tbuckley/cabot-search huggingface dataset:
Lifetime Risk for Developing Congestive Heart Failure
Authors: Donald M. Lloyd-Jones, Martin G. Larson, Eric P. Leip, Alexa Beiser, Ralph B. D’Agostino, William B. Kannel, Joanne M. Murabito, Ramachandran S. Vasan, Emelia J. Benjamin, Daniel Levy
Journal: Circulation (2002)

Background— Congestive heart failure (CHF) is an increasing public health problem. Methods and Results— Among Framingham Heart Study subjects who were free of CHF at baseline, we determined the lifetime risk for developing overt CHF at selected index ages. We followed 3757 men and 4472 women from 1971 to 1996 for 124 262 person-years; 583 subjects developed CHF and 2002 died without prior CHF. At age 40 years, the lifetime risk for CHF was 21.0% (95% CI 18.7% to 23.2%) for men and 20.3% (95% CI 18.2% to 22.5%) for women. Remaining lifetime risk did not change with advancing index age because of rapidly increasing CHF incidence rates. At age 80 years, the lifetime risk was 20.2% (95% CI 16.1% to 24.2%) for men and 19.3% (95% CI 16.5% to 22.2%) for women. Lifetime risk for CHF doubled for subjects with blood pressure ≥160/100 versus &lt;140/90 mm Hg. In a secondary analysis, we only considered those who developed CHF without an antecedent myocardial infarction; at age 40 years, the lifetime risk for CHF was 11.4% (95% CI 9.6% to 13.2%) for men and 15.4% (95% CI 13.5% to 17.3%) for women. Conclusions— When established clinical criteria are used to define overt CHF, the lifetime risk for CHF is 1 in 5 for both men and women. For CHF occurring in the absence of myocardial infarction, the lifetime risk is 1 in 9 for men and 1 in 6 for women, which highlights the risk of CHF that is largely attributable to hypertension. These results should assist in predicting the population burden of CHF and placing greater emphasis on prevention of CHF through hypertension control and prevention of myocardial infarction.
Proteolysis in Neuropeptide Processing and Other Neural Functions
Authors: Y. Peng Loh, Michael J. Brownstein, Harold Gainer
Journal: Annual Review of Neuroscience (1984)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Epidemiology and Outcomes From Out-of-Hospital Cardiac Arrest in Children
Authors: Dianne L. Atkins, Siobhan Everson-Stewart, Gena K. Sears, Mohamud Daya, Martin H. Osmond, Craig R. Warden, Robert A. Berg
Journal: Circulation (2009)

Background— Population-based data for pediatric cardiac arrest are scant and largely from urban areas. The Resuscitation Outcomes Consortium (ROC) Epistry–Cardiac Arrest is a population-based emergency medical services registry of out-of-hospital nontraumatic cardiac arrest (OHCA). This study examined age-stratified incidence and outcomes of pediatric OHCA. We hypothesized that survival to hospital discharge is less frequent from pediatric OHCA than adult OHCA. Methods and Results— This prospective population-based cohort study in 11 US and Canadian ROC sites included persons &lt;20 years of age who received cardiopulmonary resuscitation or defibrillation by emergency medical service providers and/or received bystander automatic external defibrillator shock or who were pulseless but received no resuscitation by emergency medical services between December 2005 and March 2007. Patients were stratified a priori into 3 age groups: &lt;1 year (infants; n=277), 1 to 11 years (children; n=154), and 12 to 19 years (adolescents; n=193). The incidence of pediatric OHCA was 8.04 per 100 000 person-years (72.71 in infants, 3.73 in children, and 6.37 in adolescents) versus 126.52 per 100 000 person-years for adults. Survival for all pediatric OHCA was 6.4% (3.3% for infants, 9.1% for children, and 8.9% for adolescents) versus 4.5% for adults ( P =0.03). Unadjusted odds ratio for pediatric survival to discharge compared with adults was 0.71 (95% confidence interval, 0.37 to 1.39) for infants, 2.11 (95% confidence interval, 1.21 to 3.66) for children, and 2.04 (95% confidence interval, 1.24 to 3.38) for adolescents. Conclusions— This study demonstrates that the incidence of OHCA in infants approaches that observed in adults but is lower among children and adolescents. Survival to discharge was more common among children and adolescents than infants or adults.
Connexin45 Cannot Replace the Function of Connexin40 in Conducting Endothelium-Dependent Dilations Along Arterioles
Authors: Stephanie E. Wölfle, Volker J. Schmidt, Bernd Hoepfl, Andreas Gebert, Sébastien Alcoléa, Daniel Gros, Cor de Wit
Journal: Circulation Research (2007)

Intercellular communication through gap junctions coordinates vascular tone by the conduction of vasomotor responses along the vessel wall. Gap junctions in arterioles are composed of different connexins (Cxs) (Cx40, Cx37, Cx45, Cx43), but it is unknown whether Cxs are interchangeable. We used mice with a targeted replacement of Cx40 by Cx45 (Cx40KI45) to explore whether Cx45 can functionally replace Cx40 in arterioles. Arterioles were locally stimulated using acetylcholine, bradykinin, adenosine, and K(+) in the cremaster of Cx40KI45, Cx40-deficient (Cx40ko), and wild-type mice, and diameter changes were assessed by intravital microscopy. Additionally, arterial pressure was measured by telemetry and Cx expression verified by immunofluorescence. Acetylcholine initiated a local dilation of a similar amplitude in all genotypes ( approximately 50%), which was rapidly conducted to upstream sites (1200 mum distance) without attenuation in wild type. In marked contrast, the remote dilation was significantly reduced in Cx40ko (25+/-3%) and Cx40KI45 (24+/-2%). Likewise, dilations initiated by bradykinin application were conducted without attenuation up to 1200 mum in wild type but not in Cx40ko and Cx40KI45. Adenosine-induced dilations and K(+)-induced constrictions were conducted similarly with decaying amplitude in all genotypes. Arterial pressure was strongly elevated in Cx40ko (161+/-1 versus 116+/-2 mm Hg) but only moderately in Cx40KI45 (133+/-8 mm Hg). This demonstrates that Cx40 function is critical for the conduction of acetylcholine and bradykinin dilations and cannot be substituted by Cx45. Therefore, unique properties of Cx40 are required for endothelial signal conduction, whereas nonspecific restoration of communication maintains additional functions related to blood pressure control.
Thoracic duct and hepatic lymph in idiopathic portal hypertension
Authors: A. K. S. Samanta, V. K. Saini, P. N. Chhuttani, B. S. Patra, S. Vashista, D. V. Datta
Journal: Gut (1974)

Lymph dynamics in idiopathic portal hypertension has been studied in two phases. In the first phase thoracic duct lymph transport was studied in 11 patients with idiopathic portal hypertension by cannulating the duct. This revealed altered lymph transport in the form of a distended thoracic duct, raised pressure in the duct, and haemorrhagic lymph with an increased flow rate. The lymph flow rate was analysed in relation to various hepatic haemodynamic and biochemical parameters. In the second phase of the study hepatic lymphatics were studied by percutaneous hepatography in 16 patients with idiopathic portal hypertension. By this technique hepatic lymphatics were opacified in patients with idiopathic portal hypertension and cirrhosis with equal frequency. The significance of this finding in relation to the altered hepatic haemodynamics and thoracic duct lymph transport is discussed.
Neurogenic Orthostatic Hypotension
Authors: Roy Freeman
Journal: New England Journal of Medicine (2008)

A 65-year-old man reports a 6-month history of dizziness, light-headedness, weakness, and fatigue while upright. He takes no medication and has no personal or family history of neurologic disease. On physical examination, his supine blood pressure is 160/100 mm Hg, with a heart rate of 72 beats per minute; on standing, his blood pressure falls to 70/40 mm Hg, with no change in heart rate. The results of the remainder of the examination, including neurologic examination, are normal. How should he be evaluated and treated?
Effects of Increasing Carboxyhemoglobin on the Single Breath Carbon Monoxide Diffusing Capacity
Authors: Brian L. Graham, Joseph T. Mink, David J. Cotton
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Although carboxyhemoglobin (COHb) is often increased in smokers, American Thoracic Society recommendations for adjusting the single breath carbon monoxide (CO) diffusing capacity (DlCOSB) for COHb remain optional. Using a previously described 3-equation technique, we measured DlCOSB and an index of diffusion inhomogeneity (DI) in 10 healthy, nonsmoking subjects who performed DlCOSB maneuvers both before and after increasing COHb. CO backpressure (FaCO) was measured from the exhaled gas of a standardized deep breath of room air that immediately preceded each DlCOSB and was validated by measurement of FaCO from an identical “sham” maneuver without inhaling CO. Without adjustments for FaCO or COHb, DlCOSB decreased with increasing COHb. This effect persisted when DlCOSB was adjusted only for FaCO, but it was eliminated with further adjustment for the anemia effect of increasing COHb. The anemia adjustment was proportional to the fractional COHb. DI, adjusted for FaCO, was unaffected by increasing COHb. We conclude that DlCOSB must be adjusted for both the buildup of CO backpressure and the anemia effect of increasing COHb. Adequate corrections of DlCOSB can be implemented using FaCO measured during a standardized deep breath immediately preceding the DlCOSB maneuver. Current American Thoracic Society recommendations for DlCOSB standardization do not adequately compensate for COHb.
Real-Time Optical Mapping of Neuronal Activity: From Single Growth Cones to the Intact Mammalian Brain
Authors: A Grinvald
Journal: Annual Review of Neuroscience (1985)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
MHC-Restricted Phosphopeptides from Insulin Receptor Substrate-2 and CDC25b Offer Broad-Based Immunotherapeutic Agents for Cancer
Authors: Angela L. Zarling, Rebecca C. Obeng, A. Nicole Desch, Joel Pinczewski, Kara L. Cummings, Donna H. Deacon, Mark Conaway, Craig L. Slingluff, Victor H. Engelhard
Journal: Cancer Research (2014)

Abstract Cancer cells display novel phosphopeptides in association with MHC class I and II molecules. In this study, we evaluated two HLA-A2–restricted phosphopeptides derived from the insulin receptor substrate (IRS)-2 and the cell-cycle regulator CDC25b. These proteins are both broadly expressed in multiple malignancies and linked to cancer cell survival. Two phosphopeptides, termed pIRS-21097–1105 and pCDC25b38–46, served as targets of strong and specific CD8 T-cell memory responses in normal human donors. We cloned T-cell receptor (TCR) cDNAs from murine CD8 T-cell lines specific for either pIRS-21097–1105 or pCDC25b38–46. Expression of these TCRs in human CD8 T cells imparted high-avidity phosphopeptide-specific recognition and cytotoxic and cytokine-secreting effector activities. Using these cells, we found that endogenously processed pIRS-21097–1105 was presented on HLA-A2+ melanomas and breast, ovarian, and colorectal carcinomas. Presentation was correlated with the level of the Ser1100-phosphorylated IRS-2 protein in metastatic melanoma tissues. The highest expression of this protein was evident on dividing malignant cells. Presentation of endogenously processed pCDC25b38–46 was narrower, but still evident on HLA-A2+ melanoma, breast carcinoma, and lymphoblastoid cells. Notably, pIRS-21097–1105–specific and pCDC25b38–46–specific TCR-expressing human CD8 T cells markedly slowed tumor outgrowth in vivo. Our results define two new antigens that may be developed as immunotherapeutic agents for a broad range of HLA-A2+ cancers. Cancer Res; 74(23); 6784–95. ©2014 AACR.
Communications Satellites in Health Education and Health Care Provision
Authors: M. Roy Schwarz
Journal: JAMA (1983)

Since 1971, the University of Washington School of Medicine, Seattle, has operated a four-state, medical education program covering Washington, Alaska, Montana, and Idaho. This WAMI Program involves four universities without medical schools and 15 communities. To maintain this program, communication between the sites is imperative and mandates travel. The experiments described in this article were undertaken to determine whether full-duplex audio and color-video interactions via communications satellites could replace the travel requirements of the WAMI Program. Experiments involving the administration of the program, the presentation of the undergraduate medical education curriculum, the provision of health services, and the formation of public policies were conducted. The results suggest that satellite communication has broad applicability in medical education and health care provision.
Increased levels of serum glucose-dependent insulinotropic polypeptide as a novel risk factor for human colorectal adenoma
Authors: Yu Sasaki, Hiroaki Takeda, Takeshi Sato, Tomohiko Orii, Shoichiro Fujishima, Ko Nagino, Shoichi Nishise, Hideki Saito, Yasuhisa Tanaka, Sumio Kawata
Journal: Metabolism (2011)
Intracardiac Echocardiography During Interventional and Electrophysiological Cardiac Catheterization
Authors: Ziyad M. Hijazi, Kalyanam Shivkumar, David J. Sahn
Journal: Circulation (2009)

ust as the growing interest and proliferation of methods to reperfuse the coronary artery system with transcatheter techniques spurred interest and utilization of intracoronary ultrasound (at least in academic centers), so the growth of anatomic cardiac transcatheter interventions and increasingly aggressive transcatheter ablative strategies to treat cardiac arrhythmias has stimulated the use of and development of new methods for intracardiac echocardiography (ICE).This article will review the development, present state of the art, and applications of ICE as well as project its evolution from 2-dimensional to 3-dimensional/4-dimensional visualization and integration of therapy with imaging in the near future.
Time to peak tidal expiratory flow and the neuromuscular control of expiration
Authors: CK van der Ent, CP van der Grinten, NE Meessen, SC Luijendijk, PG Mulder, JM Bogaard
Journal: European Respiratory Journal (1998)

The ratio of the time needed to reach peak tidal expiratory flow (tPTEF) and the duration of expiration (tE) is used to detect airflow obstruction in young children. tPTEF is decreased in patients with asthma, but knowledge about the physiological determinants of this parameter is scarce. This study examined the relationship between tPTEF and postinspiratory activities of inspiratory muscles and evaluated the effects of changing sensory information from the lung. Airflow patterns and electromyographic (EMG) activity of inspiratory muscles were recorded in seven spontaneously breathing, anaesthetized cats. The trachea was cannulated and, as a result, the larynx and upper airways were bypassed. Changes in postinspiratory muscle activity were induced by changing afferent sensory nerve information (by cooling the vagus nerves, by administration of histamine and by additional application of continuous positive airway pressure (CPAP)). Durations of postinspiratory activities of the diaphragm and intercostal muscles (characterized by their time constants tau diaphr and tau interc) correlated strongly with tPTEF (r=0.85 and 0.77, respectively). Tau diaphr, tau interc and tPTEF were significantly increased during cooling of the vagus nerves (4-8 degrees C) compared with values at 22 and 37 degrees C (p<0.05). Conversely, administration of histamine and CPAP caused significant decreases in tau diaphr, tau interc and tPTEF, which were absent during cooling of the vagus nerves. In conclusion, the time needed to reach peak tidal expiratory flow is highly influenced by the activities of inspiratory muscles during the early phase of expiration which, in turn, depend on the activities of vagal receptors in the lung.
Myocardial Protection During Cardiac Surgery
Authors: B A Reitz
Journal: Annual Review of Medicine (1982)

In recent years there have been important advances in understanding causes of myocardial injury during cardiac surgery, in the introduction of mea­ sures to minimize this injury, and in improving the conditions for perform­ ing the surgery itself. Coronary artery surgery has been a major stimulus for this advance, since the flaccid and still myocardium provided by cold cardioplegic arrest greatly facilitates the performance of small-vessel anas­ tomoses. Since 1970, surgery for coronary artery disease has grown from several thousand procedures per year to more than 100,000 operations in 1980 (1). The improvement in operative technique for coronary artery bypass and the very low risk now associated with such procedures is in large part due to improved myocardial preservation. During the first decade of open heart surgery, which began in 1955, postoperative low cardiac output was usually believed to be secondary to the preoperative condition of the patient. However, by 1970 three observa­ tions were accepted: (a) inadequate myocardial protection during surgery was implicated as a major cause of postoperative low cardiac output and death (2); (b) inadequate myocardial protection was associated with the late development of myopathy, even after successful value replacement or repair of congenital defects (3, 4); and (c) a rare and extreme form of intraopera­ tive damage, stoneheart, was recognized to be secondary to poor intraop­ erative myocardial protection of severely hypertrophied hearts (5). These observations clearly reflected the need for substantial improvement in myo­ cardial protection in use at that time.
Urinary LTE<sub>4</sub> excretion in antigen‐provoked asthmatic patients treated with the inhaled LTD<sub>4</sub> antagonist, L‐648,051
Authors: J. B. Rasmussen, L.‐O. Eriksson, P. Tagari, D.J. Margolskee, Y. Girard, K.‐E. Andersson
Journal: Allergy (1992)

Leukotriene (LT) E 4 represents the major LT metabolite in man, and its urinary excretion can be used as an indirect marker of systemic LTC 4 and/or LTD 4 synthesis and release. In the present study LTE 4 excretion was monitored for 24 h in 12 atopic patients with mild asthma undergoing antigen bronchoprovocation as part of a double‐blind, placebo‐controlled, two‐period cross‐over study of the aerosol‐delivered LTD 4 antagonist, L‐648,051. Urinary LTE 4 excretion was also studied separately in six of the patients after inhaling only diluent. Urine was sampled before, and serially after antigen challenge, at intervals corresponding to the immediate (0–3 h postchallenge) and late (3–6, 6–12, 12–24 h postchallenge) asthmatic reactions. LTE 4 was determined by reversed‐phase HPLC and radioimmunoassay. Forced expiratory volume in 1 s (FEV), was recorded serially through 8 h after inhalation of antigen and diluent. Compared to base‐line measurements, antigen bronchoprovocation induced significant increases in mean LTE 4 excretion rates 0–3 h postchallenge (i.e. during the immediate asthmatic response) after treatment with both placebo ( P &lt;0.01) and L‐648,051 ( P &lt;0.05). These mean LTE 4 excretion rates in the immediate phase were also significantly higher than the mean rates in the late phase (3–6 h and beyond); the excretion rates of LTE 4 at these later time intervals were similar to base‐line values. After inhalation of diluent, the LTE 4 excretion rates in the intervals 0–3, 3–6, 6–12 and 12–24 h were unchanged from base‐line values. Administration of L‐648,051 caused a modest but significant inhibition of the immediate airway response, whereas the late response was not significantly reduced. The LTE 4 excretion rates did not correlate with the maximum percent falls in FEV, after antigen challenge in the immediate or the late phases. These results suggest that peptidoleukotrienes are released by inhaled antigen in atopic asthmatic patients, and suggest a direct involvement of leukotrienes in the immediate airway response.
Pharmacokinetics and Pharmacodynamics of Therapeutic Doses of Basal Insulins NPH, Glargine, and Detemir After 1 Week of Daily Administration at Bedtime in Type 2 Diabetic Subjects
Authors: Paola Lucidi, Francesca Porcellati, Paolo Rossetti, Paola Candeloro, Patrizia Cioli, Stefania Marzotti, Anna Marinelli Andreoli, Raffaela Fede, Geremia B. Bolli, Carmine G. Fanelli
Journal: Diabetes Care (2011)

To compare the pharmacokinetics and pharmacodynamics of NPH, glargine, and detemir insulins in type 2 diabetic subjects.This study used a single-blind, three-way, cross-over design. A total of 18 type 2 diabetic subjects underwent a euglycemic clamp for 32 h after a subcutaneous injection of 0.4 units/kg at 2200 h of either NPH, glargine, or detemir after 1 week of bedtime treatment with each insulin.The glucose infusion rate area under the curve(0-32 h) was greater for glargine than for detemir and NPH (1,538 ± 688; 1,081 ± 785; and 1,170 ± 703 mg/kg, respectively; P < 0.05). Glargine suppressed endogenous glucose production more than detemir (P < 0.05) and similarly to NPH (P = 0.16). Glucagon, C-peptide, free fatty acids, and β-hydroxy-butyrate were more suppressed with glargine than detemir. All 18 subjects completed the glargine study, but two subjects on NPH and three on detemir interrupted the study because of plasma glucose >150 mg/dL.Compared with NPH and detemir, glargine provided greater metabolic activity and superior glucose control for up to 32 h.
Biomarkers Predicting Recurrence and Progression of Ductal Carcinoma In Situ Treated by Lumpectomy Alone
Authors: D. C. Allred
Journal: JNCI Journal of the National Cancer Institute (2010)

An interesting article by Kerlikowske et al. ( 1 ) in this issue of the Journal describes how certain biomarkers in ductal carcinoma in situ (DCIS) treated with lumpectomy alone may improve our ability to predict the risk of disease recurrence and progression to invasive breast cancer (IBC).Once DCIS is detected, this therapeutic setting reflects the natural history of any residual disease, and the likelihood of regrowth and progression largely determines the use of adjuvant therapy.The tumor samples used in this retrospective study were a casecontrol subset nested within a cohort of nearly 1200 patients who were diagnosed with DCIS between 1983 and 1994 and for whom long-term clinical follow-up data were available.In assembling samples from this cohort, the investigators have created a rare and valuable resource, and they have used it in previous enlightening studies of DCIS published in this Journal ( 2 ) and elsewhere ( 3 ).Cases of primary DCIS in the study population with available glass slides (n = 502) were comprehensively evaluated for standard histopathologic features, including tumor size, nuclear grade, and status of surgical margins.A subset of the reviewed cases with available paraffi n blocks (n = 329) were further evaluated by immunohistochemistry for expression of several biomarkers.Many of the biomarkers are well known in this setting, including the estrogen receptor (ER), progesterone receptor, p53, human epidermal growth factor receptor 2 (ERBB2, also known as HER2), and Ki67, whereas others are relatively novel, including p16 and cyclooxygenase-2 (COX-2).All of these factors, and available clinical characteristics, were evaluated individually for their univariate associations (hazard ratio [HR]) with recurrence of DCIS or progression to IBC, with a median follow-up of about 8 years.Larger tumor size, positive surgical margins, and higher nuclear grade were each associated with modestly increased risks for recurrent DCIS (HR = 1.4 to 3.6) and IBC (HR = 1.2 to 1.6), although the latter were not statistically