tbuckley/cabot-search huggingface dataset:
Diabetes and Cardiovascular Disease During Androgen Deprivation Therapy: Observational Study of Veterans With Prostate Cancer
Authors: N. L. Keating, A. J. O'Malley, S. J. Freedland, M. R. Smith
Journal: JNCI Journal of the National Cancer Institute (2009)

Previous studies indicate that androgen deprivation therapy for prostate cancer is associated with diabetes and cardiovascular disease among older men. We evaluated the relationship between androgen deprivation therapy and incident diabetes and cardiovascular disease in men of all ages with prostate cancer. We conducted an observational study of 37 443 population-based men who were diagnosed with local or regional prostate cancer in the Veterans Healthcare Administration from January 1, 2001, through December 31, 2004, with follow-up through December 31, 2005. Cox proportional hazards models were used to assess whether androgen deprivation therapy with gonadotropin-releasing hormone (GnRH) agonists, oral antiandrogens, the combination of the two (ie, combined androgen blockade), or orchiectomy was associated with diabetes, coronary heart disease, myocardial infarction, sudden cardiac death, or stroke, after adjustment for patient and tumor characteristics. All statistical tests were two-sided. Overall, 14 597 (39%) of the 37 443 patients were treated with androgen deprivation therapy. Treatment with GnRH agonists was associated with statistically significantly increased risks of incident diabetes (for GnRH agonist therapy, 159.4 events per 1000 person-years vs 87.5 events for no androgen deprivation therapy, difference = 71.9, 95% confidence interval [CI] = 71.6 to 72.2; adjusted hazard ratio [aHR] = 1.28, 95% CI = 1.19 to 1.38), incident coronary heart disease (aHR = 1.19, 95% CI = 1.10 to 1.28), myocardial infarction (12.8 events per 1000 person-years for GnRH agonist therapy vs 7.3 for no androgen deprivation therapy, difference = 5.5, 95% CI = 5.4 to 5.6; aHR = 1.28, 95% CI = 1.08 to 1.52), sudden cardiac death (aHR = 1.35, 95% CI = 1.18 to 1.54), and stroke (aHR = 1.22, 95% CI = 1.10 to 1.36). Combined androgen blockade was statistically significantly associated with an increased risk of incident coronary heart disease (aHR = 1.27, 95% CI = 1.05 to 1.53), and orchiectomy was associated with coronary heart disease (aHR = 1.40, 95% CI = 1.04 to 1.87) and myocardial infarction (aHR = 2.11, 95% CI = 1.27 to 3.50). Oral antiandrogen monotherapy was not associated with any outcome studied. Androgen deprivation therapy with GnRH agonists was associated with an increased risk of diabetes and cardiovascular disease.
Calcium channel antagonist properties of Bay K 8644 in single guinea pig ventricular cells.
Authors: R W Hadley, J R Hume
Journal: Circulation Research (1988)

The effects of Bay K 8644 on the high-threshold calcium channel was investigated by means of the whole-cell patch-clamp technique in single guinea pig ventricular myocytes. The goal of the experiments was to characterize the inhibitory effects of Bay K 8644 on the calcium channel, and identify the factors that influence the inhibition. Bay K 8644 was found to have strong calcium channel antagonist properties, which were both dose- and voltage-dependent. Channel block by Bay K 8644 had both a tonic and a use-dependent component. The stimulatory effect of the drug was found to have little obvious dependence on the holding potential. The accumulation of use-dependent block during trains of pulses was facilitated by faster rates of stimulation, longer pulse durations, and more positive holding potentials. Application of the drug induced the appearance of a second, slow component of calcium channel recovery. Both the time-constant and relative proportion of the slow component of recovery were found to be voltage-dependent. Bay K 8644 was also found to cause a hyperpolarizing shift of the inactivation curve for the calcium current, suggesting that it has strong interactions with the inactivated state of the calcium channel. Thus, Bay K 8644 has, along with its stimulatory effects, inhibitory effects that strongly resemble those of typical calcium channel antagonists.
Oral Appliance Therapy in Patients With Daytime Sleepiness and Snoring or Mild to Moderate Sleep Apnea
Authors: Marie Marklund, Bo Carlberg, Lars Forsgren, Tommy Olsson, Hans Stenlund, Karl A. Franklin
Journal: JAMA Internal Medicine (2015)

IMPORTANCEOral appliances that move the mandible forward during sleep are suggested as treatment for mild to moderate obstructive sleep apnea.OBJECTIVE To test whether an adjustable, custom-made oral appliance improves daytime sleepiness and quality of life in patients with daytime sleepiness and snoring or mild to moderate obstructive sleep apnea.DESIGN, SETTING, AND PARTICIPANTS Ninety-six patients with daytime sleepiness and an apnea-hypopnea index (AHI) lower than 30 were included in a randomized, placebo-controlled, parallel trial in Umeå, Sweden, from May 2007 through August 2011.INTERVENTIONS Four months' intervention with an oral appliance or a placebo device.MAIN OUTCOMES AND MEASURES Daytime sleepiness was measured with the Epworth Sleepiness Scale, the Karolinska Sleepiness Scale, and the Oxford Sleep Resistance (OSLER) test.Quality of life was assessed with the Short-Form 36-Item Health Survey (SF-36) and the Functional Outcomes of Sleep Questionnaire (FOSQ).Secondary outcomes included the apnea-hypopnea index, headaches, symptoms of restless legs, and insomnia. RESULTSOral appliance therapy was not associated with improvements in daytime sleepiness from baseline to 4-month follow-up when compared with the placebo device; Epworth score >10: 53% at baseline to 24% at follow-up for the oral appliance group vs 54% at baseline to 40% at follow-up for the placebo device group, P = .11;median (IQR) for Karolinska score Ն7/wk: 10 (8 to 14) at baseline to 7 (4 to 9) at follow-up for the oral appliance group vs 12 (6 to 15) at baseline to 8 (5 to 12) at follow-up for the placebo device group, P = .11;mean between-group difference in OSLER test, -2.4 min (95% CI, -6.3 to 1.4).The mean between-group difference for the total FOSQ score was insignificant (-1.2 [95% CI, -2.5 to 0.1]).No domain of the SF-36 differed significantly between the groups.The AHI was below 5 in 49% of patients using the active appliance and in 11% using placebo, with an odds ratio of 7.8 (95% CI, 2.6-23.5)and a number needed to treat of 3. Snoring (P < .001)and symptoms of restless legs (P = .02)were less frequent when using the oral appliance vs placebo, but this did not apply to headache or insomnia.CONCLUSIONS AND RELEVANCE A custom-made, adjustable oral appliance reduces obstructive sleep apnea, snoring, and possibly restless legs without effects on daytime sleepiness and quality of life among patients with daytime sleepiness and snoring or mild to moderate sleep apnea.
Low Levels of Intraplatelet cGMP in IDDM
Authors: Jose A Amado, Eduardo Salas, Manuel A Botana, Juan J Poveda, Jose R Berrazueta
Journal: Diabetes Care (1993)

OBJECTIVE To determine the levels of intraplatelet cGMP, an index of activity of the antiaggregatory nitric oxide pathway, in IDDM patients. RESEARCH DESIGN AND METHODS We measured intraplatelet and plasmatic cGMP levels in 22 IDDM patients and 22 age- and sex-matched control subjects. RESULTS Intraplatelet cGMP levels decreased in the IDDM patients (0.32 ±; 0.16 pmol/109 platelets) when compared with the control group (0.52 ±; 0.32 pmol/109 platelets), P = 0.032. Plasmatic cGMP levels were not significantly different between groups. Intraplatelet cGMP levels correlated negatively with the duration of the disease (r = −0.43, P &amp;lt; 0.05). CONCLUSIONS IDDM patients have lower levels of intraplatelet cGMP, which may be responsible in part for their platelet hyperactivity.
Mechanisms of Defibrillation
Authors: Derek J. Dosdall, Vladimir G. Fast, Raymond E. Ideker
Journal: Annual Review of Biomedical Engineering (2010)

Electrical shock has been the one effective treatment for ventricular fibrillation for several decades. With the advancement of electrical and optical mapping techniques, histology, and computer modeling, the mechanisms responsible for defibrillation are now coming to light. In this review, we discuss recent work that demonstrates the various mechanisms responsible for defibrillation. On the cellular level, membrane depolarization and electroporation affect defibrillation outcome. Cell bundles and collagenous septae are secondary sources and cause virtual electrodes at sites far from shocking electrodes. On the whole-heart level, shock field gradient and critical points determine whether a shock is successful or whether reentry causes initiation and continuation of fibrillation.
The Relation of Psychological Stress to Onset of Medical Illness
Authors: M W Hurst, C D Jenkins, R M Rose
Journal: Annual Review of Medicine (1976)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Hypercapnic acidosis attenuates pulmonary epithelial wound repair by an NF- B dependent mechanism
Authors: D O'Toole, P Hassett, M Contreras, B D Higgins, S T W McKeown, D F McAuley, T O'Brien, J G Laffey
Journal: Thorax (2009)

<h3>Background:</h3> Hypercapnic acidosis exerts protective effects in acute lung injury but may also slow cellular repair. These effects may be mediated via inhibition of nuclear factor-κB (NF-κB), a pivotal transcriptional regulator in inflammation and repair. <h3>Objectives:</h3> To determine the effects of hypercapnic acidosis in pulmonary epithelial wound repair, to elucidate the role of NF-κB and to examine the mechanisms by which these effects are mediated. <h3>Methods:</h3> Confluent small airway epithelial cell, human bronchial epithelial cell and type II alveolar A549 cell monolayers were subjected to wound injury under conditions of hypercapnic acidosis (pH 7.0, carbon dioxide tension (Pco<sub>2</sub>) 11 kPa) or normocapnia (pH 7.37, Pco<sub>2</sub> 5.5 kPa) and the rate of healing determined. Subsequent experiments investigated the role of hypercapnia versus acidosis and elucidated the role of NF-κB and mitogen-activated protein kinases. The roles of cellular mitosis versus migration and of matrix metalloproteinases in mediating these effects were then determined. <h3>Results:</h3> Hypercapnic acidosis reduced wound closure (mean (SD) 33 (6.3)% vs 64 (5.9)%, p&lt;0.01) and reduced activation of NF-κB compared with normocapnia. Buffering of the acidosis did not alter this inhibitory effect. Prior inhibition of NF-κB activation occluded the effect of hypercapnic acidosis. Inhibition of ERK, JNK and P38 did not modulate wound healing. Hypercapnic acidosis reduced epithelial cell migration but did not alter mitosis, and reduced matrix metalloproteinase-1 while increasing concentrations of tissue inhibitor of metalloproteinase-2. <h3>Conclusions:</h3> Hypercapnic acidosis inhibits pulmonary epithelial wound healing by reducing cell migration via an NF-κB dependent mechanism that may involve alterations in matrix metalloproteinase activity.
Identification of ten loci associated with height highlights new biological pathways in human growth
Authors: Guillaume Lettre, Anne U Jackson, Christian Gieger, Fredrick R Schumacher, Sonja I Berndt, Serena Sanna, Susana Eyheramendy, Benjamin F Voight, Johannah L Butler, Candace Guiducci, Thomas Illig, Rachel Hackett, Iris M Heid, Kevin B Jacobs, Valeriya Lyssenko, Manuela Uda, Michael Boehnke, Stephen J Chanock, Leif C Groop, Frank B Hu, Bo Isomaa, Peter Kraft, Leena Peltonen, Veikko Salomaa, David Schlessinger, David J Hunter, Richard B Hayes, Gonçalo R Abecasis, H-Erich Wichmann, Karen L Mohlke, Joel N Hirschhorn
Journal: Nature Genetics (2008)
Priorities for the Treatment of Latent Tuberculosis Infection in the United States
Authors: C. Robert Horsburgh
Journal: New England Journal of Medicine (2004)

The prevention of active tuberculosis through the treatment of latent tuberculosis infection is a major element of the national strategy for eliminating tuberculosis in the United States. Targeted treatment for persons who are at the highest risk for reactivation tuberculosis will be needed to achieve this goal. A more precise assessment of the lifetime risk of reactivation tuberculosis, usually estimated at 5 to 10 percent, could help to identify patients who are at the highest risk and motivate them to complete treatment. Currently, the rate of completion of treatment is low.Published reports were reviewed to obtain estimates of the risk of tuberculosis among persons with a positive tuberculin skin test. Using these data, I constructed a model to estimate the lifetime risk of tuberculosis among persons with specific medical conditions.The lifetime risk of reactivation tuberculosis is 20 percent or more among most persons with induration of 10 mm or more on a tuberculin skin test and either human immunodeficiency virus infection or evidence of old, healed tuberculosis. The lifetime risk is 10 to 20 percent among persons with recent conversion of a tuberculin skin test and among most persons younger than 35 years of age who are receiving infliximab therapy and have induration of 15 mm or more on a tuberculin skin test. The risk is also 10 to 20 percent among children five years of age or younger who have induration of 10 mm or more on a tuberculin skin test.Persons with these characteristics should be targeted for intensive efforts to ensure full treatment of latent tuberculosis. Improved rates of completion of treatment among such persons could help to eliminate tuberculosis in the United States.
STUDIES ON EXPERIMENTAL HYPERTENSION
Authors: Harry Goldblatt, James Lynch, Ramon F. Hanzal, Ward W. Summerville
Journal: The Journal of Experimental Medicine (1934)

These experiments indicate that, in dogs at least, ischemia localized to the kidneys is a sufficient condition for the production of persistently elevated systolic blood pressure. When the constriction of both main renal arteries is made only moderately severe in the beginning, the elevation of systolic blood pressure is unaccompanied by signs of materially decreased renal function. In this respect the hypertension in these animals resembles the hypertension which is associated with so called benign nephrosclerosis in man. Subsequent increase of the constriction of the main renal arteries does not materially damage renal function, probably because of adequate development of accessory circulation. More delicate methods for detecting a change may yet prove that some damage does occur. Almost complete constriction of both main renal arteries, from the beginning, results in great elevation of systolic blood pressure which is accompanied by severe disturbance of renal function and uremia. This resembles the type of hypertension which is associated with so called malignant nephrosclerosis, in the sense of Fahr (17). In several of the animals with persistent elevation of systolic blood pressure, anatomical changes were observed in the glomeruli, vessels and parenchyma of the kidneys which are most probably directly referable to the ischemia. It is hoped that these investigations will afford a means of studying the pathogenesis of hypertension that is associated with renal vascular disease.
Impact of surgery on survival in palliative patients with metastatic colorectal cancer after first line treatment with weekly 24-hour infusion of high-dose 5-fluorouraeil and folinic acid
Authors: A. Wein, C. Riedel, F. Köckerling, P. Martus, U. Baum, W.M. Brueckl, T. Reck, R. Ott, J. Hänsler, T. Bernatik, D. Becker, T. Schneider, W. Hohenberger, E.G. Hahn
Journal: Annals of Oncology (2001)
Can We Identify Predictive Biomarkers for Antiangiogenic Therapy of Cancer Using Mathematical Modeling?
Authors: Dan G. Duda, Lance L. Munn, Rakesh K. Jain
Journal: JNCI Journal of the National Cancer Institute (2013)

Angiogenesis (the term referring generically to new blood vessel formation) is a hallmark of all solid tumors (1), and vascular endothelial growth factor (VEGF) is the most prevalent and potent angiogenic growth factor in these tumors (2,3).For this reason, there have been
Levels of the human hepatocyte growth factor in serum of patients with various liver diseases determined by an enzyme-linked immunosorbent assay
Authors: Hirohito Tsubouchi, Yoshiyuki Niitani, Shuichi Hirono, Hiroyuki Nakayama, Eiichi Gohda, Naokatu Arakaki, Osami Sakiyama, Kozo Takahashi, Masayoshi Kimoto, Shuichi Kawakami, Minami Setoguchi, Tetsuya Tachikawa, Sadahito Shin, Terukatsu Arima, Yasushi Daikuhara
Journal: Hepatology (1991)

We have found a hepatotrophic factor in plasma or sera of patients with fulminant hepatic failure and have purified human hepatocyte growth factor from plasma of these patients. In this study we developed an enzyme-linked immunosorbent assay with high specificity and sensitivity for human hepatocyte growth factor in human serum. This assay for serum human hepatocyte growth factor is a sandwich method consisting of three steps. The standard curve for human hepatocyte growth factor appeared to be linear in the range of 0.20 to 12.50 ng purified human hepatocyte growth factor/ml (2.35 to 147 pmol/L). The assay took about 4 hr. Serum human hepatocyte growth factor values in patients with fulminant hepatic failure measured by enzyme-linked immunosorbent assay showed a strong positive correlation with that by bioassay using rat hepatocytes in primary culture. The mean value of serum human hepatocyte growth factor for 30 normal subjects was 0.24 +/- 0.12 (S.D.) ng/ml; that for 23 patients with fulminant hepatic failure was 8.06 +/- 1.76 (S.E.M.) ng/ml- greater than 30 times greater than the mean value for normal subjects. Serum human hepatocyte growth factor levels in patients with acute hepatitis, chronic hepatitis and cirrhosis were found to be slightly higher than those in normal subjects, but only the increase in serum human hepatocyte growth factor of acute hepatitis patients was statistically significant. The enzyme-linked immunosorbent assay for serum human hepatocyte growth factor should prove useful for serum human hepatocyte growth factor level measurement in patients with various liver diseases.
The Double-Edged Sword of Autophagy Modulation in Cancer
Authors: Eileen White, Robert S. DiPaola
Journal: Clinical Cancer Research (2009)

Abstract Macroautophagy (autophagy) is a lysosomal degradation pathway for the breakdown of intracellular proteins and organelles. Although constitutive autophagy is a homeostatic mechanism for intracellular recycling and metabolic regulation, autophagy is also stress responsive, in which it is important for the removal of damaged proteins and organelles. Autophagy thereby confers stress tolerance, limits damage, and sustains viability under adverse conditions. Autophagy is a tumor-suppression mechanism, yet it enables tumor cell survival in stress. Reconciling how loss of a prosurvival function can promote tumorigenesis, emerging evidence suggests that preservation of cellular fitness by autophagy may be key to tumor suppression. As autophagy is such a fundamental process, establishing how the functional status of autophagy influences tumorigenesis and treatment response is important. This is especially critical as many current cancer therapeutics activate autophagy. Therefore, efforts to understand and modulate the autophagy pathway will provide new approaches to cancer therapy and prevention. (Clin Cancer Res 2009;15(17):5308–16)
Temporo-mandibular joint disease in ankylosing spondylitis.
Authors: C Davidson, J A Wojtulewski, P A Bacon, D Winstock
Journal: Annals of the Rheumatic Diseases (1975)

The occurrence of temporo-mandibular joint (TMJ) disease in ankylosing spondylitis is not widely recognized and its incidence is disputed. Seventy-nine patients attending two routine rheumatology clinics were therefore examined by dental surgeon and nine (11-5 per cent) were considered to have specific TMJ involvement. These patients were older than the remainder, and had more extensive spinal and peripheral joint disease. Symptoms were mild and the predominant clinical feature was restricted mouth opening, which could present considerable difficulties during emergency anaesthesia. Bilateral condylectomy was undertaken in one patient with some benefit.
Mutations in mRNA export mediator GLE1 result in a fetal motoneuron disease
Authors: Heidi O Nousiainen, Marjo Kestilä, Niklas Pakkasjärvi, Heli Honkala, Satu Kuure, Jonna Tallila, Katri Vuopala, Jaakko Ignatius, Riitta Herva, Leena Peltonen
Journal: Nature Genetics (2008)
New Considerations in the Treatment of Sickle Cell Disease
Authors: W. Reed, E. P. Vichinsky
Journal: Annual Review of Medicine (1998)

The familial pattern of recurring pain and early death seen so often among those affected by sickle cell disease has been long recognized within African cultures, though its first clear description in Western medical literature did not appear until 1910 ( 1 ). Although most common in persons of African ancestry, the mutation giving rise to the sickle gene arose independently in several locations where malaria was prevalent ( 2 ), traveled with migrating populations, and is now widely distributed among regions and ethnic groups. Recognizing the qualitative abnormality of sickle hemoglobin as a prototype, Pauling &amp; Castle established the notion of a molecular disease ( 3 ). Ironically, while the biochemistry and molecular biology of sickle cell disease has been intensively investigated, research into patient care has been limited in scope until recently. Prospective study of large patient groups diagnosed at birth is now providing insight into the disease's natural history and facilitating investigational treatments. Newborn diagnosis, combined with study of new drugs, cytokines, surgical procedures, and a more proactive utilization of transfusion is leading to greatly improved care and survival. Life expectancy is increasing ( 4 ) but adults are experiencing more complications of chronic organ dysfunction. A few patients have been cured by stem-cell transplantation, but difficult problems will continue to limit its application.
Suppressors of Cytokine Signaling 2 and 3 Diametrically Control Macrophage Polarization
Authors: Shaun Spence, Amy Fitzsimons, Caroline R. Boyd, Julia Kessler, Denise Fitzgerald, Joanne Elliott, Joan Ní Gabhann, Siobhan Smith, Antonio Sica, Emily Hams, Sean P. Saunders, Caroline A. Jefferies, Padraic G. Fallon, Danny F. McAuley, Adrien Kissenpfennig, James A. Johnston
Journal: Immunity (2013)