tbuckley/cabot-search huggingface dataset:
Determinants of the optimal first‐line therapy for follicular lymphoma: A decision analysis
Authors: Rebecca L. Olin, Peter A. Kanetsky, Thomas R. Ten Have, Sunita D. Nasta, Stephen J. Schuster, Charalambos Andreadis
Journal: American Journal of Hematology (2010)

Combination immunochemotherapy is the most common approach for initial therapy of patients with advanced-stage follicular lymphoma, but no consensus exists as to the optimal selection or sequence of available regimens. We undertook this decision analysis to systematically evaluate the parameters affecting the choice of early therapy in patients with this disease. We designed a Markov model incorporating the three most commonly utilized regimens (RCVP, RCHOP, and RFlu) in combinations of first- and second-line therapies, with the endpoint of number of quality-adjusted life years (QALYs) until disease progression. Data sources included Phase II and Phase III trials and literature estimates of long-term toxicities and health state utilities. Meta-analytic methods were used to derive the values and ranges of regimen-related parameters. Based on our model, the strategy associated with the greatest number of expected quality-adjusted life years was treatment with RCHOP in first-line therapy followed by treatment with RFlu in second-line therapy (9.00 QALYs). Strategies containing RCVP either in first- or second-line therapy resulted in the lowest number of QALYs (range 6.24-7.71). Sensitivity analysis used to determine the relative contribution of each model parameter identified PFS after first-line therapy and not short-term QOL as the most important factor in prolonging overall quality-adjusted life years. Our results suggest that regimens associated with a longer PFS provide a greater number of total QALYs, despite their short-term toxicities. For patients without contraindications to any of these regimens, use of a more active regimen may maximize overall quality of life.
THE RELATION OF PREMATURITY AND PREVIOUS FETAL LOSS TO CHILDHOOD SCHIZOPHRENIA
Authors: MILTON TERRIS, REMA LAPOUSE, MARY A. MONK
Journal: American Journal of Psychiatry (1964)

A study of 463 childhood schizophrenics and their matched controls disclosed no evidence of an association of childhood schizophrenia with prematurity. There was, however, a definite association with a history of previous fetal loss. The relation of these findings to various etiologic hypotheses is discussed. It is considered doubtful that childhood schizophrenia is included in the continuum of reproductive casualty associated with maternal and fetal factors causing anoxia or nonmechanical injury. In view of current uncertainty and disagreement concerning the nosology and diagnosis of childhood schizophrenia, interpretation of the results of this investigation must be made with caution. Further studies of the relation of previous fetal loss, prematurity and complications of pregnancy to childhood schizophrenia, carried out in a number of different centers, are necessary to evaluate the findings indicated in this report.
Biosynthesis of coagulation Factor V by a human hepatocellular carcinoma cell line.
Authors: D B Wilson, H H Salem, J S Mruk, I Maruyama, P W Majerus
Journal: Journal of Clinical Investigation (1984)

A human hepatocellular carcinoma line, HepG2, was found to secrete coagulation Factor V. Factor V activity in HepG2 culture fluid increased nearly linearly during a 20-h time course (5 ng Factor Va/h per 10(6) cells). Thrombin treatment increased Factor V activity in HepG2 culture medium six- to ninefold, indicating that the medium accumulates a mixture of Factors V and Va. To demonstrate de novo synthesis of Factor V, HepG2 cells were incubated in culture medium containing [35S]methionine. Labeled Factor V was immunoprecipitated from the medium and was shown to co-migrate with purified plasma Factor V upon sodium dodecyl sulfate polyacrylamide gel electrophoresis and fluorography. When medium was treated with thrombin before immunoprecipitation and fluorography, the 330,000-Mr [35S]methionine-labeled Factor V was converted to Factor Va. Factor Va coagulant activities from HepG2 cells and human plasma were inhibited in parallel by anti-Factor V antibody, indicating that HepG2 and plasma Factor Va have the same intrinsic activity. If normal hepatocytes synthesize Factor V at the same rate as HepG2 cells, then hepatocyte secretion can account for the total Factor V present in plasma. The production of Factor V by cultured human umbilical vein endothelial cells was also examined. Spent culture medium from endothelial cells contained only Factor Va and the amount was less than 1% of the activity found in medium from HepG2 cells under comparable conditions. The amount of Factor V activity in endothelial cell culture fluid did not change with time in culture.
Idelalisib, a selective inhibitor of phosphatidylinositol 3-kinase-δ, as therapy for previously treated indolent non-Hodgkin lymphoma
Authors: Ian W. Flinn, Brad S. Kahl, John P. Leonard, Richard R. Furman, Jennifer R. Brown, John C. Byrd, Nina D. Wagner-Johnston, Steve E. Coutre, Don M. Benson, Sissy Peterman, Yoonjin Cho, Heather K. Webb, David M. Johnson, Albert S. Yu, Roger G. Ulrich, Wayne R. Godfrey, Langdon L. Miller, Stephen E. Spurgeon
Journal: Blood (2014)
Surgeon general resigns in masturbation row
Authors: J. Roberts
Journal: BMJ (1994)

America's chief doctor resigned last week after saying that masturbation could be an appropriate subject to teach schoolchildren. Surgeon General Joycelyn Elders was asked to go by President Bill Clinton after she angered conservatives by discussing the possibility of encouraging masturbation to prevent sexually transmitted diseases. Her remarks were made at an AIDS meeting held by the United Nations in New York.

Elders, who is 61, has been outspoken on public health since she was appointed nearly two years ago. She suggested handing out free condoms in …
Pathologists' work load
Authors: T. Keable-Elliott
Journal: BMJ (1979)

In the traditional approach to buffering of H<sup>+</sup> during metabolic acidosis, the sole focus is on lowering the H<sup>+</sup> concentration, but this overlooks several important points. First, increased binding of H<sup>+</sup> to proteins changes their charge, shape, and possibly function. Second, organs in which buffering of H<sup>+</sup> occurs is not assessed even though it would be advantageous to spare brain proteins in this process. Third, only the arterial and not the capillary Pco<sub>2</sub> of individual organs is considered. This article provides a “brain protein–centered” view, which leads to different conclusions concerning the way H<sup>+</sup> are removed physiologically.
Localized Phlegmonous Gastritis: Endoscopic View
Authors: J.F. Avilés, J. Fernández-Seara, R. Bárcena, F. Domíinguez, C. Fernández, L. Ledo
Journal: Endoscopy (1988)

A case of localized phlegmonous gastritis is reported. Features of this condition and the diagnostic and therapeutic usefulness of endoscopy are briefly considered.
Scottish doctors call for better protection when speaking out about concerns
Authors: B. Christie
Journal: BMJ (2010)

Doctors in Scotland are calling on the government to ensure that colleagues who raise concerns about patient care can do so without fear of being victimised.

The call from the BMA in Scotland follows an online survey which found that four in 10 doctors had failed to report concerns because they did not think it would make a difference or they feared the consequences of speaking out. One in ten of those who did act were given some indication that speaking out could have a negative impact on their employment.

The consequences of suppressing …
Comparing percutaneous tracheostomy with open surgical tracheostomy
Authors: I. Susanto
Journal: BMJ (2002)

Tracheostomy is one of the most frequent surgical procedures carried out in critically ill patients.1 Traditionally, open surgical tracheostomy has been done by surgeons in the operating room, and in many institutions it remains that way. In the past 50 years, however, several methods of doing percutaneous tracheostomy at the bedside have been introduced. Some of these methods did not get far because of high complication rates. The most popular technique today is the percutaneous dilatational tracheostomy described by Ciaglia in 1985.2 This technique uses serial dilators over a guide wire and is usually done at the bedside in the intensive care unit under bronchoscopic guidance. Ciaglia later introduced a single tapered dilator to replace the serial dilators, further simplifying the technique. In experienced hands, percutaneous tracheostomy can be done in five to 10 minutes and will rarely require more than 15 minutes. The low cost of percutaneous tracheostomy initially was an important reason …
Leflunomide as a novel treatment option in severe atopic dermatitis
Authors: J. Schmitt, G. Wozel, C. Pfeiffer
Journal: British Journal of Dermatology (2004)

Based on the increasing knowledge of T-cell-mediated pathogenesis in atopic dermatitis (AD), systemic immunosuppressive drugs are increasingly applied. The chronic, relapsing course of severe AD necessitates a drug, both efficacious and safe in long-term application. Leflunomide is a pyrimidine de novo synthesis-inhibiting immunosuppressant exhibiting an extremely long in vivo half life of its active metabolite.To evaluate the efficacy of leflunomide in long-term treatment of AD.As a proof of principle, we treated two patients with severe AD, recalcitrant to different systemic treatment modalities, for 20 months with leflunomide (loading dose 100 mg daily during 3 days; maintenance dose 20 mg daily). At regular visits physical examination, eczema area and severity index (EASI), visual analogue scale (VAS) for itching, and laboratory findings were assessed with according adjustment of the leflunomide dose.At the initiation of leflunomide therapy, both patients presented with almost erythrodermic AD (patient 1, EASI 40.0, VAS 10; patient 2, EASI 43.0, VAS 8). Partial remission was observed within 4 and 7 weeks, respectively, and maintained over 20 months (patient 1, median EASI 4.2, median VAS 2; patient 2, median EASI 8.4, median VAS 2) except for one episode of exacerbation in each case. In one patient, remission was stable even after cessation of drug dosing. Severe adverse events were not observed.Leflunomide was efficient in the long-term treatment of recalcitrant AD. Controlled studies will be necessary to evaluate the subset of severe AD patients benefiting most from this drug.
Injury prevention methods among athletes: how are they really performed?
Authors: G Cerulli, A Caraffa, F Ponteggia, G Potalivo, R Rende, V Conti, E Benvenuti
Journal: British Journal of Sports Medicine (2011)

<h3>Background</h3> The effectiveness of prevention programmes in diminishing the incidence of ankle and knee ligament injuries has been established and published in literature but we do not know exactly the real diffusion among athletes. <h3>Objective</h3> To assess the application of prevention methods. <h3>Design</h3> Retrospective Survey. <h3>Setting</h3> Youth sport, amateur, professionals and elite teams. <h3>Material and Method</h3> Coaches of 176 basketball, handball and volleyball teams (in total 2936 players, 1315 males and 1621 females: average age 15.6 years) in the Umbria region (central Italy) answered an anonymous original questionnaire regarding prevention methods (quantitative evaluation, balance training, landing technique, sport specific movements, video analysis, rapid deceleration and cutting manoeuvre). <h3>Results</h3> quantitative evaluations are performed in 26% of the teams; video analysis of sport-specific movements and playing situations are used in 51% of the teams to improve performance but not to prevent injuries (assessing at risk situations or reviewing the injuries); balance training with board is performed by 55% of the teams (an additional 10% use the board only during rehabilitation); sport specific at risk movements like rapid deceleration and crosscut maneouver are reproduced during training respectively in 49% and 42% of the teams while correction of jump landing strategies is not applied; 38% of the trainers declare they are aware of and use prevention methods. <h3>Conclusions</h3> Surveys are a fundamental way to know if the prevention measures are employed. These studies should be performed in every sport and in every country, according also by age, sex and level. The knowledge of basic prevention methods and their use by all the teams is a target that should be rapidly obtained with courses for both trainers and athletes. Moreover these results are helpful in combination with epidemiological data to decide the need of interventions, saving resources.
Tranexamic acid for surgical bleeding
Authors: Katharine Ker, Ian Roberts
Journal: BMJ (2014)

Uncertainty over vascular occlusive events warrants an adequately powered RCT

Joint replacement accounts for a large share of the 230 million major operations carried out each year worldwide. Each year in England and Wales alone there are about 180 000 hip and knee replacements.1 Bleeding is an important complication, and many patients require a blood transfusion. One strategy to reduce surgical bleeding is to use the antifibrinolytic drug tranexamic acid.

Tranexamic acid inhibits clot breakdown by reducing the binding of plasminogen to fibrin. A recent systematic review and meta-analysis of randomised controlled trials showed that tranexamic acid reduces surgical bleeding and blood transfusion by about one third.2 However, the effect of the antifibrinolytic on the risk of vascular occlusive events remains uncertain. Perioperative myocardial infarction often goes undetected as many patients do not experience ischaemic symptoms.3 Nevertheless, an increased cardiac troponin level, a sensitive marker of myocardial injury, is common after major surgery and is associated with appreciable morbidity and mortality.4

In a linked article (doi:10.1136/bmj.g4829), the effort by Poeran and colleagues to resolve the uncertainty …
Palpation of Basal Cell Epithelioma
Authors: Howard P. Baden
Journal: JAMA (1970)

To the Editor:—  A useful sign aids in the differentiation of nonulcerating papular and nodular basal cell carcinoma from other common cutaneous growths.  Basal cell carcinoma is a locally invasive, rarely metastasizing tumor of skin. It is usually recognizable by its pearl-like border, central ulceration, and telangiectasia. It may, however, present as a well-marginated papule or plaque and be confused with the elevated melanocytic nevus observed in adults. This latter lesion is common on the face, may be nonpigmented, and shows telangiectatic vessels. Because of its similarity to basal cell carcinoma, this innocuous nevus can be misdiagnosed particularly when present as a single lesion.  The patients reported in this study were personally observed andthe diagnosis established by biopsy and pathological examination of the tissue. Only facial lesions were studied.Twenty-five patients thought to have nonpigmented nevi and 25 patients with papular or nodular lesions thought to be basal cell epitheliomas
A Prospective, Randomized Controlled Trial of Sedation vs. No Sedation in Outpatient Diagnostic Upper Gastrointestinal Endoscopy
Authors: N. C. Fisher, S. Bailey, J. A. Gibson
Journal: Endoscopy (1998)

The majority of gastrointestinal endoscopists in the United Kingdom routinely use intravenous sedation prior to diagnostic upper gastrointestinal endoscopy. We conducted a prospective, randomized controlled clinical trial to help determine whether the use of sedation influences the duration, safety, and tolerance of diagnostic upper gastrointestinal endoscopy.Adults referred for outpatient diagnostic upper gastrointestinal endoscopy were invited to participate in the study. Patients with a history of previous upper gastrointestinal endoscopy or dysphagia were excluded. Patients were prospectively randomized to sedation with intravenous midazolam (5 mg for those under 65 years or 3 mg for those aged 65 or more), or no sedation. All patients were given topical oropharyngeal anaesthesia with 100 mg lignocaine spray. Outcome measures included duration of procedure, ease of procedure (as assessed by medical and nursing staff), tolerance of procedure (as assessed by patients), and incidence of complications.100 patients were randomized to receive sedation or no sedation. The two groups were well matched for age, sex, and number of biopsies taken during the procedure. In the non-sedated group, the duration of endoscopy tended to be reduced and the procedure tended to be easier according to the endoscopists' assessment (neither of these observations was significant). The sedated group reported greater comfort for the procedure (P < 0.001), although both groups tolerated the procedure well, and the majority in both groups preferred to have any future procedure repeated in the same manner. There were no serious adverse events in either group.In patients who are willing to contemplate upper gastrointestinal endoscopy without sedation, the avoidance of sedation may lead to faster and easier endoscopies, without any increased risk of procedural difficulties or adverse events.
Identification and Management of Patients with Failed Thrombolysis after Acute Myocardial Infarction
Authors: Lorne E. Goldman, Mark J. Eisenberg
Journal: Annals of Internal Medicine (2000)

Clinical outcome after thrombolytic therapy for acute myocardial infarction is closely related to restoration of flow in the infarct-related artery. Because thrombolytic therapy does not achieve coronary artery patency in 15% to 50% of patients, the early identification and treatment of patients with failed thrombolysis may lead to improved clinical outcomes. Unfortunately, the noninvasive identification of patients with failed thrombolysis continues to be problematic. Reduction in chest pain, decrease in ST-segment elevation, and presence of arrhythmias, although suggestive of reperfusion, are not diagnostic. Biochemical markers may hold promise for improved early identification of failed thrombolysis. In the setting of failed thrombolysis, clinical outcome may be improved by "rescue" percutaneous transluminal coronary angioplasty (PTCA) of the infarct-related artery. Several studies suggest that successful rescue PTCA is associated with high technical success rates and improved clinical outcomes. However, these same studies also suggest that patients with failed rescue PTCA may have higher mortality rates than patients who are treated conservatively. On the basis of current data, if failed thrombolysis is suspected, rescue PTCA should be considered, particularly in patients with anterior myocardial infarction and early presentation. Further investigations are needed to study the role of adjunctive methods such as stenting, glycoprotein IIb/IIIa inhibition, and intra-aortic balloon counterpulsation in the setting of rescue PTCA. Because of the relative lack of prospective data in this area, additional studies are urgently needed to help improve the ability to identify and manage patients with failed thrombolysis after acute myocardial infarction.
507 Early prediction of sustained virological response (SVR) during treatment with peginterferon alfa-2A (40KD) (PEGASYS®) plus ribavirin (RBV) (COPEGUS®) in patients with HCV/HIV co-infection: Results from the aids pegasys ribavirin international co-infectio (abstract withdrawn)
Authors: M. Rodriguez-Torres, F.J. Torriani, E. Lissen, N. Brau, M. Sulkowski, R. Sola, B. Clotet, N. Clumeck, D. Cooper, D. Dieterich
Journal: Journal of Hepatology (2004)
Esophageal Dislodgment of a Variceal Ligator Cap Due to Size Mismatch Between the Ligator Cap and the Endoscope
Authors: C. T. Wai, K. Y. Ho, F. Y. Kwok
Journal: Endoscopy (2003)

Endoscopic variceal ligation (EVL) is an effective therapy for prophylaxis and treatment of bleeding varices [1] [2] [3]. We describe a case of dislodgment of the ligator cap in a patient without esophageal stricture.
Abstract A08: Analysis of MRGBP and PPIL1 genes in colon cancer
Authors: Ebru Akisik, Nejat Dalay, Sumer Yamaner, Dursun Bugra
Journal: Cancer Research (2013)

Abstract Colorectal cancer is one of the most common causes of cancer death throughout the world. Colorectal carcinogenesis is a multi-step process and in addition to genetic changes significant changes in DNA methylation and epigenetic events such as histone modifications can also lead to deregulation of gene expression. The histone proteins play a dynamic role in the chromatin structure and transcription. Aberrant protein acetylation, particularly on histones, has been related to cancer while abnormal expression of histone deacetlytransferases (HDACs) are observed in a broad range of cancer types. Therefore, HDACs have emerged as promising targets in cancer therapeutics. The MRG-binding protein (MRGBP / C20orf20) is a component of the NuA4 histone acetyltransferase (HAT) complex and is involved in the transcriptional activation of specific genes. The MRGBP gene is frequently upregulated in tumors and is thought to play a role in cancer development. On the other hand removal of introns from pre-mRNA is carried out by a large macromolecular spliceosome complex. PPIL1 (Peptidyl-prolylisomerase-like 1) is a component of the human spliceosome and plays a primary role in pre-mRNA splicing for catalyzing isomerization of the peptide bonds. Overexpression of the PPIL1 protein in cancer suggest a potential role of PPIL1 in the in the development and promotion of colon cancer. In the present study we analyzed MRGBP and PPIL1 gene expression levels in matched tumor and normal tissue samples from patients with colorectal cancer. Tissue samples were collected from 51 patients with colorectal cancer who underwent surgery for tumor resection. The normal tissue specimens used in the study were histologically confirmed to be free of cancer. The HPRT (hypoxanthine-Guanine phosphoribosyltransferase) gene was used as reference. The target and reference genes were amplified in the same multiplex PCR using the LightCycler 480 System. 8-9 nucleotide long UPL probes were labeled with fluorescein (FAM) and TAMRA at the 5′ and 3′ ends, respectively. Expression levels were determined using the Basic Relative Quantification analysis software and the results were evaluated by the Mann-Whitney U test. Although the median MRGBP expression levels in the tumor tissue were higher than normal tissue (1,72 vs.1,41) the difference was not significant. The median expression levels of PPIL1 in the tumors and normal tissue samples (1,97 vs 1,86) were also similar. Our results indicate that neither MRGBP nor PPIL1 gene expression levels are upregulated in colon cancer cells indicating that these are not directly associated with colorectal cancer. Citation Format: Ebru Akisik, Nejat Dalay, Sumer Yamaner, Dursun Bugra. Analysis of MRGBP and PPIL1 genes in colon cancer. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr A08.