regulation of PDGF-D leads to the inactivation of Notch-1 and NF-κB DNA-binding activity and, in turn, down regulates the expression of its target genes, such as VEGF and MMP-9. We also found that the down-regulation of PDGF-D by small interfering RNA (siRNA) decreased tumor cell invasion, whereas PDGF-D overexpression by cDNA transfection led to increased cell invasion. Consistent with these results, we also found that the down-regulation of PDGF-D not only decreased MMP-9 mRNA and its protein expression but also inhibited the processing of pro-MMP-9 protein to its active form. Moreover, conditioned medium from PDGF-D siRNA–transfected cells showed reduced levels of VEGF and, in turn, inhibited the tube formation of human umbilical vascular endothelial cells, suggesting that down-regulation of PDGF-D leads to the inhibition of angiogenesis. Taken together, we conclude that the down-regulation of PDGF-D by novel approaches could lead to the down-regulation of Notch-1 and, in turn, inactivate NF-κB and its target genes (i.e., MMP-9 and VEGF), resulting in the inhibition of invasion and angiogenesis. [Cancer Res 2007;67(23):11377–85]
TrkA alternative splicing
Authors: Antonella Tacconelli, Antonietta R. Farina, Lucia Cappabianca, Giuseppina DeSantis, Alessandra Tessitore, Antonella Vetuschi, Roberta Sferra, Nadia Rucci, Beatrice Argenti, Isabella Screpanti, Alberto Gulino, Andrew R. Mackay
Journal: Cancer Cell (2004)
Anti-cardiolipin antibodies (anti-CL) in patients with hepatitis C virus (HCV) infection are independent of beta2-glycoprotein I (b2GPI) co-factor or features of antiphospholipid syndrome (APS)
Authors: Kalliopi Zachou, Christos Liaskos, Demitrios Christodoulou, Mara Kardasi, Georgia Papadamou, Nikolaos Gatselis, Fotios Gerovasilis, Epameinondas Tsianos, Georgios Dalekos
Journal: Journal of Hepatology (2002)