tbuckley/cabot-search huggingface dataset:
Depression and Insulin Resistance
Authors: Sue Pearson, Mike Schmidt, George Patton, Terry Dwyer, Leigh Blizzard, Petr Otahal, Alison Venn
Journal: Diabetes Care (2010)

To examine the association between depressive disorder and insulin resistance in a sample of young adults using the Composite International Diagnostic Interview to ascertain depression status.Cross-sectional data were collected from 1,732 participants aged between 26 and 36 years. Insulin resistance was derived from blood chemistry measures of fasting insulin and glucose using the homeostasis model assessment method. Those identified with mild, moderate, or severe depression were classified as having depressive disorder.The 12-month prevalence of depressive disorder was 5.4% among men and 11.7% among women. In unadjusted models mean insulin resistance was 17.2% (95% CI 0.7-36.0%, P = 0.04) higher in men and 11.4% (1.5-22.0%, P = 0.02) higher in women with depressive disorder. After adjustment for behavioral and dietary factors, the increased level of insulin resistance associated with depressive disorder was 13.2% (-3.1 to 32.3%, P = 0.12) in men and 6.1% (-4.1 to 17.4%, P = 0.25) in women. Waist circumference was identified as a mediator in the relationship between depression and insulin resistance, reducing the beta coefficient in the fully adjusted models in men by 38% and in women by 42%.A positive association was found between depressive disorder and insulin resistance in this population-based sample of young adult men and women. The association seemed to be mediated partially by waist circumference.
Contribution of Pain to Inspiratory Muscle Dysfunction after Upper Abdominal Surgery
Authors: THEODOROS VASSILAKOPOULOS, ZAFIRIA MASTORA, PARASKEVI KATSAOUNOU, GEORGE DOUKAS, SERAFIM KLIMOPOULOS, CHARIS ROUSSOS, SPYROS ZAKYNTHINOS
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Upper abdominal surgery causes respiratory muscle dysfunction. Multiple factors have been implicated in the occurrence of such dysfunction; however, the role of pain remains unclear. To elucidate the role of pain, we studied 50 patients undergoing elective upper abdominal surgery in a randomized, controlled investigation. Inspiratory and expiratory muscle function were assessed through sniff mouth pressure (Psniff) and maximal expiratory pressure (MEP), respectively. Pain during the pressure maneuvers was assessed with a visual analog scale (VAS). Measurements were made before surgery (Session 1), 24 h after surgery (Session 2), and 1 h later, after intramuscular administration of pethidine (analgesia group) or placebo (placebo group) (Session 3). To evaluate the effect of pain, we used a mixed-effects model with random intercept, having either Psniff or MEP as the dependent variable and both surgical operation and the level of pain as fixed effects. Upper abdominal surgery decreased Psniff in both the analgesia and placebo groups (from 70 ± 15 to 42 ± 11 cm H2O [p < 0.05] in the analgesia group, and from 69 ± 15 to 42 ± 10 cm H2O [p < 0.05] in the placebo group). Intramuscular pethidine caused an increase in Psniff to 56 ± 14 cm H2O (p < 0.05), whereas placebo had no effect. Pain increased comparably after upper abdominal surgery in both groups (from 0.3 ± 0.6 to 4.4 ± 1.5) [p < 0.05] in the analgesia group and from 0.4 ± 0.5 to 4.3 ± 1.5 [p < 0.05] in the placebo group). Intramuscular pethidine decreased pain as measured by VAS score to 2.1 ± 1.0 (p < 0.05) in the analgesia group, whereas placebo had no effect. Psniff had a statistically significant relationship to pain (p < 0.001). Adjusting for the occurrence of surgical operation did not affect this result. MEP showed the same tendency as Psniff, but the observed changes did not reach statistical significance. We conclude that pain contributes to inspiratory muscle dysfunction after upper abdominal surgery.
Insulin resistance reduces arterial prostacyclin synthase and eNOS activities by increasing endothelial fatty acid oxidation
Authors: Xueliang Du, Diane Edelstein, Silvana Obici, Ninon Higham, Ming-Hui Zou,, Michael Brownlee
Journal: Journal of Clinical Investigation (2006)

Insulin resistance markedly increases cardiovascular disease risk in people with normal glucose tolerance, even after adjustment for known risk factors such as LDL, triglycerides, HDL, and systolic blood pressure. In this report, we show that increased oxidation of FFAs in aortic endothelial cells without added insulin causes increased production of superoxide by the mitochondrial electron transport chain. FFA-induced overproduction of superoxide activated a variety of proinflammatory signals previously implicated in hyperglycemia-induced vascular damage and inactivated 2 important antiatherogenic enzymes, prostacyclin synthase and eNOS. In 2 nondiabetic rodent models--insulin-resistant, obese Zucker (fa/fa) rats and high-fat diet-induced insulin-resistant mice--inactivation of prostacyclin synthase and eNOS was prevented by inhibition of FFA release from adipose tissue; by inhibition of the rate-limiting enzyme for fatty acid oxidation in mitochondria, carnitine palmitoyltransferase I; and by reduction of superoxide levels. These studies identify what we believe to be a novel mechanism contributing to the accelerated atherogenesis and increased cardiovascular disease risk occurring in people with insulin resistance.
Sequential Morphological Changes in &lt;italic&gt;N&lt;/italic&gt;-Methyl-&lt;italic&gt;N&lt;/italic&gt;′-Nitro-&lt;italic&gt;N&lt;/italic&gt;-Nitrosoguanidine Carcinogenesis in the Glandular Stomach of Rats&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: T Saito, K Inokuchi, S Takayama, T Sugimura
Journal: JNCI Journal of the National Cancer Institute (1970)

Morphological changes were studied in the glandular stomach of rats with carcinogenesis induced by N-methyl-N′-nitro-N-nitrosoguanidine (NG). NG was given to 100 rats in their drinking water at the level of 167 μg/ml for 40 weeks and then 84 μg/ml until the end of the experiment. Rats were killed periodically and histological changes in the glandular stomach were examined. Three types of glandular proliferation were distinguished: regenerative glandular hyperplasia, adenomatous hyperplasia, and adenocarcinoma. These lesions were mainly in the antrat region of the stomach. After atrophy and erosion of the mucosa, regenerative glandular hyperplasia, with irregular glands at the margins of erosions, developed in the 3d–5th week, and these lesions persisted for the rest of the experiment. Adenomatous hyperplasia, characterized by excessive glandular proliferation with scanty cellular atypism, developed in the 20th week, and these lesions were found in the middle of the experimental period. Adenocarcinoma, consisting of excessive glandular proliferation with cellular atypism, appeared in the 30th week and gradually invaded to the submucosa, the muscularis propria, and the serosa. After the 60th week, almost all rats had adenocarcinoma with serosal invasion.
Cellular immunity to a determinant common to glutamate decarboxylase and coxsackie virus in insulin-dependent diabetes.
Authors: M A Atkinson, M A Bowman, L Campbell, B L Darrow, D L Kaufman, N K Maclaren
Journal: Journal of Clinical Investigation (1994)

Insulin-dependent diabetes (IDD) results from the autoimmune destruction of the insulin-producing pancreatic beta cells. Autoreactive T-lymphocytes are thought to play a pivotal role in the pathogenesis of IDD; however, the target antigens of these cells, as well as the inductive events in the disease, are unclear. PBMC in persons with or at increased risk for IDD show elevated reactivity to the beta cell enzyme glutamate decarboxylase (GAD). To identify the T-lymphocyte-reactive determinants of GAD, an overlapping set of synthetic peptides was used to stimulate the PBMC from these individuals, PBMC responsiveness to GAD peptides was not restricted to those with IDD, and a number of peptides elicited responses in PBMC. However, the major determinant of GAD recognized by persons at increased risk for IDD was amino acids 247-279, a region which has significant sequence similarity to the P2-C protein of Coxsackie B virus (47% of 15 increased risk [islet cell autoantibody-positive relatives]; 25% of 16 newly diagnosed IDD patients; and 0% of 13 healthy control subjects). Responses to tetanus and insulin antigens were not different between the study groups. In addition, PBMC from individuals responding to GAD peptides within 247-279 also responded to a Coxsackie viral peptide (i.e., P2-C amino acids 32-47), an observation supporting potential molecular mimicry in this immune response. Although the role of environmental agents in the pathogenesis of the disease remains unclear, these cellular immunological findings support the epidemiological evidence suggesting an inductive role for enteroviruses like Coxsackie B in the autoimmunity underlying IDD.
Authors’ response: Epithelial-mesenchymal Transition (EMT) is a common molecular programme in epithelial cells which can be triggered by injury
Authors: Domokos Bartis, David R Thickett
Journal: Thorax (2014)

We thank Sohal et al 1 for commenting on our recent paper.2 The authors argue in their commentary that morphological/histological signs of epithelial-mesenchymal transition (EMT) in patients’ samples, for example, reticular basement membrane fragmentation, are more relevant in detecting EMT than looking for typical EMT-associated molecular patterns in the first place.

EMT is defined as the gradual differentiation of epithelial cells into mesenchymal cells involving intermediate phenotypes. Different types of EMT seem to be quite universally present in organ development …
Oxygen saturation during endoscopic retrograde cholangiopancreatography: a comparison of two protocols of oxygen administration.
Authors: J D Rigg, T C Watt, D E Tweedle, D F Martin
Journal: Gut (1994)

Patients having endoscopic retrograde cholangiopancreatography (ERCP) are generally elderly and require sedation while in the prone position. These factors may be expected to aggravate any risk of arterial hypoxia. This study evaluated two protocols of oxygen administration, one with and one without pre-oxygenation. In 25 patients in whom pre-oxygenation with 4 litres/minute for five minutes before sedation was used, followed by continuous oxygen administration, arterial oxygen saturation did not fall below 90% at any stage during the procedure. By contrast, in 25 patients who were not pre-oxygenated oxygen saturation fell below 90% in nine (36%). As expected, hypoxia occurred most frequently during the early stages of sedation and endoscope insertion. Hypoxia did not occur in association with operations such as sphincterotomy, stone extraction or stent insertion. This study confirms that arterial hypoxia is a common event during ERCP and can be completely prevented by pre-oxygenation with four litres of oxygen given intranasally for five minutes before sedation.
Dead space and slope indices from the expiratory carbon dioxide tension-volume curve
Authors: AH Kars, JM Bogaard, T Stijnen, J de Vries, AF Verbraak, C Hilvering
Journal: European Respiratory Journal (1997)

The slope of phase 3 and three noninvasively determined dead space estimates derived from the expiratory carbon dioxide tension (PCO2) versus volume curve, including the Bohr dead space (VD,Bohr), the Fowler dead space (VD,Fowler) and pre-interface expirate (PIE), were investigated in 28 healthy control subjects, 12 asthma and 29 emphysema patients (20 severely obstructed and nine moderately obstructed) with the aim to establish diagnostic value. Because breath volume and frequency are closely related to CO2 elimination, the recording procedures included varying breath volumes in all subjects during self-chosen/natural breathing frequency, and fixed frequencies of 10, 15 and 20 breaths x min(-1) with varying breath volumes only in the healthy controls. From the relationships of the variables with tidal volume (VT), the values at 1 L were estimated to compare the groups. The slopes of phase 3 and VD,Bohr at 1 L VT showed the most significant difference between controls and patients with asthma or emphysema, compared to the other two dead space estimates, and were related to the degree of airways obstruction. Discrimination between no-emphysema (asthma and controls) and emphysema patients was possible on the basis of a plot of intercept and slope of the relationship between VD,Bohr and VT. A combination of both the slope of phase 3 and VD,Bohr of a breath of 1 L was equally discriminating. The influence of fixed frequencies in the controls did not change the results. The conclusion is that Bohr dead space in relation to tidal volume seems to have diagnostic properties separating patients with asthma from patients with emphysema with the same degree of airways obstruction. Equally discriminating was a combination of both phase 3 and Bohr dead space of a breath of 1 L. The different pathophysiological mechanisms in asthma and emphysema leading to airways obstruction are probably responsible for these results.
Resistance to collagen-induced arthritis in a nonhuman primate species maps to the major histocompatibility complex class I region.
Authors: N P Bakker, M G van Erck, N Otting, N M Lardy, R C Noort, B A 't Hart, M Jonker, R E Bontrop
Journal: The Journal of Experimental Medicine (1992)

Type II collagen-induced arthritis (CIA) is an experimentally inducible autoimmune disorder that is, just like several forms of human arthritis, influenced by a genetic background. Immunization of young rhesus monkeys (Macaca mulatta) with type II collagen (CII) induced CIA in about 70% of the animals. One major histocompatibility complex (MHC) class I allele was present only in young animals resistant to CIA and absent in arthritic animals. This strong association suggests that the MHC class I allele itself, or a closely linked gene, determines resistance to CIA. The mechanism controlling the resistance to CIA becomes less efficient in aged animals since older rhesus monkeys, which were positive for the resistance marker, developed a mild form of arthritis. At the cellular level it is demonstrated that resistance to CIA is reflected by a low responsiveness of T cells to CII. This association between a specified MHC class I allele and resistance to an autoimmune disease points at the importance of the MHC class I region in the regulation of the immune response to an autoantigen.
Inflammation and postinfarct remodeling: Overexpression of IκB prevents ventricular dilation via increasing TIMP levels
Authors: K TRESCHER, O BERNECKER, B FELLNER, M GYONGYOSI, R SCHAFER, S AHARINEJAD, R DEMARTIN, E WOLNER, B PODESSER
Journal: Cardiovascular Research (2006)

Objective: Nuclear factor-kappa B (NF-κB) orchestrates genes involved in inflammation and extracellular matrix (ECM) remodeling following myocardial infarction (MI). The objective of the present study was to investigate the effect of overexpression and mode of function of IκB, the natural inhibitor of NF-κB, on ECM remodeling in a rat model of MI.
Costs to Medicare of the Informatics for Diabetes Education and Telemedicine (IDEATel) Home Telemedicine Demonstration
Authors: Lorenzo Moreno, Stacy B. Dale, Arnold Y. Chen, Carol A. Magee
Journal: Diabetes Care (2009)

OBJECTIVE To estimate the impacts on Medicare costs of providing a particular type of home telemedicine to eligible Medicare beneficiaries with type 2 diabetes. RESEARCH DESIGN AND METHODS Two cohorts of beneficiaries (n = 1,665 and 504, respectively) living in two medically underserved areas of New York between 2000 and 2007 were randomized to intensive nurse case management via televisits or usual care. Medicare service use and costs covering a 6-year follow-up period were drawn from claims data. Impacts were estimated using regression analyses. RESULTS Informatics for Diabetes Education and Telemedicine (IDEATel) did not reduce Medicare costs in either site. Total costs were between 71 and 116% higher for the treatment group than for the control group. CONCLUSIONS Although IDEATel had modest effects on clinical outcomes (reported elsewhere), it did not reduce Medicare use or costs for health services. The intervention's costs were excessive (over $8,000 per person per year) compared with programs with similar-sized clinical impacts.
Noninvasive Imaging of Transgene Expression by Use of Positron Emission Tomography in a Pig Model of Myocardial Gene Transfer
Authors: Frank M. Bengel, Martina Anton, Thomas Richter, Marcus V. Simoes, Roland Haubner, Julia Henke, Wolf Erhardt, Sybille Reder, Terry Lehner, Wolfgang Brandau, Peter Boekstegers, Stephan G. Nekolla, Bernd Gansbacher, Markus Schwaiger
Journal: Circulation (2003)

Background— Radionuclide imaging of reporter gene expression may be useful for noninvasive monitoring of clinical cardiac gene therapy. Experience until now, however, has been limited to small animals. Methods and Results— To evaluate feasibility in a clinically applicable setting, pigs were studied by conventional positron emission tomography (PET) 2 days after regional intramyocardial injection of control adenovirus or adenovirus carrying herpesviral thymidine kinase reporter gene (HSV1-tk). Myocardial blood flow was quantified by use of [ 13 N]ammonia. Subsequently, kinetics of the reporter substrate [ 124 I]-2′-fluoro-2′-deoxy-5-iodo-1-β- d -arabino-furanosyluracil (FIAU) were assessed over a period of 2 hours. Areas infected with adenovirus expressing HSV1-tk showed significantly elevated FIAU retention during the first 30 minutes after injection. At later times, washout was observed, and retention was not different from that in areas infected with control virus or remote myocardium. Early in vivo FIAU uptake correlated with ex vivo images, autoradiography, and immunohistochemistry for reporter gene product after euthanasia. After intramyocardial injection of both adenoviruses, myocardial blood flow was mildly elevated compared with that in remote areas, consistent with histological signs of regional inflammation. Conclusions— In vivo quantification of regional myocardial transgene expression is feasible with clinical PET methodology, the radioiodinated reporter probe FIAU, and the HSV1-tk reporter gene. Radioactivity efflux after specific initial uptake was not observed previously in tumor studies, suggesting that tissue-specific differences in nucleoside metabolism influence reporter probe kinetics. By coregistering reporter gene expression with additional biological parameters such as myocardial blood flow, PET allows for noninvasive characterization of the success of cardiac gene transfer along with its functional correlates.
S126 Measuring quality in pneumonia care. The north west advancing quality programme 2008-2009
Authors: M. Woodhead, J. Butterworth, L.-A. Myers
Journal: Thorax (2010)

As part of an initiative within the North West Strategic Health Authority to improve the quality of care, ‘quality markers’ (QMs) were measured in all adult admissions with pneumonia in all 24 Acute Trusts in the North West Region for 1 year (discharges from October 2008 to September 2009). Only adults who fulfilled a prescribed definition of ‘pneumonia’ were included. QMs were taken from a USA initiative and adapted for UK use. Patient identification was based on clinical coding. Data were recorded in each individual Trust and centrally collated. <h3>Combined data from all trusts</h3> QMs were recorded with the following frequencies (no in parentheses is number of patients included): Oxygenation assessment within 24 h or prior to hospital arrival 96.9% (11 127), blood culture performed in the A &amp; E prior to initial antibiotic received in hospital 58.5% (3323), smoking cessation advice/counselling given in 38.1% (2788), initial antibiotic consistent with local CAP guidelines 80.8% (6337) and initial antibiotic received within 6 h of hospital arrival 64.6% (7889). Over the four quarters of the year there was no change in the frequency (%) of oxygenation assessment (96.0, 96.1, 97.6, 98.8), initial antibiotic selection (81.9, 77.9, 80.9, 83.7), or initial antibiotic within 6 h (67.1, 64.0, 63.6, 63.5) or blood cultures performed before antibiotics (58.8, 56.3, 57.9, 62.4) but a small rise in smoking cessation advice (36.4, 32.6, 40.3, 45.5). Overall score, whether composite or appropriate did not change. <h3>Individual trusts</h3> Of the 22 Trusts with complete results, overall score over the year was &lt;80% in one, 80–85% in two, 85–90% in three, 90–95% in 13 and &gt;95% in three. Comparing last with first quarter scores only five individual Trusts showed a rise in score of &gt;5%, three a fall of &gt;5% and all others changed less than this amount. The biggest change was in the Trust that performed worst in the first quarter. Practical problems identified included accurate case identification and case note data recording. Despite this the Advancing Quality programme is a practical way of measuring QMs in pneumonia. Further work is required to generate improvements in patient care.
Dermatologic Infections in Cancer Patients Treated With Epidermal Growth Factor Receptor Inhibitor Therapy
Authors: R. E. Eilers, M. Gandhi, J. D. Patel, M. F. Mulcahy, M. Agulnik, T. Hensing, M. E. Lacouture
Journal: JNCI Journal of the National Cancer Institute (2009)

Patients treated with epidermal growth factor receptor inhibitors (EGFRIs) frequently experience dermatologic toxic effects. Whereas the impact of these effects on quality of life and EGFRI dosing has been described, their impact on physical health has not been ascertained. We examined the prevalence of infections that complicate dermatologic toxic effects of EGFRIs.We used retrospective chart review methods to analyze 221 patients who were treated in the Skin and Eye Reactions to Inhibitors of EGFR and Kinases clinic, a referral clinic for dermatologic toxic effects of cancer therapies. We reviewed results of bacterial cultures, histopathologic assessment of biopsy samples, and immunohistochemical staining of skin specimens for viral pathogens that were recorded in the patients' medical records. Associations between patient demographic and treatment characteristics and the development of infections were examined using the Fisher exact test. All statistical tests were two-sided.Eighty-four (38%) of the 221 patients showed evidence of infection at sites of dermatologic toxic effect. Fifty (22.6%) of the 221 patients had cultures positive for Staphylococcus aureus, and 12 (5.4%) of the 221 patients cultured positive for methicillin-resistant S aureus. Less frequent infections included herpes simplex (3.2%), herpes zoster (1.8%), and dermatophytes (10.4%). The seborrheic region was the most prevalent site of infection, and patients with leukopenia had higher risk for infection than patients who did not have leukopenia (P = .005). Demographic factors and associated treatments were not associated with the occurrence of a dermatologic infection (P > or = .05).Patients with dermatologic toxic effects following treatment with EGFRIs have a high prevalence of cutaneous infections. Most notably, bacterial infections developed at sites previously affected by dermatologic toxic effects, with leukopenic patients being at greater risk.