tbuckley/cabot-search huggingface dataset:
8 EVOLUTION OF TREATMENT-EMERGENT RESISTANT VARIANTS IN TELAPREVIR PHASE 3 CLINICAL TRIALS
Authors: J.C. Sullivan, S. De Meyer, D.J. Bartels, I. Dierynck, E. Zhang, J. Spanks, A. Tigges, N. Adda, E.C. Martin, M. Beumont, I.M. Jacobson, K.E. Sherman, S. Zeuzem, G. Picchio, T.L. Kieffer
Journal: Journal of Hepatology (2011)
Vitamin D status in patients with COPD who participate in pulmonary rehabilitation (PR): Characteristics and effects of PR
Authors: Thomas Ringbaek, Jane Thoegersen, Gerd Martinez, Peter Lange
Journal: European Respiratory Journal (2011)

Vitamin D deficiency is common in COPD patients, however no study has evaluated the influence of vitamin D status on effects of pulmonary rehabilitation.

We studied 311 patients, who participated in a 7-week outpatient pulmonary rehabilitation programme (PR). Vitamin D status was assessed at entry and examined for association with patients' characteristics, drop out from PR, and effect on endurance shuttle walk time (ESWT).

Vitamin D level ≤25 nM was seen in 61 (19.6%) of the patients. They were significantly younger, were more frequently on long-term oxygen therapy, had higher BMI and FFMI, had worse quality of life score, tended to have lower FEV1% predicted value and more frequently to be current smokers. They had a 3-times higher risk of drop out from the PR programme (p=0.003) compared to patients with normal vitamin D status and a poorer improvement in ESWT (p=0.03).

![Figure][1] 



In conclusion, vitamin D deficiency was significantly associated with higher drop out rates from PR and there was a tendency towards a poorer improvement in ESWT.

 [1]: pending:yes
Recommendations for standards of sedation and patient monitoring during gastrointestinal endoscopy.
Authors: G D Bell, R F McCloy, J E Charlton, D Campbell, N A Dent, M W Gear, R F Logan, C H Swan
Journal: Gut (1991)

(1) Safety and monitoring should be part of a quality assurance programme for endoscopy units. (2) Resuscitation equipment and drugs must be available in the endoscopy and recovery areas. (3) Staff of all grades and disciplines should be familiar with resuscitation methods and undergo periodic retraining. (4) Equipment and drugs necessary for the maintenance of airway, breathing, and circulation should be present in the endoscopy unit and recovery area (if outside the unit) and checked regularly. (5) A qualified nurse, trained in endoscopic techniques and adequately trained in resuscitation techniques, should monitor the patient9s condition during procedures. (6) Before endoscopy, adverse risk factors should be identified. This may be aided by the use of a check list. (7) The dosage of all drugs should be kept to the minimum necessary. There is evidence that benzodiazepine/opioid mixtures are hazardous. (8) Specific antagonists for benzodiazepines and opioids exist and should be available in the event of emergency. (9) A cannula should be placed in a vein during endoscopy on 9at risk9 patients. (10) Oxygen enriched air should be given to 9at risk9 patients undergoing endoscopic procedures. (11) The endoscopist should ensure the well being and clinical observation of the patient undergoing endoscopy in conjunction with another individual. This individual should be a qualified nurse trained in endoscopic techniques or another medically qualified practitioner. (12) Monitoring techniques such as pulse oximetry are recommended. (13) Clinical monitoring of the patient must be continued into the recovery area. (14) Records of management and outcome should be collected and will provide data for appropriate audit.
Normal Glucose Tolerance and Gestational Diabetes Mellitus
Authors: Graziano Di Cianni, Giuseppe Seghieri, Cristina Lencioni, Ilaria Cuccuru, Roberto Anichini, Alessandra De Bellis, Alessandra Ghio, Federica Tesi, Laura Volpe, Stefano Del Prato
Journal: Diabetes Care (2007)

The aim of this article was to define the metabolic phenotype of pregnant women with one abnormal value (OAV) during an oral glucose tolerance test (OGTT) and to test whether OAV could be considered metabolically comparable to gestational diabetes mellitus (GDM) or a specific entity between GDM and normal pregnancy.After 100-g 3-h OGTTs, 4,053 pregnant women were classified as having GDM, OAV, or normal glucose tolerance (NGT). Those with OAV were subdivided into three subgroups: fasting hyperglycemia (one abnormal value at fasting during an OGTT), 1-h hyperglycemia (one abnormal value at 1 h during an OGTT [1h-OAV]), or 2- or 3-h hyperglycemia (one abnormal value at 2 or 3 h during an OGTT). As derived from the OGTT, we measured insulin sensitivity (insulin sensitivity index [ISI] Matsuda) and insulin secretion (homeostasis model assessment for the estimation of beta-cell secretion [HOMA-B], first- and second-phase insulin secretion). The product of the first-phase index and the ISI was calculated to obtain the insulin secretion-sensitivity index (ISSI).GDM was diagnosed in 17.9% and OAV in 18.7% of pregnant women; women with GDM and OAV were older and had higher BMI and serum triglyceride levels than those with NGT (all P < 0.05). Women with NGT had the highest ISI followed by those with OAV (-21.7%) and GDM (-32.1%). HOMA-B results were comparable with those for OAV and GDM but significantly (P < 0.01) lower than those for NGT; first- and second-phase insulin secretion appeared progressively reduced from that in women with NGT to that in women with OAV and GDM (P < 0.01). ISSI was higher in women with NGT than in women with either OAV (-34%) or GDM (-51.7%) (P < 0.001). Among OAV subgroups, the 1h-OAV subgroup showed the lowest ISSI (P < 0.05).OAV and GDM are clinically indistinguishable, and both groups are different from women with NGT. Women with GDM and OAV showed impaired insulin secretion and insulin sensitivity, although these defects are more pronounced in women with GDM. Compared with other OAV subgroups, 1h-OAV could be considered a more severe condition.
Synovial Chlamydia trachomatis up regulates expression of a panel of genes similar to that transcribed by Mycobacterium tuberculosis during persistent infection
Authors: H C Gérard, J A Whittum-Hudson, H R Schumacher, A P Hudson
Journal: Annals of the Rheumatic Diseases (2005)

<b>Background:</b> Synovial tissues in patients with <i>Chlamydia</i> associated arthritis are persistently infected by <i>C trachomatis</i>, an organism for which genetic manipulation is not possible. <i>M tuberculosis</i> also engages in persistent infection, and because this bacterium is genetically tractable many groups have been able to define transcriptional characteristics of mycobacterial growth and persistence. <b>Objective:</b> To investigate whether the pattern of gene expression underlying chlamydial persistence is similar to that underlying mycobacterial persistence. <b>Methods:</b> 194 genes in <i>M tuberculosis</i> that are transcriptionally up regulated to support in vivo growth and persistence of that organism have previously been identified. Each of those genes was compared with the <i>C trachomatis</i> genome to identify orthologues. Expression of selected chlamydial orthologues so identified was assessed by real time RT-PCR in an in vitro model of chlamydial persistence and synovial tissues from patients who were PCR positive for <i>C trachomatis</i> at that site. <b>Results:</b> 67 <i>C trachomatis</i> genes were identified as being orthologous to mycobacterial persistence related genes, representing 35% of the genes tested. The chlamydial orthologues fell into similar metabolic and other categories as those in <i>M tuberculosis</i>. Expression of a majority of selected chlamydial orthologues was strongly up regulated in an in vitro model of chlamydial persistence and in synovial tissues of relevant patients, compared with their expression during active infection. <b>Conclusions:</b> These observations provide new insight into the molecular genetic basis underlying chlamydial persistence, and indicate that this information can be obtained, in some instances, by extrapolating observations made in other biological systems and/or organisms.
On some Superficial Affections of the Red Portion of the Lips
Authors: W. A. Jamieson
Journal: BMJ (1895)

the bounden duty of mistress, parent, and doctor at once to insist on the cessation of all severe study as soon as any of the physical signs of illness have shown themselves, such as it is impossible to be mistaken in, as, for example, chlorosis, amenorrheea, or menorrhagia, wasting, complete loss of appetite, and the like, and yet this is not generally done.Quite recently I was consulted by a medical man, whose daughter was a pupil at one of the principal and best known colleges for girls.Her menstruation had ceased for a year, and she had lost over a stone in weight.On this account her father, as I think very properly, removed her, on which the head mistress remonstrated, and wrote saying that they con- sidered the menstrual function was not of consequence, and that when it was in abeyance for a time it came all right after- wards, when the girls left school.Any theory more unphysiological and more likely to lead to subsequent shattered health in girls it would be difficult to imagine.It is not work which, in my judgment, hurts, but the perse- verance in work after Nature has hung out its danger signals, work in an unhealthy body; the attempt, in fact, to fight Nature.Then, indeed, the careless, prejudiced, or unwise mistress or parent may well find that " over-pressure," the very existence of which so many deny, is a stern reality, which may shatter the whole future of the girl.
Telomerase Reverse Transcriptase Locus Polymorphisms and Cancer Risk: A Field Synopsis and Meta-Analysis
Authors: Simone Mocellin, Daunia Verdi, Karen A. Pooley, Maria T. Landi, Kathleen M. Egan, Duncan M. Baird, Jennifer Prescott, Immaculata De Vivo, Donato Nitti
Journal: JNCI Journal of the National Cancer Institute (2012)

Several recent studies have provided evidence that polymorphisms in the telomerase reverse transcriptase ( TERT ) gene sequence are associated with cancer development, but a comprehensive synopsis is not available. We conducted a systematic review and meta-analysis of the available molecular epidemiology data regarding the association between TERT locus polymorphisms and predisposition to cancer. A systematic review of the English literature was conducted by searching PubMed, Embase, Cancerlit, Google Scholar, and ISI Web of Knowledge databases for studies on associations between TERT locus polymorphisms and cancer risk. Random-effects meta-analysis was performed to pool per-allele odds ratios for TERT locus polymorphisms and risk of cancer, and between-study heterogeneity and potential bias sources (eg, publication and chasing bias) were assessed. Because the TERT locus includes the cleft lip and palate transmembrane 1-like ( CLPTM1L ) gene, which is in linkage disequilibrium with TERT , CLPTM1L polymorphisms were also analyzed. Cumulative evidence for polymorphisms with statistically significant associations was graded as "strong," "moderate," and "weak" according to the Venice criteria. The joint population attributable risk was calculated for polymorphisms with strong evidence of association. Eighty-five studies enrolling 490 901 subjects and reporting on 494 allelic contrasts were retrieved. Data were available on 67 TERT locus polymorphisms and 24 tumor types, for a total of 221 unique combinations of polymorphisms and cancer types. Upon meta-analysis, a statistically significant association with the risk of any cancer type was found for 22 polymorphisms. Strong, moderate, and weak cumulative evidence for association with at least one tumor type was demonstrated for 11, 9, and 14 polymorphisms, respectively. For lung cancer, which was the most studied tumor type, the estimated joint population attributable risk for three polymorphisms ( TERT rs2736100, intergenic rs4635969, and CLPTM1L rs402710) was 41%. Strong evidence for lack of association was identified for five polymorphisms in three tumor types. To our knowledge, this is the largest collection of data for associations between TERT locus polymorphisms and cancer risk. Our findings support the hypothesis that genetic variability in this genomic region can modulate cancer susceptibility in humans.
DIFFICULTIES IN THE DIAGNOSIS OF CEREBELLAR ABSCESS
Authors: R. S. Stevenson
Journal: BMJ (1925)

is aged 28 years, the " tubercles " are numerous and stand out boldly, the central giant cell being surrounded by endothelioid cells of fibroblastic tendency, for the fibrous areas mentioned above are most marked where the giant- celled formations ar-e most numerous.In M. C., who is 65 years of age, the typical " tubereles " are few and far between, but scattered throughout the section are large numbers of " lonely," somewhat atrophic, giant cells, with no tissue reaction (fibrosis, etc.) around them.This latter appearance has been observed not infrequently by one of us in senile tuberculosis of lymphatic glands, and is, after all, what one might expect in old age where tissue reaction to inifection is often half-hearted and atypical.It is further of interest from this point of view to remark that, of the sections examined, it is onlv in those of M. C. that necrosis of tissue was found.Although sections were dili- gently searehed for tubercle bacilli by three competent observers, none were seen.These two cases well illustrate the type described by Winternitz in his study of fifty-one examples.The com- paratively mild symptomatology, the size of the spleen, thle existence of tuberculosis in the liver and lvmplhatic glands leading to it, and in the lung in the one case; the super- vention of generalization in the otlher, despite splenectomy (performed, as Dr. Ward suggests to us, " too late "), and the microscopical findings, are all in accordance with the general picture.No inoculation experiments were performed in our cases.Although no definite primalry focus was found, and although the splenic lesion dominated the clinical picture and was the sour-ce of spread, we hesitate to accept the term " primarv tuberculosis " of the spleen.Firom a -surgical point of view the conclusion to be drawn from a study of these cases is that splenectomy should be performed early, and that, for what it is worth, irregular fever with splenomegaly should suggest tuber-cullosis; but wi-e admit that though, having seen one of these cases recentlv, onie of us (J. A. B. H.) did suggest the diagnosis in the (other, yet in the presence of the splenomegaly syndrome we are still very mulch in the dark as to diagnosis and rational treatment.
Subthalamic deep brain stimulation with a constant-current device in Parkinson's disease: an open-label randomised controlled trial
Authors: Michael S Okun, Bruno V Gallo, George Mandybur, Jonathan Jagid, Kelly D Foote, Fredy J Revilla, Ron Alterman, Joseph Jankovic, Richard Simpson, Fred Junn, Leo Verhagen, Jeff E Arle, Blair Ford, Robert R Goodman, R Malcolm Stewart, Stacy Horn, Gordon H Baltuch, Brian H Kopell, Frederick Marshall, DeLea Peichel, Rajesh Pahwa, Kelly E Lyons, Alexander I Tröster, Jerrold L Vitek, Michele Tagliati
Journal: The Lancet Neurology (2012)
Randomized Controlled Trial of Barbed Polyglyconate Versus Polyglactin Suture for Robot-Assisted Laparoscopic Prostatectomy Anastomosis: Technique and Outcomes
Authors: Stephen B. Williams, Mehrdad Alemozaffar, Yin Lei, Nathanael Hevelone, Stuart R. Lipsitz, Blakely A. Plaster, Jim C. Hu
Journal: European Urology (2010)
Impact of Socioeconomic Status on Cardiovascular Disease and Mortality in 24,947 Individuals With Type 1 Diabetes
Authors: Araz Rawshani, Ann-Marie Svensson, Annika Rosengren, Björn Eliasson, Soffia Gudbjörnsdottir
Journal: Diabetes Care (2015)

OBJECTIVE Socioeconomic status (SES) is a powerful predictor of cardiovascular disease (CVD) and death. We examined the association in a large cohort of patients with type 1 diabetes. RESEARCH DESIGN AND METHODS Clinical data from the Swedish National Diabetes Register were linked to national registers, whereby information on income, education, marital status, country of birth, comorbidities, and events was obtained. Patients were followed until a first incident event, death, or end of follow-up. The association between socioeconomic variables and the outcomes was modeled using Cox regression, with rigorous covariate adjustment. RESULTS We included 24,947 patients. Mean (SD) age and follow-up was 39.1 (13.9) and 6.0 (1.0) years. Death and fatal/nonfatal CVD occurred in 926 and 1378 individuals. Compared with being single, being married was associated with 50% lower risk of death, cardiovascular (CV) death, and diabetes-related death. Individuals in the two lowest quintiles had twice as great a risk of fatal/nonfatal CVD, coronary heart disease, and stroke and roughly three times as great a risk of death, diabetes-related death, and CV death as individuals in the highest income quintile. Compared with having ≤9 years of education, individuals with a college/university degree had 33% lower risk of fatal/nonfatal stroke. Immigrants had 19%, 33%, and 45% lower risk of fatal/nonfatal CVD, all-cause death, and diabetes-related death, respectively, compared with Swedes. Men had 44%, 63%, and 29% greater risk of all-cause death, CV death, and diabetes-related death. CONCLUSIONS Low SES increases the risk of CVD and death by a factor of 2–3 in type 1 diabetes.
TCT-194 5-Year Outcome Of Zotarolimus-Eluting Versus Sirolimus-Eluting Coronary Stent Implantation In Patients With And Without Diabetes Mellitus
Authors: Michael Maeng, Evald H. Christiansen, Lisette Okkels Jensen, Anne Kaltoft, Morten Madsen, Jan Ravkilde, Henrik T. Soerensen, Per Thayssen, Leif Thuesen, Hans-Henrik Tilsted, Jens F. Lassen
Journal: Journal of the American College of Cardiology (2013)
Joint British Association of Dermatologists and U.K. Cutaneous Lymphoma Group guidelines for the management of primary cutaneous T-cell lymphomas
Authors: S.J. Whittaker, J.R. Marsden, M. Spittle, R. Russell Jones
Journal: British Journal of Dermatology (2003)

These guidelines were commissioned by the British Association of Dermatologists guidelines and therapeutics subcommittee. Members of the committee are N.H.Cox (Chairman), A.S.Highet, D.Mehta, R.H.Meyrick Thomas, A.D.Ormerod, J.K.Schofield, C.H.Smith and J.C.Sterling. Members of the U.K. Cutaneous Lymphoma Group who have contributed include C.Benton, R.Cowan, C.Deardon, B.Hancock, H.Lucraft and D.Slater.
Identification of Stk6/STK15 as a candidate low-penetrance tumor-susceptibility gene in mouse and human
Authors: Amanda Ewart-Toland, Paraskevi Briassouli, John P de Koning, Jian-Hua Mao, Jinwei Yuan, Florence Chan, Lucy MacCarthy-Morrogh, Bruce A J Ponder, Hiroki Nagase, John Burn, Sarah Ball, Maria Almeida, Spiros Linardopoulos, Allan Balmain
Journal: Nature Genetics (2003)
Clinical proteomics of myeloid leukemia
Authors: Sigrun M Hjelle, Rakel B Forthun, Ingvild Haaland, Håkon Reikvam, Gry Sjøholt, Øystein Bruserud, Bjørn T Gjertsen
Journal: Genome Medicine (2010)

Myeloid leukemias are a heterogeneous group of diseases originating from bone marrow myeloid progenitor cells. Patients with myeloid leukemias can achieve long-term survival through targeted therapy, cure after intensive chemotherapy or short-term survival because of highly chemoresistant disease. Therefore, despite the development of advanced molecular diagnostics, there is an unmet need for efficient therapy that reflects the advanced diagnostics. Although the molecular design of therapeutic agents is aimed at interacting with specific proteins identified through molecular diagnostics, the majority of therapeutic agents act on multiple protein targets. Ongoing studies on the leukemic cell proteome will probably identify a large number of new biomarkers, and the prediction of response to therapy through these markers is an interesting avenue for future personalized medicine. Mass spectrometric protein detection is a fundamental technique in clinical proteomics, and selected tools are presented, including stable isotope labeling with amino acids in cell culture (SILAC), isobaric tags for relative and absolute quantification (iTRAQ) and multiple reaction monitoring (MRM), as well as single cell determination. We suggest that protein analysis will play not only a supplementary, but also a prominent role in future molecular diagnostics, and we outline how accurate knowledge of the molecular therapeutic targets can be used to monitor therapy response.
Inhibition of MicroRNA-92a Protects Against Ischemia/Reperfusion Injury in a Large-Animal Model
Authors: Rabea Hinkel, Daniela Penzkofer, Stefanie Zühlke, Ariane Fischer, Wira Husada, Quan-Fu Xu, Elisabeth Baloch, Eva van Rooij, Andreas M. Zeiher, Christian Kupatt, Stefanie Dimmeler
Journal: Circulation (2013)

MicroRNAs (miRs) are small noncoding RNAs that posttranscriptionally control gene expression. Small-animal studies suggest that miRs might offer novel therapeutic targets in cardiovascular diseases such as cardioprotection of murine hearts after myocardial infarction via miR-92a inhibitors. Because the functional benefits of miR-92a inhibitors in larger preclinical models are not known, we assessed the therapeutic efficacy of miR-92a inhibition in a porcine model of ischemia and reperfusion.Pigs (n=5 per group) underwent percutaneous ischemia/reperfusion (60 min/72 h or 7 days, respectively). Locked nucleic acid-modified antisense miR-92a (LNA-92a) was applied either regionally (antegrade or retrograde) with a catheter or systemically (intravenously). LNA-92a significantly (P<0.01) reduced miR-92a expression in the infarct zone regardless of the application venue. However, catheter-based delivery, but not intravenous infusion, of LNA-92a significantly (P<0.05) reduced the infarct size compared with control LNA-treated pigs, which correlated with an improved ejection fraction and left ventricular end-diastolic pressure (P<0.05). Histochemistry revealed that LNA-92a increased capillary density but decreased leukocyte influx and cardiac cell death. Complete loss of miR-92a in mice attenuated the infarct-related myocardial dysfunction to a larger extent than cardiomyocyte-specific miR-92a deletion. In vitro, LNA-92a protected against hypoxia/reoxygenation-induced cardiomyocyte cell death.Regional LNA-92a delivery reduces miR-92a levels and infarct size and postischemic loss of function. LNA-92a exerts cell-protective, proangiogenic, and anti-inflammatory effects. miR-92a inhibition might be a novel therapeutic tool to preserve cardiac function after ischemia.
Inhaled corticosteroids: effects on the airway vasculature in bronchial asthma
Authors: G. Horvath, A. Wanner
Journal: European Respiratory Journal (2005)

Inhaled corticosteroids suppress airway inflammation and components of airway remodelling in bronchial asthma. In the tracheobronchial (airway) vasculature, these include the inhibition of inflammatory hyperperfusion, microvascular hyperpermeability, mucosal oedema formation, and the formation of new blood vessels (angiogenesis). Corticosteroids are now known to exert their effects on the airway vasculature through genomic and nongenomic mechanisms. Genomic actions involve the regulation of target genes, and suppress most of the vascular elements of inflammation and angiogenesis in the airway. In contrast, nongenomic actions are mediated by rapid cellular mechanisms, and induce transient vasoconstriction in the airway, thereby reversing inflammatory hyperperfusion. The vascular actions of corticosteroids contribute to controlling clinical symptoms of asthma primarily by influencing airway calibre in the lung periphery and airway hyperreactivity. In this review article, recent advances into the understanding of cellular mechanisms and the clinical implications of the interaction of inhaled corticosteroids and the airway vasculature in asthma are reviewed.