tbuckley/cabot-search huggingface dataset:
British respiratory trainee practice in consenting and preparation for conventional bronchoscopy
Authors: Haider Al-Najjar, Hilmi Lockman
Journal: European Respiratory Journal (2014)

Introduction   Pre-procedure preparation, including the consent process, is as important as manual bronchoscopy skills and trainees should have sufficient knowledge of bronchoscopy to understand the risks involved. To have effective discussions with patients about risk, potential adverse outcomes must be identified.   Objective   To assess if bronchoscopy pre-procedure preparation and consent by British respiratory specialist trainees is in keeping with current guidelines and evidence.   Methods   A national survey was designed to assess several issues pertaining to bronchoscopy training, including preparation and consent. This was piloted locally then circulated nationally.   Results   151 replies represented 26% of potential survey recipients. With the exception of bleeding (100%) and fever/infection (91%) there were no other complications mentioned by an overwhelming majority of trainees when consenting. Other common complications mentioned were pneumothorax (68%), hypoxaemia (58%), oversedation (54%), death (32%), cardiac arrhythmia (25%), sore throat (14%) and cough (13%).  When asked which anticoagulants they would stop for a period pre-bronchoscopy when biopsies are planned all trainees mentioned warfarin. However, significant numbers would continue clopidogrel (19%), Rivaroxaban (18%), Dabigatran (17%) and treatment dose low molecular weight heparin (9%). Also, 28% would stop aspirin.   Conclusions   There is great variation among British trainees in bronchoscopy consent and which risks are mentioned. This could be remedied by a uniform consenting proforma or formal training in the consent process. Furthermore, additional training in anticoagulant management pre-procedure appears to be indicated.
Defective B cell tolerance checkpoints in systemic lupus erythematosus
Authors: Sergey Yurasov, Hedda Wardemann, Johanna Hammersen, Makoto Tsuiji, Eric Meffre, Virginia Pascual, Michel C. Nussenzweig
Journal: The Journal of Experimental Medicine (2005)

A cardinal feature of systemic lupus erythematosus (SLE) is the development of autoantibodies. The first autoantibodies described in patients with SLE were those specific for nuclei and DNA, but subsequent work has shown that individuals with this disease produce a panoply of different autoantibodies. Thus, one of the constant features of SLE is a profound breakdown in tolerance in the antibody system. The appearance of self-reactive antibodies in SLE precedes clinical disease, but where in the B cell pathway tolerance is first broken has not been defined. In healthy humans, autoantibodies are removed from the B cell repertoire in two discrete early checkpoints in B cell development. We found these checkpoints to be defective in three adolescent patients with SLE. 25-50% of the mature naive B cells in SLE patients produce self-reactive antibodies even before they participate in immune responses as compared with 5-20% in controls. We conclude that SLE is associated with abnormal early B cell tolerance.
Left Ventricular Volumes by Angiocardiography: Comparison of Methods and Simplification of Techniques
Authors: H. J. Hermann, S. H. Bartle
Journal: Cardiovascular Research (1968)

Left ventricular volumes were measured by angiocardiography in 66 patients using different biplane and single plane methods. Regression formulae were calculated so that single plane equipment might be better utilized for volume measurements. A modification of the area-length method is described that simplifies considerably the calculations without altering the final result. A simple method of calculating LV mass is also presented.
TR-05 * ER STRESS INDUCING DRUGS DOWNREGULATES MGMT AND MPG SENSITIZING PEDIATRIC GLIOMA CELL LINES TO TMZ
Authors: E. Xipell, N. Martinez-Velez, M. Gonzalez-Huarriz, A. A. d. l. Rocha, C. Jones, M. M. Alonso
Journal: Neuro-Oncology (2015)

Pediatric patients with glioblastoma multiforme (pGBM) are in desperate need of new therapies. Temozolamide (TMZ) is one of the preferred treatments however its clinical benefit is meager. Salinomycin (SLM) is a potassium ionophore (K+) that has proven efficient against different type of tumors. However, its antitumor effect has never been evaluated in pGBM. The main goal of this work was to characterized the antitumor effect of SLM in pGBM cell lines and improve our understanding of its mechanism action. SLM induced a potent antitumor effect against pGBM cell lines. Moreover, treatment with this drug resulted in an aberrant autophagic flux that led to regulated necrosis cell death. Our data showed that the cell death was mediated by AIF release which induced lysosomal membrane permeability. Of importance, SLM induced a potent ER stress in pGBM cell lines which was accompanied by the downregulation of MGMT and MPG, both proteins are involve in the DNA damage response to TMZ. We observed the same phenomenon when we treated the cells with other ER stress inducing drugs (i.e.: thapsigergin and tunicamycin). Chemical inhibition of ER stress resulted in abrogation of MGMT and MPG downregulation suggesting a common mechanism to ER stress inducing drugs. The results prompted us to combined SLM with TMZ resulting in a synergistic antiglioma effect. SLM induced a significant increment in the amount of DNA damage induced by TMZ, probably mediated by the downregulation of MGMT and MPG. Similarly, to SLM alone combination with TMZ induced ER stress and aberrant autophagy due to impairment of lysosomal activity that in turn led to regulated necrosis undercovering the crosstalk between ER stress and regulated necrosis. These findings provide a strong rationale for further exploring the combination of TMZ with ER stress inducing drugs as a therapeutic strategy for pGBM.
Cost-effectiveness of Combined Treatment for Endocervical Gonorrhea
Authors: A. Eugene Washington
Journal: JAMA (1987)

Three treatment regimens are currently recommended for penicillin-susceptible<i>Neisseria gonorrhoeae</i>infection of the cervix: ampicillin, tetracycline, and a combination of ampicillin and tetracycline. To evaluate the cost-effectiveness of these options, we developed a decision analysis model and analyzed the efficacy of each treatment in curing gonorrhea, as well as coexisting<i>Chlamydia trachomatis</i>infection, and in preventing subsequent pelvic inflammatory disease, ectopic pregnancy, and infertility. We included direct costs of medication and expenditures for management of unresolved infections and associated complications. Combination treatment is more than twice as cost-effective as tetracycline and seven times as cost-effective as ampicillin when the medical cost of managing pelvic inflammatory disease is considered. When the costs of ectopic pregnancies and infertility are included, the cost-effectiveness of combination treatment increases further. (<i>JAMA</i>1987;257:2056-2060)
Being More Realistic about the Public Health Impact of Genomic Medicine
Authors: Wayne D. Hall, Rebecca Mathews, Katherine I. Morley
Journal: PLoS Medicine (2010)

Advocates of the preventive use of genetic risk information often simply assume that preventive interventions will be cost-effective if genotypic information can be shown to predict disease risk (e.g.The Policy Forum allows health policy makers around the world to discuss challenges and opportunities for improving health care in their societies.
CLASS II ANTIGENS AND DISEASE SUSCEPTIBILITY
Authors: Gerald T. Nepom, M.D., Ph.D
Journal: Annual Review of Medicine (1995)

▪ Abstract The role for HLA typing in autoimmune disease is changing with the recognition that HLA markers can identify patients with poor prognosis in some autoimmune disease. Aggressive therapeutic intervention in patients with such HLA prognostic markers has the potential to improve or prevent progressive disease outcomes in a select group of patients.
WEE1 Kinase Targeting Combined with DNA-Damaging Cancer Therapy Catalyzes Mitotic Catastrophe
Authors: Philip C. De Witt Hamer, Shahryar E. Mir, David Noske, Cornelis J.F. Van Noorden, Tom Würdinger
Journal: Clinical Cancer Research (2011)

WEE1 kinase is a key molecule in maintaining G₂-cell-cycle checkpoint arrest for premitotic DNA repair. Whereas normal cells repair damaged DNA during G₁-arrest, cancer cells often have a deficient G₁-arrest and largely depend on G₂-arrest. The molecular switch for the G₂-M transition is held by WEE1 and is pushed forward by CDC25. WEE1 is overexpressed in various cancer types, including glioblastoma and breast cancer. Preclinical studies with cancer cell lines and animal models showed decreased cancer cell viability, reduced tumor burden, and improved survival after WEE1 inhibition by siRNA or small molecule inhibitors, which is enhanced by combination with conventional DNA-damaging therapy, such as radiotherapy and/or cytostatics. Mitotic catastrophe results from premature entry into mitosis with unrepaired lethal DNA damage. As such, cancer cells become sensitized to conventional therapy by WEE1 inhibition, in particular those with insufficient G₁-arrest due to deficient p53 signaling, like glioblastoma cells. One WEE1 inhibitor has now reached clinical phase I studies. Dose-limiting toxicity consisted of hematologic events, nausea and/or vomiting, and fatigue. The combination of DNA-damaging cancer therapy with WEE1 inhibition seems to be a rational approach to push cancer cells in mitotic catastrophe. Its safety and efficacy are being evaluated in clinical studies.
ELECTROCARDIOGRAPHY AS A ROUTINE ADMISSION PROCEDURE IN A LARGE NEUROPSYCHIATRIC HOSPITAL: AN EVALUATION
Authors: PHILIP H. ROSS, JOHN R. SHAWVER, STANLEY M. TARNOWSKI
Journal: American Journal of Psychiatry (1959)

The routine use of the electrocardiogram on admission of patients to a large neuropsychiatric hospital has been found to be of considerable value. It has demonstrated a large number of patients (16.6%) to have significant electrocardiographic abnormalities. This has made possible, at a very early stage, the following appropriate measures: 1. Proper treatment of the cardiac, or related, disorder. 2. Rapid evaluation of eligibility for desirable neuropsychiatric therapeutic regime, especially shock therapy. 3. Proper occupational therapy. 4. Realistic rehabilitation planning. It should further be mentioned that only a small percentage of these patients were suspected of cardiac abnormalities after clinical examination and other laboratory tests. The procedure of taking routine electrocardiograms on all patients admitted to a neuropsychiatric hospital is highly recommended. [SEE TABLE 1 IN SOURCE PDF]
Dynamic Contrast-enhanced Magnetic Resonance Imaging as a Predictor of Clinical Outcome in Canine Spontaneous Soft Tissue Sarcomas Treated with Thermoradiotherapy
Authors: Benjamin L. Viglianti, Michael Lora-Michiels, Jeanie M. Poulson, Lan Lan, Dahio Yu, Linda Sanders, Oana Craciunescu, Zeljko Vujaskovic, Donald E. Thrall, James MacFall, Cecil H. Charles, Terence Wong, Mark W. Dewhirst
Journal: Clinical Cancer Research (2009)

This study tests whether dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters obtained from canine patients with soft tissue sarcomas, treated with hyperthermia and radiotherapy, are predictive of therapeutic outcome. Thirty-seven dogs with soft tissue sarcomas had DCE-MRI done before and following the first hyperthermia. Signal enhancement for tumor and reference muscle were fitted empirically, yielding a washin/washout rate for the contrast agent and tumor area under the signal enhancement curve (AUC) calculated from 0 to 60 seconds, 90 seconds, and the time of maximal enhancement in the reference muscle. These parameters were then compared with local tumor control, metastasis-free survival, and overall survival. Pretherapy rate of contrast agent washout was positively predictive of improved overall and metastasis-free survival with hazard ratio of 0.67 (P = 0.015) and 0.68 (P = 0.012), respectively. After the first hyperthermia washin rate, AUC60, AUC90, and AUCt-max were predictive of improved overall and metastasis-free survival with hazard ratio ranging from 0.46 to 0.53 (P < 0.002) and 0.44 to 0.55 (P < 0.004), respectively. DCE-MRI parameters were compared with extracellular pH and (31)P MR spectroscopy results (previously published) in the same patients showing a correlation. This suggested that an increase in perfusion after therapy was effective in eliminating excess acid from the tumor. This study shows that DCE-MRI has utility predicting overall and metastasis-free survival in canine patients with soft tissue sarcomas. To our knowledge, this is the first time that DCE-MRI parameters are predictive of clinical outcome for soft tissue sarcomas.
Sex Hormone Levels and Risks of Estrogen Receptor-Negative and Estrogen Receptor-Positive Breast Cancers
Authors: G. N. Farhat, S. R. Cummings, R. T. Chlebowski, N. Parimi, J. A. Cauley, T. E. Rohan, A. J. Huang, M. Vitolins, F. A. Hubbell, J. E. Manson, B. B. Cochrane, D. S. Lane, J. S. Lee
Journal: JNCI Journal of the National Cancer Institute (2011)

Endogenous sex hormone levels are associated with risks of breast cancer overall and estrogen receptor (ER)-positive breast tumors; however, their associations with ER-negative tumors remain unclear.In a case-cohort study within the Women's Health Initiative Observational Study among postmenopausal women aged 50-79 years, we examined associations between endogenous testosterone and estradiol levels and the risks of ER-negative and ER-positive breast cancers. Serum levels of bioavailable testosterone and estradiol were assessed at the baseline visit in 317 invasive breast cancer case subjects and in a subcohort of 594 women. Bioavailable sex hormone levels were calculated using the total hormone level and the sex hormone-binding globulin concentration (measured by radioimmunoassays and a chemiluminescent immunoassay, respectively). Cox proportional hazards regression was used for statistical analysis. All statistical tests were two-sided.The unadjusted absolute rates of ER-negative breast cancer for testosterone quartiles 1-4 were 0.34, 0.20, 0.23, and 0.21 per 10,000 person-years, respectively. Compared with women in the lowest quartile of testosterone level, those in quartile 2 had a 56% lower risk of ER-negative cancer (hazard ratio [HR] = 0.44, 95% confidence interval [CI] = 0.23 to 0.85), those in quartile 3 had a 45% lower risk (HR = 0.55, 95% CI = 0.30 to 1.01), and those in quartile 4 had a 49% lower risk (HR = 0.51, 95% CI = 0.28 to 0.94), independent of other risk factors. Estradiol level was not associated with ER-negative breast cancer. ER-positive breast cancer risk increased with higher testosterone levels (P(trend) = .04), but this trend was not statistically significant after adjustment for estradiol (P(trend) = .15). ER-positive cancer risk was approximately twofold higher in women with estradiol levels in quartiles 2-4 compared with women in quartile 1, independent of risk factors.Higher serum levels of bioavailable testosterone are associated with lower risks of ER-negative breast cancer in postmenopausal women.
Different cytokine profiles in cryptogenic fibrosing alveolitis and fibrosing alveolitis associated with systemic sclerosis A quantitative study of open lung biopsies
Authors: S. Majumdar, D. Li, T. Ansari, P. Pantelidis, C.m Black, M. Gizycki, R.M. du Bois, P.K. Jeffery
Journal: European Respiratory Journal (1999)

Differences in the inflammatory response and prognosis of cryptogenic fibrosing alveolitis (CFA) and that associated with systemic sclerosis (FASSc) are beginning to emerge. It is hypothesized that these differences may be reflected in a distinct pattern of T-helper (Th)-1 and Th-2-type cytokines. Open lung biopsies were obtained from clinically well-documented cases of CFA and FASSc and, as a control, compared with grossly and histologically normal parenchyma obtained from smokers whose lungs were resected for cancer (n=5 in each group). In situ hybridization (ISH) was applied to the samples using anti-sense and sense 35S-labelled riboprobes to detect messenger ribonucleic acid (mRNA) for interleukins (IL)-2, IL-4, IL-5 and interferon (IFN)-gamma. Between 52-91% of cells expressing the cytokines studied were present in the alveolar interstitium rather than in lumenal cells or the alveolar epithelial lining. The highest values for all four cytokines were present in the patients with FASSc, i.e., 22-39 ISH positive cells x mm(-2) alveolar tissue compared with 1-19 cells x mm(-2) and 4-5 cell x mm(-2) in CFA and control subjects, respectively. Whereas the proportions of the four cytokines in FASSc were similar to the control subjects, IL-4 and IL-5 predominated significantly in CFA (p<0.001). For example, the ratio of IL-5 to IFN-gamma was 22:1 in CFA, significantly higher than in the cases with FASSc (2:1) or the control subjects (4:1) (p<0.05). In conclusion, cryptogenic fibrosing alveolitis is an inflammatory condition which is characterized, like asthma, by a predominance of gene expression for T-helper-2-type regulatory cytokines, whereas cryptogenic fibrosing alveolitis associated with systemic sclerosis appears to have a distinct mixed T-helper-1/T-helper-2 functional phenotype and a greater number of cells expressing each of these pro-inflammatory cytokines.
Learning to perform endoscopic resection of esophageal neoplasia is associated with significant complications even within a structured training program
Authors: F. van Vilsteren, R. Pouw, L. Herrero, F. Peters, R. Bisschops, M. Houben, F. Peters, B. Schenk, B. Weusten, M. Visser, F. Ten Kate, P. Fockens, E. Schoon, J. Bergman
Journal: Endoscopy (2011)

Endoscopic resection is the cornerstone of endoscopic treatment of esophageal high grade dysplasia or early cancer. Endoscopic resection is, however, a technically demanding procedure, which requires training and expertise. The aim of the current study was to prospectively evaluate efficacy and safety of the first 120 endoscopic resection procedures of early esophageal neoplasia performed by six endoscopists (20 endoscopic resections each) who were participating in an endoscopic resection training program.The program consisted of four tri-monthly 1-day courses with lectures, live-demonstrations, hands-on training on anesthetized pigs, and one-on-one hands-on training days. Gastroenterologists from centers with multidisciplinary expertise in upper gastrointestinal oncology participated, together with an endoscopy nurse and a pathologist. Outcome measures were complete endoscopic removal of the target area and acute complications.A total of 120 consecutive esophageal endoscopic resection procedures (85 ER-cap, 35 multiband mucosectomy [MBM]) were performed by six endoscopists: 109 in Barrett's esophagus, 11 for squamous neoplasia; 85 piecemeal endoscopic resections (median 3 specimens, interquartile range 2 - 4 specimens). Complete endoscopic removal was achieved in 111 /120 cases (92.5 %). Six perforations occurred (5.0 %): five were effectively treated endoscopically (clips, covered stent), and one patient underwent esophagectomy. There were 11 acute mild bleedings (9.2 %), which were managed endoscopically. Perforations occurred in ER-cap procedures performed by four participants (7.1 % ER-cap vs. 0 % MBM; P = 0.18), and in 1.7 % of the first 10 endoscopic resections and 8.3 % of the second 10 endoscopic resections per endoscopist (P = 0.26).In this intense, structured training program, the first 120 esophageal endoscopic resections performed by six participants were associated with a 5.0 % perforation rate. Although perforations were adequately managed, performing 20 endoscopic resections may not be sufficient to reach the peak of the learning curve in endoscopic resection.
Patients' perspectives on electroconvulsive therapy: systematic review
Authors: D. Rose
Journal: BMJ (2003)

<h3>Abstract</h3> <b>Objective</b> To ascertain patients9 views on the benefits of and possible memory loss from electroconvulsive therapy. <b>Design</b> Descriptive systematic review. <b>Data sources</b> Psychinfo, Medline, Web of Science, and Social Science Citation Index databases, and bibliographies. <b>Study selection</b> Articles with patients9 views after treatment with electroconvulsive therapy. <b>Data extraction</b> 26 studies carried out by clinicians and nine reports of work undertaken by patients or with the collaboration of patients were identified; 16 studies investigated the perceived benefit of electroconvulsive therapy and seven met criteria for investigating memory loss. <b>Data synthesis</b> The studies showed heterogeneity. The methods used were associated with levels of perceived benefit. At least one third of patients reported persistent memory loss. <b>Conclusions</b> The current statement for patients from the Royal College of Psychiatrists that over 80% of patients are satisfied with electroconvulsive therapy and that memory loss is not clinically important is unfounded.
Multilocus Phylogeny of Chichlid Fishes (Pisces: Perciformes): Evolutionary Comparison of Microsatellite and Single-Copy Nuclear Loci
Authors: J. T. Streelman, R. Zardoya, A. Meyer, S. A. Karl
Journal: Molecular Biology and Evolution (1998)

Among vertebrates, cichlid fishes are the paradigmatic example of adaptive radiation and ecological specialization. In turn, molecular genetic studies of cichlids have focused primarily on more recently diverged groups. Here, we present an evolutionary hypothesis of the major lineages of cichlid fishes based on DNA sequence data from two nuclear loci. One marker, Tmo-4C4, is a single-copy locus containing a region of amino acid similarity to the muscle protein TITIN. Flanking sequence from a second, microsatellite, locus Tmo-M27, shows similarity to mammalian RAS guanine nucleotide-releasing factor. We compare and combine data from these loci to evaluate phylogenetic performance. In separate and combined analyses, the sequence data support and clarify previous morphological hypotheses of cichlid major-group relationships. Indian and Malagasy cichlids form a basal, paraphyletic group. Neotropical cichlids are the sister clade to an African assemblage composed of the paraphyletic west and Pan-African lineages and a group of east African rift lake taxa. We use a consensus phylogeny of the Cichlidae to trace evolutionary changes in the microsatellite repeat motif at Tmo-M27. Analysis reveals that the repeat region was nearly lost in the ancestor to cichlids and then amplified extensively in African taxa. Results demonstrate that the two new DNA markers could be widely applied in perciform systematics. Furthermore, the comparative approach can unveil mutational dynamics of simple-sequence repeat loci over long periods of fish evolution. Simple-sequence repeat regions are increasingly being found in introns of important regulatory genes. We address issues involving their function and suggest caution in making assumptions of strict neutrality.
NHS is too slow to adopt NICE approved treatments, MPs hear
Authors: A. O'Dowd
Journal: BMJ (2012)

The NHS is too slow in adopting treatments approved by the drugs watchdog the National Institute for Health and Clinical Excellence, MPs have been told.

Witnesses appearing before the parliamentary health select committee on 27 November said that good guidance from NICE was too often ignored or delayed by commissioners as a way to save money.

MPs, holding an evidence session as part of their inquiry into the institute, asked about implementation of guidance, which provoked different views from the witnesses present.

Laura Weir, chairwoman of Patients Involved in NICE, a coalition group representing more than 80 patients’ groups, said that patients had a legal right to receive drugs and other …