tbuckley/cabot-search huggingface dataset:
Driving Times and Distances to Hospitals With Percutaneous Coronary Intervention in the United States
Authors: Brahmajee K. Nallamothu, Eric R. Bates, Yongfei Wang, Elizabeth H. Bradley, Harlan M. Krumholz
Journal: Circulation (2006)

The success of prehospital triage protocols for patients with ST-elevation myocardial infarction (STEMI) will depend, in part, on how patients are geographically distributed around hospitals that perform percutaneous coronary intervention (PCI). Accordingly, we determined the proportion of the adult population in the United States with timely access to PCI hospitals using driving times and distances.We performed a cross-sectional study using hospital-level data from the American Hospital Association Annual Survey and Census tract-level data on adults 18 years of age or older from the 2000 United States Census. Our aims were to determine the proportion of the adult population who (1) lived within 60 minutes of a PCI hospital and (2) had additional transport times within 30 minutes if directly referred to a PCI hospital as opposed to a closer, non-PCI hospital. Median times and distances to the closest PCI hospital were 11.3 (interquartile range [IQR] 5.7 to 28.5) minutes and 7.9 (IQR 3.5 to 22.4) miles, respectively. A total of 79.0% of the adult population lived within 60 minutes of a PCI hospital. Among those with a non-PCI hospital as their closest facility, 74.0% required additional transport times of <30 minutes if directly referred to a PCI hospital as opposed to the non-PCI hospital. These estimates varied substantially across regions and urban, suburban, and rural Census tracts.Nearly 80% of the adult population in the United States lived within 60 minutes of a PCI hospital in 2000. Even among those living closer to non-PCI hospitals, almost three fourths would experience <30 minutes of additional delay with direct referral to a PCI hospital, which suggests that such a strategy might be feasible for these individuals.
Transcriptional Regulation by the Helix Bundle Peptide Hormones: Growth Hormone, Prolactin, and Hematopoietic Cytokines
Authors: NELSON D. HORSEMAN, LI-YUAN YU-LEE
Journal: Endocrine Reviews (1994)

TODAY it is stylish to remark with fascination at the multiple overlapping functions of interleukins, colonystimulating factors, and a host of other "cytokines" that have been discovered in recent years. As a reminder that this is not really a new observation, the first HBP hormone to be purified was PRL (1), and it was recognized to have such a variety of biological actions that by 1963 there had been created a "vast and confusing literature" (2) replete with multiple names for the same hormone and arguments about how many hormones were responsible for each biological activity. The pleiotropy of PRL actions prompted Bern and Nicoll (3) to suggest in 1968 that it be renamed either "versatilin" or "omnipotin" (3), and by 1980 more than 200 actions of PRL had been documented in the various vertebrate classes (4). Redundancies between actions of PRL and GH were widely appreciated by the 1950s, and the similarities of human (h) PRL and hGH actions resulted in such controversies that many doubted the existence of separate human PRL and GHs until hPRL was definitively purified by Friesen's group in 1972 (5).
Gemcitabine and capecitabine with or without telomerase peptide vaccine GV1001 in patients with locally advanced or metastatic pancreatic cancer (TeloVac): an open-label, randomised, phase 3 trial
Authors: Gary Middleton, Paul Silcocks, Trevor Cox, Juan Valle, Jonathan Wadsley, David Propper, Fareeda Coxon, Paul Ross, Srinivasan Madhusudan, Tom Roques, David Cunningham, Stephen Falk, Nick Wadd, Mark Harrison, Pippa Corrie, Tim Iveson, Angus Robinson, Karen McAdam, Martin Eatock, Jeff Evans, Caroline Archer, Tamas Hickish, Angel Garcia-Alonso, Marianne Nicolson, William Steward, Alan Anthoney, William Greenhalf, Victoria Shaw, Eithne Costello, Dean Naisbitt, Charlotte Rawcliffe, Gemma Nanson, John Neoptolemos
Journal: The Lancet Oncology (2014)
Expression of ARC (apoptosis repressor with caspase recruitment domain), an antiapoptotic protein, is strongly prognostic in AML
Authors: Bing Z. Carter, Yi Hua Qiu, Nianxiang Zhang, Kevin R. Coombes, Duncan H. Mak, Deborah A. Thomas, Farhad Ravandi, Hagop M. Kantarjian, Erich Koller, Michael Andreeff, Steven M. Kornblau
Journal: Blood (2010)
Byssinosis: a disease or a symptom?
Authors: W R Lee, T B Stretton
Journal: Thorax (1986)

<h3>BACKGROUND:</h3> Optimal titration of inspired oxygen is important to prevent hyperoxia in mechanically ventilated patients in ICUs. There is mounting evidence of the deleterious effects of hyperoxia; however, there is a paucity of data about F<sub>IO<sub>2</sub></sub> practice and oxygen exposure among patients in ICUs. We therefore sought to assess excessive F<sub>IO<sub>2</sub></sub> exposure in mechanically ventilated patients with acute lung injury and to evaluate the effect on pulmonary outcomes. <h3>METHODS:</h3> From a database of ICU patients with acute lung injury identified by prospective electronic medical record screening, we identified those who underwent invasive mechanical ventilation for &gt; 48 hours from January 1 to December 31, 2008. Ventilator settings, including F<sub>IO<sub>2</sub></sub> and corresponding S<sub>pO<sub>2</sub></sub>, were collected from the electronic medical record at 15-min intervals for the first 48 hours. Excessive F<sub>IO<sub>2</sub></sub> was defined as F<sub>IO<sub>2</sub></sub> &gt; 0.5 despite S<sub>pO<sub>2</sub></sub> &gt; 92%. The association between the duration of excessive exposure and pulmonary outcomes was assessed by change in oxygenation index from baseline to 48 hours and was analyzed by univariate and multivariate linear regression analysis. <h3>RESULTS:</h3> Of 210 patients who met the inclusion criteria, 155 (74%) were exposed to excessive F<sub>IO<sub>2</sub></sub> for a median duration of 17 hours (interquartile range 7.5–33 h). Prolonged exposure to excessive F<sub>IO<sub>2</sub></sub> correlated with worse oxygenation index at 48 hours in a dose-response manner (<i>P</i> &lt; .001.). Both exposure to higher F<sub>IO<sub>2</sub></sub> and longer duration of exposure were associated with worsening oxygenation index at 48 hours (<i>P</i> &lt; .001), more days on mechanical ventilation, longer ICU stay, and longer hospital stay (<i>P</i> = .004). No mortality difference was noted. <h3>CONCLUSIONS:</h3> Excessive oxygen supplementation is common in mechanically ventilated patients with ALI and may be associated with worsening lung function.
Association of hyperlipidaemia, inflammation and serological status and coronary heart disease among patients with rheumatoid arthritis: data from the National Veterans Health Administration
Authors: Iris Navarro-Millán, Shuo Yang, Scott L DuVall, Lang Chen, John Baddley, Grant W Cannon, Elizabeth S Delzell, Jie Zhang, Monika M Safford, Nivedita M Patkar, Ted R Mikuls, Jasvinder A Singh, Jeffrey R Curtis
Journal: Annals of the Rheumatic Diseases (2015)

To examine the association of serum lipids, inflammation and seropositivity on coronary heart disease (CHD) and stroke in patients with rheumatoid arthritis (RA).The incidence of hospitalised myocardial infarction (MI) or stroke was calculated in a cohort of patients with RA receiving care within the national Veterans Health Administration from 1998 to 2011. Cox proportional hazard models were used to examine the association between these outcomes and low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), C reactive protein (CRP) and erythrocyte sedimentation rate (ESR) as time-varying variables, divided into quintiles.There were 37,568 patients with RA in the cohort with mean age of 63 years (SD 12.1); 90% were men. There was a no clear association between LDL-C and CHD/stroke. Compared with lower HDL-C (<34 mg/dL), higher HDL-C (≥54 mg/dL) was inversely associated with MI (hazard ratio (HR)=0.68, 95% CI 0.55 to 0.85) and stroke (HR=0.69, 95% CI 0.50 to 0.96). Higher CRP >2.17 mg/dL (vs CRP <0.26 mg/dL) was associated with increased risk (HR=2.43, 95% CI 1.77 to 3.33) for MI and 2.02 (95% CI 1.32 to 3.08) for stroke. ESR >47 mm/h compared with <8 mm/h had an HR 1.87 (95% CI 1.39 to 2.52) for MI and 2.00 (95% CI 1.26 to 3.18) for stroke. The association between MI was significant for RA seropositivity (HR=1.23, 95% CI 1.03 to 1.48).In this predominantly older male RA cohort, there was no clear association between LDL-C and CHD, whereas higher HDL-C was inversely associated with MI and stroke. CRP and ESR were similarly associated with increase MI risk and stroke, reflecting the prominent role of inflammation in CHD risk in RA.
Products of 12/15-Lipoxygenase Upregulate the Angiotensin II Receptor
Authors: Zhong-Gao Xu, Hang Yuan, Linda Lanting, Shu-Lian Li, Mei Wang, Narkunaraja Shanmugam, Mitsuo Kato, Sharon G. Adler, Marpadga A. Reddy, Rama Natarajan
Journal: Journal of the American Society of Nephrology (2008)

Angiotensin II and its type 1 receptor (AT1R) play important roles in the pathogenesis of renal disease and diabetic nephropathy. The 12/15-lipoxygenase pathway of arachidonate metabolism and its lipid products have also been implicated in diabetic nephropathy. However, it is unclear whether 12/15-lipoxygenase regulates expression of AT1R. In cultured rat mesangial cells, we found that the 12/15-lipoxygenase product 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE) increased AT1R mRNA and protein expression, primarily by stabilizing AT1R mRNA. Pretreatment with 12(S)-HETE also amplified the signaling effects of angiotensin II, likely due to the increased AT1R expression. Levels of AT1R protein expression decreased when 12/15-lipoxygenase was knocked down with specific short hairpin RNA (shRNA) compared with control cells. Similarly, levels of the AT1 receptor, but not the AT2 receptor, were significantly lower in mesangial cells and glomeruli derived from 12/15-lipoxygenase knockout mice compared with control mice. Reciprocally, stable overexpression of 12/15-lipoxygenase increased AT1R expression in cultured mesangial cells. In vivo, modified siRNA targeting 12/15-lipoxygenase reduced glomerular AT1R expression in a diabetic mouse model. Interestingly, angiotensin II induced greater levels of 12/15-lipoxygenase, TGF-β1, and fibronectin (FN) in AT1R-overexpressing mesangial cells compared with control cells. Therefore, oxidized lipids generated by the 12/15-lipoxygenase-mediated metabolism of arachidonic acid can enhance AT1R expression in mesangial cells and augment the profibrotic effects of angiotensin II.
Increased Impulsivity Associated With Severity of Suicide Attempt History in Patients With Bipolar Disorder
Authors: Alan C. Swann, Donald M. Dougherty, Peggy J. Pazzaglia, Mary Pham, Joel L. Steinberg, F. Gerard Moeller
Journal: American Journal of Psychiatry (2005)

Impulsivity is a prominent and measurable characteristic of bipolar disorder that can contribute to risk for suicidal behavior. The purpose of this study was to investigate the relationship between impulsivity and severity of past suicidal behavior, a potential predictor of eventual suicide, in patients with bipolar disorder.In bipolar disorder subjects with either a definite history of attempted suicide or no such history, impulsivity was assessed with both a questionnaire (Barratt Impulsiveness Scale) and behavioral laboratory performance measures (immediate memory/delayed memory tasks). Diagnosis was determined with the Structured Clinical Interview for DSM-IV. Interviews of patients and review of records were used to determine the number of past suicide attempts and the medical severity of the most severe attempt.Subjects with a history of suicide attempts had more impulsive errors on the immediate memory task and had shorter response latencies, especially for impulsive responses. Impulsivity was highest in subjects with the most medically severe suicide attempts. Effects were not accounted for by presence of depression or mania at the time of testing. Barratt Impulsiveness Scale scores were numerically, but not significantly, higher in subjects with suicide attempts. A history of alcohol abuse was associated with greater probability of a suicide attempt. Multivariate analysis showed that ethanol abuse history and clinical state at the time of testing did not have a significant effect after impulsivity was taken into account.These results suggest that a history of severe suicidal behavior in patients with bipolar disorder is associated with impulsivity, manifested as a tendency toward rapid, unplanned responses.
The Endothelin Antagonist Atrasentan Lowers Residual Albuminuria in Patients with Type 2 Diabetic Nephropathy
Authors: Dick de Zeeuw, Blai Coll, Dennis Andress, John J. Brennan, Hui Tang, Mark Houser, Ricardo Correa-Rotter, Donald Kohan, Hiddo J. Lambers Heerspink, Hirofumi Makino, Vlado Perkovic, Yili Pritchett, Giuseppe Remuzzi, Sheldon W. Tobe, Robert Toto, Giancarlo Viberti, Hans-Henrik Parving
Journal: Journal of the American Society of Nephrology (2014)

Despite optimal treatment, including renin-angiotensin system (RAS) inhibitors, patients with type 2 diabetic nephropathy have high cardiorenal morbidity and mortality related to residual albuminuria. We evaluated whether or not atrasentan, a selective endothelin A receptor antagonist, further reduces albuminuria when administered concomitantly with maximum tolerated labeled doses of RAS inhibitors. We enrolled 211 patients with type 2 diabetes, urine albumin/creatinine ratios of 300-3500 mg/g, and eGFRs of 30-75 ml/min per 1.73 m(2) in two identically designed, parallel, multinational, double-blind studies. Participants were randomized to placebo (n=50) or to 0.75 mg/d (n=78) or 1.25 mg/d (n=83) atrasentan for 12 weeks. Compared with placebo, 0.75 mg and 1.25 mg atrasentan reduced urine albumin/creatinine ratios by an average of 35% and 38% (95% confidence intervals of 24 to 45 and 28 to 47, respectively) and reduced albuminuria≥30% in 51% and 55% of participants, respectively. eGFR and office BP measurements did not change, whereas 24-hour systolic and diastolic BP, LDL cholesterol, and triglyceride levels decreased significantly in both treatment groups. Use of atrasentan was associated with a significant increase in weight and a reduction in hemoglobin, but rates of peripheral edema, heart failure, or other side effects did not differ between groups. However, more patients treated with 1.25 mg/d atrasentan discontinued due to adverse events. After stopping atrasentan for 30 days, measured parameters returned to pretreatment levels. In conclusion, atrasentan reduced albuminuria and improved BP and lipid spectrum with manageable fluid overload-related adverse events in patients with type 2 diabetic nephropathy receiving RAS inhibitors.
THE ORIGIN AND KINETICS OF MONONUCLEAR PHAGOCYTES
Authors: Ralph van Furth, Zanvil A. Cohn
Journal: The Journal of Experimental Medicine (1968)

The origin and turnover of efferent populations of mouse mononuclear phagocytes has been described. Mononuclear phagocytes were defined as mononuclear cells which are able to adhere to glass and phagocytize. In vitro labeling studies with thymidine-(3)H showed that monocytes in the peripheral blood and peritoneal macrophages do not multiply and can be considered end cells in a normal, steady state situation. However, the mononuclear phagocytes of the bone marrow appear to be rapidly dividing cells. This conclusion was supported by in vivo labeling experiments. A peak of labeled mononuclear phagocytes of the bone marrow was found 24 hr after a pulse of thymidine-(3)H. This was followed, 24 hr later, by a peak of labeled monocytes in the peripheral blood. From these experiments it was concluded that the rapidly dividing mononuclear phagocytes of the bone marrow, called promonocytes, are the progenitor cells of the monocytes. Labeling studies after splenectomy and after X-irradiation excluded other organs as a major source of the monocytes. Peak labeling of both the blood monocyte and peritoneal macrophages occurred at the same time. A rapid entry of monocytes from the blood into the peritoneal cavity was observed, after a sterile inflammation was evoked by an injection of newborn calf serum. These data have led to the conclusion that monocytes give rise to peritoneal macrophages. No indications have been obtained that mononuclear phagocytes originate from lymphocytes. In the normal steady state the monocytes leave the circulation by a random process, with a half-time of 22 hr. The average blood transit time of the monocytes has been calculated to be 32 hr. The turnover rate of peritoneal macrophages was low and estimated at about 0.1% per hour. On the basis of these studies the life history of mouse mononuclear phagocytes was formulated to be: promonocytes in the bone marrow, --> monocytes in the peripheral blood, --> macrophages in the tissue.
Reduced Mechanical Efficiency in Chronic Obstructive Pulmonary Disease but Normal Peak V̇<scp>o</scp><sub>2</sub>with Small Muscle Mass Exercise
Authors: Russell S. Richardson, Bryan T. Leek, Timothy P. Gavin, Luke J. Haseler, Sundar R. D. Mudaliar, Robert Henry, Odile Mathieu-Costello, Peter D. Wagner
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

We studied six patients with chronic obstructive pulmonary disease (COPD) (FEV1 = 1.1 ± 0.2 L, 32% of predicted) and six age- and activity level–matched control subjects while performing both maximal bicycle exercise and single leg knee-extensor exercise. Arterial and femoral venous blood sampling, thermodilution blood flow measurements, and needle biopsies allowed the assessment of muscle oxygen supply, utilization, and structure. Maximal work rates and single leg V̇O2max (control subjects = 0.63 ± 0.1; patients with COPD = 0.37 ± 0.1 L/minute) were significantly greater in the control group during bicycle exercise. During knee-extensor exercise this difference in V̇O2max disappeared, whereas maximal work capacity was reduced (flywheel resistance: control subjects = 923 ± 198; patients with COPD = 612 ± 81 g) revealing a significantly reduced mechanical efficiency (work per unit oxygen consumed) with COPD. The patients had an elevated number of less efficient type II muscle fibers, whereas muscle fiber cross-sectional areas, capillarity, and mitochondrial volume density were not different between the groups. Therefore, although metabolic capacity per se is unchanged, fiber type differences associated with COPD may account for the reduced muscular mechanical efficiency that becomes clearly apparent during knee-extensor exercise, when muscle function is no longer overshadowed by the decrement in lung function.
The Na+, K+-ATPase: more than just a sodium pump
Authors: G. Scheiner-Bobis
Journal: Cardiovascular Research (2010)

This editorial refers to ‘Cardioprotection induced by Na+/K+-ATPase activation involves extracellular signal-regulated kinase 1/2 and phosphoinositide 3-kinase/Akt pathway’ by J. Zheng et al ., doi:10.1093/cvr/cvq263. 

Cardiotonic steroids (CTS) such as digitalis were introduced as medicine for the treatment of congestive heart failure by William Withering more than 200 years ago. Their beneficial effect in stimulating heart muscle contractility (positive inotropy) via their inhibition of the cardiac sodium pump (Na+, K+-ATPase) is often overshadowed by serious toxic effects resulting in cardiac arrhythmias and a variety of neuronal irritations. Because of a rather fluid transition between therapeutic and toxic concentrations of CTS, i.e. a narrow therapeutic window, severe toxicity as a result of overdose is not uncommon.

The investigation of Zheng et al .1 might provide the basis for a new approach in the treatment of congestive heart failure while avoiding the danger of toxicity. These authors demonstrate that an antibody directed against the L7/8 extracellular domain of the α-subunit of the sodium pump not only activates the enzyme, but also generates multiple cardioprotective events and induces positive inotropy in cardiac myocytes. This very intriguing observation might result in a new therapeutic concept; nevertheless, how does it fit into our knowledge about the function and physiological significance of the sodium pump?

Schatzman's2 discovery in 1953 that the sodium pump of animal plasma membranes is the receptor for CTS and the identification of the Na+, K+-ATPase by Skou3 in 1957 as the biochemical equivalent of the sodium pump, in conjunction with the discovery of the Na+/Ca2+-exchanger (NCX) in the late 1960s, helped to develop a model for the CTS-induced positive inotropic effect on the heart muscle.4 This model couples the function of the sodium pump to that of …
Pyoderma gangrenosum following treatment with isotretinoin
Authors: H.B. Gangaram, L.P. Tan, A.T. Gan, H.H. Suraiya, T. Ganesapillai
Journal: British Journal of Dermatology (1997)

Journal Article Pyoderma gangrenosum following treatment with isotretinoin Get access H.B. Gangaram, H.B. Gangaram Department of Dermatology, Kuala Lumpur Hospital, 50586 Kuala Lumpur Search for other works by this author on: Oxford Academic Google Scholar L.P. Tan, L.P. Tan Department of Dermatology, Kuala Lumpur Hospital, 50586 Kuala Lumpur Search for other works by this author on: Oxford Academic Google Scholar A.T. Gan, A.T. Gan Department of Dermatology, Kuala Lumpur Hospital, 50586 Kuala Lumpur Search for other works by this author on: Oxford Academic Google Scholar H.H. Suraiya, H.H. Suraiya Department of Dermatology, Kuala Lumpur Hospital, 50586 Kuala Lumpur Search for other works by this author on: Oxford Academic Google Scholar T. Ganesapillai T. Ganesapillai Department of Dermatology, Kuala Lumpur Hospital, 50586 Kuala Lumpur Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 136, Issue 4, 1 April 1997, Pages 636–637, https://doi.org/10.1111/j.1365-2133.1997.tb02168.x Published: 01 April 1997
Adiponectin isoforms: a potential therapeutic target in rheumatoid arthritis?
Authors: Klaus W Frommer, Andreas Schäffler, Christa Büchler, Jürgen Steinmeyer, Markus Rickert, Stefan Rehart, Fabia Brentano, Steffen Gay, Ulf Müller-Ladner, Elena Neumann
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objectives</h3> Several clinical studies have suggested the adipocytokine adiponectin is involved in the progression of rheumatoid arthritis (RA). From this point of view, adiponectin might present a new therapeutic target. However, as adiponectin also exerts beneficial effects in the human organism, a strategy that would allow its detrimental effects to be abolished while maintaining the positive effects would be highly favourable. To elucidate such a strategy, the authors analysed whether the different adiponectin isoforms induce diverging effects, especially with regard to rheumatoid arthritis synovial fibroblasts (RASF), a central cell type in RA pathogenesis capable of invading into and destroying cartilage. <h3>Methods</h3> Affymetrix microarrays were used to screen for changes in gene expression of RASF. Messenger RNA levels were quantified by real-time PCR, protein levels by immunoassay. The migration of RASF and primary human lymphocytes was analysed using a two-chamber migration assay. <h3>Results</h3> In RASF, the individual adiponectin isoforms induced numerous genes/proteins relevant in RA pathogenesis to clearly different extents. In general, the most potent isoforms were the high molecular weight/middle molecular weight isoforms and the globular isoform, while the least potent isoform was the adiponectin trimer. The chemokines secreted by RASF upon adiponectin stimulation resulted in an increased migration of RASF and lymphocytes. <h3>Conclusion</h3> The results clearly suggest a pro-inflammatory and joint-destructive role of all adiponectin isoforms in RA pathophysiology, indicating that in chronic inflammatory joint diseases the detrimental effects outweigh the beneficial effects of adiponectin.