tbuckley/cabot-search huggingface dataset:
Is There a Recreational Misuse Potential for Pregabalin Analysis of Anecdotal Online Reports in Comparison with Related Gabapentin and Clonazepam Data
Authors: Fabrizio Schifano, Stefano D’Offizi, Michele Piccione, Ornella Corazza, Paolo Deluca, Zoe Davey, Giuditta Di Melchiorre, Lucia Di Furia, Magí Farré, Liv Flesland, Miia Mannonen, Aino Majava, Stefania Pagani, Teuvo Peltoniemi, Holger Siemann, Arvid Skutle, Marta Torrens, Cinzia Pezzolesi, Peer van der Kreeft, Norbert Scherbaum
Journal: Psychotherapy and Psychosomatics (2011)

Background: Although pregabalin abuse potential is reportedly low, online data related to its recreational misuse potential have recently been identified.We aimed here at formally analysing pregabalin misuse web reports and comparing these with data pertaining to similar drugs, e.g.gabapentin and clonazepam, for which an abuse potential has already been identified.Methods: An 8-language analysis of the online information on pregabalin acquisition/misuse was carried out.An initial sample of 203 websites was considered and 108 relevant websites were monitored on a regular basis.To obtain material relating to gabapentin and clonazepam, an English-language search was carried out and 32 relevant websites were examined.Results: Misuse of pregabalin, which is commonly offered for sale online, was allegedly associated with sedative and/or psychedelic effects.This was associated with both higher dosages than clinically advised and idiosyncratic (i.e.: IV, rectal, intranasal) drug intake modalities.Although perceived as less powerful than pregabalin, gabapentin misuse was associated with similar sedative/psychedelic effects.Clonazepam allegedly induced either sedation or stimulation, depending on the dosage.Conclusions: Pregabalin experimenters might be profiled as individuals with a history of recreational polydrug misuse.Pregabalin misuse might be facilitated by easy online accessibility; potency; and peculiar, including anxiolytic, psychoactive effects.Physicians should carefully evaluate patients for history of drug abuse and observe them for signs of pregabalin/gabapentin/clonazepam misuse.
Adjuvant chemotherapy plus tamoxifen compared with tamoxifen alone for postmenopausal breast cancer: meta-analysis of quality-adjusted survival
Authors: R.D. Gelber, B.F. Cole, A. Goldhirsch, C. Rose, B. Fisher, C.K. Osborne, F. Boccardo, R. Gray, N.H. Gordon, N-O. Bengtsson, P. Sevelda
Journal: The Lancet (1996)
BRCA1 DNA-Binding Activity Is Stimulated by BARD1
Authors: Amanda M. Simons, Andrew A. Horwitz, Lea M. Starita, Karen Griffin, R. Scott Williams, J.N. Mark Glover, Jeffrey D. Parvin
Journal: Cancer Research (2006)

Abstract The breast- and ovarian-specific tumor suppressor BRCA1 has been implicated in numerous cellular processes, including transcription, ubiquitination, and DNA repair. Its tumor suppression activity is tightly linked to that of BARD1, a protein that heterodimerizes with BRCA1. It has been previously shown that BRCA1 binds to DNA, an interesting functional observation in light of the genetic data linking BRCA1 to DNA repair pathways. In this work, we reexamine the DNA-binding properties of BRCA1, comparing them with the DNA-binding properties of the BRCA1/BARD1 heterodimer. Because nuclear BRCA1 exists as a heterodimer with BARD1, it is likely that in vitro studies of the heterodimer will provide a more accurate model of physiologic conditions. Our results indicate that whereas BARD1 cannot directly bind DNA, it does enhance DNA binding by BRCA1. This is a surprising observation as both DNA-binding domains are distal to the BARD1-interacting RING domain of BRCA1. Further analysis of the dimerization reveals that the BRCA1/BARD1 interaction is not limited to the amino-terminal RING domains of each protein. The carboxyl terminus of BRCA1 contributes significantly to the stability of the heterodimer. We also show that the presence of BARD1 has a secondary effect, as autoubiquitination of BRCA1/BARD1 heterodimers additionally enhances the affinity of BRCA1 for DNA. Together, these data suggest that BRCA1 and BARD1 heterodimerization is stabilized via domains not previously thought to interact and that BARD1 acts in both ubiquitination-dependent and ubiquitination-independent ways to influence the role of BRCA1 in DNA repair. (Cancer Res 2006; 66(4): 2012-8)
Reactive Oxygen Species‐Scavenging Nanomedicines for the Treatment of Oxidative Stress Injuries
Authors: Toru Yoshitomi, Yukio Nagasaki
Journal: Advanced Healthcare Materials (2014)

This Progress Report describes a development of two types of reactive oxygen species (ROS)‐scavenging nanomedicines for the treatment of oxidative stress injuries, referred to as pH‐sensitive redox nanoparticle (RNP N ) and pH‐insensitive redox nanoparticle (RNP O ), which are prepared by self‐assembling amphiphilic block copolymers possessing nitroxide radicals as a side chain of hydrophobic segment via amine and ether linkages, respectively. Due to a protonation of amino groups in hydrophobic core, RNP N disintegrates in low pH environments such as ischemic, inflamed, and tumor tissues, resulting in increased ROS‐scavenging activity because of the exposed nitroxide radicals from the core. Utilizing pH‐responsiveness of RNP N , it shows remarkable therapeutic effects on oxidative stress injuries such as renal and cerebral ischemia–reperfusion injuries after intravenous administration. Moreover, RNP N shows an enhancement of the activity of anticancer drugs by suppression of activation of transcription factors in tumor due to the ROS scavenging. On the other hand, orally administered RNP O has notable characteristics such as preferential accumulation in mucosa and inflamed area of gastrointestinal tract and no uptake into blood stream. Based on these characters, RNP O shows a remarkable therapeutic effect for the gastrointestinal inflammation without any adverse effects. Thus, ROS‐scavenging nanomedicines have therapeutic efficacy in numerous oxidative stress diseases.
Widened Cranial Sutures in Metastatic Neuroblastoma
Authors: Carl Pochedly
Journal: JAMA (1974)

<h3>To the Editor.—</h3> Enlargement of the head and widening of the cranial sutures are fairly common complications of metastatic neuroblastoma. The cause is not clearly understood. We recently observed these signs in a child with a rapidly progressive tumor. <h3>Report of a Case.—</h3> An 18-month-old girl with persistent fever and vomiting developed an ear infection, treated with antibiotics. Examination three and a half weeks later showed ecchymosis of the left upper eyelid, and a large mass in the left side of the abdomen extending to the iliac crest. The hemoglobin level was 6.5 gm/100 ml; hematocrit reading, 22%. A bone marrow aspiration showed tumor cells. Serum alkaline phosphatase, lactic dehydrogenase, and serum glutamic oxaloacetic transaminase levels were all markedly elevated. A large mass (shown by intravenous pyelogram) displaced the left kidney laterally and inferiorly. Osteolytic lesions appeared in both lower femurs, and skull roentgenogram showed slight separation of the cranial
EFFECT OF 14-HYDROXYDIHYDROMORPHINONE ON RESPIRATION
Authors: Myron E. Resnick
Journal: JAMA (1960)

The effect on respiration of 14-hydroxydihydromorphinone was tested in 16 patients, 6 healthy young men, and 10 older patients with cardiovascular, pulmonary, or hepatic disease. After subcutaneous injection of 1.5 mg. of the drug (said to be equivalent to 15 mg. of morphine) changes in minute ventilation, respiratory rate, and tidal volume were determined and related to oxygen saturation, carbon dioxide tension, and pH of arterial blood. Definite depression of respiration and a marked reduction in sensitivity of the respiratory center to carbon dioxide stimulation were observed in all 16 subjects. The respiratory depression was subclinical in the young, normal subjects but was usually apparent in the 10 older patients. Caution must be exercised with doses of this amount in elderly persons and in patients such as those with cardiovascular, pulmonary, or hepatic disease, who are known to be sensitive to central nervous system depressants.
Interactions of the platelets in paroxysmal nocturnal hemoglobinuria with complement. Relationship to defects in the regulation of complement and to platelet survival in vivo.
Authors: D V Devine, R S Siegel, W F Rosse
Journal: Journal of Clinical Investigation (1987)

The blood cells of patients with paroxysmal nocturnal hemoglobinuria (PNH) have abnormal interactions with complement. The activity of the alternative pathway C3 convertase on the platelets of 9 out of 19 patients with PNH was elevated. 10 patients had C3 convertase activity within the normal range even though 80-95% of their platelets lacked the complement regulatory protein decay accelerating factor (DAF) that is absent from the affected blood cells in PNH. PNH and normal platelets released factor H when C3 was bound to their surfaces. This may account for the apparent regulation of C3 convertase activity on platelets that lack DAF. The abnormal uptake of the membrane attack complex of complement by PNH III erythrocytes was not seen in PNH platelets. 111Indium-labeled platelet survival times were normal in five of eight patients, which suggests that the lack of the membrane attack complex defect results in normal platelet survival in PNH.
The Brain Vascular System
Authors: Charles B. Wilson
Journal: JAMA (1966)

In the 300 years since Thomas Willis described the remarkable circle which bears his name, anatomists have studied the several arteries related to this complex vascular ring. Despite our knowledge of vessels coursing over and beneath the brain surface, we still know relatively little about the architecture of deeper cerebral vessels. The authors, a neurosurgeon and an anatomist, combine conventional anatomical methods with radiographic techniques to provide this monograph on blood vessels within the central nervous system. The book begins with a detailed description of cerebrovascular embryology. While containing nothing original, this section furnishes a readable account of developmental anatomy. The second portion, occupying 100 pages, concerns the anatomy of the adult vascular system. Radiographs of injected specimens add a new dimension to conventional methods for portraying blood vessels and afford crisp detail of finer ramifications of selectively injected arteries and veins. Brief consideration of cerebral collateral circulation and vascular
Contraceptive services for women in UK could deteriorate when responsibility transfers to local authorities, report says
Authors: C. White
Journal: BMJ (2012)

Primary care trusts are spending too little on contraceptive services and failing to give them the priority they deserve, a report from All-Party Parliamentary Group on Sexual and Reproductive Health in the UK says.

But things could get worse when local authorities take over responsibility for commissioning sexual health services next April, the report says. Local councils are getting little guidance or support on how to commission these services, and the responsibility for them is likely to be split between local authorities and clinical commissioning groups.

The written and oral evidence taken from service users, clinicians, charities, and the shadow public health minister during the inquiry “shocked many of us who have worked in the field of sexual health,” said its chair, Baroness Gould …
Exocytosis: Proteins and Perturbations
Authors: G. J. Augine
Journal: The Annual Review of Pharmacology and Toxicology (1996)

Heme oxygenases (HO) catabolize free heme, that is, iron (Fe) protoporphyrin (IX), into equimolar amounts of Fe2+, carbon monoxide (CO), and biliverdin. The stress-responsive HO-1 isoenzyme affords protection against programmed cell death. The mechanism ...Read More
Removal of central venous catheter and venous air embolism.
Authors: G. A. Baer, I. Nordback
Journal: BMJ (1992)

I have knowledge of 50 deaths (this includes unpublished cases from personal communica- tions).The problem is sporadic and rare; because the consequences are so devastating for the patient, however, the medical and nursing staff managing patients with central venous catheters must prevent air gaining access to the venous circulation.4"
Endothelin induced contractility of stellate cells from normal and cirrhotic rat liver: implications for regulation of portal pressure and resistance
Authors: D C Rockey, R A Weisiger
Journal: Hepatology (1996)

Hepatic stellate cells are similar to tissue pericytes and have been shown to be contractile. In this study, we examined the effects of known mediators of stellate cell contraction on portal pressure in rat livers after carbon tetrachloride induced injury (including cirrhosis) and investigated the contractility of stellate cells as a function of liver injury. Sarafotoxin S6C, an endothelin B (ETB) receptor agonist, had minor effects on portal pressure when perfused into normal livers at concentrations known to elicit stellate cell contraction (2 nmol/L). In contrast, both endothelin–1 (2 nmol/L) and angiotensin II (8.6 nmol/L) caused a rapid and pronounced rise in portal pressure. The effects of sarafotoxin S6C (a potent stellate cell contractile agonist) on portal pressure were greater in cirrhotic than normal liver, whereas those of angiotensin II were unchanged after liver injury. Endothelin–1 and sarafotoxin S6C induced contractility of stellate cells increased in proportion to the degree of liver injury. Contractility was greatest for stellate cells isolated from cirrhotic livers, a population of cells that displayed the most activated phenotype, as measured by immunoblot of smooth muscle alpha actin. Autoradiography of cirrhotic livers after perfusion with 125I–endothelin–1 revealed binding to cells in both sinusoidal spaces and collagenous fibrotic bands, consistent with known locations of stellate cells. Finally, the mixed endothelin–A (ETA) and ETB receptor antagonist, bosentan, reduced portal pressure in portal hypertensive animals, consistent with its inhibitory effect on stellate cell contraction. We conclude that stellate cell contractility increases with progressive liver injury and is proportional to the degree of stellate cell activation, becoming most prominent in the cirrhotic liver. Endothelin–stimulated contraction of stellate cells in cirrhotic liver may contribute to increased intrahepatic resistance and portal pressure.
Reduction in Raf Kinase Inhibitor Protein Expression Is Associated with Increased Ras-Extracellular Signal-Regulated Kinase Signaling in Melanoma Cell Lines
Authors: Marion M. Schuierer, Frauke Bataille, Suzanne Hagan, Walter Kolch, Anja-Katrin Bosserhoff
Journal: Cancer Research (2004)

Abstract Mutations in the Raf signaling pathway are known to play a pivotal role in the progression of malignant melanoma. In this study, we provide evidence that the Raf-1 kinase inhibitory protein (RKIP) and its effects on Raf-1-mediated activation of mitogen-activated protein/extracellular signal-regulated kinase kinase are important for the metastatic potential of malignant melanoma. Screening nine melanoma cell lines at mRNA and protein levels, we detected significant down-regulation of RKIP expression in comparison with normal melanocytes. Loss of RKIP expression in transformed cells in vivo was confirmed in immunohistochemical analyses demonstrating reduction of RKIP expression already in primary melanoma and even stronger down-regulation or complete loss in melanoma metastases. Stable transfection of the melanoma cell line Mel Im with an RKIP expression plasmid blocked the Raf kinase pathway, resulting in down-regulation of extracellular signal-regulated kinase 1/2 and activator protein 1 activity. In very good agreement with the in vivo finding that down-regulation of RKIP expression is most obvious in melanoma metastasis, overexpression of RKIP in the highly invasive Mel Im cell line leads to a significant inhibition of invasiveness in vitro. Taken together, our results suggest that loss of RKIP in malignant melanoma contributes to enhanced invasiveness of transformed cells and therefore to progression of the disease.
Anticancer agents coupled to N-(2-hydroxypropyl)methacrylamide copolymers. 3. Evaluation of adriamycin conjugates against mouse leukaemia L1210 in vivo
Authors: Ruth Duncan, Isabella C. Hume, Pavla Kopečková, Karel Ulbrich, Jiří Strohalm, Jindřich Kopeček
Journal: Journal of Controlled Release (1989)
Surgical Injuries to the Ureter
Authors: Harry M. Spence
Journal: JAMA (1961)

In a series of 31 patients with surgical injury to the ureters, the most frequent causes of trouble were a difficult operation within the pelvis, inadequate exposure, and persistent bleeding. More frequent preoperative use of the excretory urogram is recommended. The preoperative insertion of indwelling ureteral catheters is helpful but often difficult; hence, visual exposure of the ureter seems desirable. If the injury is recognized at the time of operation, a spatulated end-to-end anastomosis or reimplantation into the bladder with splints is preferred. When the injury becomes apparent during convalescence, immediate repair has given acceptable results. In the present series, which included 2 cases of bilateral injury, 27 kidneys were salvaged and 5 nephrectomies were done.
What Are We Going to Do About Mother?
Authors: Evalynn Morgan Quisenberry
Journal: JAMA (1990)

Martha means well. It's just that she has been doing some pretty crazy things lately. I've been wanting to tell the doctor every time we go. But, as usual, Martha does all the talking for both of us. I don't talk much at all anymore, but I keep thinking about what I want to say. Martha called in the burglar alarm people. She told them she wanted to install a system for keeping people in the house, not for keeping people out. They were as puzzled as I was. Next time I really will speak up; I'll tell the doctor. This latest thing Martha did really has me bugged. She bought a small green bath mat and put it by the front door. She told me it was a hole and if I stepped on it I'd fall in. I don't think a sane person would say that. The doctor
Thousands of patients who lack mental capacity are to have care reviewed after Supreme Court ruling
Authors: C. Dyer
Journal: BMJ (2014)

Tens of thousands of patients in NHS hospitals, care homes, and state funded residential accommodation who lack mental capacity to take their own decisions will have to be reviewed to check whether they are being illegally detained, after a landmark judgment by the UK Supreme Court.

The judgment last month from the UK’s highest court sets out a new test for deprivation of liberty.1 As a result, anyone without capacity whose care has been arranged by the state, who is under continuous supervision and control, and who is not free to leave must be considered to be deprived of liberty.

The new test means that many more patients than had been thought will meet the criteria. Those in hospitals and care homes will have to have their placements formally authorised under the deprivation of liberty safeguards in the Mental Capacity Act 2005 …
Treatment options in skeletal localizations of hairy cell leukemia: A systematic review on the role of radiation therapy
Authors: Andrea R. Filippi, Pierfrancesco Franco, Carlo Marinone, Corrado Tarella, Umberto Ricardi
Journal: American Journal of Hematology (2007)

Abstract Skeletal localizations are a rare complication in hairy cell leukaemia patients, with an extimated incidence of 3%. These lesions, mainly osteolytic, can occur at various sites and are almost always symptomatic. Localized radiation therapy (RT) has been extensively used as effective palliative treatment in such cases, with different total doses and fractionation schedules. In this article, a systematic review of all reported cases with osseous complications is presented, to underline the role of RT and to define the most appropriate approach in this subset of patients. Am. J. Hematol., 2007. © 2007 Wiley‐Liss, Inc.
Abstract 5468: Transgenic mice ectopically express <i>miR-31</i> in basal keratinocyte, exhibit high potential for oral tumorigenesis
Authors: Shu-Chun Lin, Ssu-Hsueh Tseng
Journal: Cancer Research (2012)

Abstract Oral squamous cell carcinoma (OSCC) is one of the leading causes of cancer mortality in the world. Despite that numerous advances have resulted in better control of patient morbidity, overall survival for OSCC has remained low for the past decades due to relapse and metastases. Besides, resistance to conventional therapeutic modalities stands for another important cause of treatment failure. OSCC adopts multiple genetic alterations for pathogenesis including activation of EGFR, AKT and hypoxia pathway, and other oncogenic events. Novel targeting therapy against these alterations in rodent tumors genetically resemble human tumors may confer tremendous abrogation benefits. MiRNAs are small non-coding RNAs mediating the translational repression of target mRNAs. miR-31 is among the most eminently up-regulated miRNAs in OSCC. Our works defined that miR-31 ablated expression of the HIF regulatory factor FIH (factor-inhibiting hypoxia-inducible factor) to activate hypoxia signaling and up-regulate VEGF, which contributed to OSCC pathogenesis. We established K14-GFP-miR-31 transgenic mouse lines in this study. GFP and miR-31 were detected in basal and suprabasal layers of the squamous epithelium of skin, oral cavity and esophagus in these transgenic mice. The transgenic mice exhibited higher potential for tumor induction on oral tongue and esophagus by 4-nitroquinoline 1-oxide treatment than wild type mice. The tumors induced in transgenic mice expressed more abundant K14, miR-31, VEGF and Ki-67 than tumors in wild type mice. The preneoplastic lesions on oral tongues of transgenic mice were also in more advanced stages in contrast to counterparts in wild type mice. Spontaneous occurrences of tumors in transgenic mice are being observed to insight additional oncogenic alterations essential for OSCC pathogenesis. We identified the high sensitivity of this transgenic mouse model for chemical carcinogen-induced oral tumorigenesis, and this model will be developed to select drugs or targeting strategies to facilitate human OSCC interception. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5468. doi:1538-7445.AM2012-5468
Randomized trial comparing liposomal daunorubicin with idarubicin as induction for pediatric acute myeloid leukemia: results from Study AML-BFM 2004
Authors: Ursula Creutzig, Martin Zimmermann, Jean-Pierre Bourquin, Michael N. Dworzak, Gudrun Fleischhack, Norbert Graf, Thomas Klingebiel, Bernhard Kremens, Thomas Lehrnbecher, Christine von Neuhoff, Jörg Ritter, Annette Sander, André Schrauder, Arend von Stackelberg, Jan Starý, Dirk Reinhardt
Journal: Blood (2013)
Physical Fitness in Military Personnel
Authors: Hans Kraus
Journal: JAMA (1971)

<h3>To the Editor.—</h3> Twenty years ago, we examined the minimum muscular fitness of children here and abroad (Switzerland, Italy, Austria). The key posture muscles of our children proved considerably weaker and less flexible than their counterparts abroad, proving that our children are too sedentary. These findings were submitted to President Eisenhower at a White House luncheon conference and prompted him to establish the President's Council on Physical Fitness, then called Youth Fitness. Unfortunately, except for isolated programs, no national or even state efforts have been made except in the field of public relations. At this time, when the need for preventive medical care is of special interest, preventive programs should be started at once. We agree with Cooper that the time to keep the cardiovascular system in good working condition is before it starts to disintegrate, and would add exercise programs and training of exercise habits not at 18 years