tbuckley/cabot-search huggingface dataset:
OBSERVATIONS on the PATHOLOGY of ENLARGED or HYPERTROPHIED PROSTATE
Authors: R. Harrison
Journal: BMJ (1895)

fbe patient's word for it, as the temperature showed nothing, but there was no reason why he should have complained of more pain just at the -time the drugs were altered.CASE vii.-H.K., aged 66.This case, very similar to the above, was suffering from chronic rheumatism and sciatica.He was admitted into the Metropolitan Hospital on January 15th, 1895.There was a history of having suffered for nine years.Pains were now chiefly in left knee and hip.He also was put on salicylate, and improved considerably, but he also later on got bronchitis.and on March 20th was gien the same ammonia mixture as in the other case.On February 23rd the note says: " Can get about better and pain is, comparatively speaking, gone."On March 20th he got some bronchitis.The sali ylate was stopped, and mixt.senegae cum ammoniii ordered.On March 26th the pains were -decidedly worse again, especially in the knee.He was ordered to have the salicylate mixture as well as the ammonia, and the pains soon got better.
O128 SURGICAL RESECTION VERSUS RADIOFREQUENCY ABLATION IN THE TREATMENT OF PATIENTS WITH SOLITARY HEPATOCELLULAR CARCINOMA WITHOUT PORTAL HYPERTENSION: A 10-YEAR OUTCOME STUDY
Authors: G.-A. Kim, J.H. Shim, S.Y. Kim, H.J. Won, Y.M. Shin, P.N. Kim, Y.-J. Lee, S.-G. Lee, D. Lee, K.M. Kim, Y.-S. Lim, H.C. Lee, Y.-H. Chung, D.J. Suh
Journal: Journal of Hepatology (2014)
New safety study quantifies medical errors in Canadian hospitals
Authors: Barbara Kermode-Scott
Journal: BMJ (2004)

The first national study in Canada of the safety of hospital patients estimates that one in 13 people (7.5%) hospitalised have experienced an adverse event as a result of their care.

Researchers from seven Canadian universities analysed data on adverse events from 3745 adult patients' charts, randomly selected from 20 acute care hospitals in five provinces ( CMAJ 2004;170:1678-86). They described an adverse event as “an unintended injury or complication resulting in death, disability or prolonged hospital stay caused by health care management rather than the patient's underlying condition.”

Of the 255 adverse …
1028. Use of Antisense Oligonucleotides To Restore Activity in Mutant p53
Authors: Daniel J. Catron, Paloma H. Giangrande, Bruce A. Sullenger
Journal: Molecular Therapy (2006)

The tumor suppressor p53 protects the cell against cancer by inducing cell cycle arrest and apoptosis in response to oncogenic stress. Over 50% of human malignancies are associated with missense mutations within the protein's central sequence-specific DNA- binding domain. The C-terminus of p53 contains a regulatory domain that binds to specific structural features of damaged DNA (ends, distortions, modifications caused by gamma irradiation). Deletion or inactivation of the C-terminal regulatory domain (CTRD), using peptides or monoclonal antibodies in culture, has been shown to compensate for missense mutations in the sequence-specific DNA- binding domain. Unfortunately, peptides and monoclonal antibodies are difficult to deliver to cells and are immunogenic when used in vivo. Several RNA antisense oligonucleotides (ASOs), modified for increased stability, have been designed to alter the splicing of the p53 pre-mRNA to delete the CTRD. TOV-112D is a human endometrioid carcinoma cell line, which harbors a mutant p53 (Arg175His). We are testing a variety of ASOs in TOV-112D cells to assay for transcriptionally active mutant p53s. Apoptosis and p53 reporter assays will also be used to indicate restored p53 functional activity. The results of these experiments will be presented at the meeting. ASOs are more amenable to therapeutic application in comparison to antibodies and peptides given increased stability of modified RNA, decreased immunogenicity, and relative ease of delivery.
Abstract 4480: Double targeting nanoscale drug delivery system for treatment and imaging of metastatic solid cancers
Authors: Md Shakir U. Ahmed, Mohamed O. Abdalla, Timothy Turner
Journal: Cancer Research (2014)

Abstract Purpose: As an alternative to the drawbacks of current advanced cancer treatments such as conventional chemotherapy, we propose a multifunctional double targeting drug delivery system that utilizes the combination of cancer-targeting peptides fused to amphiphilic polymer coated iron oxide nanoparticles (IONPs) and loaded with suitable anticancer drugs as the payload. Methods: PC3 human prostate cancer cell line will be used initially to test the efficiency of the proposed drug delivery system. Our target sites of choice are the luteinizing hormone releasing hormone receptor (LHRH-R) and the urokinase-type plasminogen activator receptor (uPAR), and docetaxel was selected as the payload. A modified LHRH (ligand for LHRH-R) and AE105 (ligand for uPAR) were conjugated to polymer coated IONPs according to the manufacturer's protocol. Results: Conjugated IONPs were characterized by gel electrophoresis and Dynamic Light Scattering (DLS). IONPs showed expected narrow size distribution after conjugation with peptide ligand. The average hydrodynamic size of non targeted IONPs (36.84 nm) was increased upon conjugation of double peptide to their surface (44.06 nm). Conjugation of peptides to carboxylic groups of polymer coating on IONPs resulted in a decrease of zeta potential from -70.43 mV to -58.06 mV. Prussian blue staining demonstrated that LHRH and AE105 conjugated IONPs were internalized efficiently by the PC3 cells. The drug loading and release capability of conjugated IONPs will be evaluated by HPLC. In addition the internalization of conjugated IONPs will also be examined utilizing Magnetic Resonance Imaging (MRI), and tumor eradication will be determined by MTT assay. Conclusions: We expect a significant enhancement in the binding efficiency of the LHRH-IONPs-AE105 to the prostate cancer cells, increased efficiency in tumor eradication, and better imaging and monitoring capabilities because IONPs can be visualized by MRI during molecular imaging of the prostate cancer cells. Therefore, we believe the optimization of the proposed system will enhance targeted nanomedicine and significantly improve the health outcomes and quality of life for cancer patients because of the following reasons: 1) its ability to deliver anticancer drugs specifically to cancer cells while sparing the surrounding normal tissues, and 2) the capability of in situ monitoring of the therapeutics. Citation Format: Md Shakir U. Ahmed, Mohamed O. Abdalla, Timothy Turner. Double targeting nanoscale drug delivery system for treatment and imaging of metastatic solid cancers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4480. doi:10.1158/1538-7445.AM2014-4480
Easy yet so easily missed
Authors: A K Siotia, R Muthusamy
Journal: BMJ (2005)

It has been an interesting few weeks. So many doctors from all over the world have responded to Miss Webb's case.1 Numerous differential diagnoses were suggested, including Eisenmenger's syndrome, obstructive sleep apnoea, chest infection, drug overdose, heart failure, pulmonary embolism, myasthenia gravis, Guillan-Barre syndrome, atlanto-axial subluxation, Addison's disease, hypoparathyroidism, glomerulonephritis, sepsis with immune deficiency, atrial septal defect, and adult respiratory distress syndrome. Some readers questioned the diagnosis of Down's syndrome and some felt that we had deliberately withheld relevant information to make the case more interesting (definitely, not true).

Nevertheless, many respondents got the diagnosis of hypothyroidism, even from just the first part of the …
P94 Transforming acute care in COPD: findings from a national programme of service improvement
Authors: C. Thompson, P. Duncan, C. Blackaby, Z. Lord, O. Okosi, H. Wall, A. Porter
Journal: Thorax (2011)

<h3>Introduction</h3> Respiratory disease presents a significant financial burden to the UK. 40% of the cost of managing respiratory disease is spent on hospital admissions. Admissions for respiratory disease account for 12% of all medical admissions and 94 000 are for exacerbation of Chronic Obstructive Pulmonary Disease (COPD). Between 1991 and 2001 admissions for COPD rose by 50% and data suggest the admissions trend continues to increase, representing an increasing burden to the NHS. The aims of this programme of work were to reduce admissions, readmissions at 30 days, length of stay (LOS) for exacerbation of COPD and to improve the quality of patient care and the patient9s experience. <h3>Methods</h3> Twelve project sites from primary care, secondary care and community services took part in an improvement workstream. They were supported by a national programme of information sharing and peer support. Service improvement methodology was used including a series of diagnostic tools. Secondary care data were used to demonstrate areas of duplication, bottlenecks and gaps within services. The Plan Do Study Act (PDSA) cycle was used to implement changes to services and to evaluate the impact of service redesign. <h3>Results</h3> Data from five sites demonstrate £202k savings/cost avoidance through reductions in LOS and hospital admissions. Several important key learning points emerged from the programme of work: Cohorts of frequent attenders via the Emergency Department can be identified. One site identified 34 patients who accounted for 157 admissions in a 12-month period. Coordinated case management in this cohort may be effective in reducing admissions; data are not yet available to support this. Early access to specialist respiratory care is effective in reducing LOS. One site demonstrated a mean reduction in LOS of 0.4 days and another site a reduction of 1.5 days by instigating early specialist review. Improving communication and service integration is effective in reducing admissions. One site prevented 33 admissions through closer working between GP and Hospital at Home services. <h3>Conclusion</h3> Effective service redesign can deliver improvements in the quality of respiratory services for patients with COPD and simultaneously deliver productivity gains and cost savings.
Hsp27 Promotes Insulin-Like Growth Factor-I Survival Signaling in Prostate Cancer via p90Rsk-Dependent Phosphorylation and Inactivation of BAD
Authors: Amina Zoubeidi, Anousheh Zardan, Romina M. Wiedmann, Jennifer Locke, Eliana Beraldi, Ladan Fazli, Martin E. Gleave
Journal: Cancer Research (2010)

Abstract Hsp27 is highly expressed in castrate-resistant prostate cancer. Although its overexpression confers resistance to androgen ablation and chemotherapy, the mechanisms by which Hsp27 inhibits treatment-induced apoptosis are incompletely defined. Castrate-resistance often correlates with increased activity of autocrine and/or paracrine growth/survival stimulatory loops including the mitogen-activated protein kinase (MAPK) and Akt pathways and insulin-like growth factor (IGF) axis components. Because Hsp27 can be activated by both MAPK and Akt pathways, it is possible that interactions between IGF-I signaling and Hsp27 phosphoactivation function to promote castrate-resistant progression. Here, we report that Hsp27 expression and phosphorylation levels correlate with IGF-I signaling and castrate-resistant progression in human prostate cancer specimens and cell lines. IGF-I induces Hsp27 phosphorylation in a time- and dose-dependent manner via p90Rsk, which interacts directly with and phosphorylates Hsp27 in vitro and in vivo. Conversely, p90Rsk inhibition using short interfering RNA or a dominant negative mutant abolishes IGF-I–induced Hsp27 phosphorylation. Hsp27 overexpression increases IGF-I–induced phosphorylation of Erk, p90Rsk, and Akt. Conversely, Hsp27 knockdown abrogates IGF-I–induced phosphorylation of Erk, p90Rsk, and Akt, thereby destabilizing Bad/14-3-3 complexes and increasing apoptotic rates. These data elucidate the interactions between Hsp27 phosphorylation and the IGF-I receptor signaling pathway and support targeting Hsp27 as a therapeutic strategy for castrate-resistant prostate cancer. Cancer Res; 70(6); 2307–17
(15) Familial Kyrle's disease
Authors: R.A. Fulton
Journal: British Journal of Dermatology (1984)

Journal Article (15) Familial Kyrle's disease Get access R.A. Fulton R.A. Fulton Altnagelvin Hospital, Londonderry Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 111, Issue s26, 1 July 1984, Pages 61–62, https://doi.org/10.1111/j.1365-2133.1984.tb05285.x Published: 01 July 1984
Schizophrenia is associated with increased rates of violence and suicide, Swedish study finds
Authors: J. Wise
Journal: BMJ (2014)

Schizophrenia and related disorders are associated with substantially increased rates of violent offences, suicide, and premature mortality, a 38 year total population study in Sweden has found.1

The study, funded by the Wellcome Trust and the Swedish Research Council, tracked 24 297 patients who had schizophrenia and related disorders from January 1972 to December 2009. These were matched by age and sex to 485 950 people from the general population and to 26 357 unaffected sibling controls.

Within five years of a first …
2009 Biospecimen Research Network Symposium: Advancing Cancer Research through Biospecimen Science
Authors: Helen M. Moore, Carolyn C. Compton, Mark D. Lim, Jimmie Vaught, Katerina N. Christiansen, Joe Alper
Journal: Cancer Research (2009)

This report details the proceedings of the 2009 Biospecimen Research Network (BRN) Symposium that took place on March 16 to 18, 2009, the second in a series of annual symposia sponsored by the National Cancer Institute Office of Biorepositories and Biospecimen Research. The BRN Symposium is a public forum addressing the relevance of biospecimen quality to progress in cancer research and the systematic investigation needed to understand how different methods of collection, processing, and storage of human biospecimens affect subsequent molecular research results. More than 300 participants from industry, academia, and government attended the symposium, which featured both formal presentations and a day of workshops aimed at addressing several key issues in biospecimen science. An additional 100 individuals participated via a live webcast (archived at http://brnsymposium.com). The BRN Symposium is part of a larger program designed as a networked, multidisciplinary research approach to increase the knowledge base for biospecimen science. Biospecimens are generally understood to represent an accurate representation of a patient's disease biology, but can instead reflect a combination of disease biology and the biospecimen's response to a wide range of biological stresses. The molecular signatures of disease can thus be confounded by the signatures of biospecimen biological stress, with the potential to affect clinical and research outcomes through incorrect diagnosis of disease, improper use of a given therapy, and irreproducible research results that can lead to misinterpretation of artifacts as biomarkers. Biospecimen research represents the kind of bricks-and-mortar research that provides a solid scientific foundation for future advances that will directly help patients.
Examples of the Acute Radiation Syndrome in Man
Authors: L. H. Hempelmann
Journal: New England Journal of Medicine (1952)

THE acute radiation syndrome is an illness produced by exposure of the entire body, or a large part of the body, to ionizing radiations of a penetrating character. Although virtually unknown in clinical medicine before the close of the last war, it is now a type of injury with which the practicing physician must become acquainted. Many reports have described the clinical syndrome as it was observed in the Japanese injured by radiation in the atomic explosions in 1945. The few cases of acute radiation injury that have occurred in this country have only recently been recorded in the open . . .
Science and the 'Human Life Bill'
Authors: Harriet S. Meyer
Journal: JAMA (1981)

RECENTLY, the Subcommittee on Separation of Powers of the Senate Judiciary Committee heard testimony on S 158, the "human life bill." The hearings raise interesting questions about the role of science in the resolution of moral issues and about scientific consensus. <h3>Background</h3> In a 1973 decision, the Supreme Court of the United States in<i>Roe vs Wade</i>upheld the right of a woman to obtain an abortion until the stage of fetal "viability" without the interference of the state.<sup>1,2</sup>An amendment to the Constitution could reverse this decision, and, in fact, one has been proposed. Meanwhile, however, a bill has also been proposed to Congress by which its sponsors would attempt to reverse the 1973 Supreme Court decision. The bill (S 158) states: Congress finds that present day scientific evidence indicates a significant likelihood that actual human life exists from conception. The Congress further finds that the fourteenth amendment
Abstract 5436: Oct4 interaction with Hmgb2 regulates Akt signaling and the pluripotent gene expression signature.
Authors: Pearl A. Campbell, David J. Stewart, Michael A. Rudnicki
Journal: Cancer Research (2013)

Abstract Akt signaling impacts multiple cellular functions associated with the hallmark characteristics of pluripotency such as cell cycle progression, cell growth, and enhanced cellular survival. Constitutive Akt activation promotes the pluripotent state and has also been implicated in several forms of cancer. Recent studies have suggested that while Akt activation may be a positive factor, the active nuclear form of Akt is associated with poor prognosis for many cancers, including lung cancer. Here, we describe a novel transcriptional regulatory feedback loop between Oct4, Hmgb2, and Akt. We show that Akt signaling promotes Oct4 phosphorylation and stability. This maintains interaction with Akt, Hmbg2 and other members of the SET complex such as Nme1 and Set. Upon differentiation, when Akt is inactive, their decreased interaction is observed. A functional genomics approach was therefore employed to determine the relevance of Oct4 interaction with Hmgb2 in maintaining the pluripotent state. Despite its previously described role in Polycomb group recruitment and transcriptional repression in Drosophila, we find that Hmgb2 knockdown results in decreased Akt signaling and decreased expression of many Oct4 transcriptional targets including genes implicated in cell cycle regulation, DNA repair, chromatin structure, as well as the pluripotency regulators Oct4, Sox2, and Nanog. Taken together, our results suggest that Oct4, Hmgb2, and the SET complex participate in a PTM-dependent feed forward regulatory loop that promotes active Akt signaling and the pluripotent gene expression signature. Future work will be focused upon dissecting the role of this network in maintaining constitutive nuclear Akt activation and promoting the primitive epigenetic state found in cancer. These findings may provide insight into the role of Akt in lung cancer chemoresistance and suggest alternate targets for more efficacious treatment. Citation Format: Pearl A. Campbell, David J. Stewart, Michael A. Rudnicki. Oct4 interaction with Hmgb2 regulates Akt signaling and the pluripotent gene expression signature. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5436. doi:10.1158/1538-7445.AM2013-5436
Sex steroid hormones, bone mineral density, and risk of breast cancer.
Authors: L H Kuller, J A Cauley, L Lucas, S Cummings, W S Browner
Journal: Environmental Health Perspectives (1997)

Increased bone mineral density (BMD), as a marker of higher integrated estrogen exposure over time, could be an important risk factor for postmenopausal breast cancer. In the Study of Osteoporotic Fractures 8065 non-black women age 65 years and older were followed for an average of 3.2 years. There were 121 incident breast cancer cases. The age adjusted incidence rate/1000 person years of breast cancer was substantially higher among women with high BMD at several measured bone sites. There was approximately a 2-fold higher risk of breast cancer for women in the upper as compared to the lower 25th percentile of BMD. Considerable controversy exists about the association of hormone replacement therapy (HRT) and increased risk of breast cancer. In this paper we modeled the effects of selection for HRT, presuming that women with lower BMD would be more likely to be on HRT, then estimated the observed versus potential risk of breast cancer among HRT users as compared to nonusers. The model suggests that the potential risk of breast cancer associated with HRT could be greatly underestimated and that postmenopausal women with high BMD who are placed on HRT could have a substantially increased risk of breast cancer. This model of increased risk of breast cancer associated with BMD and HRT needs to be evaluated within clinical trials and larger observational studies that include measures of BMD.
Managerial Issues in the Reformed NHS
Authors: D J Hunter
Journal: BMJ (1994)

Ed M Malek, P Vacani, J Rasquinha, P Davey Wiley, £ 27.50,pp 262 ISBM 0-471-94033-X

The need for sound empirical evidence on what is happening in (and to) the NHS after the 1991 reforms is urgent. Given that all those concerned in implementing the reforms from the secretary of state for health down are engaged in a process of learning by doing, the paucity of evaluative research is astonishing. But there is a difficulty, amply demonstrated by this collection of papers, in producing material that is scientifically sound in a short time and in a situation of great instability in which events move swiftly and are forever shifting and assuming new forms. While acknowledging the problem and bravely seeking to fill the gap in knowledge, the editors ultimately fall seriously short of delivering their ambitious promise to map out the direction …
Redistribution of canalicular organic anion transport activity in isolated and cultured rat hepatocytes*1
Authors: H ROELOFSEN
Journal: Hepatology (1995)

The hepatocanalicular transport of a large number of organic anions, such as bilirubin glucuronides and glutathione conjugates in the rat, is mediated by an adenosine triphosphate (ATP)-dependent transport system, which is termed canalicular multispecific organic anion transporter (cMOAT). This system is mainly defined by its deficiency in mutant TR rats. We have previously reported that in cultured hepatocytes the fluorescent organic anion glutathione-bimane (GS-B) accumulates in intracellular vesicles and that this transport is mediated by cMOAT. We now show that this intracellular accumulation of fluorescent organic anion is largely absent in freshly isolated hepatocytes but appears when cells are incubated in suspension at 37 degrees C or cultured for periods of 1 to 24 hours. The appearance of intracellular cMOAT activity coincides with the disappearance of 70% of cMOAT activity from the plasma membrane as measured by the transport activity of the cells for the organic anion dinitrophenyl-glutathione (GS-DNP). Both the appearance of intracellular cMOAT and the disappearance of transport activity from the plasma membrane were completely inhibited at temperatures below 20 degrees C. Residual cMOAT activity in 24-hour cultured hepatocytes could be further diminished by incubation of the cells with 1 mumol/L monensin or 10 mmol/L methylamine. We conclude that after disruption of the cell polarity by collagenase isolation of the hepatocytes, remnants of apical membrane containing cMOAT are rapidly endocytosed when the cells are kept at 37 degrees C. Evidence suggests that at least part of the transporters may recycle back to the plasma membrane after endocytosis. These observations may be relevant for the understanding of regulation of canalicular transport.