tbuckley/cabot-search huggingface dataset:
Phase II study of depsipeptide (DEP) in radioiodine (RAI)-refractory metastatic nonmedullary thyroid carcinoma
Authors: E. J. Sherman, M. G. Fury, R. M. Tuttle, R. Ghossein, H. Stambuk, M. Baum, D. Lisa, Y. B. Su, A. Shaha, D. G. Pfister
Journal: Journal of Clinical Oncology (2009)

6059 Background: Historically, systemic therapy for radioactive iodine (RAI)-refractory thyroid cancer has been understudied. Available drugs have modest efficacy. Depsipeptide (DEP) is a histone deacetylase inhibitor with potent anti-tumor effects both in vitro and in vivo. In thyroid cancer cell lines, DEP increases expression of both thyroglobulin and the sodium/iodine symporter messenger RNAs, offering the possibility of improved iodine concentrating ability of radioactive iodine (RAI)-resistant tumors. Methods: Eligible patients (pts) must have progressive, RAI-refractory, recurrent/metastatic, non-medullary, non-anaplastic thyroid cancer; RECIST measurable disease; and adequate organ/marrow function. Exclusionary criteria include prior chemotherapy in the recurrent/metastatic setting; cardiac disease or dysfunction; QTc prolongation or co-administration of drugs that prolong the QTc. DEP 13 mg/m 2 IV is administered on days 1, 8, 15, every 28 days. The primary endpoint is response rate by RECIST criteria; change in RAI avidity is a secondary endpoint. The study closed early due to poor accrual after an unexpected grade 5 adverse event (AE) that prompted protocol suspension. Results: 20 pts were enrolled: female-50%; median age-64 years; histology-papillary (8)/follicular (1)/Hürthle (11). Grade 4–5 AE possibly related to drug: grade 5 sudden death (1); grade 4 -pulmonary embolus (1). Twelve of 20 subjects had a reported AE. No RECIST major responses have been seen. Evaluation of response: stable disease (10); progression (3); early death (1); unknown/inevaluable (6: 5 - temporary protocol suspension; 1 - withdrew consent). Restoration of RAI avidity was documented in 2 pts. For evaluable patients (14) only, median overall survival and time on study was 36 (.5–45+) months and 1.7 (0.46–12) months, respectively. Conclusions: We observed preliminary signs of in vivo reversal of RAI resistance after treatment with DEP. However, no major responses were observed and accrual was poor after the grade 5 AE. (Study funded by grant N01 CM 62206) No significant financial relationships to disclose.
Testing Source Patient Blood for HIV Antibodies After Accidental Exposure of Health Care Workers to Blood and Body Fluids
Authors: Stanley Bauer
Journal: JAMA (1989)

To the Editor.—  Until recently, if a health care worker was exposed to the blood or body fluids of a human immunodeficiency virus (HIV)-infected individual little was done except to counsel the worker and follow up the worker for evidence of HIV infection. If the HIV status of the source patient is not known, the Centers for Disease Control, Atlanta, Ga, has recommended that informed consent be obtained to test for HIV antibodies. Moreover, informed consent for HIV antibody testing is required by many states.  However, there now is positive action that may be taken after accidental exposure. There is evidence based on animal studies that zidovudine, alone or in combination with interferon alfa, can prevent or alter experimental retrovirus infection and that the effectiveness of zidovudine in preventing disease is greatest when it is administered soon after inoculation rather than after a delay. 1-4 The National Institutes of Health,
THE WORST SYMPTOM VISUAL ANALOGUE SCALE: A PROSPECTIVE ANCILLARY STUDY FROM THE RENAL OPTIMIZATION STRATEGIES EVALUATION IN ACUTE HEART FAILURE (ROSE-AHF) TRIAL
Authors: Omar AbouEzzeddine, Anu Lala, Yee Weng Wong, Robert Mentz, Prateeti Khazanie, Steven McNulty, Kevin Anstrom, Adrian Hernandez, Peter Pang, Monica Shah, Michael Givertz, Inderjit Anand, Javed Butler, Marc Semigran, Eugene Braunwald, Lynne Stevenson, Margaret Redfield
Journal: Journal of the American College of Cardiology (2014)
Increased embolic risk in patients with left ventricular thrombi.
Authors: J R Stratton, A D Resnick
Journal: Circulation (1987)

Although left ventricular thrombi are associated with an increased embolic risk in the first few weeks after acute myocardial infarction, the long-term risk remains undefined. To ascertain the incidence of strictly defined systemic emboli, we followed 85 patients with echocardiographically documented left ventricular thrombi. At the time of the entry echocardiogram, most patients (n = 57) had remote myocardial infarction, while 19 had recent (less than 1 month) infarction, and nine had idiopathic cardiomyopathy. Because of the difficulty in classifying events as embolic in patients with advanced atherosclerosis, a matched control group of 91 patients without thrombi was also studied. The thrombus and control groups were similar with regard to recent myocardial infarction, remote infarction, anterior infarction, ejection fraction, atrial fibrillation, echocardiographic referral for source of emboli, and warfarin therapy. During a mean follow-up of 22 months after echocardiography, embolic events occurred in 13% (11 of 85) of patients with thrombi compared with 2% (two of 91) control patients (p less than .01). The actuarial probability of being embolus free at 2 years after echocardiography was 86% in patients with thrombi compared with 97% in control patients (p less than .01). All embolic events occurred greater than 1 month after myocardial infarction (range 1 to 96 months). The only clinical or echocardiographic features predictive of embolization were protrusion and mobility of thrombus (both p less than .02). We conclude that the incidence of embolic events is definitely increased in patients with left ventricular thrombi compared with control subjects during long-term follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)
Cancer of the urogenital tract: bladder cancer. Comment: an occupational disease
Authors: P. Rubin
Journal: JAMA (1968)

Cancer is most often thought of as a spontaneous process in which no known inciting agent has been identified. This does not mean that known causes do not exist. There is an extensive literature dealing with carcinogenic agents, and Dr. McDonald has succinctly defined those related to chronic industrial exposures in bladder tumorigenesis. Despite the known relationship between certain chemical carcinogens and bladder cancer, the translation of scientific facts into effective legislation is slow and virtually nonexistent in the United States. It should be emphasized that despite the facts that cancer of the bladder has been produced in workers in chemical, rubber, cable, and a number of other industries, and that its incidence is on the increase, to date—with the exception of the Commonwealth of Pennsylvania— no federal or state legislation exists in the United States for the regulation of the manufacture, use, or importation of these chemicals. The lack
Baculovirus GP64-pseudotyped HIV-based lentivirus vectors are stabilized against complement inactivation by codisplay of decay accelerating factor (DAF) or of a GP64–DAF fusion protein
Authors: Ghiabe H. Guibinga, Theodore Friedmann
Journal: Molecular Therapy (2005)

The eventual development of efficient gene transfer vectors for in vivo gene delivery will require the development of a number of important new technologies such as stabilization of vectors against protective mechanisms that destroy or otherwise inactivate foreign infectious agents like gene transfer vectors. It is known that the baculovirus envelope protein GP64 of Autographa californica nucleopolyhedrovirus can efficiently pseudotype lentivirus vectors and that modified forms of the baculovirus envelope protein GP64 can also assemble efficiently into baculovirus particles to display functional foreign proteins on the baculovirus surface. In the present study we have combined these techniques to prepare HIV-based lentivirus vectors pseudotyped with GP64 envelope protein and coexpressing a fusion protein of GP64 with the complement-regulatory, decay accelerating factor (DAF, CD55). In addition, we have also prepared GP64-pseudotyped vectors in the presence of a DAF expression plasmid to allow the incorporation of DAF protein into viral particles. Our results demonstrate both the efficient expression and the high-titer production of GP64/GP64-DAF and GP64/DAF-pseudotyped particles and their stability against inactivation by human and nonhuman primate serum.
A Single Intravenous rAAV Injection as Late as P20 Achieves Efficacious and Sustained CNS Gene Therapy in Canavan Mice
Authors: Seemin Seher Ahmed, Huapeng Li, Chunyan Cao, Elif M Sikoglu, Andrew R Denninger, Qin Su, Samuel Eaton, Ana A Liso Navarro, Jun Xie, Sylvia Szucs, Hongwei Zhang, Constance Moore, Daniel A Kirschner, Thomas N Seyfried, Terence R Flotte, Reuben Matalon, Guangping Gao
Journal: Molecular Therapy (2013)

Canavan's disease (CD) is a fatal pediatric leukodystrophy caused by mutations in aspartoacylase (AspA) gene. Currently, there is no effective treatment for CD; however, gene therapy is an attractive approach to ameliorate the disease. Here, we studied progressive neuropathology and gene therapy in short-lived (≤1 month) AspA−/− mice, a bona-fide animal model for the severest form of CD. Single intravenous (IV) injections of several primate-derived recombinant adeno-associated viruses (rAAVs) as late as postnatal day 20 (P20) completely rescued their early lethality and alleviated the major disease symptoms, extending survival in P0-injected rAAV9 and rAAVrh8 groups to as long as 2 years thus far. We successfully used microRNA (miRNA)-mediated post-transcriptional detargeting for the first time to restrict therapeutic rAAV expression in the central nervous system (CNS) and minimize potentially deleterious effects of transgene overexpression in peripheral tissues. rAAV treatment globally improved CNS myelination, although some abnormalities persisted in the content and distribution of myelin-specific and -enriched lipids. We demonstrate that systemically delivered and CNS-restricted rAAVs can serve as efficacious and sustained gene therapeutics in a model of a severe neurodegenerative disorder even when administered as late as P20. Canavan's disease (CD) is a fatal pediatric leukodystrophy caused by mutations in aspartoacylase (AspA) gene. Currently, there is no effective treatment for CD; however, gene therapy is an attractive approach to ameliorate the disease. Here, we studied progressive neuropathology and gene therapy in short-lived (≤1 month) AspA−/− mice, a bona-fide animal model for the severest form of CD. Single intravenous (IV) injections of several primate-derived recombinant adeno-associated viruses (rAAVs) as late as postnatal day 20 (P20) completely rescued their early lethality and alleviated the major disease symptoms, extending survival in P0-injected rAAV9 and rAAVrh8 groups to as long as 2 years thus far. We successfully used microRNA (miRNA)-mediated post-transcriptional detargeting for the first time to restrict therapeutic rAAV expression in the central nervous system (CNS) and minimize potentially deleterious effects of transgene overexpression in peripheral tissues. rAAV treatment globally improved CNS myelination, although some abnormalities persisted in the content and distribution of myelin-specific and -enriched lipids. We demonstrate that systemically delivered and CNS-restricted rAAVs can serve as efficacious and sustained gene therapeutics in a model of a severe neurodegenerative disorder even when administered as late as P20.
The right way, the wrong way, and the army way: A dendritic parable
Authors: Arnold B. Scheibel
Journal: Behavioral and Brain Sciences (1997)

We suggest that neither selectionism nor constructivism alone are responsible for learning-based changes in the brain. On the basis of quantitative structural studies of human brain tissue it has been possible to find evidence of both increase and decrease in tissue mass at synaptic and dendritic levels. It would appear that both processes are involved in the course of learning-dependent changes.
OBSERVATIONS ON CONGENITAL DISLOCATION OF THE HIP.
Authors: BERNARD E. BRODHURST
Journal: JAMA (1896)

Congenital dislocations of the hip are for the most part traumatic. Displacements occur also, however, through deficient development. Any obstruction at birth, whether through malformation of the pelvis or caused by the position of the child—the breech for instance, presenting, or the child or its head being unusually large, may occasion this dislocation. In a breech presentation the thighs are flexed upon the abdomen, so that the head of the femur presses on the posterior and inferior portion of the capsule of the joint. But in this position, the application of the slightest force in downward traction will displace the head of the bone and cause it to pass away from the acetabulum and to lie upon its brim. And lying on the border of the cotyloid cavity, extension of the limb at birth is alone sufficient to displace the head beyond the brim. The blunt hook or the finger
Use of administrative data or clinical databases as predictors of risk of death in hospital: comparison of models
Authors: Paul Aylin, Alex Bottle, Azeem Majeed
Journal: BMJ (2007)

<b>Objective</b> To compare risk prediction models for death in hospital based on an administrative database with published results based on data derived from three national clinical databases: the national cardiac surgical database, the national vascular database and the colorectal cancer study. <b>Design</b> Analysis of inpatient hospital episode statistics. Predictive model developed using multiple logistic regression. <b>Setting</b> NHS hospital trusts in England. <b>Patients</b> All patients admitted to an NHS hospital within England for isolated coronary artery bypass graft (CABG), repair of abdominal aortic aneurysm, and colorectal excision for cancer from 1996-7 to 2003-4. <b>Main outcome measures</b> Deaths in hospital. Performance of models assessed with receiver operating characteristic (ROC) curve scores measuring discrimination (&lt;0.7=poor, 0.7-0.8=reasonable, &gt;0.8=good) and both Hosmer-Lemeshow statistics and standardised residuals measuring goodness of fit. <b>Results</b> During the study period 152 523 cases of isolated CABG with 3247 deaths in hospital (2.1%), 12 781 repairs of ruptured abdominal aortic aneurysm (5987 deaths, 46.8%), 31 705 repairs of unruptured abdominal aortic aneurysm (3246 deaths, 10.2%), and 144 370 colorectal resections for cancer (10 424 deaths, 7.2%) were recorded. The power of the complex predictive model was comparable with that of models based on clinical datasets with ROC curve scores of 0.77 (<i>v</i> 0.78 from clinical database) for isolated CABG, 0.66 (<i>v</i> 0.65) and 0.74 (<i>v</i> 0.70) for repairs of ruptured and unruptured abdominal aortic aneurysm, respectively, and 0.80 (<i>v</i> 0.78) for colorectal excision for cancer. Calibration plots generally showed good agreement between observed and predicted mortality. <b>Conclusions</b> Routinely collected administrative data can be used to predict risk with similar discrimination to clinical databases. The creative use of such data to adjust for case mix would be useful for monitoring healthcare performance and could usefully complement clinical databases. Further work on other procedures and diagnoses could result in a suite of models for performance adjusted for case mix for a range of specialties and procedures.
Papilloma of Cusp of the Aortic Valve
Authors: J. SCOTT BUTTERWORTH, CHARLES A. POINDEXTER
Journal: Circulation (1973)

This is a case report of sudden death in a 50 year old man with a history of recent onset of atypical anginal pain. Death appears to have been caused by a small papilloma attached by a pedicle to the edge of the right cusp of the aortic valve. This papilloma occluded the right coronary ostium in a heart with a predominant right coronary circulation.
EVOLUTION OF THE PULP.
Authors: EUGENE S. TALBOT
Journal: JAMA (1902)

It has often occurred to me that conditions other than the toxins producing lactic acid were instrumental in decay of the teeth. This and interstitial gingivitis result from a struggle for assimilable nutriment dependent upon the action of the nervous system, operating through the law of economy of growth. Elsewhere I have demonstrated the relation of degeneracy to the struggle for existence between the face and brain, the jaws and brain, the alveolar process and the jaws and face. I shall now discuss degeneracy of the teeth and their pulps, in relation to evolution. In its evolution every structure in the body passes through embryologic phases<sup>1</sup>resembling types found in the lower vertebrates. In such evolution it is affected beneficially by both degeneracy or the suppressive phase of evolution and the advance phase. These phases constitute a struggle for existence for assimilable nutriment which proceeds under the law of
Ultrasonic Cardiac Echography for Determining Stroke Volume and Valvular Regurgitation
Authors: RICHARD L. POPP, DONALD C. HARRISON
Journal: Circulation (1970)

The ventricular dimensions of 51 patients with heart disease were determined by ultrasonic echography during cardiac catheterization. These data were used to calculate end-diastolic and end-systolic volumes and stroke volume, using a prolate ellipse as a geometric model of the left ventricle. In 30 patients without valvular regurgitation the stroke volumes determined by the echographic method were compared with those determined simultaneously by the standard Fick method with a correlation coefficient of r = 0.966. In 21 patients with valvular regurgitation, the severity of regurgitation was estimated by comparing the forward stroke volume determined by the Fick method with the total left ventricular stroke volume determined by the echographic method. These calculations of regurgitation correlated reasonably well with the degree of valvular regurgitation estimated from angiocardiographic study. It is suggested that these echographic determinations of stroke volume are an atraumatic, safe, and acceptable method in patients without valvular regurgitation. Moreover, these preliminary studies suggest that the severity of valvular regurgitation can be estimated by utilizing ultrasound echocardiography.
NIH Support for Basic and Clinical Research
Authors: David G. Nathan, Alan N. Schechter
Journal: JAMA (2006)

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Smoking in teenagers and watching films showing smoking
Authors: S. A Glantz
Journal: BMJ (2001)

Papers p 1394 

The tobacco industry recruits and retains smokers by associating its products with excitement, sex, wealth, rebellion, and independence. Films are a powerful way to make this connection—and, as a paper in this week's issue of Tobacco Control shows,1 they succeed.

The tobacco industry has cultivated its relationship with Hollywood using everything from large payments to film studios to distributing free cigarettes to the people who make films. 2 3 And it has been a two way street. For example, in 1972 the president of a production company wrote to RJ Reynolds Tobacco reporting that all the characters in a suspense thriller his company was producing smoked, and added, “Movies are better than any commercial that has been run on television or any magazine, because the audience is totally unaware of any sponsor involvement.”4 The public has viewed smoking in films with increasing alarm, particularly after it became known that the tobacco industry was making large surreptitious payments to get scenes with smoking in …
A Human- and Male-Specific Protocadherin that Acts through the Wnt Signaling Pathway to Induce Neuroendocrine Transdifferentiation of Prostate Cancer Cells
Authors: Xuezhen Yang, Min-Wei Chen, Stephane Terry, Francis Vacherot, Dominique K. Chopin, Debra L. Bemis, Jan Kitajewski, Mitchell C. Benson, Yinglu Guo, Ralph Buttyan
Journal: Cancer Research (2005)

Abstract Protocadherin-PC (PCDH-PC)is a gene on the human Y chromosome that is selectively expressed in apoptosis- and hormone-resistant human prostate cancer cells. The protein encoded by PCDH-PC is cytoplasmically localized and has a small serine-rich domain in its COOH terminus that is homologous to the β-catenin binding site of classical cadherins. Variants of prostate cancer cells that express PCDH-PC have high levels of nuclear β-catenin protein and increased wnt-signaling. In this study, we show that transfection of human prostate cancer cells (LNCaP) with PCDH-PC or culture of these cells in androgen-free medium (a condition that up-regulates PCDH-PC expression) activates wnt signaling as assessed by nuclear accumulation of β-catenin, increased expression of luciferase from a reporter vector promoted by Tcf binding elements and increased expression of wnt target genes. Moreover, LNCaP cells transfected with PCDH-PC or grown in androgen-free medium transdifferentiate to neuroendocrine-like cells marked by elevated expression of neuron-specific enolase and chromogranin-A. Neuroendocrine transdifferentiation was also observed when LNCaP cells were transfected by stabilized β-catenin. Increased wnt signaling and neuroendocrine transdifferentiation of LNCaP cells induced by culture in androgen-free medium was suppressed by short interfering RNAs that target PCDH-PC as well as by dominant-negative Tcf or short interfering RNA against β-catenin, supporting the hypothesis that increased expression of PCDH-PC is driving neuroendocrine transdifferentiation by activating wnt signaling. These findings have significant implications for the process through which prostate cancers progress to hormone resistance in humans.