tbuckley/cabot-search huggingface dataset:
Organ donation from intensive care units.
Authors: A. Bodenham
Journal: BMJ (1992)

ficulties of taking into account the comparative purchasing power of currencies -outside the Organisation for Economic Cooperation and Development,4 and the countries' large "black economy."But people in most types of occupation, both manual and non-manual, seem to work in the black economy.Relative deprivation was seen not necessarily in relation to direct income distribution but in relation to privileges such as the ability to travel abroad or access to Western goods, privileges that in the West are related to income.Eastern Europe will be a testing ground for Wilkinson's hypothesis in view of the introduction of market forces, which will widen income dif- ferentials appreciably.
Small-duct primary sclerosing cholangitis: A long-term follow-up study
Authors: Paul Angulo, Yaakov Maor-Kendler, Keith D. Lindor
Journal: Hepatology (2002)

Some patients with inflammatory bowel disease (IBD) have chronic cholestasis and hepatic histology compatible with primary sclerosing cholangitis (PSC) but normal findings on cholangiography. These patients with small-duct PSC have remained largely unstudied. Our aim was to determine the prevalence and long-term outcomes of patients with small-duct PSC. Eighteen patients with small-duct PSC (7 female and 11 male patients; mean age, 39.9 +/- 15.3 years [range, 13-68 years]) seen over a 4-year period were matched blindly by age and sex to 36 patients with classic PSC and followed up for 32.5 years. Small-duct PSC represented 5.8% of patients (18 of 309) with sclerosing cholangitis. Subsequent endoscopic retrograde cholangiography (ERC) performed in 5 patients with small-duct PSC showed progression to typical PSC in 3 patients at 4, 5.5, and 21 years of follow-up. None of the patients with small-duct PSC but 4 of the patients with classic PSC developed hepatobiliary malignancy. There were 3 deaths (17%) or liver transplantations in patients with small-duct PSC (2 after progressing to classic PSC) and 15 (42%) in the classic PSC group. Survival free of liver transplantation was significantly greater in the small-duct than in the classic PSC group (P =.04). Compared with the general U.S. population, survival in patients with small-duct PSC was similar (P =.4) but significantly lower in patients with classic PSC (P <.001). In conclusion, small-duct PSC may represent an earlier stage of PSC associated with a significantly better long-term prognosis. Some patients, however, progress to classic PSC and/or end-stage liver disease with the consequent necessity of liver transplantation.
Managing Incidental Genomic Findings in Clinical Trials: Fulfillment of the Principle of Justice
Authors: Rafael Dal-Ré, Nicholas Katsanis, Sara Katsanis, Lisa S. Parker, Carmen Ayuso
Journal: PLoS Medicine (2014)

Rafael Dal-Ré and colleagues discuss how incidental findings are likely to be viewed as potential benefits of research participation in genomics trials, and investigators should implement mechanisms to ensure provision of timely and appropriate care. Ensuring provision of such interventions in countries lacking a universal public health care system may prove challenging. Please see later in the article for the Editors' Summary
Abstract B65: MicroRNAs in cancer drug resistance and sensitivity
Authors: Jian Zhu
Journal: Clinical Cancer Research (2012)

Abstract microRNAs are small noncoding RNAs of 18–25 nucleotides that have been shown to regulate gene expression posttranscriptionally and play fundamental roles in diverse biological and pathological processes. MiRNApedia is an in silico discovery tool designed to integrate all microRNA-related information including genetic variation, gene expression, epigenetic regulation, pathways, diseases, clinical outcomes and particularly drug actions. The system documented more than 1,000 microRNAs and 600 therapeutic and experimental compounds including well-known cancer drugs cisplatin, doxorubicin, 5-flouracil, gemicitabine, paclitaxel, docetaxal, imatinib, vorinostat, sorafenib and gefitinib etc. For each compound, microRNAs and genes related to its sensitivity and function were compiled from literature and used to construct comprehensive drug-gene-microRNA networks. MicroRNAs played important roles in determining resistance and sensitivity of cancer drugs. For example, miR-21 reduced sensitivities to daunorubicin, topotecan, 5-FU, taxol, doxorubicin, docetaxel, ara-C, arsenic trioxide, gemcitabine and dexamethasome, while miR-146a increased sensitivity to bleomycin and over-expression of miR-221 conferred resistance to tamoxifen. Multiple microRNAs might be involved in the efficacy of a single drug. MiRs -98, -214, -106a, -125b and -630 contributed to cisplatin resistance, while -451, -181a, -148a, -138 and let-7i enhanced its sensitivity. Meanwhile, cisplatin was shown to down-regulate miRs -150 and -106 while up-regulated miRs -34, -16, -17-5p and -125. Drug combination would be the choice to overcome resistance in mono-therapies. Prior to experimental testing, the combination effects of multiple drugs could be assessed computationally by combining annotated information in microRNA targets, signaling pathways and transcriptional regulations etc. For example, trichostatin A (TSA), a HDAC inhibitor, might enhance sensitivity of cisplatin by up-regulating p53 and its transcriptional target miR-34 which subsequently down-regulated BCL2, a well-known drug resistance factor. However, if miR-125b, another transcriptional target of p53, was up-regulated, the combination might turn out to be antagonistic. Mechanistically, miR-125b targeted BAK1 which was required for cisplatin sensitivity. Such in silico modeling exercises not only predicted synergism or antagonism, but also identified underlined drivers which could serve as biomarkers for desired therapeutic effects. The potential biomarkers identified by the network modeling approach could be used to guide selection of experimental system (e.g., cell line models) and monitor the combination effectiveness. The present study devised a mechanism to systematically capture microRNA information in regards to cancer drug resistance and established a computational framework to identify potential drug combinations to overcome resistance in cancer therapies.
The Inebriate Diathesis.
Authors: T. L. Wright
Journal: JAMA (1892)

duced by passive motion a return of the pain and stiffness in the joint.Dr. Townsend could not see how anyone could believe that an osteitis due to traumatism represented the same pathological process as one due to tuberculosis, although the clinical symptoms might be identical.The Chairman said, that while all must admit that the sta¬ tistics presented in the paper are not only brilliant, but ex¬ ceedingly valuable, in comparing them with the statistics of those who do not resort to excision of joints, allowance must be made for those joints which had gone on to excision.This would also affect the mortality.One point which was very strongly brought out in the paper, was the positive, de¬ cided, and immediate relief of pain obtained in the majority of cases from traction properly applied.In hip joint dis¬ ease, it is fair to infer, as is also evident from the results
Interobserver and Intraobserver Variability in Measurement of Non–Small-Cell Carcinoma Lung Lesions: Implications for Assessment of Tumor Response
Authors: Jeremy J. Erasmus, Gregory W. Gladish, Lyle Broemeling, Bradley S. Sabloff, Mylene T. Truong, Roy S. Herbst, Reginald F. Munden
Journal: Journal of Clinical Oncology (2003)

Response of solid malignancies to therapy is usually determined by serial measurements of tumor size. The purpose of our study was to assess the consistency of measurements performed by readers evaluating lung tumors.The study group was composed of 33 patients with lung tumors more than 1.5 cm. Bidimensional (BD) and unidimensional (UD) measurements were performed on computed tomography (CT) scans according to the World Health Organization (WHO) criteria and the Response Evaluation Criteria in Solid Tumors (RECIST), respectively. Measurements were performed independently by five thoracic radiologists using printed film and were repeated after 5 to 7 days. Inter- and intraobserver measurement variations were estimated through statistical modeling.There were 40 tumors with an average size of 1.8 to 8.0 cm (mean, 4.1 cm). Analysis of variance showed a significant difference (P <.05) among readers and among the measured nodules for UD and BD measurements. Interobserver misclassification rates were more than intraobserver misclassification rates using either progressive disease or response criteria. The probability of misclassifying a tumor with the WHO criteria or RECIST was greatest with interobserver measurements when criteria for progression (43% BD, 30% UD) were used and lowest with intraobserver measurements when criteria for response (2.5% BD, 3.0% UD) were used. In addition, interobserver misclassification rates were more than intraobserver misclassification rates for both regular and irregular tumors.Measurements of lung tumor size on CT scans are often inconsistent and can lead to an incorrect interpretation of tumor response. Consistency can be improved if the same reader performs serial measurements for any one patient.
Rapid Resolution of Pulmonary Thromboemboli
Authors: John A. Udall
Journal: JAMA (1966)

To the Editor:—  An appreciation of the dynamic interplay which exists between thrombus formation, anticoagulant therapy, and natural fibrinolysis appears to be lacking in the excellent article by Fred et al 196 :1137, 1966).  The authors disclaimed knowledge of the mechanism of embolus dissolution, even though natural fibrinolysis was almost certainly responsible.  They assigned   to anticoagulant therapy in the unexpectedly rapid dissolution of pulmonary emboli in man, even though six of their seven patients received such. Because one patient did not receive anticoagulant therapy, there is no proof that this therapy played no role in the other six cases. The opposite conclusion, if any, is warranted.  The authors cited Sabiston's first case report ( Ann Surg  160 :575, 1964) showing resolution of a pulmonary thromboembolus in eight weeks. But they failed to cite Sabiston's second report ( J Thorac Cardiov Surg  50 :339, 1965) in which he documented a complete
Abstract 2501: Rapamycin inhibits epidermal cell proliferation in a xenograft model of tuberous sclerosis skin tumors
Authors: Shaowei Li, Rajesh Thangapazham, Ji-an Wang, Sangeetha Rajesh, Joel Moss, Thomas N. Darling
Journal: Cancer Research (2010)

Abstract Patients with tuberous sclerosis complex (TSC) develop hamartomatous tumors of the skin that have increased dermal fibroblast-like cells and a thickened epidermis. Our previous studies indicate that dermal cells are neoplastic, showing loss of TSC1/TSC2 function and activation of signaling through the mTORC1 pathway, and that overlying epidermal keratinocytes are reactive. The goals of this study were to determine whether TSC skin tumor cells induce epidermal changes and to assess the potential utility and mechanism of action of rapamycin, an mTORC1 inhibitor. TSC2-null skin tumor cells or fibroblasts from patient normal-appearing skin were incorporated into collagen gels overlaid with normal human neonatal keratinocytes, and these constructs were grafted to the backs of nude mice. Mice grafted with TSC tumor cells (n=27) or TSC normal fibroblasts (n=23) received rapamycin (2 mg/kg) (n=24) or an equal volume of vehicle (n=26) by intraperitoneal injection on alternate days for 12 weeks beginning 5 weeks after grafting. Mice were sacrificed 24 hours after the last injection for analysis of the grafts by immunohistochemistry. Grafts containing TSC tumor cells showed greater activation of the mTORC1 signaling pathway than grafts with normal fibroblasts, as shown by greater numbers of dermal cells staining for phosphorylated ribosomal protein S6 (p-S6). Xenografted epidermis overlying TSC tumor cells also showed stronger p-S6 staining than epidermis overlying TSC fibroblasts, replicating what we had observed in TSC skin tumors. Rapamycin treatment of tumor xenografts dramatically inhibited p-S6 staining in both epidermal and dermal cells. Tumor xenografts showed greater epidermal cell proliferation (as determined by staining with anti-Ki-67 specific antibody) than normal xenografts (p=0.009). Rapamycin treatment decreased the number of Ki-67 positive epidermal cells in grafts containing TSC tumor cells (p=0.046) but not in grafts with TSC normal fibroblasts. These results indicate that TSC tumor cells stimulate mTORC1 signaling and proliferation of overlying epidermal cells, and suggest that one of rapamycin effects on TSC skin tumors is through decreasing epidermal cell proliferation. This work was supported by an Idea Development Award (TS080064) from the Congressionally Directed Medical Research Program to Dr. Darling. Dr. Moss was supported by the Intramural Research Program, NIH, NHLBI. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2501.
A lesson from a death
Authors: R N Das
Journal: BMJ (2005)

Neurocysticercosis is a major public health problem in many developing countries in Asia and has a profound impact on productivity, health, economy, and quality of life. It is endemic in Nepal and is the commonest parasitic infestation of the central nervous system, caused by larvae of the tapeworm Taenia solium . Neurological manifestations vary from a simple chronic headache to life threatening meningoencephalitis depending on the location and number of the parasites in the brain.

In August 2000, I came from Britain (free from neurocysticercosis) to join the Manipal Teaching …
Abstract 2223: Epigenetic silencing of ribosomal RNA genes by Mybbp1a
Authors: Hsuan Liu, Bertrand Tan, Benjamin Y.-M. Yung
Journal: Cancer Research (2012)

Abstract Transcription of the ribosomal RNA gene repeats by Pol I occurs in the nucleolus and is a fundamental step in ribosome biogenesis and protein translation. Due to tight coordination between ribosome biogenesis and cell proliferation, transcription of rRNA and stable maintenance of rDNA clusters are thought to be under intricate control by intercalated mechanisms, particularly at the epigenetic level. Here we identify the nucleolar protein Myb-binding protein 1a (Mybbp1a) as a novel negative regulator of rRNA expression. Suppression of rDNA transcription by Mybbp1a was linked to promoter regulation as illustrated by its binding to the chromatin around the hypermethylated, inactive rDNA gene promoters. Our data further showed that downregulation of Mybbp1a abrogated the local DNA methylation levels and histone marks associated with gene silencing, and altered the promoter occupancy of various factors such UBF and HDACs, consequently leading to elevated rRNA expression. Mechanistically, we propose that Mybbp1a maintains rDNA repeats in a silenced state while in association with the negative epigenetic modifiers HDAC1/2. Results from our present work reveal a previously unrecognized co-repressor role of Mybbp1a in rRNA expression. They are further consistent with the scenario that Mybbp1a is an integral constituent of the rDNA epigenetic regulation that underlies the balanced state of rDNA clusters. 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 2223. doi:1538-7445.AM2012-2223
Abstract LB-131: Elevated (L) -2-hydroxyglutarate promotes loss of 5-hydroxymethylcytosine in clear cell renal cancer
Authors: Eun-Hee Shim, Carolina B. Livi, John Knight, Ross P. Holmes, Dinesh Rakheja, Sadanan Velu, Eun-Young Kho, Balachandra Chenna, Shane L. Rea, Daniel Benson, Richard Kirkman, Arindam Ghosh, Qiuhua Li, Sejong Bae, Shi Wei, Karen L. Block, Sunil Sudarshan
Journal: Cancer Research (2014)

Abstract We undertook an unbiased metabolomics profile of clear cell renal cell carcinoma (ccRCC), the most common histological subtype, to gain deeper insight into the metabolic basis of this disease. Here, we demonstrate elevations of the metabolite 2-hydroxyglutarate (2HG) in kidney cancer. Elevation of 2HG, specifically the D- enantiomer, has been linked to transformation and identified in the context of gain of function mutations of isocitrate dehydrogenase (IDH1 and IDH2). Notably, enantiomeric resolution demonstrates that, in contrast to IDH1/IDH2 mutant tumors, kidney tumors demonstrate elevations of the L enantiomer of 2HG (L-2HG). Moreover, high 2HG tumors demonstrate reduced DNA levels of 5-hydroxymethylcytosine (5hmC) consistent with the ability of L-2HG to inhibit TET (Ten Eleven Translocation) enzymes which convert 5-methylcystoine to 5-hmC. Finally, we demonstrate that these changes are mediated by the reduced expression of L-2HG dehydrogenase (L2HGDH) in ccRCC. Here, we report elevations of the putative oncometabolite L-2HG in the most common subtype of kidney cancer and describe a novel mechanism for the regulation of DNA 5hmC levels. Our findings provide new insight into the metabolic basis for the epigenetic landscape of renal cancer. Citation Format: Eun-Hee Shim, Carolina B. Livi, John Knight, Ross P. Holmes, Dinesh Rakheja, Sadanan Velu, Eun-Young Kho, Balachandra Chenna, Shane L. Rea, Daniel Benson, Richard Kirkman, Arindam Ghosh, Qiuhua Li, Sejong Bae, Shi Wei, Karen L. Block, Sunil Sudarshan. Elevated (L) -2-hydroxyglutarate promotes loss of 5-hydroxymethylcytosine in clear cell renal cancer. [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 LB-131. doi:10.1158/1538-7445.AM2014-LB-131
Negligence of medical experts
Authors: John Vinen
Journal: BMJ (2005)

Reduction in mortality from breast cancerDecrease with screening was marked in younger age group Editor-Based on a complicated statistical model, Olsen et al reported that the breast cancer mortality in Copenhagen dropped by 25% for women aged 50-79 when comparing mortality in the screening period (1991-2001) with a pre-screening period (1981-91) and claimed that this decrease was caused by screening. 1According to Statistics Denmark, 217 breast cancer deaths occurred in Copenhagen in the age group 35-54 years in the period 1981-90 and 196 deaths in 1991-2000. 2By comparing these data with those in the article by Olsen et al we calculate that less than 5% of the breast cancer mortality in this age group is caused by tumours diagnosed after age 50 years when women were invited to screening.The number of exposure years increased from about 484 000 to about 538 000.This gives a significant 19% (age adjusted) reduction in breast cancer mortality in the age group 35-54 years.No reduction at all occurred in the age group 55-79. 2Our estimates are based on raw and complete data.In contrast, the estimates in the paper by Olsen et al are sensitive to exclusion of data and model choice.In Copenhagen a drop in breast cancer mortality may reflect a higher fertility quotient due to non-Western immigration, fewer nulliparous women, and other non-screening related factors.It is therefore strange that no causal note was made by Olsen et al on the marked decrease in the breast cancer mortality in the age group 35-54 years.
High levels of urinary pentosidine, an advanced glycation end product, in children with acute exacerbation of atopic dermatitis: relationship with oxidative stress
Authors: Hirokazu Tsukahara, Rumiko Shibata, Naoko Ohta, Shuko Sato, Masahiro Hiraoka, Setsuko Ito, Eisei Noiri, Mitsufumi Mayumi
Journal: Metabolism (2003)
Efforts to Address the Problem of Physician Self-Referral
Authors: John K. Iglehart
Journal: New England Journal of Medicine (1991)

On the basis of laws that more sharply define the legality or illegality of certain medical business practices, the federal government has circumscribed further the limits physicians must observe if they refer patients to independent, "free-standing" facilities that they own or have an investment in. At the same time that it exhorts physicians to recognize their professional responsibilities, the American Medical Association (AMA) is planning new measures to curtail the questionable business practices of some doctors. The AMA took action after reports indicated that the opinion of its Council on Ethical and Judicial Affairs "regarding conflicts of interest, specifically, referral . . .
PURE-FOOD LEGISLATION VS. POOR FOOD-LEGISLATION.
Authors: MURRAY GALT MOTTER
Journal: JAMA (1901)

For the purposes of this paper, it matters but little which of the above titles is taken; the one representing what is admittedly desirable, the other—unfortunately to a large extent—what actually exists. The problem involved is by no means so easy as, at first sight, it might seem. Much of our knowledge of the general subject is, as yet, but tentative and, in attempting to formulate it, so much depends upon our definitions. Certain general principles, however, seem to have been fairly established; and legislative enactments embodying them prove efficient or futile just in proportion as these fundamental principles are kept well to the front, or are lost in a mass of minor detail. For the present we shall use the term food in its broadest sense, meaning thereby "the substances taken into the body which are utilized in maintaining the functional activity of the organism." This definition, given by
Case of Colloid or Gelatiniform Cancer of the Peritoneum and Colon: with Remarks
Authors: R. H. Semple, E. Ballard
Journal: BMJ (1851)

aged 66, an inmate of the Islington Workhouse, moderately well-formed, rather thin and pale, but not remarkably so, presented herself for medical relief on the 23rd of April, 1851.She complained of pain in the bowvcls, with purging, and some vomiting.She did not represent her case as a serious one, and she vas not in the infirmary.The disease was considered as a common disorder of the bowels; and she was accordingly ordered to take the followving: i Tr. opii 5ss, mag.carb.5ss, sulph.mag.5ij, aq.menth.pip.zvj.Sumat coch.ij magna 4tis horis.