tbuckley/cabot-search huggingface dataset:
Gene-by-occupational exposure interaction and gene expression analysis on the level of FEV1
Authors: Kim de Jong, Judith Vonk, Wim Timens, Yohan Bossé, Don Sin, Ke Hao, Hans Kromhout, Roel Vermeulen, Dirkje Postma, Marike Boezen
Journal: European Respiratory Journal (2014)

Background   Thus far, genome-wide association studies aiming to find novel susceptibility loci associated with chronic obstructive pulmonary disease (COPD) have largely disregarded environmental factors, like occupational exposures that may underlie disease development. Therefore we performed a genome-wide interaction study to identify novel susceptibility loci for occupational exposure to biological dust, mineral dust or gases and fumes in relation to the level of FEV 1 .   Methods   Genome-wide SNP-by occupational exposure interactions were identified in 12,400 subjects and verified in 1,436 subjects from two independent general population-based samples (figure 1). Additionally we assessed whether replicated SNPs were cis-acting expression quantitative trait loci (eQTL) in lung tissue.   Results   Of the 7 replicated SNPs that interacted with one of the occupational exposures, several were plausible candidates involved in biological pathways leading to impaired lung function, for example  PCDH9  and  GALNT13 . Two of the 7 replicated SNPs were cis-acting eQTL associated with gene expression of neighboring genes  PDE4D  and  TMEM176A  in lung tissue (figure 1).   Conclusions   We identified several novel genes that interacted with occupational exposures on the level of FEV 1 . Findings from the gene expression analysis provide additional support for a role of these genes in lung function impairment in subjects occupationally exposed.
Clinical parameters and biomarkers for the early detection of impaired glucose tolerance in OSA patients
Authors: Radostina Cherneva, Ognian Georgiev, Daniela Petrova, Adelina Cakova, Valentin Lozanov, Vanio Mitev
Journal: European Respiratory Journal (2012)

The role of different clinical parameters regarding inflammation and oxidative stress has largely been debated in the etiology of impaired glucose tolerance in OSA patients.

To determine the plasma levels of free fatty acids (FFA) and resistin in patients with OSA and impaired glucose tolerance (IGT) and compare them to those with normal blood glucose (NBG).

30 patients with newly diagnosed OSA have participated in the study. OSA was defined using a full polysomnography study. The glucose metabolism was investigated by oral glucose tolerant test. Blood glucose and IRI were determined on the 0, 60th, 120th, 180th min. 18 patients were with newly diagnosed IGT. 12 patients had NBG. Resistin (RayBio) and FFA (Wako) were determined in both groups.

IRI was 25,29 mU/l in IGT patients. In patients with NBG, IRI was 21,3mU/l. BMI did not differ significantly between patients with IGT and NBG. BMI was 40,42 in patients with IGT and 41,7 in those with NBG. AHI (60,8) was higher in patients with NBG compared to those with IGT – 50,6. Patients with NBG had also higher plasma levels of FFA – 0,360mmol/l/ compared to patients with IGT – 0,305mmol/l. Only resistin was higher - 4,46ng/ml in IGT patients compared to NBG – 3,98 ng/ml. IRI in IGT patients was 25,29mU/l and correlated best to the levels of resistin (p<0,05).

The commonly used clinical parameters – BMI, AHI, FFA were higher in patients with OSA and NBG. They are not reliable clinical markers for the early detection of impaired blood glucose metabolism in OSA patients. Only resistin correlated to the levels of IRI and could be applied as a predictor and early detection marker of impaired blood glucose metabolism in OSA patients.
Improvement of junior doctors' knowledge of the British Thoracic Society guidelines for the management of spontaneous pneumothorax and insertion of chest drain post educational interventions
Authors: Victoria Connor, Zaroug Wahbi
Journal: European Respiratory Journal (2014)

Objective: To investigate junior doctors9 knowledge the BTS guidelines pre and post basic educational interventions.  Methods: 50 junior doctors were asked questions on the management of spontaneous pneumothorax and marked on a diagram where they would insert a chest drain.  Educational interventions were implemented (including lectures, emails and the creation of a quick reference guide), repeat survey of 50 junior doctors at the same hospital was carried out after 8 months.  Results:Very good results were seen pre and post education when evaluating knowledge of imaging recommendations for suspected spontaneous pneumothorax (92% vs. 90%) and treatment of a symptomatic patient with a large secondary pneumothorax (92% vs. 88%).  Improvement were seen in participants knowledge post education in 7 questions, including awareness of the size of a large pneumothorax and where to measure this, advice on air travel (p-0.0009), identification of the 9safety triangle9 for insertion of chest drain(p-0.0143) and 3 patient scenario questions including 2 significant results; managment of an asymptomatic patient with small primary pneumthroax (p-0.0025) and an asymptomatic patient with one previous failed aspiration (p-0.0321).  The only question which was poorly answered across the board was the management of an asymptomatic patient with a 1-2cm secondary pneumothorax (28% correctly answered pre and post intervention).  Conclusion: It is clear that there is a lack of familiarity with the BTS guidelines but basic education interventions can significantly improve junior doctors9 knowledge and confidence.
Rituximab therapy in Waldenstrom's macroglobulinemia: Preliminary evidence of clinical activity
Authors: J.C. Byrd, C.A. White, B. Link, M.S. Lucas, W.S. Velasquez, J. Rosenberg, A.J. Grillo-López
Journal: Annals of Oncology (1999)

To assess the preliminary efficacy of rituximab therapy in Waldenstrom's macroglobulinemia (WM), we examined the clinical and laboratory data for all patients with WM treated on IDEC Pharmaceuticals sponsored trials and one patient treated at Walter Reed Army Medical Center. Seven symptomatic patients with WM were treated with four (n = 6) or eight (n = 1) weekly infusions of rituximab (375 mg/m2). Patients had received a median of three prior therapies (range 1-4) which included alkylator therapy in all (five patients refractory) and fludarabine in four (all refractory). Therapy was tolerated well in all patients without decrement in cellular immune function or significant infectious morbidity. Partial responses were noted in three of these patients, including two with fludarabine-refractory disease. The median progression-free survival for these patients was 6.6 months (range 2.2-29+ months). These data suggest that rituximab has clinical activity in heavily pre-treated patients with Waldenstrom's macroglobulinemia. Based on these data, clinical studies of Rituximab in previously untreated and treated WM appear indicated.
Core temperature and hydration status during an Ironman triathlon
Authors: P B Laursen, R Suriano, M J Quod, H Lee, C R Abbiss, K Nosaka, D T Martin, D Bishop
Journal: British Journal of Sports Medicine (2006)

Background: Numerous laboratory based studies have documented that aggressive hydration strategies (∼1–2 litres/h) are required to minimise a rise in core temperature and minimise the deleterious effects of hyperthermia on performance. However, field data on the relations between hydration level, core body temperature, and performance are rare. Objective: To measure core temperature (T core ) in triathletes during a 226 km Ironman triathlon, and to compare T core with markers of hydration status after the event. Method: Before and immediately after the 2004 Ironman Western Australia event (mean (SD) ambient temperature 23.3 (1.9)°C (range 19–26°C) and 60 (14)% relative humidity (44–87%)) body mass, plasma concentrations of sodium ([Na + ]), potassium ([K + ]), and chloride ([Cl − ]), and urine specific gravity were measured in 10 well trained triathletes. T core was measured intermittently during the event using an ingestible pill telemetry system, and heart rate was measured throughout. Results: Mean (SD) performance time in the Ironman triathlon was 611 (49) minutes; heart rate was 143 (9) beats/min (83 (6)% of maximum) and T core was 38.1 (0.3)°C. Body mass significantly declined during the race by 2.3 (1.2) kg (−3.0 (1.5)%; p&lt;0.05), whereas urine specific gravity significantly increased (1.011 (0.005) to 1.0170 (0.008) g/ml; p&lt;0.05) and plasma [Na + ], [K + ], and [Cl − ] did not change. Changes in body mass were not related to finishing T core ( r = −0.16), plasma [Na + ] ( r = 0.31), or urine specific gravity ( r = −0.37). Conclusion: In contrast with previous laboratory based studies examining the influence of hypohydration on performance, a body mass loss of up to 3% was found to be tolerated by well trained triathletes during an Ironman competition in warm conditions without any evidence of thermoregulatory failure.
The comparison of average volume assured pressure support and spontaneous/timed modes of noninvasive mechanical ventilation in acute hypercapnic respiratory failure
Authors: Fatma Ciftci, Aydin Ciledag, Mirac Oz, Duygu Acar, Akin Kaya
Journal: European Respiratory Journal (2013)

Recently, hybrid modes have been developed in treatment of acute hypercapnic respiratory failure (AHRF). Average volume assured pressure support (AVAPS) is one of those newly developed modes. In this prospective, randomized study the effectiveness of AVAPS and spontaneous/timed (S/T) modes were compared in patients with AHRF. Patients considered to have noninvasive mechanical ventilation (NIMV) indication after clinical assessment and arterial blood gases analysis were randomized into two groups; S/T mode (n:10) and AVAPS mode (n:15). The study included 25 patients. The etiology of the AHRF was acute exacerbation of COPD in 20 (80%) patients, a sequela of tuberculosis in 1 (4%), bronchiectasis in 2 (8%), obesity-hypoventilation syndrome in 1 (4%), and overlap syndrome (COPD and obstructive sleep apnea) in 1 (4%). Initial pH (7,29±0,04 vs 7,28±0,03), PaCO2 (67,87±14,77 vs 69,12±16,45), PaO2 (52,30±16,81 vs 49,62±14,63) values, GCS (14.1±0,9 vs 12,67±2,33) and APACHE II (23.2±5.5 vs 18.7±4.8) scores were similar in both groups. Three (12%) patients in the S/T group and 2 (8%) patients in the AVAPS group were intubated. Mortality rates at seven days were similar in both groups (8%). A more rapid pH compensation (76±12 vs 43±13 hours, p 2 , and a shorter daily of NIMV duration at the end of 72 hour (14±2 vs 9±3 hours) (p  In conclusion, AVAPS is an effective mode of NIMV in treatment of AHRF.
Clinical use of prostate-specific antigen density in treatment decision for localized prostate cancer
Authors: J. Pujadas, B. Guix
Journal: Journal of Clinical Oncology (2004)

4719 Background: Current treatment of localized Prostate cancer includes different options: Surgery, Radiotherapy or Watchful Waiting (WW). It is well known that surgery treatment is inappropriate when extrapostatic disease (EPD) exists. However, to date, still 25–33% of prostatectomies are shown to be EPD on pathological examination. An explanation for that might be the lack of a good imaging diagnostic test and the inaccuracy of the Gleason and prostatic specific antigen (PSA) as pathological predictors. PSA is not a good predictor mainly due to the contribution of non tumoral prostatic volume to its serum levels. On contrary, it has been suggested that PSA density (PSAD) values are not influenced by non tumoral prostatic volume, thus, becoming more useful. The purpose of the present study was to evaluate whether PSAD might have a role in the treatment decision making. Methods: The cases of 103 consecutive patients who underwent Radical Prostatectomy were reviewed. Preoperative PSA and PSAD were obtained. PSAD was calculated according to the formula: PSAD = serum PSA / prostatic volume determined by TRUS (prolate ellipse formula). Currently accepted PSA cut-off of 10 was compared with PSAD cut-off of 0.15 and 0.20 to determine its accuracy in detecting OCD. Results: The pathological examinations of the 103 prostatectomy specimens revealed EPD in 26 cases (25%). Using a PSA cut-off < 10 resulted in 59 out of 73 patients (80%) with confirmed OCD. On contrary, PSAD cut-off < 0.15 and < 0.20, resulted in 26/27 (96%) and 41/46 (89%) patients, respectively, with OCD. Conclusions: PSAD is a more accurate marker to discriminate OCD than PSA and, therefore, may lead to a more appropriate treatment decision making. No significant financial relationships to disclose.
Changes in DSM-III-R axis II diagnoses following treatment of obsessive- compulsive disorder
Authors: J N Ricciardi, L Baer, M A Jenike, S C Fischer, D Sholtz, M L Buttolph
Journal: American Journal of Psychiatry (1992)

Seventeen patients with obsessive-compulsive disorder and concomitant personality disorders were treated with pharmacologic and/or behavioral therapy and reassessed after 4 months. Nine of the 10 patients who responded to treatment for obsessive-compulsive disorder no longer met criteria for a personality disorder. Of the seven nonresponders, five continued to meet criteria for a personality disorder.
Abstract 107: MicroRNA-31: A Novel Therapeutic Target for Ischemic Heart Disease
Authors: Eliana C Martinez, Shera Lilyanna, Leah A Vardy, Arunmozhiarasi Armugam, Kandiah Jeyaseelan, Arthur M Richards
Journal: Circulation Research (2014)

MicroRNAs (miRNA), small sequences of non-coding RNA which interact with complementary sequences on the 3’untranslated region of target messenger RNAs to modulate translation, have a pivotal role in the development of the heart and its response to injury. Myocardial infarction (MI) triggers a dynamic miRNA response with the potential of yielding therapeutic targets. Following miRNA array profiling in rat hearts 2, 7 and 14 days after MI induced by coronary ligation, we identified a progressive time-dependent up-regulation of miR-31 compared to sham rats. Increase of miR-31 in heart tissue in the acute and subacute phases after MI (up to 90-fold) was also detected by Real-Time PCR (P=0.02 at day 2; P&lt;0.0001 at days 7 and 14, vs. sham). We found that miR-31 has a repressive effect on tissue mRNA expression of cardiac troponin-T (TNNT2), E2F transcription factor 6 (E2F6) and mineralocorticoid receptor (NR3C2). Reporter gene assays showed that miR-31 targets the 3′UTR of these genes, with a marked repressive effect on TNNT2. In vitro, exposure to hypoxia significantly induced the expression of miR-31 in neonatal rat cardiomyocytes (nRCM), rat cardiac fibroblasts (nRCF) and cardiomyoblasts (H9C2) and suppressed the expression of TNNT2, E2F6 and NR3C2 in nRCM and H9C2 cells, and of E2F6 and NR3C2 in nRCF. LNA-based oligonucleotide inhibition of miR-31(miR-31i) in vitro reversed its repressive effect on translation from target genes. Therapeutic modulation of miR-31 expression in vivo after MI via subcutaneous administration of miR-31i (25mg/Kg/q2w) in rats, led to cardiac repression of miR-31 and subsequent enhanced expression of target genes. Also, miR-31i led to preservation of cardiac function and structure by day 14 after treatment. An absolute 10% improvement in left ventricular (LV) ejection fraction (EF) was observed in miR-31i-treated rats from day 2 to 16 after MI, while control rats that received scrambled LNA inhibitor or placebo displayed 23% deterioration in EF (n=6-8/group, P&lt;0.0001). We conclude that miR-31 induction after MI is deleterious to cardiac function and plays an important role in adverse remodeling, while its therapeutic inhibition in vivo ameliorates cardiac dysfunction and prevents the development of post-ischemic heart failure.
Abstract 575: Human Stro1 Mesenchymal Precursor Cells Induce Proliferative Effects on Vascular Smooth Muscle Cells and Endothelium via PI3 Kinase Dependent Pathways
Authors: Fiona See, Tetsunori Seki, Peter Psaltis, Timothy Martens, Stan Gronthos, Stephen Worthley, Hugo Sondermeijer, Klaas Govaert, Andrew Zannettino, Silviu Itescu
Journal: Circulation (2007)
Evolutionary relationships between sporadic and epidemic strains of healthcare-associated methicillin-resistant Staphylococcus aureus
Authors: M. Hallin, O. Denis, A. Deplano, R. De Ryck, S. Crèvecoeur, S. Rottiers, R. de Mendonça, M.J. Struelens
Journal: Clinical Microbiology and Infection (2008)
Unrecognized pediatric foreign body aspiration (FBA) with emphasis on the errors in the diagnosis in outhospital health services
Authors: Slobodanka Petrovic, Ljlja Vlaski, Dunja Kordic
Journal: European Respiratory Journal (2013)

Introduction: Aim of study was to evaluate the yield of epidemiological caracteristics,clinical symptoms and most common errors in the diagnostic procedurs in outhospital health services in the diagnosis of FBA. Material and methods: A retrospective analysis of FB in 72 patients, with emphasis on 32 cases with unrecognised aspiration, over a period of 10 years was conducted. Rigid bronchoscopy was done in all patients. Results: The highest incidence of aspiration was from the age of 1 to 3 years (68.06%); 63.89% of them were male. Analyzis of years distribution revealed that the highest incidence of aspiration was in 2006. and 2012. year, 15.28%. Most of the patients (55.56%) requested medical attention within the first 48 hours of aspiration while 44.44% of the cases were not recognised after this period. In 68.75% of cases were treated before hospitalization longer than 5 days, mostly by pediatricians (71.88%). Accident of aspiration was confirmed immediately or later in 62, 50% childrens who were, despite this data, treated by primary caregivers. Main symptoms were the following: prolonged cough (100%), wheezing (25%), and non-resolving pneumonia with temperature (75%). None of the patients with undiscovered aspiration had normal breath sound; the predominant auscultatory finding was decreased breath sound and/or wheezing, in 62.50% childrens.Conclusion: It is very important that the outpatient physician have the time to take detailed information on medical history and pay attention in next cases: if previously healthy child have persistent or reccurent respiratory sympthoms and signs or unsatisfactory therapeutic response.
Lipids in Non-insulin Dependent Diabetes: A Case for Treatment?
Authors: R S Elkeles
Journal: Journal of the Royal Society of Medicine (1991)

The results of treatment in 22 patients with anal carcinoma are reviewed. The overall results are disappointing with only five (28%) surviving more than 5 years. The commonest form of treatment during the study period was an abdomino-perineal excision of rectum (APER). For patients with tumours less than 2 cm in diameter local excision is an acceptable alternative. The majority (76%) of tumours were diagnosed as common benign conditions by the referring practitioners leading to a delay in initiating definitive treatment. Most tumours (81%) were greater than 2 cm in diameter and therefore unsuitable for local excision. There was a high recurrence rate (76%) amongst the group treated by APER. This along with the poor overall survival is probably due to late presentation.
In vivo and in vitro effects of glucocorticosteroids on arachidonic acid metabolism and monocyte function in nonasthmatic humans
Authors: G Manso, A J Baker, I K Taylor, R W Fuller
Journal: European Respiratory Journal (1992)

Glucocorticosteroids are used as anti-inflammatory agents in a range of diseases, however, their mechanism of action is unknown. Recently, inhibition of arachidonic acid metabolism has been suggested as one possible mechanism of action. A series of experiments were undertaken in nonasthmatic humans to examine the effects of oral prednisolone and dexamethasone and inhaled budesonide on the excretion of the urinary leukotriene E4 (LTE4), an established marker of total body leukotriene generation in vivo. In addition, the effect of the drugs on the in vitro and ex-vivo function of monocytes was examined. In vitro dexamethasone greater than 10(-8) M inhibited the thromboxane A2 (TxA2) release from human monocytes, an effect which recovered within 24 h. In vivo, neither inhaled budesonide (1.6 mg.day-1 for 7 days), nor a standard therapeutic dose of oral prednisolone (30 mg.day-1 for 3 days), nor high doses of oral dexamethasone (8 mg.day-1 for 2 days) altered the excretion of urinary LTE4, despite the latter completely suppressing endogenous cortisol production. The ex-vivo zymosan stimulated release of TxA2 release from monocytes was not altered by the standard dose prednisolone, but was reduced by high dose dexamethasone and inhaled budesonide. This study shows that high doses of systemic steroids have little effect on arachidonic acid metabolism in normal nonasthmatic humans. Inhaled budesonide, however, does reduce arachidonic acid metabolism in circulating monocytes, presumably by affecting these cells during their passage through the lung.
Unique characteristics in Japanese dermatitis herpetiformis
Authors: C. Ohata, N. Ishii, H. Niizeki, Y. Shimomura, M. Furumura, H. Inoko, S. Mitsunaga, M. Saiki, M. Shigeta, S. Fujiwara, K. Yamakawa, S. Kobayashi, M. Kamata, M. Inaba, T. Ito, H. Uhara, R. Watanabe, S. Ohtoshi, T. Ohashi, T. Tanaka, M. Suzuki, C. Sitaru, S. Kárpáti, J.J. Zone, T. Hashimoto
Journal: British Journal of Dermatology (2015)

Funding sources: this study was supported by MEXT KAKENHI [Grant‐in‐Aid for Scientific Research (C)] Grant Number 25461678, and by a grant from the Ishibashi Foundation for the Promotion of Science. Conflicts of interest: none declared. Dear Editor, Dermatitis herpetiformis (DH) is an intensely pruritic papulovesicular skin disease, and is considered to be a cutaneous manifestation of gluten sensitivity, that is, an extraintestinal presentation of coeliac disease (CD).1 The processing of the dietary gluten antigen (gliadin) requires human leucocyte antigen (HLA)‐DQ2 or HLA‐DQ8,2 and approximately 85% of white patients with DH carry HLA‐DQ2; the majority of the remaining 15% carry HLA‐DQ8.3 Tissue transglutaminase (tTG) (transglutaminase 2) is the major autoantigen in CD,1 whereas epidermal transglutaminase (eTG) (transglutaminase 3) is the major autoantigen in DH.4 5 6 We previously reported that the unique features of Japanese DH were (i) a high frequency of fibrillar deposition of IgA in the papillary dermis; (ii) the rare occurrence of gluten sensitive enteropathy (GSE); (iii) the absence of HLA‐DQ2 and HLA‐DQ8; and (iv) a rare association with autoimmune diseases or lymphomas. In this study, between April 2012 and December 2013, we sent questionnaires about DH to the dermatology departments of all Japanese universities and major hospitals. Finally, we obtained clinical data, skin biopsy specimens, frozen skin sections, sera and DNA samples from 21 patients newly diagnosed with DH and who were not included in our previous study.7 We performed a HLA study, serological tests and immunofluorescent (IF) studies for TG (detailed methodology can be found in Data S1; see Supporting Information). Approval for this study was obtained from the ethics committee of Kurume University.
The PIAS-like Coactivator Zmiz1 Is a Direct and Selective Cofactor of Notch1 in T Cell Development and Leukemia
Authors: Nancy Pinnell, Ran Yan, Hyo Je Cho, Theresa Keeley, Marcelo J. Murai, Yiran Liu, Amparo Serna Alarcon, Jason Qin, Qing Wang, Rork Kuick, Kojo S.J. Elenitoba-Johnson, Ivan Maillard, Linda C. Samuelson, Tomasz Cierpicki, Mark Y. Chiang
Journal: Immunity (2015)