tbuckley/cabot-search huggingface dataset:
PROGNOSIS IN DRUG ADDICTION
Authors: M. J. PESCOR.
Journal: American Journal of Psychiatry (1941)

1. Statistically significant criteria distinguishing good, guarded and poor prognoses from each other were determined on the basis of the clinical records of 1,036 drug addicts admitted to the U. S. Public Health Service Hospital at Lexington, Kentucky, during the fiscal year July 1, 1936 to June 30, 1937. 2. Case histories of composite individuals most representative of their respective prognoses are presented. 3. Follow-up studies made of the patients after release from the hospital reveal that 43.8 per cent with a good prognosis, 36.9 per cent with a guarded prognosis, and 20.7 per cent with a poor prognosis were still abstinent. 4. For practical purposes the prognosis may be reduced to two categories, poor and guarded.
A Phase 1 Study of AS1409, a Novel Antibody-Cytokine Fusion Protein, in Patients with Malignant Melanoma or Renal Cell Carcinoma
Authors: Sarah M. Rudman, Michael B. Jameson, Mark J. McKeage, Philip Savage, Duncan I. Jodrell, Mark Harries, Gary Acton, Fredrik Erlandsson, James F. Spicer
Journal: Clinical Cancer Research (2011)

Abstract Purpose: AS1409 is a fusion protein comprising a humanized antibody BC1 linked to interleukin-12 (IL-12). It is designed to deliver IL-12 to tumor-associated vasculature using an antibody targeting the ED-B variant of fibronectin. Experimental Design: We conducted a phase 1 trial of weekly infusional AS1409 in renal carcinoma and malignant melanoma patients. Safety, efficacy, markers of IL-12–mediated immune response, and pharmacokinetics were evaluated. Results: A total of 11 melanoma and 2 renal cell carcinoma patients were treated. Doses of 15 and 25 μg/kg were studied. Most drug-related adverse events were grade 2 or less, and included pyrexia, fatigue, chills, headache, vomiting, and transient liver function abnormalities. Three dose limiting toxicities of grade 3 fatigue and transaminase elevation were seen at 25 μg/kg. IFN-γ and interferon-inducible protein-10 (IP-10) were elevated in all patients, indicating activation of cell-mediated immune response; this was attenuated at subsequent cycles. Antidrug antibody responses were seen in all patients, although bioassays indicate these do not neutralize AS1409 activity. Plasma half-life was 22 hours and not dose-dependent. Five patients received 6 cycles or more and a best response of at least stable disease was seen in 6 (46%) patients. Partial response was seen in a melanoma patient, and disease shrinkage associated with metabolic response was maintained beyond 12 months in another melanoma patient despite previous rapid progression. Conclusions: The maximum tolerated dose was established at 15 μg/kg weekly. AS1409 is well tolerated at this dose. Evidence of efficacy assessed by RECIST, functional imaging, and biomarker response warrants the planned further investigation using this dose and schedule in malignant melanoma. Clin Cancer Res; 17(7); 1998–2005. ©2011 AACR.
Middle East respiratory syndrome coronavirus in dromedary camels: an outbreak investigation
Authors: Bart L Haagmans, Said H S Al Dhahiry, Chantal B E M Reusken, V Stalin Raj, Monica Galiano, Richard Myers, Gert-Jan Godeke, Marcel Jonges, Elmoubasher Farag, Ayman Diab, Hazem Ghobashy, Farhoud Alhajri, Mohamed Al-Thani, Salih A Al-Marri, Hamad E Al Romaihi, Abdullatif Al Khal, Alison Bermingham, Albert D M E Osterhaus, Mohd M AlHajri, Marion P G Koopmans
Journal: The Lancet Infectious Diseases (2013)
The impact of primary tumour origins in patients with advanced oesophageal, oesophago–gastric junction and gastric adenocarcinoma—individual patient data from 1775 patients in four randomised controlled trials
Authors: I. Chau, A.R. Norman, D. Cunningham, J. Oates, R. Hawkins, T. Iveson, M. Nicolson, P. Harper, M. Seymour, T. Hickish
Journal: Annals of Oncology (2009)
Suboptimal Use of Cardioprotective Drugs in Newly Treated Elderly Individuals With Type 2 Diabetes
Authors: Caroline Sirois, Jocelyne Moisan, Paul Poirier, Jean-Pierre Grégoire
Journal: Diabetes Care (2007)

Cardiovascular disease is the main complication experienced by elderly individuals with diabetes (1). Despite randomized trials showing the benefits of individual (2–4) or combined (5) pharmacological treatments of cardiovascular risk factors in diabetes, observational studies have shown suboptimal use of medications (6–8). However, little is known about the use of cardioprotective medication among elderly individuals who were not already taking it before diabetes treatment was undertaken. We therefore studied a population of elderly individuals with type 2 diabetes in the province of Quebec, Canada, who had not been treated with any antihypertensive, lipid-lowering, or antiplatelet drugs in the year before oral antidiabetes drug initiation. We assessed whether they used a comprehensive cardioprotective regimen (CCR) of those three medications in the year following oral antidiabetic initiation. We also identified the determinants of a CCR use.

We carried out a population-based inception cohort study using the Quebec Diabetes Surveillance System, which is the product of linking public health administrative databases managed by the Quebec Health Insurance Board. It includes information on patient demographics, physician and hospital services, and data from the public drug plan for individuals who had been diagnosed with diabetes.

We selected individuals aged ≥66 years who had initiated an oral antidiabetes medication treatment between 1 January 1998 and 31 December 2002. The date of the first claim was the index date. We excluded individuals who had …
Endothelium-Dependent Relaxation of Small Resistance Vessels Is Impaired in Patients with Autosomal Dominant Polycystic Kidney Disease
Authors: DAN WANG, JENS IVERSEN, SVEND STRANDGAARD
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Impaired endothelium-dependent relaxation has been demonstrated previously in resistance vessels of Han:SPRD polycystic kidney disease rats. The aim of the present study was to investigate whether endothelium-dependent relaxation is reduced also in patients with autosomal dominant polycystic kidney disease (ADPKD) and whether this is influenced by the nitric oxide (NO) system. Small subcutaneous resistance vessels from normotensive ADPKD patients with normal or near-normal renal function ( n = 9) and from healthy control subjects ( n = 10) were mounted in a Mulvany-Halpern myograph. The morphology of the vessels and acetylcholine (ACh)-induced endothelium-dependent relaxation, as well as 3-morpholino-sydnonimine (SIN-1, NO donor)-induced endothelium-independent relaxation were investigated. The results showed that: ( 1 ) there were no significant differences in morphologic parameters of resistance vessels between the two groups; ( 2 ) the maximal ACh-induced relaxation rate was decreased in ADPKD patients compared with control subjects (71.5 ± 12.1 versus 85.2 ± 8.7%, P &lt; 0.01); ( 3 ) in the presence of L-arginine (a substrate of NO synthase), a left shift of the ACh dose-response curves was found in control subjects, but not in ADPKD patients; ( 4 ) in the presence of the N G -nitro-L-arginine methyl ester (an inhibitor of NO synthase), a right shift of the ACh dose-response curve was found in control subjects, but not in ADPKD patients; and ( 5 ) endothelium-independent relaxation rate induced with SIN-1 was similar in patients and control subjects. In conclusion, endothelium-dependent relaxation was impaired in resistance vessels from patients with ADPKD. The reduced response of the vessels to both the substrate and inhibitor of NO synthase in ADPKD suggests that an impairment of NO synthase may be involved in the mechanism of endothelial dysfunction in ADPKD.
The DEAD-box RNA helicase Vad1 regulates multiple virulence-associated genes in Cryptococcus neoformans
Authors: John Panepinto, Lide Liu, Jeanie Ramos, Xudong Zhu, Tibor Valyi-Nagy, Saliha Eksi, Jianmin Fu, H. Ari Jaffe, Brian Wickes, Peter R. Williamson
Journal: Journal of Clinical Investigation (2005)

The study of fungal regulatory networks is essential to the understanding of how these pathogens respond to host environmental signals with effective virulence-associated traits. In this study, a virulence-associated DEAD-box RNA helicase–encoding gene (VAD1) was isolated from a mutant defective in the virulence factor laccase. A Δvad1 mutant exhibited a profound reduction in virulence in a mouse model that was restored after reconstitution with WT VAD1. Loss of VAD1 resulted in upregulation of NOT1, a gene encoding a global repressor of transcription. NOT1 was found to act as an intermediary transcriptional repressor of laccase. Vad1 was located within macromolecular complexes that formed cytoplasmic granular bodies in mature cells and during infection of mouse brain. In addition, VAD1 was shown by in situ hybridization to be expressed in the brain of an AIDS patient coinfected with C. neoformans. To understand the role of VAD1 in virulence, a functional genomics approach was used to identify 3 additional virulence determinants dependent on VAD1: PCK1, TUF1, and MPF3, involved in gluconeogenesis, mitochondrial protein synthesis, and cell wall integrity, respectively. These data show that fungal virulence-associated genes are coordinately regulated and that an analysis of such transcriptomes allows for the identification of important new genes involved in the normal growth and virulence of fungal pathogens.
Making cervical screening work
Authors: C. Smith
Journal: BMJ (1989)

to devolve more of its negotiating to local units but also to work at all levels of the service with other professions, consumer organisations, and even with politicians to make managers more aware of patients' needs.Perhaps the association's greatest challenge, however, will be to maintain the profession's unity as devolution of power might well lead to fragmentation of doctors' influence.Special pleading and defence of traditional boundaries-whether craft or specialty, academic or service, career or training grade-will not necessarily serve the interests of patients or the profession.If doctors follow that route politicians and managers will divide and rule.The association has the capability through its national, regional, and divisional structure to build on the present consensus and use it to serve the interests of patients and those who work in the service.The continued commitment of staff is vital.
B-Crystallin is a novel oncoprotein that predicts poor clinical outcome in breast cancer
Authors: J. V. Moyano
Journal: Journal of Clinical Investigation (2005)

Recent gene profiling studies have identified a new breast cancer subtype, the basal-like group, which expresses genes characteristic of basal epithelial cells and is associated with poor clinical outcomes. However, the genes responsible for the aggressive behavior observed in this group are largely unknown. Here we report that the small heat shock protein α-basic–crystallin (αB-crystallin) was commonly expressed in basal-like tumors and predicted poor survival in breast cancer patients independently of other prognostic markers. We also demonstrate that overexpression of αB-crystallin transformed immortalized human mammary epithelial cells (MECs). In 3D basement membrane culture, αB-crystallin overexpression induced luminal filling and other neoplastic-like changes in mammary acini, while silencing αB-crystallin by RNA interference inhibited these abnormalities. αB-Crystallin overexpression also induced EGF- and anchorage-independent growth, increased cell migration and invasion, and constitutively activated the MAPK kinase/ERK (MEK/ERK) pathway. Moreover, the transformed phenotype conferred by αB-crystallin was suppressed by MEK inhibitors. In addition, immortalized human MECs overexpressing αB-crystallin formed invasive mammary carcinomas in nude mice that recapitulated aspects of human basal-like breast tumors. Collectively, our results indicate that αB-crystallin is a novel oncoprotein expressed in basal-like breast carcinomas that independently predicts shorter survival. Our data also implicate the MEK/ERK pathway as a potential therapeutic target for these tumors.
Peptide-Mediated Targeting to Tumor Blood Vessels of Lung Cancer for Drug Delivery
Authors: Tong-Young Lee, Chin-Tarng Lin, Szu-Yao Kuo, De-Kuan Chang, Han-Chung Wu
Journal: Cancer Research (2007)

Antiangiogenesis therapies for the treatment of cancers hold the promise of high efficacy and low toxicity. In vivo phage display was used to identify peptides specifically targeting tumor blood vessels. The peptide SP5-52 recognized tumor neovasculature but not normal blood vessels in severe combined immunodeficiency mice bearing human tumors. Synthetic peptide was shown to inhibit the binding of PC5-52 phage particles to the tumor mass in the competitive inhibition assay. Several selected phage clones displayed the consensus motif, proline-serine-proline, and this motif was crucial for peptide binding to the tumor neovasculature. SP5-52 peptides also bound vascular endothelial growth factor-stimulated human umbilical vein endothelial cells and blood vessels of human lung cancer surgical specimens. Furthermore, this targeting phage was shown to home to tumor tissues from eight different types of human tumor xenografts following in vivo phage display experiments. An SP5-52 peptide-linked liposome carrying doxorubicin enhanced the therapeutic efficacy of the drug, markedly decreased tumor blood vessels, and resulted in higher survival rates of human lung and oral cancer-bearing xenograft mice. The current study indicates that ligand-targeted therapy offers improved therapeutic effects over conventional anticancer drug therapy, and that the peptide SP5-52 specifically targets tumor neovasculature and is a good candidate for targeted drug delivery to solid tumors.
Diagnostic aids for detection of oral precancerous conditions
Authors: Diana V Messadi
Journal: International Journal of Oral Science (2013)

Oral cancer has a tendency to be detected at late stage which is detrimental to the patients because of its high mortality and morbidity rates. Early detection of oral cancer is therefore important to reduce the burden of this devastating disease. In this review article, the most common oral precancerous lesions are discussed and the importance of early diagnosis is emphasized. In addition, the most common non-invasive oral cancer devices that can aid the general practitioners in early diagnosis are also discussed. A number of diagnostic techniques exist to ascertain whether a mouth lesion could become an oral cancer. In a review article, Diana V Messadi from the University of California, Los Angeles School of Dentistry, USA, details the known pathological conditions considered to be precancerous. These include leukoplakia and erythroplakia, both of which are marked by abnormally colored patches of cells on the mucous membrane that lines that inside of our cheeks, as well as the inflammatory diseases oral lichen planus and oral submucous fibrosis. Messadi also catalogues non-invasive screening tools such as dye systems, fluorescent technologies and cell-collection kits, all of which can catch signs of cancer before lesions turn malignant. She notes that early diagnosis is the most important predictor of patient outcome for anyone with oral cancer, requiring dentists to have adequate knowledge and training.
Mechanism of cAMP regulation of renin gene transcription by proximal promoter.
Authors: K Tamura, S Umemura, S Yamaguchi, T Iwamoto, S Kobayashi, A Fukamizu, K Murakami, M Ishii
Journal: Journal of Clinical Investigation (1994)

Renin is produced mainly by the kidney, and cAMP is a main positive regulator of its synthesis. This study was undertaken to analyze the molecular mechanism of cAMP-mediated regulation of Ren-1C gene transcription by the proximal promoter. We first showed that the promoter region from -365 to +16 of the mouse renin gene (Ren-1C) mediated the cAMP-induced chloramphenicol acetyltransferase gene expression in embryonic kidney-derived 293 cells. Deletion analysis and heterologous promoter assay disclosed that the proximal promoter region from -75 to +16 was able to activate chloramphenicol acetyltransferase expression by cAMP, and indicated that the proximal promoter element from -75 to -47 (RP-2 element) overlapping the TATA-like region was able to confer cAMP responsiveness. Electrophoretic mobility shift assay and DNase I footprinting analysis demonstrated that novel nuclear factors in 293 cells interacted with the RP-2 element, and that cAMP increased the binding activity of these nuclear factors to the RP-2 element. Furthermore, we demonstrated that cAMP enhanced the binding of nuclear factors derived from juxtaglomerular cells, the main production site of renin in the kidney, to the RP-2 element in vivo. These results suggest that the RP-2 element plays an important role in the cAMP-mediated regulation of Ren-1C gene transcription through the proximal promoter.
Neuronal Na+ channel blockade suppresses arrhythmogenic diastolic Ca2+ release
Authors: Przemysław B. Radwański, Lucia Brunello, Rengasayee Veeraraghavan, Hsiang-Ting Ho, Qing Lou, Michael A. Makara, Andriy E. Belevych, Mircea Anghelescu, Silvia G. Priori, Pompeo Volpe, Thomas J. Hund, Paul M. L. Janssen, Peter J. Mohler, John H. B. Bridge, Steven Poelzing, Sándor Györke
Journal: Cardiovascular Research (2014)

AimsSudden death resulting from cardiac arrhythmias is the most common consequence of cardiac disease. Certain arrhythmias caused by abnormal impulse formation including catecholaminergic polymorphic ventricular tachycardia (CPVT) are associated with delayed afterdepolarizations resulting from diastolic Ca2+ release (DCR) from the sarcoplasmic reticulum (SR). Despite high response of CPVT to agents directly affecting Ca2+ cycling, the incidence of refractory cases is still significant. Surprisingly, these patients often respond to treatment with Na+ channel blockers. However, the relationship between Na+ influx and disturbances in Ca2+ handling immediately preceding arrhythmias in CPVT remains poorly understood and is the object of this study.
Elevated superoxide generation in mononuclear phagocytes by treatment with 1 alpha hydroxyvitamin D3
Authors: A Deutsch, C Chaimovitzch, O Nagauker-Shriker, M Zlotnik, S Shany, R Levy
Journal: Journal of the American Society of Nephrology (1995)

The effect of 1 alpha-hydroxyvitamin D3 (1 alpha OHD3) treatment on the superoxide production of phagocytic cells in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) was studied. A 3-day treatment of CAPD patients with 3 micrograms per day of 1 alpha OHD3 (high-dose treatment) significantly increased NADPH oxidase and killing activities in peritoneal macrophages and peripheral blood monocytes (P < 0.001) as compared with low-dose (0.25 microgram/day of 1 alpha OHD3) treatment or nontreatment. The high oxidase activity observed in macrophages and monocytes after the treatment with 1 alpha OHD3, correlated significantly to the increase in the amount of the cytosolic factor p47 of the NADPH oxidase as detected by western blotting analysis. Superoxide production by the peripheral blood neutrophils of these patients only slightly increased with 1 alpha OHD3 treatment, and the amount of p47 was not affected by 1 alpha OHD3 administration. In order to evaluate the significance of the oxidase cytosolic factor in dictating oxidase activity, a reconstitution of NADPH oxidase was conducted by mixing macrophage cytosols and membranes in a cell-free system. The addition of macrophage cytosol from patients on high-dose treatment to macrophage membranes from patients in all of the categories of treatment resulted in significantly higher (P < 0.001) superoxide production as opposed to the macrophage cytosol from nontreated patients. These results suggest that 1,25(OH)2D3 causes an increase in NADPH oxidase activity in the peritoneal macrophages and monocytes of CAPD patients by inducing synthesis and elevating the amount of the cytosolic factor p47.(ABSTRACT TRUNCATED AT 250 WORDS)
Intravenous Amiodarone for Incessant Tachyarrhythmias in Children
Authors: J. Philip Saul, William A. Scott, Stephen Brown, Pablo Marantz, Valeria Acevedo, Susan P. Etheridge, James C. Perry, John K. Triedman, Susan W. Burriss, Paul Cargo, Jay Graepel, Eeva-Kaarina Koskelo, Rebecca Wang
Journal: Circulation (2005)

Background— Intravenous (IV) amiodarone has proven efficacy in adults. However, its use in children is based on limited retrospective data. Methods and Results— A double-blind, randomized, multicenter, dose-response study of the safety and efficacy of IV amiodarone was conducted in 61 children (30 days to 14.9 years; median, 1.6 years). Children with incessant tachyarrhythmias (supraventricular arrhythmias [n=26], junctional ectopic tachycardia [JET, n=31], or ventricular arrhythmias [n=4]) were randomized to 1 of 3 dosing regimens (low, medium, or high: load plus 47-hour maintenance) with up to 5 open-label rescue doses. The primary efficacy end point was time to success. Of 229 patients screened, 61 were enrolled during 13 months by 27 of 48 centers in 7 countries. Median time to success was significantly related to dose (28.2, 2.6, and 2.1 hours for the low-, medium-, and high-dose groups, respectively; P =0.028). There was no significant association with dose for any arrhythmia subgroup, including JET, but the subgroups were too small for an accurate assessment. Adverse events (AEs) were common (87%), leading to withdrawal of 10 patients. There were 5 deaths in the 30-day follow-up period (2 possibly related to the study drug). Dose-related AEs included hypotension (36%), vomiting (20%), bradycardia (20%), atrioventricular block (15%) and nausea (10%). Conclusions— In children, the overall efficacy of IV amiodarone, as measured by time to success, was dose related but not significantly for any arrhythmia subgroup. AEs were common and appeared to be dose related. Although efficacious for critically ill patients, the dose-related risks of IV amiodarone should be taken into account when treating children with incessant arrhythmias. Prospective, placebo-controlled trials would be helpful in assessing antiarrhythmic drug efficacy in children, because their results may differ from retrospective series and adult studies.
Human Diploid Cell Rabies Vaccine: More Protection for Less Risk?
Authors: E. Russell Alexander
Journal: JAMA (1980)

It is estimated that animal bites come to medical attention at an annual rate of 1/200 persons.<sup>1</sup>This encounter results in rabies vaccination for 30,000 persons per year. As an infectious diseases consultant, I can certify that the complications and concerns surrounding rabies vaccination are the most frequent problems that are brought to us—as they are to the local, state, or federal epidemiologist. The concern is well based. In 1957, duck embryo vaccine (DEV) was substituted for nerve-tissue—Origin vaccine (Semple type), because the same protection could be gained for a significant decrease in reactions—from neuroparalytic reaction of about 1/2,000 vaccinates to 1/24,400 (twenty-one among 512,000 recipients of DEV 1958-1975).<sup>2</sup>Although this was a 12-fold reduction, the price of rabies protection remained high. The 21 reactions included five cases of transverse myelitis, seven cases of cranial or peripheral neuropathy, and nine cases of encephalopathy. Virtually all recipients of DEV