tbuckley/cabot-search huggingface dataset:
Abstract 954: Multidrug resistance transcriptome analysis highlights compounds that sensitize resistant hepatocellular carcinoma through increased histone acetylation.
Authors: Jean-Pierre Gillet, Jesper B. Andersen, James P. Madigan, Sudhir Varma, Chung-Pu Wu, Anna M. Calcagno, Suresh V. Ambudkar, Snorri S. Thorgeirsson, Michael M. Gottesman
Journal: Cancer Research (2013)

Abstract No effective systemic therapy exists for patients with advanced hepatocellular carcinoma (HCC). Surgery is the mainstay treatment for patients with early stage HCC tumors. Either resection or transplantation is advocated if the HCC is within the Milan criteria. Nonsurgical treatments including percutaneous ethanol injection, radiofrequency ablation, and transcatheter arterial chemoembolization (TACE) are used as adjuvant therapy to surgery but also to treat unresectable HCC. Although a meta-analysis showed a beneficial survival effect for patients with intermediate HCC treated by TACE using doxorubicin and cisplatin, the survival benefit of systemic chemotherapy for the treatment of liver cancer is marginal at best. Although Sorafenib, a multi-tyrosine kinase inhibitor, is becoming established as the first line of therapy for advanced HCC, it was recently shown to be a substrate of ABCB1 and ABCG2, two major transporters involved in multidrug resistance (MDR) and expressed in hepatocytes. In this study, the MDR transcriptome was analyzed in a cohort of 38 patients using TaqMan-based qRT-PCR, with the aim of finding ways to sensitize this intrinsically MDR cancer. The study reveals a 45-gene signature, validated using an independent cohort of 53 patients, that predicts overall survival (OS). We used the Connectivity Map tool, designed to reveal connections among drugs, genes, and pathological states, to identify three compounds that converted the gene expression profile of HCC cell lines from one matching patients with poor OS to one with good OS. These compounds increased histone acetylation, resulting in the sensitization of tumor cells to conventional chemotherapy including cisplatin, sorafenib and 5-FU. This work provides new treatment strategies based on gene expression profiling and connectivity data for a disease for which no effective systemic treatments exist. More importantly, the current study reveals a new strategy to sensitize any type of refractory cancer to chemotherapy. Citation Format: Jean-Pierre Gillet, Jesper B. Andersen, James P. Madigan, Sudhir Varma, Chung-Pu Wu, Anna M. Calcagno, Suresh V. Ambudkar, Snorri S. Thorgeirsson, Michael M. Gottesman. Multidrug resistance transcriptome analysis highlights compounds that sensitize resistant hepatocellular carcinoma through increased histone acetylation. [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 954. doi:10.1158/1538-7445.AM2013-954
The automation of systematic reviews
Authors: G. Tsafnat, A. Dunn, P. Glasziou, E. Coiera
Journal: BMJ (2013)

Would lead to best currently available evidence at the push of a button 

The Cochrane handbook stipulates that systematic reviews should be examined every two years and updated if needed,1 but time and resource constraints mean that this occurs for only a third of reviews.2 Indeed, it may take as much time to update a review as it did to produce the original review. If this effort were redirected at developing methods to automate reviews, then updating might one day become almost effortless, immediate, and universal.

In his novel Player Piano , Kurt Vonnegut Jr described machines that record the hand motions of artisans and replay them to reproduce a perfect copy of the artefact, more quickly and more economically. Such automation is needed in the update and even creation of systematic reviews, because the capability of the human machinery for review increasingly lags behind our capacity to produce primary evidence.3 The current reality is that many reviews are missing or outdated,4 and it is hard to imagine a solution that does not involve some automation.5

Technology has advanced such that software can be used …
Thallium-201 Scintigraphic Visualization at Rest of a Dilated and Hypertrophied Right Ventricle in a Patient with Sarcoidosis Complicated by Cor Pulmonale
Authors: WEI-JEN SHIH, BRUCE FRIEDMAN, PEGGY A. DOMSTAD, FRANK H. DeLAND
Journal: Clinical Nuclear Medicine (1985)

Visualization, by resting TI-201 scintigraphy, of a markedly enlarged right ventricle (RV) in a 48-year-old black man with a 20-year history of pulmonary sarcoidosis is presented. The RV was three to four times larger than the left ventricle. Sarcoidosis resulted in marked distortion of the thoracic contents, as shown by the radiograph. This distortion possibly accounts for optimal scintigraphic visualization of the enlarged RV in the left lateral projection rather than in the left anterior projection. Because of the distortion, the chest radiograph could not be used to evaluate the cardiac contour; TI-201 scintigraphy demonstrated the RV enlargement.
THE EFFECT OF CERTAIN EXPERIMENTAL PROCEDURES ON THE ISLANDS OF LANGERHANS
Authors: Russell L. Cecil
Journal: The Journal of Experimental Medicine (1912)

Although the results of this study have been of a negative character, the conclusions that may be drawn from it have an important bearing on the true anatomical character of the islands. 1. Neither inanition nor the prolonged injection of secretin has any noteworthy effect upon the number, size, or structure of the islands of Langerhans in the dog's pancreas. 2. The islands of Langerhans in the guinea pig's pancreas are in no way altered in phlorizin diabetes. 3. The islands of Langerhans are not formed out of exhausted or degenerated acini, but develop from the ducts or acini with which they are often in direct continuity.
THE FAMILIAL INFLUENCE IN GASTRIC FUNCTION
Authors: F. L. Apperly, J. H. Norris
Journal: BMJ (1931)

IMDCLJUNL from the drain.About the fourth or fifth day the general condition of the patients improved, and some foul discharge came away alongside, and not through, the drain; came, in fact, from the abdominal wall.In such cases the edges of the wound felt indurated and were tender, and, if stitches were taken out, foul sloughy material escaped.Anaerobic infection had been locked up in the abdominal wall, and had led to necrosis of fat, aponeuirosis, and muscle.It was this that had accounted for the pronounced post-operative constitutional sym- ptoms.Surely it must be that this added abdominal wall infection in some cases turns the scale between recovery and death.
Age-related changes in the cellular composition of the thymus in children
Authors: Floor Weerkamp, Edwin F.E. de Haas, Brigitta A.E. Naber, W. Marieke Comans-Bitter, Ad J.J.C. Bogers, Jacques J.M. van Dongen, Frank J.T. Staal
Journal: Journal of Allergy and Clinical Immunology (2005)
Diagnosis of "Renal" Hypertension and Prediction of Surgical Outcome
Authors: Chester C. Winter
Journal: JAMA (1961)

THIS SUBJECT has created intense interest and diverse opinions recently among those who treat patients having hypertension and renal disorders. Part of the interest may be attributed to rapid advances in diagnostic and surgical procedures. This is especially true of renal-vascular lesions responsible for the renal stimulus of hypertension. When the proper method of investigation is carried out, a higher incidence of renal arterial lesions is found than formerly thought. These lesions include atherosclerotic plaques, thrombosis, aneurysm, fibrosis, and arteriovenous fistula. The parenchymal lesions of unilateral pyelonephritis, infarct, cyst, tumor, and hydronephrosis continue to account for 2% of the causes of remedial hypertension. Many investigators place great emphasis upon 1 or 2 diagnostic tests for the evaluation of "renal" hypertension. Their application may be advocated out of proportion to actual value. Thus many equally valuable diagnostic procedures may receive inadequate attention. With our incomplete knowledge of the etiology of
The host response to anthrax lethal toxin: unexpected observations
Authors: Alice S. Prince
Journal: Journal of Clinical Investigation (2003)

Bacillus anthracis, the causative agent of anthrax, is believed to induce disease and death in humans in an endotoxic shock–like manner. A comprehensive study of the effects of anthrax toxin in mice demonstrates that toxin-induced death is mediated not by cytokine release, as previously thought, but by hypoxia-induced liver failure. The study strongly suggests that the therapies developed for treatment of cytokine-mediated septic shock will not be appropriate for the treatment of anthrax.
Constant replenishment from circulating monocytes maintains the macrophage pool in the intestine of adult mice
Authors: Calum C Bain, Alberto Bravo-Blas, Charlotte L Scott, Elisa Gomez Perdiguero, Frederic Geissmann, Sandrine Henri, Bernard Malissen, Lisa C Osborne, David Artis, Allan McI Mowat
Journal: Nature Immunology (2014)
THE DEVELOPMENT OF INTESTINAL SURGERY
Authors: HARRY HYLAND KERR
Journal: JAMA (1923)

There is no more fascinating story in the history of medicine than the development of intestinal surgery. In the very earliest medical writings occur occasional cases of spontaneous recovery following perforating abdominal wounds. The study of these isolated cases showed that the intestinal wound had agglutinated to the parietes, thus preventing effusion of the intestinal contents into the abdomen. In one of the earliest textbooks, Lanfrank's "Science of Cirurgie," published in 1396, we find the treatment of intestinal wounds outlined in this quaint language: Take that one side of mirac (the outer or parietal peritoneum) and siphac (the inner or visceral peritoneum) together, so that they be one. And look that the nedel be three square and then make one point brought together. In the same manner in the other and there thou shalt make there-on as many points as thou thinkest necessary. And when thou hast sewd mirac and
Commentary: What can we learn from the continuing regulatory focus on the thiazolidinediones?
Authors: N. Freemantle
Journal: BMJ (2010)

Should rosiglitazone be withdrawn from use? An answer is hampered by the inadequacies of the data collected to date. In particular, regulators have tolerated loss to follow-up in trials designed to examine the effects of rosiglitazone on surrogate outcomes (haemoglobin A1c) despite relying on these same trials to provide evidence on safety (mortality and morbidity). The more robust regulatory approach required for new diabetes drugs introduced in late 2008 should prevent this situation recurring in diabetes, but if we are to avoid similar problems in other clinical areas, we need a far more widespread overhaul in the standards of regulatory trials.

Few would disagree that large scale randomised trials provide the most reliable evidence on the safety of interventions.1 Through randomisation, both known and unknown biases are distributed between the experimental groups by the play of chance.2 Because of random allocation of participants, any observed difference between groups on an outcome of interest may be attributed either to the play of chance or to the random treatment allocation. If chance is unlikely (for example, if the confidence intervals are relatively narrow and the corresponding P value small) the only plausible alternative is that the randomised treatment is responsible for the difference.

When …
Human thrombomodulin is not an efficient inhibitor of the procoagulant activity of thrombin.
Authors: I Maruyama, H H Salem, H Ishii, P W Majerus
Journal: Journal of Clinical Investigation (1985)

The effect of human thrombomodulin isolated from placenta on the procoagulant activity of thrombin was studied and compared to that of rabbit thrombomodulin. The isolated protein was proved to be thrombomodulin because a rabbit antibody against the isolated protein blocked protein C activation by thrombomodulin in solution and also blocked the protein-C-activating cofactor activity of human umbilical vein endothelial cells. The affinity of human thrombomodulin for human thrombin in the presence of fibrinogen is 30 times less than that of rabbit thrombomodulin. This value is based on the measurements of the clotting time of human fibrinogen and thrombin in the presence of increasing amounts of thrombomodulin. Human thrombomodulin was also much less effective compared with rabbit thrombomodulin in inhibiting thrombin-induced human coagulation factor V activation. The ability to inhibit release of [3H]serotonin from washed human platelets was at least 10 times less using human thrombomodulin compared with rabbit thrombomodulin. A partially purified preparation of human lung thrombomodulin was also relatively ineffective in inhibiting thrombin-induced serotonin release from platelets, indicating that the difference between rabbit and human thrombomodulin is one of species rather than of tissue. Thus, while human thrombomodulin is a potent cofactor in protein C activation, it is not an efficient inhibitor of the procoagulant actions of thrombin.
Perioperative Cardiac Risk Assessment and Management
Authors: Steven L. Cohn
Journal: Annals of Internal Medicine (1998)

Letters15 April 1998Perioperative Cardiac Risk Assessment and ManagementSteven L. Cohn, MDSteven L. Cohn, MDState University of New York Health Science Center at Brooklyn; Brooklyn, NY 11203Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-128-8-199804150-00018 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:After reviewing the American College of Physicians' guidelines for perioperative cardiac risk assessment [1], I thought that the recommendations overly relied on Detsky and colleagues' modified cardiac risk index [2]. In contrast to the American College of Cardiology/American Heart Association guidelines [3], the College's position paper was written by two physicians, one of whom may have been biased by his own risk index. Another possible problem is that the College's guidelines do not include use of exercise capacity in risk assessment, despite the fairly widespread use of this measure. At the same time, however, the guidelines recommend ...References1. American College of Physicians. Guidelines for assessing and managing the perioperative risk from coronary artery disease associated with major noncardiac surgery. Ann Intern Med. 1997; 127:309-12. Google Scholar2. Detsky AS, Abrams HB, McLaughlin JR, Drucker DJ, Sasson Z, Johnston N, et al. Predicting cardiac complications in patients undergoing non-cardiac surgery. J Gen Intern Med. 1986; 1:211-9. Google Scholar3. Eagle KA, Brundage BH, Chaitman BR, Ewy GA, Fleisher LA, Hertzer NR, et al. Guidelines for perioperative cardiovascular evaluation for noncardiac surgery. Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Perioperative Cardiovascular Evaluation for Noncardiac Surgery). J Am Coll Cardiol. 1996; 27:910-48. Google Scholar4. Mangano DT, Layug EL, Wallace A, Tateo I. Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery. Multicenter Study of Perioperative Ischemia Research Group. N Engl J Med. 1996; 335:1713-20. Google Scholar5. Goldman L, Caldera DL, Nussbaum SR, Southwick FS, Krogstad D, Murray B, et al. Multifactorial index of cardiac risk in noncardiac surgical procedures. N Engl J Med. 1977; 297:845-50. Google Scholar Author, Article, and Disclosure InformationAuthors: Steven L. Cohn, MDAffiliations: State University of New York Health Science Center at Brooklyn; Brooklyn, NY 11203 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 April 1998Volume 128, Issue 8Page: 693-694KeywordsAnginaAngiographyCardiac surgeryExerciseHeartIschemiaMyocardial infarctionRisk assessmentsSurgeryVascular surgery ePublished: 15 August 2000 Issue Published: 15 April 1998 Copyright & PermissionsCopyright © 1998 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Toxic chemical story ends happily
Authors: William A. Check
Journal: JAMA (1979)

One neurotoxic industrial chemical that you will probably not hear much about is dimethylaminopropionitrile (DMAPN). Reason: Only one month elapsed between the initial discovery that DMAPN causes severe bladder dysfunction in industrial workers and removal of this chemical from production. Responsible for the quick action were the physicians who established DMAPN's toxicity, the Occupational Safety and Health Administration (OSHA), and the companies that manufactured and used the substance. At the recent American Academy of Neurology meeting in Chicago, two participants described the investigations. The first patient was seen in March 1978 in Baltimore by Alan Pestronk, MD, assistant professor of neurology at the Johns Hopkins University School of Medicine. The patient had difficulty urinating and some sensory loss in the hands and feet. Three days later one of Pestronk's colleagues, James Keogh, MD, assistant professor of medicine at Johns Hopkins, saw a patient with similar symptoms. While discussing the two
The peroxisomal proliferator clofibrate enhances the hepatic cytoplasmic movement of fatty acids in rats
Authors: Michael T. Milliano, Bruce A. Luxon
Journal: Hepatology (2001)

The role of cytosolic fatty acid binding protein (FABP) in cellular fatty acid metabolism remains poorly defined. The intracellular movement of fatty acids is thought to be facilitated through codiffusion with FABP. Peroxisomal proliferators like clofibrate induce FABP and may stimulate fatty acid use by increasing cytoplasmic diffusion rates. Our aim was to determine if induction of FABP by clofibrate increases the cytoplasmic transport of a fluorescent fatty acid NBD–stearate. Male rats were fed clofibrate for 9 days to increase the hepatic concentration of FABP. Hepatocytes were isolated using collagenase perfusion. Cytosolic FABP was measured by enzyme–linked immunosorbent assay (ELISA) using a specific antibody to hepatic FABP. Two–dimensional laser photobleaching (FRAP) was used to measure the cytoplasmic movement of NBD–stearate in hepatocytes. Cytoplasmic transport of NBD–stearate occurred by isotropic diffusion with no evidence for convective or directed transport. Treatment with clofibrate increased FABP levels, the fraction of NBD–stearate found in cytosol, and the observed cytoplasmic diffusion rate. The increase in cytoplasmic movement exceeded that predicted from FABP binding changes suggesting that clofibrate also enhances fatty acid diffusion within intracellular membranes. Nonspecific effects of clofibrate on cytoplasmic viscosity or pore size were not observed. These data suggest that clofibrate treatment induces cytosolic FABP and stimulates the intracellular movement of fatty acids by 2 distinct mechanisms. Soluble proteins like FABP promote the cytoplasmic transport of fatty acids by increasing diffusion. These data further support a role for intracellular binding proteins in facilitating the intracellular movements of fatty acids.
Suspended consultant surgeon challenges official inquiry
Authors: C. Dyer
Journal: BMJ (1998)

A consultant general surgeon who was suspended nine months ago after an inquest into a patient's death has won the right to mount an unprecedented legal challenge to the report of an NHS Executive inquiry into three of his operations.

Christopher Ingoldby, who was suspended last January from his job at Pinderfields Hospital in Wakefield, West Yorkshire, was given the go ahead by the High Court last week to seek a judicial review of the report by a clinical panel headed by Professor Liam Donaldson, the newly appointed chief medical officer.

The case is thought to be …
Combination chemotherapy with low‐dose cytarabine, homoharringtonine, and granulocyte colony‐stimulating factor priming in patients with relapsed or refractory acute myeloid leukemia
Authors: Wang‐Gang Zhang, Fang‐Xia Wang, Yin‐Xia Chen, Xin‐Mei Cao, Ai‐Li He, Jie Liu, Xiao‐Rong Ma, Wan‐Hong Zhao, Su‐Hu Liu, Jian‐Li Wang
Journal: American Journal of Hematology (2007)

Abstract As sensitization of leukemic cells with granulocyte colony‐stimulating factor (G‐csf) can enhance the cytotoxicity of chemotherapy in acute myeloid leukemia (AML), a pilot study was conducted in order to evaluate the effect of G‐csf priming combined with low‐dose chemotherapy in patients with relapsed and refractory AML. The regimen, G‐HA, consisted of cytarabine 7.5 mg/m 2 /12 hr by subcutaneous injection, days 1–14, homoharringtonine 1.5 mg/m 2 /day by intravenous continuous infusion, days 1–14, and G‐csf 150 μg/m 2 /day by subcutaneous injection, days 0–14. Thirty‐six AML patients were enrolled, 23 refractory and 13 relapsed. Eighteen patients (50%, 95% confidence interval: 33–67%) achieved complete remission (CR) with a median CR duration of 7.2 months, and two elderly patients continued a regimen of maintenance therapy and remained in remission for 26.3 and 14.1 months, respectively, as of last follow‐up. Eight patients (22%) experienced neutropenia (median duration: 6 days; range: 2–22 days). Thirteen of the 36 (36%) developed severe infections. Grade 1–2 nonhematologic toxicities were documented, including nausea and vomiting (20%), liver function abnormality (6%), and heart function abnormality (6%). No central nervous system and kidney toxicity was observed. The G‐HA regimen is effective in remission induction for refractory and relapsed AML patients and well tolerated in maintenance therapy in some subgroups of elderly patients. Further studies are necessary to elucidate optimum dose and schedule for this regimen to enhance the treatment efficacy of relapsed or refractory AML patients. Am. J. Hematol., 2008. © 2007 Wiley‐Liss, Inc.
Diabetic crises in children treated with small doses of intramuscular insulin.
Authors: J Moseley
Journal: BMJ (1975)

A new regimen for the management of diabetic crises in children using small doses of intramuscular insulin and generous amounts of intravenous fluids has been devised. Insulin dosage was calculated from the patient's weight and was independent of the degree of hyperglycaemia. Minimum demands were made upon the laboratory.