tbuckley/cabot-search huggingface dataset:
Sleep medicine certification for physicians in Spain
Authors: Josep M. Montserrat, Joaquin Terán-Santos, F. Javier Puertas
Journal: European Respiratory Journal (2015)

Sleep medicine is a rapidly growing field. At present, there is a lack of standardisation and the quality of clinical decisions may vary widely. The best way to resolve this problem is to establish a procedure for certification, for both centres and physicians [1]. However, the implementation of a procedure of this kind is difficult, for a variety of reasons; for example, the wide range of criteria applied by different professional societies and the apparent perception that sleep diseases belong to different medical specialties. To date, several procedures have been developed to perform the certification process. In some countries, for instance, the USA [1–3], sleep medicine is considered an independent medical subspecialty, and in Germany [4, 5] and Saudi Arabia [6], its status as a subspecialty has been officially acknowledged. In other countries, expertise is certified by scientific societies or academic institutions. The European Sleep Research Society started to certify sleep physicians in 2012 and it recently published its catalogue for sleep medicine certification [7, 8]. There should be a procedure for certification of sleep centres and physicians <http://ow.ly/HLGm3>
Effect of β radiation on success of glaucoma drainage surgery in South Africa: randomised controlled trial
Authors: James F Kirwan, Simon Cousens, Lynette Venter, Colin Cook, Andries Stulting, Paul Roux, Ian Murdoch
Journal: BMJ (2006)

<h3>Abstract</h3> <b>Objective</b> To evaluate whether β radiation may offer a practical method of improving surgical success for glaucoma drainage surgery in South Africa. <b>Design</b> Double blind, randomised controlled trial. <b>Setting</b> Three public hospitals in South Africa. <b>Participants</b> 450 black Africans with primary glaucoma. <b>Interventions</b> Trabeculectomy with 1000 cGy β radiation or standard trabeculectomy without β radiation (placebo). <b>Main outcome measures</b> Primary outcome measure was surgical failure within 12 months (intraocular pressure &gt; 21 mm Hg while receiving no treatment for ocular hypotension). Secondary outcomes were visual acuity, surgical reintervention for cataract, and intraoperative and postoperative complications. <b>Results</b> 320 people were recruited. β radiation was given to 164; 20 (6%) were not seen again after surgery. One year after surgery the estimated risk of surgical failure was 30% (95% confidence interval 22% to 38%) in the placebo arm compared with 5% (2% to 10%) in the radiation arm. The radiation group experienced a higher incidence of operable cataract (18 participants) than the placebo group (five participants; P = 0.01). At two years the estimated risks with placebo and β radiation were, respectively, 2.8% (0.9% to 8.3%) and 16.7% (10.0% to 27.3%). <b>Conclusion</b> β radiation substantially reduced the risk of surgical failure after glaucoma surgery. Some evidence was, however, found of an increased risk for cataract surgery (a known complication of trabeculectomy) in the β radiation arm during the two years after surgery. <b>Trial registration</b>ISRCTN62430622[controlled-trials.com].
Nitrogen Oxide Metabolites (Nitrite and Nitrate) in Exhaled Breath Condensates (EBC) from Patients with Mild Persistent Asthma, and Effects of Low Dose Combination Therapy Fluticasone Propionate/Salmeterol, 100/50 (FSC 100/50)
Authors: D. Jourd'heuil, P.J. Feustel, T. Smith, S. Patel, S. Sarathchandra, P. Malone, M. Evans, F. Jourd'heuil, M. Pasha
Journal: Journal of Allergy and Clinical Immunology (2011)
Incidence of Newly Diagnosed Diabetes Attributable to Atypical Antipsychotic Medications
Authors: Douglas L. Leslie, Robert A. Rosenheck
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: The purpose of the study was to determine the proportion of patients with schizophrenia with a stable regimen of antipsychotic monotherapy who developed diabetes or were hospitalized for ketoacidosis. METHOD: Patients with schizophrenia for whom a stable regimen of antipsychotic monotherapy was consistently prescribed during any 3-month period between June 1999 and September 2000 and who had no diabetes were followed through September 2001 by using administrative data from the Department of Veterans Affairs. Cox proportional hazards models were developed to identify the characteristics associated with newly diagnosed diabetes and ketoacidosis. RESULTS: Of the 56,849 patients identified, 4,132 (7.3%) developed diabetes and 88 (0.2%) were hospitalized for ketoacidosis. Diabetes risk was highest for clozapine (hazard ratio=1.57) and olanzapine (hazard ratio=1.15); the diabetes risks for quetiapine (hazard ratio=1.20) and risperidone (hazard ratio=1.01) were not significantly different from that for conventional antipsychotics. The attributable risks of diabetes mellitus associated with atypical antipsychotics were small, ranging from 0.05% (risperidone) to 2.03% (clozapine). CONCLUSIONS: Although clozapine and olanzapine have greater diabetes risk, the attributable risk of diabetes mellitus with atypical antipsychotics is small.
C2c: turning cancer into chronic disease
Authors: Stephan Beck, Tony Ng
Journal: Genome Medicine (2014)

Despite fantastic progress in research over the past decade, cancer remains a major source of mortality worldwide. In the UK, for instance, cancer overtook circulatory diseases as the leading cause of death in 2011 [1]. Early detection would obviously be best to reduce this burden, but it requires exquisitely sensitive technology and population-wide screening programs. Short of finding a cure for cancer, turning cancer into a clinically manageable chronic disease like diabetes would be a major step forward. In this Editorial, we introduce a Genome Medicine series on cancer epigenomics [http://genomemedicine.com/series/cancerepigenomics], and discuss progress towards turning cancer into chronic disease with a focus on epigenomics.

For cancers for which appropriate treatment options are available, the proposed cancer to chronic disease (C2c) approach (Figure 1) requires two key components: first, knowledge of the precise localization and quantification of the cancer burden anywhere in the body, which can be achieved by non-invasive whole-body imaging [2,3]; and second, knowledge of the precise molecular signature of the evolving cancer burden to reiteratively tailor treatments predicted to be most effective in combating the establishment of resistance and subsequent relapse. This can be achieved by (epi)genomic profiling of cancer-specific components isolated from minimally invasive blood samples, also known as liquid biopsies [4]. After all, ‘Blut ist ein ganz besonderer Saft,’ as already noted by Faust - the scholar who was striving to know everything - in Johann Wolfgang von Goethe’s 1808 play Faust Part I[5]. 



Figure 1

Illustration of the cancer to chronic disease (C2c) approach. (a) C2c core technologies: liquid biopsies (LB) and whole-body imaging (IM). For LB, current assays include circulating tumor cells and circulating tumor DNA as well as microRNAs. Examples ...
Percutaneous computed tomography-guided radiofrequency thermal ablation of small unresectable lung tumours
Authors: S. Rossi, R. Dore, A. Cascina, V. Vespro, F. Garbagnati, L. Rosa, V. Ravetta, A. Azzaretti, P. Di Tolla, G. Orlandoni, E. Pozzi
Journal: European Respiratory Journal (2006)

The aim of the current study was to evaluate the safety and the efficacy of radiofrequency thermal ablation (RFTA) for the treatment of nonsmall cell lung cancer (NSCLC) and isolated pulmonary metastases (METs) from colorectal cancer (CRC). A total of 31 patients (15 with NSCLCs and 16 with CRC lung METs), with 36 lung tumour nodules (mean± sd diameter: 22±8 mm, range: 10–35 mm) underwent computed tomography (CT)-guided RFTA using expandable electrodes. Contrast-enhanced CT was performed before and after (immediately and 30±5 days) each RFTA session to assess immediate results and complications and repeated 3 and 6 months post-RFTA, as well as every 6 months thereafter, to evaluate long-term results. Complete radiological necrosis was defined as a nonenhancing area at the tumour site that was equal to or larger than the treated tumour; persistence of enhancement at the tumour site indicated incomplete treatment. Local recurrence was defined as an increase in tumour size and/or enhancing tissue at the tumour site. Complete radiological necrosis of the 36 tumours was achieved with 39 RFTA sessions and 42 electrode insertions. No major complications or deaths were observed. Six patients experienced mild-to-moderate pain during the procedure. There were five cases of pneumothorax, none requiring drainage and four cases of pneumonia, which were successfully treated with antibiotics. After a mean follow-up of 11.4±7.7 months (range of 3–36 months), the overall local recurrence rate was 13.9% (20 and 9.5% for NSCLC and CRC-METs patients, repectively). Nineteen of the 31 (61.3%) patients were alive (15 apparently disease free) and 12 (38.7%) had died (three from causes unrelated to their cancer). Radiofrequency thermal ablation seems to be a safe, effective method for producing complete ablation of small nonsmall cell lung cancers and pulmonary colorectal cancer metastases.
Gene Expression Analysis of Murine and Human Osteoarthritis Synovium Reveals Elevation of Transforming Growth Factor β–Responsive Genes in Osteoarthritis‐Related Fibrosis
Authors: D. F. G. Remst, A. B. Blom, E. L. Vitters, R. A. Bank, W. B. van den Berg, E. N. Blaney Davidson, P. M. van der Kraan
Journal: Arthritis & Rheumatology (2013)

Synovial fibrosis is a major contributor to joint stiffness in osteoarthritis (OA). Transforming growth factor β (TGFβ), which is elevated in OA, plays a key role in the onset and persistence of synovial fibrosis. However, blocking of TGFβ in OA as a therapeutic intervention for fibrosis is not an option since TGFβ is crucial for cartilage maintenance and repair. Therefore, we undertook the present study to seek targets downstream of TGFβ for preventing OA-related fibrosis without interfering with joint homeostasis.Experiments were performed to determine whether genes involved in extracellular matrix turnover were responsive to TGFβ and were elevated in OA-related fibrosis. We analyzed gene expression in TGFβ-stimulated human OA synovial fibroblasts and in the synovium of mice with TGFβ-induced fibrosis, mice with experimental OA, and humans with end-stage OA. Gene expression was determined by microarray, low-density array, or quantitative polymerase chain reaction analysis.We observed an increase in expression of procollagen genes and genes encoding collagen crosslinking enzymes under all of the OA-related fibrotic conditions investigated. Comparison of gene expression in TGFβ-stimulated human OA synovial fibroblasts, synovium from mice with experimental OA, and synovium from humans with end-stage OA revealed that the genes PLOD2, LOX, COL1A1, COL5A1, and TIMP1 were up-regulated in all of these conditions. Additionally, we confirmed that these genes were up-regulated by TGFβ in vivo in mice with TGFβ-induced synovial fibrosis.Most of the up-regulated genes identified in this study would be poor targets for therapy development, due to their crucial functions in the joint. However, the highly up-regulated gene PLOD2, responsible for the formation of collagen crosslinks that make collagen less susceptible to enzymatic degradation, is an attractive and promising target for interference in OA-related synovial fibrosis.
Changes in the DENND1B gene increase the risk of childhood asthma
Authors: S. Haney
Journal: Thorax (2010)

Previous studies have shown associations between asthma and single nucleotide polymorphisms (SNPs) on the 17q12 chromosome, but the risk associated with these SNPs is low.

This study used children of European ancestry as a ‘discovery set’. Genome-wide association identified several SNPs in the 1q31.3 region associated with childhood onset asthma (typical …
Effect of Ranolazine on A1C and Glucose Levels in Hyperglycemic Patients With Non-ST Elevation Acute Coronary Syndrome
Authors: Jeffrey W. Chisholm, Allison B. Goldfine, Arvinder K. Dhalla, Eugene Braunwald, David A. Morrow, Ewa Karwatowska-Prokopczuk, Luiz Belardinelli
Journal: Diabetes Care (2010)

OBJECTIVE We determined the relationships between glycemia at randomization, concurrent antidiabetic therapy, and change in A1C and fasting plasma glucose (FPG) in patients with diabetes receiving standard treatment for diabetes and randomized to ranolazine or placebo within the MERLIN-TIMI-36 (MERLIN) study. Ranolazine is a novel first-in-class drug approved for treating angina pectoris. RESEARCH DESIGN AND METHODS Randomization and 4-month glycemic and antidiabetes drug usage data from MERLIN were analyzed using Spotfire and SAS version 9.1 software. RESULTS In patients with diabetes and A1C of ≥8–10% at randomization (n = 171), there was an absolute A1C reduction in the ranolazine group of 1.2% (95% CI −1.4 to −1.0), and the placebo-adjusted (n = 182) decrease in A1C by ranolazine was 0.59% (95% CI −0.99 to −0.20, P &amp;lt; 0.001). In patients with FPG of 150–400 mg/dl at randomization, ranolazine (n = 131) compared with placebo (n = 147) reduced FPG by 25.7 mg/dl (95% CI −43.3 to −8.1, P = 0.001). When changes in either A1C or FPG were correlated to A1C or FPG at randomization, the slopes were significantly steeper for ranolazine than placebo (A1C, P = 0.046; FPG, P &amp;lt; 0.001), indicating that lowering of A1C and FPG by ranolazine is related to hyperglycemia at randomization. Ranolazine, compared with placebo, was not associated with serious hypoglycemic events, associated with significant changes in concurrent antidiabetic therapy, or dependent on a history of angina. CONCLUSIONS Ranolazine, when added to concurrent antidiabetes treatment, lowers FPG and A1C in patients with cardiovascular disease and poorly controlled diabetes.
Pol ι Is a Candidate for the Mouse Pulmonary Adenoma Resistance 2 Locus, a Major Modifier of Chemically Induced Lung Neoplasia
Authors: Min Wang, Theodora R. Devereux, Haris G. Vikis, Scott D. McCulloch, Wanda Holliday, Colleen Anna, Yian Wang, Katarzyna Bebenek, Thomas A. Kunkel, Kunliang Guan, Ming You
Journal: Cancer Research (2004)

Abstract In this study, we performed systematic candidate gene analyses of the Pulmonary adenoma resistance 2 locus. Differential gene expression in lung tissues and nucleotide polymorphisms in coding regions between A/J and BALB/cJ mice were examined using reverse transcription-PCR and direct sequencing. Although not all genes in the interval were analyzed at this moment due to the recent database updating, we have found that the Pol ι gene, encoding the DNA polymerase ι, contains 25 nucleotide polymorphisms in its coding region between A/J and BALB/cJ mice, resulting in a total of ten amino acid changes. Primer extension assays with purified BALB/cJ and A/J proteins in vitro demonstrate that both forms of Pol ι are active but that they may differ in substrate discrimination, which may affect the formation of Kras2 mutations in mouse lung tumors. Altered expression of POL ι protein and an amino acid-changing nucleotide polymorphism were observed in human lung cancer cells, suggesting a possible role in the development of lung cancer. Thus, our data support the Pol ι gene as a modifier of lung tumorigenesis by altering DNA polymerase activity.
Minimal Bystander Activation of CD8 T Cells during the Virus-induced Polyclonal T Cell Response
Authors: Christopher C. Zarozinski, Raymond M. Welsh
Journal: The Journal of Experimental Medicine (1997)

Acute infections with viruses such as lymphocytic choriomeningitis virus (LCMV) are associated with a massive polyclonal T cell response, but the specificities of only a small percentage of these activated T cells are known. To determine if bystander stimulation of T cells not specific to the virus plays a role in this T cell response, we examined two different systems, HY-specific T cell receptor (TCR)-transgenic mice, which have a restricted TCR repertoire, and LCMVcarrier mice, which are tolerant to LCMV. LCMV infection of HY-transgenic C57BL/6 mice induced antiviral CTLs that lysed target cells coated with two of the three immunodominant epitopes previously defined for LCMV (glycoprotein 33 and nucleoprotein 397). Although LCMV-induced cytotoxic T lymphocytes (CTLs) from C57BL/6 mice could lyse uninfected H-2k and H-2d allogeneic targets, LCMV-induced CTLs from HY mice lysed only the H-2kexpressing cells. The HY mice generated both anti-H-2k and anti-H-2d CTL in mixed leukocyte reactions, providing evidence that the generation of allospecific CTLs during acute LCMV infection is antigen specific. During the LCMV infection there was blastogenesis of the CD8+ T cell population, but the HY-specific T cells (as determined by expression of the TCR-α chain) remained small in size. To examine the potential for bystander stimulation under conditions of a very strong CTL response, T cell chimeras were made between normal and HY mice. Even in the context of a normal virus-induced CTL response, no stimulation of HY-specific T cells was observed, and HY-specific cells were diluted in number by day 9 after infection. In LCMV-carrier mice in which donor and host T cells could be distinguished by Thy1 allotypic markers, adoptive transfer of LCMV-immune T cells into LCMV-carrier mice, whose T cells were tolerant to LCMV, resulted in activation and proliferation of donor CD8 cells, but little or no activation of host CD8 cells. These results support the hypothesis that the massive polyclonal CTL response to LCMV infection is virus-specific and that bystander activation of non–virus-specific T cells is not a significant component of this response.
Polymorphisms in the T cell regulatory gene cytotoxic T lymphocyte antigen 4 influence the rate of acute rejection after liver transplantation
Authors: O Tapirdamaz
Journal: Gut (2005)

<b>Background:</b> The cytotoxic T lymphocyte antigen 4 (CTLA-4) gene encodes for a membrane bound (mCTLA-4) and a soluble (sCTLA-4) isoform, which are both involved in regulation of T cell function. The CTLA-4 +49A/G single nucleotide polymorphism (SNP) influences expression of mCTLA-4; +6230G/A SNP affects the production of sCTLA-4. <b>Aim:</b> To examine whether these functional SNPs influence the rate of rejection after liver transplantation. <b>Patients and methods:</b> Liver graft recipients (n = 483) were genotyped for both SNPs, and haplotypes were reconstructed. Association with rejection was tested by the log rank test using the Kaplan-Meier method with time to the first acute rejection episode as outcome. Multiple analysis of SNPs together with demographic factors was performed by Cox regression. <b>Results:</b> Three haplotypes were observed in the cohort: +49A/+6230A, +49A/+6230G, and +49G/+6230G. The +49A/+6230G haplotype was significantly and dose dependently associated with acute rejection (p = 0.01). Of the demographic factors tested, only underlying liver disease was significantly associated with rejection. Adjusted for underlying liver disease, each additional +49A/+6230G haplotype allele resulted in a significantly higher risk of acute rejection (risk ratio 1.34 (95% confidence interval 1.04–1.72); p = 0.02). Patients who lacked this haplotype had the lowest, carriers an intermediate, and homozygotes the highest risk of acute rejection. <b>Conclusion:</b> The CTLA-4 +49A/+6230G haplotype, which encodes for normal mCTLA-4 expression but reduced sCTLA-4 production, is a co-dominant risk allele for acute rejection after clinical liver transplantation. This implies that even under immunosuppression, CTLA-4 is critically involved in the regulation of the human immune response to allogeneic grafts.
S21 Is There a Correlation Between Lung Function Values and Cardiopulmonary Exercise Outcome?: Abstract S21 Table 1
Authors: M Gillion, M Homsy, B Lams, E-S Suh, M Dasaolu
Journal: Thorax (2012)

<h3>Introduction</h3> Cardiopulmonary Exercise testing (CPET) has become an important tool for perioperative assessment as it may identify patients at risk of postoperative cardiopulmonary complications. Older (1) recommended that an Anaerobic Threshold (AT)&lt;11 or &gt;11ml/min/kg can be used to stratify post-operative treatment in colorectal patients (ITU, HDU or ward). The BTS guidelines (2) recommend that a Peak VO2 (PVO2)&lt;15 or &gt;15ml/min/kg can be used as a risk assessment in thoracic surgical patients. However, CPET can be difficulty to carry out. This study was undertaken to determine whether selected lung function values correlated with CPET outcome, so that they could be used as an alternative to AT and PVO2. <h3>Method</h3> 500 pre-operative colorectal (388) and oesophageal (112) patients attending the Lung Function Department were analysed. Spirometry and Gas Transfer were performed to assess lung function. CPET was performed on a cycle ergometer to calculate PVO2 and AT. <h3>Results</h3> The area under the curve (AUC) of a Receiver Operating Curve (ROC) analysis was carried out on the 500 patients. This compared percent predicted FEV1, FVC, TLco and Kco values to PVO2 and AT. <h3>Discussion</h3> Our findings indicated that analysis of lung function variables cannot reliably predict PVO2 or AT outcome. However, of the variables recorded, TLco was the best marker for predicting a PVO2&gt;15ml/min/kg (0.721). When the cut-off for TLco was set at 80% predicted it had a sensitivity and 1-specificity of 62% and 24% respectively. Interestingly, there was a significant correlation between AT and PVO2 (0.894), suggesting that AT can be used as a predictor of PVO2. If the cut-off for AT was set at 11ml/min/kg; the sensitivity was 91.7% and the 1-specificity 37.7%. However if the cut-off was adjusted to 12ml/min/kg; the sensitivity was 77.3% and the 1-specificity was 13.7%. <h3>Conclusion</h3> These results suggest that in pre-operative assessment of patients undergoing thoracic surgery, an AT&gt;12ml/min/kg could be used as an alternative measure if the patient was unable to achieve a PVO2&gt;15ml/min/kg. <h3>Reference</h3> Older (1999). Cardiopulmonary exercise testing as a screening test for perioperative management of major surgery in the elderly. Chest; 116; 355–62. BTS Guidelines on the selection of patients with lung cancer for surgery (2001). Thorax 56:89–108.
An audit of hypoxaemia, hyperoxaemia, hypercapnia and acidosis in blood gas specimens
Authors: B. R. O'Driscoll, A. Rudenski, P. M. Turkington, L. S. Howard
Journal: European Respiratory Journal (2011)

To the Editors:

The emergency management of hypoxaemic patients requires clinicians to avoid the hazard of dangerous hypoxaemia due to under-treatment with oxygen, whilst also avoiding the hazards of hypercapnic respiratory failure (iatrogenic hypercapnia) and oxygen toxicity, which may be caused by over-treatment with oxygen. In the past, many clinicians acted cautiously by giving high concentrations of oxygen to all potentially hypoxaemic patients and a culture evolved that “more is better”. However, since the 1960s, it has been known that some patient groups, particularly those with chronic obstructive pulmonary disease (COPD), are especially vulnerable to uncontrolled oxygen therapy and a recent randomised study showed that mortality in this patient group was doubled when high-concentration oxygen was used compared with controlled oxygen therapy [1–4]. It has also been demonstrated that hyperoxaemia is associated with increased mortality in patients with stroke, and in survivors of cardiac resuscitation and critically ill patients in the intensive care unit (ICU) [5–7]. The British Thoracic Society (BTS) guidelines for emergency oxygen use recommend a target oxygen saturation range of 94–98% for most emergency medical patients and a lower target range of 88–92% for those at risk of hypercapnic respiratory failure …