tbuckley/cabot-search huggingface dataset:
Comparison of the particle size distribution of fluticasone propionate/formoterol and beclometasone/formoterol MDI using laser diffraction
Authors: Peter Haidl, Gerhard Scheuch, Claudius Kietzig, Dominik Kappeler, Rolf Cloes
Journal: European Respiratory Journal (2014)

Introduction:   Fluticasone propionate/formoterol (FP/FORM;   flutiform   ® ; 125/5μg) has been shown to deliver a consistent median mass aerodynamic diameter (MMAD) and fine particle fraction (FPF), which were flow rate(FR)-independent (28.3-60L/min; MMAD: 3.15-3.52µm; FPF: 41%-44%) 1 . In contrast, the MMAD and FPF for beclometasone/formoterol (BDP/FORM;   Foster   ®  MDI; 100/6µg) 1 , were FR-dependent (28.3-60L/min; MMAD: 0.50-1.21 µm; FPF: 29%-43%). To understand these results, the particle size distribution (PSD) of both were measured by Laser Diffraction (LD).   Methods:   Volumetric Median Diameter (VMD) was measured near the mouthpiece by LD to determine if BDP/FORM released larger particles than FP/FORM directly after actuation. Both pMDIs were actuated at ∼10cm from the laser beam. Due to their bimodal PSD, measurements were made with a flow-optimized throat to filter out particles >10µm.   Results:   Mean VMD (n=6/inhaler) was 3.4±0.07µm for FP/FORM and 4.2±0.14µm for BDP/FORM. The fine particle fraction (VMD   Conclusions:   The VMD for FP/FORM was similar to its published MMAD whereas the VMD for BDP/FORM was considerably larger than the reported MMAD. BDP/FORM had a significantly higher % of large particles, which are more likely to deposit in the throat, based on total mass compared to FP/FORM. These results may explain the FR-dependency seen with BDP/FORM and why FP/FORM has previously been shown to have a higher FPF than BDP/FORM at a low FR despite BDP/FORM having a smaller MMAD.  1 Johal et al Comp Prod Ther 2013;3:39-51  Sponsor: Mundipharma GmbH.
Hyperprolactinemia and infertility: new insights
Authors: Ursula B. Kaiser
Journal: Journal of Clinical Investigation (2012)

Clinical vignette: A 29-year-old woman is referred for management of infertility. After menarche at age 12, menses occurred irregularly for a year and then became regular. She initiated use of oral contraceptive pills at the age of 18, then stopped at age 27 to try to conceive. Evaluation revealed hyperprolactinemia with serum prolactin of 90 ng/ml; pituitary MRI showed a 6-mm microadenoma. Other pituitary function tested was normal. Therapy was initiated with bromocriptine, but it was poorly tolerated, with fatigue, nausea, and lightheadedness to the point of syncopal events during her work as a hairdresser. Treatment was changed to cabergoline, with similar difficulties. Prolactin levels declined to the 30s–40s, but she was never able to tolerate the medication sufficiently to attain normal prolactin levels, and menses were sporadic and infrequent, with only 2–3 occurring per year. She and her husband had not conceived despite regular unprotected intercourse. She asks whether other medical treatment options might be available for her infertility.
Incidence and time course of everolimus-related adverse events in postmenopausal women with hormone receptor-positive advanced breast cancer: insights from BOLERO-2
Authors: H.S. Rugo, K.I. Pritchard, M. Gnant, S. Noguchi, M. Piccart, G. Hortobagyi, J. Baselga, A. Perez, M. Geberth, T. Csoszi, E. Chouinard, V. Srimuninnimit, P. Puttawibul, J. Eakle, W. Feng, H. Bauly, M. El-Hashimy, T. Taran, H.A. Burris
Journal: Annals of Oncology (2014)

In the BOLERO-2 trial, everolimus (EVE), an inhibitor of mammalian target of rapamycin, demonstrated significant clinical benefit with an acceptable safety profile when administered with exemestane (EXE) in postmenopausal women with hormone receptor-positive (HR(+)) advanced breast cancer. We report on the incidence, time course, severity, and resolution of treatment-emergent adverse events (AEs) as well as incidence of dose modifications during the extended follow-up of this study.
Diabetes and Impaired Fasting Glycemia in the Tribes of Khagrachari Hill Tracts of Bangladesh
Authors: M. Abu Sayeed, Hajera Mahtab, Parvin Akter Khanam, Khandaker Abul Ahsan, Akhter Banu, A.N.M. Bazlur Rashid, A.K. Azad Khan
Journal: Diabetes Care (2004)

To determine the prevalence of type 2 diabetes and impaired fasting glycemia (IFG) in a tribal population of Bangladesh.A cluster sampling of 1,287 tribal subjects of age > or =20 years was investigated. They live in a hilly area of Khagrachari in the far northeast of Bangladesh. Fasting plasma glucose, blood pressure, height, weight, waist girth, and hip girth were measured. Lipid fractions were also estimated. We used the 1997 American Diabetes Association diagnostic criteria.The crude prevalence of type 2 diabetes was 6.6% and IFG was 8.5%. The age-standardized (20-70 years) prevalence of type 2 diabetes (95% CI) was 6.4% (4.96-7.87) and of IFG was 8.4% (6.48-10.37). Both tribesmen and women had equal risk for diabetes and IFG. Compared with the lower-income group, the participants with higher income had a significantly higher prevalence of type 2 diabetes (18.8 vs. 3.1%, P < 0.001) and IFG (17.2 vs. 4.3%, P < 0.001). Using logistic regression, we found that increased age, high-income group, and increased central obesity were the important risk factors of diabetes.The prevalence of diabetes in the tribal population was higher than that of the nontribal population of Bangladesh. Older age, higher central obesity, and higher income were proven significant risk factors of diabetes. High prevalence of diabetes among these tribes indicates that the prevalence of diabetes and its complications will continue to increase. Evidently, health professionals and planners should initiate diabetes care in these tribal communities.
Value of bronchoalveolar lavage in the diagnosis of pulmonary infection in acquired immune deficiency syndrome.
Authors: M Orenstein, C A Webber, M Cash, A E Heurich
Journal: Thorax (1986)

Seventy five patients with pulmonary disease and suspected acquired immune deficiency syndrome (AIDS) underwent fibreoptic bronchoscopy with bronchoalveolar lavage. Of 54 cases of Pneumocystis carinii pneumonia, 53 (98%) were diagnosed by bronchoalveolar lavage. Complications were recorded in 12 instances and included pneumothorax in two and transient increase in fever and hypoxaemia in the remainder. Bronchoalveolar lavage is a safe, easy, and effective procedure for diagnosing pneumocystis pneumonia in patients at high risk of AIDS and should be done routinely when fibreoptic bronchoscopy is performed in such patients.
Chylous ascites, intestinal lymphangiectasia and the 'yellow-nail' syndrome.
Authors: P M Duhra, E M Quigley, M N Marsh
Journal: Gut (1985)

In 1964 Samman and White described 13 patients with lymphoedema of the lower extremities associated with an unusual dystrophy of the finger and toe nails: this they termed the 'yellow-nail' syndrome. Affected nails were thickened, excessively curved along both axes, very slow growing and of yellowish-grey hue; cuticle and lunula were usually absent and onycholysis was frequently evident. Lower limb lymphangiography in most individuals revealed hypoplasia, or aplasia of the lymphatics, similar to that occurring in primary lymphoedema: other patients also developed pleural effusions of high protein content or ascites suggestive of a more generalised disorder of the lymphatic system. Here we describe a patient in whom the classical 'yellow-nail' syndrome was associated with intestinal and chylous ascites.
Expression and Function of Ets-1 during Experimental Acute Renal Failure in Rats
Authors: Hiroyuki Tanaka, Yoshio Terada, Takahiko Kobayashi, Tomokazu Okado, Seiji Inoshita, Michio Kuwahara, Arun Seth, Yasufumi Sato, Sei Sasaki
Journal: Journal of the American Society of Nephrology (2004)

The Ets family of transcription factors is defined by a conserved DNA-binding Ets domain that forms a winged helix-turn-helix structure motif. The Ets family is involved in a diverse array of biologic functions, including cellular growth, migration, and differentiation. The hypothesis in this study was that Ets-1 is re-expressed during regeneration after acute renal failure (ARF) and plays a key role in the transcriptional regulation of cyclin D1 and the cell cycle progression in renal tubular cells. For clarifying the significance of Ets-1 in ARF, a rat ARF model in vivo and LLC-PK1 cells as an in vitro model were used. After the left rat renal artery was clamped for 1 h, the whole kidney homogenate was examined and total RNA was extracted at 6, 12, 24, 48, and 72 h after reperfusion by Western blot analysis and real-time reverse transcription-PCR. Ets-1 mRNA and protein expression were strongly increased at 6 to 24 h after the ischemia, respectively. The expression of hypoxia-inducible factor-1alpha was increased dramatically as early as 6 h after ischemia-reperfusion and decreased at 48 and 72 h after ischemia-reperfusion. In the immunohistologic examination, Ets-1 was expressed in the proximal tubules and coexpressed with proliferating cell nuclear antigen (PCNA). Furthermore, overexpression of Ets-1 promoted the cell cycle and increased the promoter activity and protein expression of cyclin D1 in LLC-PK1 cells. Ets-1 promoter activity increased between 3 and 6 h in hypoxia, and hypoxia also induced changes in the Ets-1 protein level in LLC-PK1 cells. The Ets-1 induction by hypoxia was abolished by the transfection of dominant-negative hypoxia-inducible factor-1alpha. A gel shift assay demonstrated that Ets-1 binds to the ets-1 binding site of the cyclin D1 promoter in the ischemia-reperfusion condition. Overexpression of Ets-1 did not significantly change the caspase 3 activity or the value of cell death ELISA in LLC-PK1 cells. Taken together, these data suggest that Ets-1 plays a key role in the cell-cycle progression of renal tubules in ARF. The Ets-1 pathway may regulate the transcription of cyclin D1 and control the regeneration of renal tubules in ARF.
A Strategy for Cost Containment in Coronary Surgery
Authors: Floyd D. Loop, Eric K. Christiansen, J. Lancelot Lester, Delos M. Cosgrove, Irving Franco, Leonard R. Golding
Journal: JAMA (1983)

Patients with multivessel coronary atherosclerosis and stable angina pectoris were examined by outpatient testing and admitted to a staging area with their families on the morning of coronary bypass surgery. This experimental group was not hospitalized before surgery. Their hospital charges were compared with those of cohorts of coronary artery surgery patients from 1977 to 1981 who met the same entrance criteria. Length of stay in the hospital was reduced by two days. A 10% savings in hospital charges was realized in the 1981 experimental group as compared with the 1981 control group. A comparison of total hospital charges, adjusted for inflation, shows that 1981 experimental group patients paid 35% less for their hospital room, 45% less for their intensive care period, and 17% less in total charges than the 1977 control group. Interviews indicated that these patients with stable cardiac conditions preferred to stay with their families or friends before surgery. (<i>JAMA</i>1983;250:63-66)
Tbx3: a new trick for an 'old' myocyte?
Authors: S. N. Ebert
Journal: Cardiovascular Research (2012)

This editorial refers to ‘T-box transcription factor TBX3 reprogrammes mature cardiac myocytes into pacemaker-like cells’ by M.L. Bakker et al ., doi:10.1093/cvr/cvs120. 

Tbx3: a new trick for an ‘old’ myocyte? Well, not quite … Tbx3 is a T-box transcription factor that is expressed in the pacemaking and conduction system myocytes beginning during early embryonic stages of cardiac development.1 When expressed in embryonic atrial chamber myocytes, ectopic induction of spontaneous pacemaking activity in atrial myocardium was observed in vivo , thereby suggesting that Tbx3 can ‘impose’ pacemaking capability upon otherwise unsuspecting working myocytes.2 Bakker et al. 3 test the hypothesis that Tbx3 would also be able to induce pacemaker activity in mature adult cardiac myocytes. Like the proverbial ‘old dog’, however, it appears that it is also difficult to teach old myocytes this new trick.

Bakker et al .3 show that while Tbx3 does repress certain genes typically excluded from pacemaking centres such as those encoding the gap junction proteins connexin 40 (Cx40) and connexin 43 (Cx43) in adult mouse atrial myocytes, it failed to induce the pacemaker channel protein encoded by the hyperpolarization-activated cyclic nucleotide-gated 4 ( Hcn4 ) gene. Consequently, no spontaneous sinusoidal action potentials characteristic of those typically observed in sinoatrial node pacemaking myocytes …
Mechanical Stimulation Regulates Voltage-Gated Potassium Currents in Cardiac Microvascular Endothelial Cells
Authors: Jinping Fan, Kenneth B. Walsh
Journal: Circulation Research (1999)

Abstract —Vascular endothelial cells are constantly exposed to mechanical forces resulting from blood flow and transmural pressure. The goal of this study was to determine whether mechanical stimulation alters the properties of endothelial voltage-gated K + channels. Cardiac microvascular endothelial cells (CMECs) were isolated from rat ventricular muscle and cultured on thin sheets of silastic membranes. Membrane currents were measured with the use of the whole-cell arrangement of the patch-clamp technique in endothelial cells subjected to static stretch for 24 hours and compared with measurements from control, nonstretched cells. Voltage steps positive to −30 mV resulted in the activation of a time-dependent, delayed rectifier K + current ( I K ) in the endothelial cells. Mechanically induced increases of 97%, 355%, and 106% at +30 mV were measured in the peak amplitude of I K in cells stretched for 24 hours by 5%, 10%, and 15%, respectively. In addition, the half-maximal voltage required for I K activation was shifted from +34 mV in the nonstretched cells to −5 mV in the stretched cells. Although I K in both groups of CMECs was blocked to a similar extent by tetraethylammonium, currents in the stretched endothelial cells displayed an enhanced sensitivity to inhibition by charybdotoxin. Preincubation of the CMECs with either pertussis toxin or phorbol 12-myristate 13-acetate during the 24 hours of cell stretch did not prevent the increase in I K . The application of phorbol 12-myristate 13-acetate and static stretch stimulated the proliferation of CMECs. Stretch-induced regulation of K + channels may be important to control the resting potential of the endothelium and may contribute to capillary growth during periods of mechanical perturbation.
Long-Term Risk of Coronary Events after AKI
Authors: Vin-Cent Wu, Che-Hsiung Wu, Tao-Min Huang, Cheng-Yi Wang, Chun-Fu Lai, Chih-Chung Shiao, Chia-Hsui Chang, Shuei-Liong Lin, Yen-Yuan Chen, Yung-Ming Chen, Tzong-Shinn Chu, Wen-Chih Chiang, Kwan-Dun Wu, Pi-Ru Tsai, Likwang Chen, Wen-Je Ko
Journal: Journal of the American Society of Nephrology (2014)

The incidence rate of AKI in hospitalized patients is increasing. However, relatively little attention has been paid to the association of AKI with long-term risk of adverse coronary events. Our study investigated hospitalized patients who recovered from de novo dialysis-requiring AKI between 1999 and 2008 using patient data collected from inpatient claims from Taiwan National Health Insurance. We used Cox regression with time-varying covariates to adjust for subsequent CKD and ESRD after discharge. Results were further validated by analysis of a prospectively constructed database. Among 17,106 acute dialysis patients who were discharged, 4869 patients recovered from dialysis-requiring AKI (AKI recovery group) and were matched with 4869 patients without AKI (non-AKI group). The incidence rates of coronary events were 19.8 and 10.3 per 1000 person-years in the AKI recovery and non-AKI groups, respectively. AKI recovery associated with higher risk of coronary events (hazard ratio [HR], 1.67; 95% confidence interval [95% CI], 1.36 to 2.04) and all-cause mortality (HR, 1.67; 95% CI, 1.57 to 1.79) independent of the effects of subsequent progression to CKD and ESRD. The risk levels of de novo coronary events after hospital discharge were similar in patients with diabetes alone and patients with AKI alone (P=0.23). Our results reveal that AKI with recovery associated with higher long-term risks of coronary events and death in this cohort, suggesting that AKI may identify patients with high risk of future coronary events. Enhanced postdischarge follow-up of renal function of patients who have recovered from temporary dialysis may be warranted.
Effects of mastectomy versus lumpectomy on emotional adjustment to breast cancer: a prospective study of the first year postsurgery.
Authors: C Pozo, C S Carver, V Noriega, S D Harris, D S Robinson, A S Ketcham, A Legaspi, F L Moffat, K C Clark
Journal: Journal of Clinical Oncology (1992)

Procedure (mastectomy v lumpectomy) and choice of procedure were examined as predictors of adjustment to breast cancer in a prospective study of the experiences of the first year after surgery.Breast cancer patients were interviewed the day before surgery, 10 days after surgery, and at the 3-month, 6-month, and 12-month follow-ups. Patients included 24 women who received mastectomy on strong recommendation, 24 who chose mastectomy for other reasons, and 15 who chose lumpectomy. Subjective well-being was assessed in terms of mood disturbance, perceived quality of life, life satisfaction, marital satisfaction, perceptions of social support, and self-rated adjustment.Surgical groups differed in well-being in only one respect: lumpectomy patients reported a higher-quality sex life at 6 and 12 months postsurgery than mastectomy patients. Choice of surgical procedure predicted higher levels of life satisfaction at 3 months.The lack of difference between surgical groups in areas other than sexual adjustment replicates previous findings, but extends them by (1) using a fully prospective design, (2) providing data on the period surrounding the surgery (as well as later periods), and (3) examining a broader range of indices of well-being than usual.
Randomised trial of glutamine, selenium, or both, to supplement parenteral nutrition for critically ill patients
Authors: P. J. D. Andrews, A. Avenell, D. W. Noble, M. K. Campbell, B. L. Croal, W. G. Simpson, L. D. Vale, C. G. Battison, D. J. Jenkinson, J. A. Cook
Journal: BMJ (2011)

<b>Objective</b> To determine whether inclusion of glutamine, selenium, or both in a standard isonitrogenous, isocaloric preparation of parenteral nutrition influenced new infections and mortality among critically ill patients. <b>Design</b> Randomised, double blinded, factorial, controlled trial. <b>Setting</b> Level 2 and 3 (or combined) critical care units in Scotland. All 22 units were invited, and 10 participated. <b>Participants</b> 502 adults in intensive care units and high dependency units for ≥48 hours, with gastrointestinal failure and requiring parenteral nutrition. <b>Interventions</b> Parenteral glutamine (20.2 g/day) or selenium (500 μg/day), or both, for up to seven days. <b>Main outcome measures</b> Primary outcomes were participants with new infections in the first 14 days and mortality. An intention to treat analysis and a prespecified analysis of patients who received ≥5 days of the trial intervention are presented. Secondary outcomes included critical care unit and acute hospital lengths of stay, days of antibiotic use, and modified SOFA (Sepsis-related Organ Failure Assessment) score. <b>Results</b> Selenium supplementation did not significantly affect patients developing a new infection (126/251 <i>v</i> 139/251, odds ratio 0.81 (95% CI 0.57 to 1.15)), except for those who had received ≥5 days of supplementation (odds ratio 0.53 (0.30 to 0.93)). There was no overall effect of glutamine on new infections (134/250 <i>v</i> 131/252, odds ratio 1.07 (0.75 to 1.53)), even if patients received ≥5 days of supplementation (odds ratio 0.99 (0.56 to 1.75)). Six month mortality was not significantly different for selenium (107/251 <i>v</i> 114/251, odds ratio 0.89 (0.62 to 1.29)) or glutamine (115/250 <i>v</i> 106/252, 1.18 (0.82 to 1.70)). Length of stay, days of antibiotic use, and modified SOFA score were not significantly affected by selenium or glutamine supplementation. <b>Conclusions</b> The primary (intention to treat) analysis showed no effect on new infections or on mortality when parenteral nutrition was supplemented with glutamine or selenium. Patients who received parenteral nutrition supplemented with selenium for ≥5 days did show a reduction in new infections. This finding requires confirmation. <b>Trial registration</b> Current Controlled Trials ISRCTN87144826
Progression of diaphragmatic fatigue during inspiratory muscle loading in normoxia and hypoxia
Authors: David Walker, Franziska Farquharson, Stephan Walterspacher, Hannes Klenze, Hans-Joachim Kabitz
Journal: European Respiratory Journal (2013)

Diaphragmatic fatigue is known to occur during heavy inspiratory muscle loading (IML) in normoxia and is suggested to be increased in hypoxia.  This study investigated the progression of diaphragmatic fatigue during IML in normoxia and hypoxia.  In a randomized-controlled, single-blinded trial transdiaphragmatic pressure after magnetic stimulation of the phrenic nerves (Pdi,tw) was assessed every 45 seconds in 20 healthy subjects during standardized IML (60-80% of maximal inspiratory pressure) in normoxia and hypoxia. Lung volume correction was applied for all Pdi,tw.  Twelve Subjects showed a reduction in Pdi,tw >10% in hypoxia during IML (i.e. fatiguer). Pdi,tw at task failure in hypoxia was lower than in normoxia (3,30±1,02kPa vs. 4.01±0,99kPa p  To conclude, Pdi,tw during IML featured different progressions during normoxia compared to hypoxia. While normoxia resulted in an early decrease followed by a leveling off, hypoxia resulted in a steady decrease and more pronounced fatigue.
IL-9– and mast cell–mediated intestinal permeability predisposes to oral antigen hypersensitivity
Authors: Elizabeth E. Forbes, Katherine Groschwitz, J. Pablo Abonia, Eric B. Brandt, Elizabeth Cohen, Carine Blanchard, Richard Ahrens, Luqman Seidu, Andrew McKenzie, Richard Strait, Fred D. Finkelman, Paul S. Foster, Klaus I. Matthaei, Marc E. Rothenberg, Simon P. Hogan
Journal: The Journal of Experimental Medicine (2008)

Previous mouse and clinical studies demonstrate a link between Th2 intestinal inflammation and induction of the effector phase of food allergy. However, the mechanism by which sensitization and mast cell responses occurs is largely unknown. We demonstrate that interleukin (IL)-9 has an important role in this process. IL-9–deficient mice fail to develop experimental oral antigen–induced intestinal anaphylaxis, and intestinal IL-9 overexpression induces an intestinal anaphylaxis phenotype (intestinal mastocytosis, intestinal permeability, and intravascular leakage). In addition, intestinal IL-9 overexpression predisposes to oral antigen sensitization, which requires mast cells and increased intestinal permeability. These observations demonstrate a central role for IL-9 and mast cells in experimental intestinal permeability in oral antigen sensitization and suggest that IL-9–mediated mast cell responses have an important role in food allergy.
Comparative effects of valsartan versus amlodipine on left ventricular mass and reactive oxygen species formation by monocytes in hypertensive patients with left ventricular hypertrophy
Authors: Kenichi Yasunari, Kensaku Maeda, Takanori Watanabe, Munehiro Nakamura, Junichi Yoshikawa, Akira Asada
Journal: Journal of the American College of Cardiology (2004)