Robert L. Johnson

The purpose of this review is to assess the relationship between mood disorders and development, course, and associated morbidity and mortality of selected medical illnesses, review evidence for treatment, and determine needs in clinical practice and research.Data were culled from the 2002 Depression and Bipolar Support Alliance Conference proceedings and a literature review addressing prevalence, risk factors, diagnosis, and treatment. This review also considered the experience of primary and specialty care providers, policy analysts, and patient advocates. The review and recommendations reflect the expert opinion of the authors.Reviews of epidemiology and mechanistic studies were included, as were open-label and randomized, controlled trials on treatment of depression in patients with medical comorbidities. Data on study design, population, and results were extracted for review of evidence that includes tables of prevalence and pharmacological treatment. The effect of depression and bipolar disorder on selected medical comorbidities was assessed, and recommendations for practice, research, and policy were developed.A growing body of evidence suggests that biological mechanisms underlie a bidirectional link between mood disorders and many medical illnesses. In addition, there is evidence to suggest that mood disorders affect the course of medical illnesses. Further prospective studies are warranted.

The population-based association between low vitamin D status and increased cancer risk can be inconsistent, but it is now generally accepted. These relationships link low serum 25OHD (25-hydroxyvitamin D) levels to cancer, whereas cell-based studies show that the metabolite 1,25(OH)2D (1,25-dihydroxyvitamin D) is a biologically active metabolite that works through vitamin D receptor to regulate gene transcription. In the present review we discuss the literature relevant to the molecular events that may account for the beneficial impact of vitamin D on cancer prevention or treatment. These data show that although vitamin D-induced growth arrest and apoptosis of tumour cells or their non-neoplastic progenitors are plausible mechanisms, other chemoprotective mechanisms are also worthy of consideration. These alternative mechanisms include enhancing DNA repair, antioxidant protection and immunomodulation. In addition, other cell targets, such as the stromal cells, endothelial cells and cells of the immune system, may be regulated by 1,25(OH)2D and contribute to vitamin D-mediated cancer prevention.

Lymphokine-rich supernates from normal human peripheral blood mononuclear cells, stimulated by the mitogen phytohemagglutinin, have been shown to cause enhanced collagen accumulation by human embryonic lung fibroblasts (WI-38), as measured by hydroxyproline content of fibroblast monolayers, [14C] proline incorporation into soluble collagen and collagenase release of radioactivity in supernates and monolayers of cultures incubated with [14C] proline. This fibroblast-stimulating activity, demonstrable by suitable dilutions of the supernates, coexisted with a number of other lymphokine activities such as lymphotoxin, proliferation inhibitory factor, and cloning inhibitory factor, which tend to reduce the numbers of function of fibroblasts. The increased content of collagen appeared to be the product of selected surviving and responding fibroblasts. The factor causing this increased collagen accumulation was nondialyzable and stable at -70 degrees C. It represents the first described lymphoid cell-derived activity capable of enhancing collagen accumulation. Fibroblast-stimulating activity may be implicated in the abnormal fibrosis seen in association with chronic inflammation in a variety of disease states. It may have special relevance to progressive systemic sclerosis.

Adolescent pregnancy, HIV, and other sexually transmitted infections (STIs) are major public health problems in the U.S. Implementing group-based interventions that address the sexual behavior of adolescents may reduce the incidence of pregnancy, HIV, and other STIs in this group.Methods for conducting systematic reviews from the Guide to Community Preventive Services were used to synthesize scientific evidence on the effectiveness of two strategies for group-based behavioral interventions for adolescents: (1) comprehensive risk reduction and (2) abstinence education on preventing pregnancy, HIV, and other STIs. Effectiveness of these interventions was determined by reductions in sexual risk behaviors, pregnancy, HIV, and other STIs and increases in protective sexual behaviors. The literature search identified 6579 citations for comprehensive risk reduction and abstinence education. Of these, 66 studies of comprehensive risk reduction and 23 studies of abstinence education assessed the effects of group-based interventions that address the sexual behavior of adolescents, and were included in the respective reviews.Meta-analyses were conducted for each strategy on the seven key outcomes identified by the coordination team-current sexual activity; frequency of sexual activity; number of sex partners; frequency of unprotected sexual activity; use of protection (condoms and/or hormonal contraception); pregnancy; and STIs. The results of these meta-analyses for comprehensive risk reduction showed favorable effects for all of the outcomes reviewed. For abstinence education, the meta-analysis showed a small number of studies, with inconsistent findings across studies that varied by study design and follow-up time, leading to considerable uncertainty around effect estimates.Based on these findings, group-based comprehensive risk reduction was found to be an effective strategy to reduce adolescent pregnancy, HIV, and STIs. No conclusions could be drawn on the effectiveness of group-based abstinence education.

Universal, school-based programs, intended to prevent violent behavior, have been used at all grade levels from pre-kindergarten through high school. These programs may be targeted to schools in a high-risk area-defined by low socioeconomic status or high crime rate-and to selected grades as well. All children in those grades receive the programs in their own classrooms, not in special pull-out sessions. According to the criteria of the systematic review methods developed for the Guide to Community Preventive Services (Community Guide), there is strong evidence that universal, school-based programs decrease rates of violence among school-aged children and youth. Program effects were consistent at all grade levels. An independent, recently updated meta-analysis of school-based programs confirms and supplements the Community Guide findings.

Disturbances in acid-base balance are commonly met problems in clinical medicine and decisions about their treatment are of great importance in patients with cardiopulmonary problems, in whom acid-base disturbances may be especially critical.Similarly, cardiopulmonary function may be significantly compromised even in patients with no intrinsic heart or lung disease, in the face of acid-base disturbances.It is essential, therefore, to understand the physiological consequences of these disturbances on the cardiovascular and pulmonary system. Of major importance is the effect of acid-base disturbances on the delivery of to the various tissue cells of the body.In order to understand all the pathophysiological mechanisms involved it is necessary to review the effects of acid-base changes on the heart, the peripheral vessels, the lungs, and the diffusion of between air, blood, and tissues. The requirement for by the various tissue cells of the body is met by the combined cardiovascular and pulmonary systems, which function as a unit termed the oxygen transport system of the body.The movement of from the ambient air to the tissue cells involves ventilation, pulmonary perfusion, diffusion, oxygen-carrying capacity of hemoglobin, cardiac output (including cardiac muscle performance), systemic distribution of flow, and finally the delivery capacity of hemoglobin.It is important to understand the effects of changes in pH on each of these steps in the chain.

Pulmonary capillary blood flow (Qc) and apparent CO diffusing capacity (Dl) were calculated from the rates of disappearance of small alveolar concentrations of inspired acetylene and carbon monoxide during breath holding. Such measurements were performed simultaneously in four normal subjects at rest, during exercise and while performing Valsalva or Mueller maneuvers; they were also made at more than one alveolar oxygen tension so that true membrane diffusing capacity (Dm) and pulmonary capillary blood volume (Vc) could be calculated by the method of Roughton and Forster. Dl, Dm and Vc were closely correlated with Qc (r = 0.92, 0.71 and 0.92, respectively), indicating that both volume and effective surface of the pulmonary capillary bed changed along with corresponding directional changes in blood flow. During transients after starting or after stopping exercise, changes in Dl lagged slightly behind the associated changes in Qc; both parameters tended to reach steady values, however, after about 1 minute of steady exercise. The average time spent by red cells in the pulmonary capillaries at rest was estimated to be 0.79 second, falling to about 0.5 second at levels of exercise at which volume flow through the capillary bed was approximately tripled. Submitted on September 18, 1959

Despite its importance little is known of the hemodynamic abnormalities which accompany acute myocardial infarction in man.Aside from clinical observations, the measurement of venous pressure (1) and total blood volume (1, 2), few systematic studies have been carried out in clinical cases.The reason for this has been the impossibility of subjecting such acutely ill patients to diffi- cult or time-consuming technical procedures.However, recent studies (3, 4) indicated that the values for cardiac output obtained with the Hamil- ton dye injection method were not significantly dif- ferent from those obtained with the intravenous catheterization method using the Fick principle.It seemed probable, therefore, that the Hamilton dye method suitably modified could be used to de- termine cardiac output at the bedside in acutely ill patients.This report describes the changes ob- served using the dye injection method and other procedures in a series of cases with myocardial in- farction as compared to a group of normal sub- jects and hypertensive patients.METHODS Fourteen hemodynamic studies were carried out in 11 patients with acute myocardial infarction, eight determi-

<h3>Context</h3> Children from low-income and racial or ethnic minority populations in the U.S. are less likely to have a conventional source of medical care and more likely to develop chronic health problems than are more-affluent and non-Hispanic white children. They are more often chronically stressed, tired, and hungry, and more likely to have impaired vision and hearing—obstacles to lifetime educational achievement and predictors of adult morbidity and premature mortality. If school-based health centers (SBHCs) can overcome educational obstacles and increase receipt of needed medical services in disadvantaged populations, they can advance health equity. <h3>Evidence acquisition</h3> A systematic literature search was conducted for papers published through July 2014. Using Community Guide systematic review methods, reviewers identified, abstracted, and summarized available evidence of the effectiveness of SBHCs on educational and health-related outcomes. Analyses were conducted in 2014–2015. <h3>Evidence synthesis</h3> Most of the 46 studies included in the review evaluated onsite clinics serving urban, low-income, and racial or ethnic minority high school students. The presence and use of SBHCs were associated with improved educational (i.e., grade point average, grade promotion, suspension, and non-completion rates) and health-related outcomes (i.e., vaccination and other preventive services, asthma morbidity, emergency department use and hospital admissions, contraceptive use among females, prenatal care, birth weight, illegal substance use, and alcohol consumption). More services and more hours of availability were associated with greater reductions in emergency department overuse. <h3>Conclusions</h3> Because SBHCs improve educational and health-related outcomes in disadvantaged students, they can be effective in advancing health equity.

This article presents the results of a systematic review of the effectiveness and economic efficiency of individual-, group-, and community-level behavioral interventions intended to reduce the risk of acquiring sexually transmitted HIV in adult men who have sex with men (MSM). These results form the basis for recommendations by the Task Force on Community Preventive Services on the use of these interventions. Sexual risk behavior and condom use were the outcomes used to assess effectiveness. Intervention effectiveness on biological outcomes could not be assessed because too few studies of adequate quality have been published. The evidence found in our review shows that individual-level, group-level, and community-level HIV behavioral interventions are effective in reducing the odds of unprotected anal intercourse (range 27% to 43% decrease) and increasing the odds of condom use for the group-level approach (by 81%). The Task Force concluded that the findings are applicable to MSM aged 20 years or older, across a range of settings and populations, assuming that interventions are appropriately adapted to the needs and characteristics of the MSM population of interest. Based on findings from economic evaluation studies, the Task Force also concluded that group- and community-level HIV behavioral interventions for adult MSM are not only cost effective but also result in actual cost savings. Additional information about other effects, barriers to implementation, and research gaps is provided in this paper. The recommendations based on these systematic reviews are expected to serve the needs of researchers, planners, and other public health decision makers.

Children and adolescents in the U.S. and worldwide are commonly exposed to traumatic events, yet practitioners treating these young people to reduce subsequent psychological harm may not be aware of—or use—interventions based on the best available evidence. This systematic review evaluated interventions commonly used to reduce psychological harm among children and adolescents exposed to traumatic events. Guide to Community Preventive Services (Community Guide) criteria were used to assess study design and execution. Meta-analyses were conducted, stratifying by traumatic exposures.

Our purpose was to reexamine the relationship of the fall in cardiac output and blood pressure which occurs during positive end-expiratory pressure (PEEP) to changes in transmural right atrial and left atrial filling pressures. Closed-chest dogs, half with pulmonary edema, were studied during spontaneous breathing and inspiratory positive-pressure breathing (IPPB) with 0–15 cmH2O PEEP. Mean esophageal pressure accurately reflected changes in pericardial pressure and was used to estimate extracardiac pressure. We found that cardiac output fell approximately 50% and blood pressure fell 20% during 15 cmH2OPEEP in spite of well maintained transmural right atrial and left atrial (or pulmonary artery wedge) pressures suggesting a primary or reflex depression of atrial or ventricular function.

An animal model was developed to determine if blood flow to the respiratory muscles limits oxygen delivery and thus work output during inspiratory resistance. With incremental increases in the rate of work of breathing to 15 times the resting level, blood flow to the diaphragm rose exponentially 26-fold. Blood flow to other inspiratory and a few expiratory muscles increased to a much smaller extent, often only at the greater work loads. Cardiac output and blood pressure did not change. Arterial-venous oxygen content difference across the diaphragm became maximal at low work rates and thereafter all increases in oxygen delivery during higher work rates were accomplished by increments in blood flow. Oxygen consumption of the respiratory musculature calculated by blood flow times oxygen extraction increased exponentially with increasing work of breathing and was less than the increase in total body oxygen consumption at each work load. Hypoxemia and respiratory acidosis occurred when the animals inspired through the highest resistance; blood flow and oxygen consumption were even higher than that observed during previous resistances and there was no evidence of a shift to anaerobic metabolsim in blood lactate and pyruvate levels. Respiratory failure did not appear to be a consequence of insufficient blood flow in this model.

ARTICLESEarly cardiovascular adaptation to simulated zero gravityJ. V. Nixon, R. G. Murray, C. Bryant, R. L. Johnson Jr, J. H. Mitchell, O. B. Holland, C. Gomez-Sanchez, P. Vergne-Marini, and C. G. BlomqvistJ. V. Nixon, R. G. Murray, C. Bryant, R. L. Johnson Jr, J. H. Mitchell, O. B. Holland, C. Gomez-Sanchez, P. Vergne-Marini, and C. G. BlomqvistPublished Online:01 Mar 1979https://doi.org/10.1152/jappl.1979.46.3.541MoreSectionsPDF (2 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByCytoskeleton structure and total methylation of mouse cardiac and lung tissue during space flight16 May 2018 | PLOS ONE, Vol. 13, No. 5The impact of ocular hemodynamics and intracranial pressure on intraocular pressure during acute gravitational changesEmily S. Nelson, Lealem Mulugeta, Andrew Feola, Julia Raykin, Jerry G. Myers, Brian C. Samuels, and C. Ross Ethier3 August 2017 | Journal of Applied Physiology, Vol. 123, No. 2Lower-body negative pressure restores leg bone microvascular flow to supine levels during head-down tiltJamila H. Siamwala, Paul C. Lee, Brandon R. Macias, and Alan R. Hargens15 July 2015 | Journal of Applied Physiology, Vol. 119, No. 2Structure of the cortical cytoskeleton in fibers of postural muscles and cardiomyocytes of mice after 30-day 2-g centrifugationIrina V. Ogneva, V. Gnyubkin, N. Laroche, M. V. Maximova, I. M. Larina, and L. Vico1 March 2015 | Journal of Applied Physiology, Vol. 118, No. 5The effect of rowing ergometry and resistive exercise on skeletal muscle structure and function during bed restFelix Krainski, Jeffrey L. Hastings, Katja Heinicke, Nadine Romain, Eric L. Pacini, Peter G. Snell, Phil Wyrick, M. Dean Palmer, Ronald G. Haller, and Benjamin D. Levine15 June 2014 | Journal of Applied Physiology, Vol. 116, No. 12Modulation of endothelial and smooth muscle function by bed rest and hypoenergetic, low-fat nutritionChristiane Hesse, Heike Siedler, Steffen P. Luntz, Bianca M. Arendt, Roland Goerlich, Ruth Fricker, Martina Heer, and Walter E. Haefeli1 December 2005 | Journal of Applied Physiology, Vol. 99, No. 6Influence of Simulated Weightlessness on the Oral Pharmacokinetics of Acetaminophen as a Gastric Emptying Probe in Man: A Plasma and a Saliva Study8 March 2013 | The Journal of Clinical Pharmacology, Vol. 43, No. 11Renal and hormonal responses to isotonic saline infusion after 3 days' head-down tilt vs. supine and seated positions28 January 2003 | Acta Physiologica Scandinavica, Vol. 177, No. 2Proposed role of the paraventricular nucleus in cardiovascular deconditioning19 December 2002 | Acta Physiologica Scandinavica, Vol. 177, No. 1Attenuated sympathetic nerve responses after 24 hours of bed restMazhar H. Khan, Allen R. Kunselman, Urs A. Leuenberger, William R. Davidson, Chester A. Ray, Kristen S. Gray, Cynthia S. Hogeman, and Lawrence I. Sinoway1 June 2002 | American Journal of Physiology-Heart and Circulatory Physiology, Vol. 282, No. 6Cardiac atrophy after bed rest and spaceflightMerja A. Perhonen, Fatima Franco, Lynda D. Lane, Jay C. Buckey, C. Gunnar Blomqvist, Joseph E. Zerwekh, Ronald M. Peshock, Paul T. Weatherall, and Benjamin D. Levine1 August 2001 | Journal of Applied Physiology, Vol. 91, No. 2Impeded Alveolar-Capillary Gas Transfer With Saline Infusion in Heart FailureHypertension, Vol. 34, No. 6Effects of a three-day head-down tilt on renal and hormonal responses to acute volume expansionPierre Mauran, Saïd Sediame, Anne Pavy-Le Traon, Alain Maillet, Alain Carayon, Christiane Barthelemy, Guillaume Weerts, Antonio Guell, and Serge Adnot1 November 1999 | American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, Vol. 277, No. 5Increase in epinephrine-induced responsiveness during microgravity simulated by head-down bed rest in humansP. Barbe, J. Galitzky, C. Thalamas, D. Langin, M. Lafontan, J. M. Senard, and M. Berlan1 November 1999 | Journal of Applied Physiology, Vol. 87, No. 5Changes in lower limb volume in humans during parabolic flightOlivier Bailliart, André Capderou, Bernard P. Cholley, Christian Kays, Daniel Rivière, Pierre Téchoueyres, Jean-Luc Lachaud, and Pierre Vaïda1 December 1998 | Journal of Applied Physiology, Vol. 85, No. 6Atrial distension in humans during microgravity induced by parabolic flightsRegitze Videbaek, and Peter Norsk1 December 1997 | Journal of Applied Physiology, Vol. 83, No. 6Pulmonary diffusing capacity and pulmonary capillary blood volume during parabolic flightsPierre Vaïda, Christian Kays, Daniel Rivière, Pierre Téchoueyres, and Jean-Luc Lachaud1 April 1997 | Journal of Applied Physiology, Vol. 82, No. 4Effect of acute head-down tilt on skeletal muscle cross-sectional area and proton transverse relaxation timeMichael S. Conley, Jeanne M. Foley, Lori L. Ploutz-Snyder, Ronald A. Meyer, and Gary A. Dudley1 October 1996 | Journal of Applied Physiology, Vol. 81, No. 4Regulation of the systemic circulation at microgravity and during readaptation to 1GMedicine &amp Science in Sports &amp Exercise, Vol. 28, No. 10Orthostatic hypotension and the role of changes in venous capacitanceMedicine &amp Science in Sports &amp Exercise, Vol. 28, No. 10Volume loading of the heart by “leg up” position and head down tilting (−6°) (HDT)Acta Astronautica, Vol. 27Effect on the cardiac function of repeated LBNP during a 1-month head down tiltActa Astronautica, Vol. 25, No. 7Mathematical modeling of acute and chronic cardiovascular changes during Extended Duration Orbiter (EDO) flightsActa Astronautica, Vol. 23Metabolism and biochemistry in hypogravityActa Astronautica, Vol. 23Viscidation of Blood during Short Term Bed Rest – Its Possible Importance in the Etiology of Deep Vein Thrombosis24 June 2016 | Phlebology: The Journal of Venous Disease, Vol. 4, No. 1Pulmonary function in microgravityActa Astronautica, Vol. 17, No. 10The endocrine system in space flightActa Astronautica, Vol. 17, No. 2Biomedical support of man in spaceActa Astronautica, Vol. 17, No. 2Environmental stressors during space flight: Potential effects on body temperatureComparative Biochemistry and Physiology Part A: Physiology, Vol. 91, No. 3Single neuron activity of rat hypothalamic paraventricular nucleus during body suspensionNeuroscience Letters, Vol. 78, No. 3Effect of 60-minute head-down tilt on arterial baroreflex function in anesthetized dogsJournal of the Autonomic Nervous System, Vol. 20, No. 1Spacelab life sciences flight experimentsActa Astronautica, Vol. 15, No. 5Orthostatic hypotension.Hypertension, Vol. 8, No. 8Cardiovascular system and microgravity simulation and inflight resultsActa Astronautica, Vol. 13, No. 1Systems interrelations of gravity responses in the human organism, and the use of modellingAdvances in Space Research, Vol. 6, No. 12Ventricular performance in human hearts aged 61 to 73 yearsThe American Journal of Cardiology, Vol. 56, No. 15Cardiovascular deconditioning produced by 20 hours of bedrest with head-down tilt (−5°) in middle-aged healthy menThe American Journal of Cardiology, Vol. 56, No. 10The effect of cardiac autonomic blockade on ventricular response to changes in preloadJournal of the Autonomic Nervous System, Vol. 13, No. 3Cardiovascular effects of simulated zero-gravity in humansActa Astronautica, Vol. 10, No. 9Spaceflight and the telltale heartThe American Journal of Surgery, Vol. 145, No. 6The first dedicated life sciences mission — Spacelab 4Advances in Space Research, Vol. 3, No. 9Effect of large variations in preload on left ventricular performance characteristics in normal subjects.Circulation, Vol. 65, No. 4U.S. manned space flight: The first twenty yearsActa Astronautica, Vol. 8, No. 9-10Early cardiovascular adaptation to zero gravity simulated by head-down tiltActa Astronautica, Vol. 7, No. 4-5 More from this issue > Volume 46Issue 3March 1979Pages 541-548 Copyright & PermissionsCopyright © 1979 the American Physiological Societyhttps://doi.org/10.1152/jappl.1979.46.3.541PubMed438025History Published online 1 March 1979 Published in print 1 March 1979 Metrics

The effects of a 20-day period of bed rest followed by a 55-day period of physical training were studied in five male subjects, aged 19 to 21. Three of the subjects had previously been sedentary, and two of them had been physically active. The studies after bed rest and after physical training were both compared with the initial control studies. Effects of Bed Rest All five subjects responded quite similarly to the bed rest period. The total body weight remained constant; however, lean body mass, total body water, intracellular fluid volume, red cell mass, and plasma volume tended to decrease. Electron microscopic studies of quadriceps muscle biopsies showed no significant changes. There was no effect on total lung capacity, forced vital capacity, one-second expiratory volume, alveolar-arterial oxygen tension difference, or membrane diffusing capacity for carbon monoxide. Total diffusing capacity and pulmonary capillary blood volume were slightly lower after bed rest. These changes were related to changes in pulmonary blood flow. Resting total heart volume decreased from 860 to 770 ml. The maximal oxygen uptake fell from 3.3 in the control study to 2.4 L/min after bed rest. Cardiac output, stroke volume, and arterial pressure at rest in supine and sitting positions did not change significantly. The cardiac output during supine exercise at 600 kpm/min decreased from 14.4 to 12.4 L/min, and stroke volume fell from 116 to 88 ml. Heart rate increased from 129 to 154 beats/min. There was no change in arterial pressure. Cardiac output during upright exercise at submaximal loads decreased approximately 15% and stroke volume 30%. Calculated heart rate at an oxygen uptake of 2 L/min increased from 145 to 180 beats/min. Mean arterial pressures were 10 to 20 mm Hg lower, but there was no change in total peripheral resistance. The A-V 0 2 difference was higher for any given level of oxygen uptake. Cardiac output during maximal work fell from 20.0 to 14.8 L/min and stroke volume from 104 to 74 ml. Total peripheral resistance and A-V 0 2 difference did not change. The Frank lead electrocardiogram showed reduced T-wave amplitude at rest and during submaximal exercise in both supine and upright position but no change during maximal work. The fall in maximal oxygen uptake was due to a reduction of stroke volume and cardiac output. The decrease cannot exclusively be attributed to an impairment of venous return during upright exercise. Stroke volume and cardiac output were reduced also during supine exercise. A direct effect on myocardial function, therefore, cannot be excluded. Effects of Physical Training In all five subjects physical training had no effect on lung volumes, timed vitalometry, and membrane diffusing capacity as compared with control values obtained before bed rest. Pulmonary capillary blood volume and total diffusing capacity were increased proportional to the increase in blood flow. Alveolar-arterial oxygen tension differences during exercise were smaller after training, suggesting an improved distribution of pulmonary blood flow with respect to ventilation. Red cell mass increased in the previously sedentary subjects from 1.93 to 2.05 L, and the two active subjects showed no change. Maximal oxygen uptake increased from a control value of 2.52 obtained before bed rest to 3.41 L/min after physical training in the three previously sedentary (+33%) and from 4.48 to 4.65 L/min in the two previously active subjects (+4%). Cardiac output and oxygen uptake during submaximal work did not change, but the heart rate was lower and the stroke volume higher for any given oxygen uptake after training in the sedentary group. In the sedentary subjects cardiac output during maximal work increased from 17.2 L/min in the control study before bed rest to 20.0 L/min after training (+16.5%). Arterio-venous oxygen difference increased from 14.6 to 17.0 ml/100 ml (+16.5%). Maximal heart rate remained constant, and stroke volume increased from 90 to 105 (+17%). Resting total heart volumes were 740 ml in the control study before bed rest and 812 ml after training. In the previously active subjects changes in heart volume, maximal cardiac output, stroke volume, and arteriovenous oxygen difference were less marked. Previous studies have shown increases of only 10 to 15% in the maximal oxygen uptake of young sedentary male subjects after training. The greater increase of 33% in maximal oxygen uptake in the present study was due equally to an increase in stroke volume and arteriovenous oxygen difference. These more marked changes may be attributed to a low initial level of maximal oxygen uptake and to an extremely strenuous and closely supervised training program.

AB S T R A C T Muscle pieces from 11 patients with dernmatomyositis or polymyositis were incubated with autologous peripheral blood lymphocytes and the super- nates examined for the production of lymphotoxin, a mediator of delayed hypersensitivity, using human fetal muscle monolayers as the target cell.In the case of all 10 active patients, production of lymphotoxin was dem- onstrated.This mediator was also demonstrated when muscle alone was incubated from two patients with ex- tensive cellular infiltration.Lymphotoxic activity was not found in supernates obtained by incubation of muscle from nine control subjects with their autologous peripheral blood lymphocytes.Addition of methyl prednisolone to active cultures inhibited the action of lymphotoxin on the muscle mono- layers.Lymphotoxin was not demonstrated when breast tumor tissue from a patient with dermatomyositis was incubated with autologous lymphocytes.The lympho- toxic agent in the active supernates had similar chro- matographic properties to those of a sample of purified lymphotoxin.These findings suggest that muscle injury in polymyositis is a result of a cellular immune re- sponse to an antigen present in involved muscle tissue.

We developed a rubric for measuring students' ability to reason and write scientifically. The Rubric for Science Writing (Rubric) was tested in a variety of undergraduate biology laboratory courses (total n = 142 laboratory reports) using science graduate students (teaching assistants) as raters. Generalisability analysis indicates that the Rubric provides a reliable measure of students' abilities (g = 0.85) in these conditions. Comparison of student performance in various biology classes indicated that some scientific skills are more challenging for students to develop than others and identified a number of previously unappreciated gaps in the curriculum. Our findings suggest that use of the Rubric provides three major benefits in higher education: (1) to increase substance and consistency of grading within a course, particularly those staffed by multiple instructors or graduate teaching assistants; (2) to assess student achievement of scientific reasoning and writing skills; and (3) when used in multiple courses, to highlight gaps in alignment among course assignments and provide a common metric for assessing to what extent the curriculum is achieving programmatic goals. Lastly, biology graduate students reported that use of the Rubric facilitated their teaching and recommended that training on the Rubric be provided to all teaching assistants.

ARTICLESMaximal oxygen uptake and cardiac output after 2 weeks at 4,300 mBengt Saltin, Robert F. Grover, C. Gunnar Blomqvist, L. Howard Hartley, and Robert L. Johnson Jr.Bengt SaltinPauline and Adolph Weinberger Laboratory for Cardiovascular Research, Department of Internal Medicine, University of Texas Southwestern Medical School, Dallas, Texas; and Department of Medicine, University of Colorado Medical Center, Denver, Colorado, Robert F. GroverPauline and Adolph Weinberger Laboratory for Cardiovascular Research, Department of Internal Medicine, University of Texas Southwestern Medical School, Dallas, Texas; and Department of Medicine, University of Colorado Medical Center, Denver, Colorado, C. Gunnar BlomqvistPauline and Adolph Weinberger Laboratory for Cardiovascular Research, Department of Internal Medicine, University of Texas Southwestern Medical School, Dallas, Texas; and Department of Medicine, University of Colorado Medical Center, Denver, Colorado, L. Howard HartleyPauline and Adolph Weinberger Laboratory for Cardiovascular Research, Department of Internal Medicine, University of Texas Southwestern Medical School, Dallas, Texas; and Department of Medicine, University of Colorado Medical Center, Denver, Colorado, and Robert L. Johnson Jr.Pauline and Adolph Weinberger Laboratory for Cardiovascular Research, Department of Internal Medicine, University of Texas Southwestern Medical School, Dallas, Texas; and Department of Medicine, University of Colorado Medical Center, Denver, ColoradoPublished Online:01 Oct 1968https://doi.org/10.1152/jappl.1968.25.4.400MoreSectionsPDF (2 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByLimitation of Maximal Heart Rate in Hypoxia: Mechanisms and Clinical Importance23 July 2018 | Frontiers in Physiology, Vol. 9Altitude20 February 2018AltitudeOmics: impaired pulmonary gas exchange efficiency and blunted ventilatory acclimatization in humans with patent foramen ovale after 16 days at 5,260 mJonathan E. Elliott, Steven S. Laurie, Julia P. Kern, Kara M. Beasley, Randall D. Goodman, Bengt Kayser, Andrew W. Subudhi, Robert C. Roach, and Andrew T. Lovering1 May 2015 | Journal of Applied Physiology, Vol. 118, No. 9Con: Hypoxic Pulmonary Vasoconstriction Is not a Limiting Factor of Exercise at High AltitudeHigh Altitude Medicine & Biology, Vol. 12, No. 4Endurance Training at AltitudeHigh Altitude Medicine & Biology, Vol. 10, No. 2Second generation Tibetan lowlanders acclimatize to high altitude more quickly than Caucasians13 April 2004 | The Journal of Physiology, Vol. 556, No. 2Intermittent altitude exposures improve muscular performance at 4,300 mBeth A. Beidleman, Stephen R. Muza, Charles S. Fulco, Allen Cymerman, Dan T. Ditzler, Dean Stulz, Janet E. Staab, Scott R. Robinson, Gary S. Skrinar, Steven F. Lewis, and Michael N. Sawka1 November 2003 | Journal of Applied Physiology, Vol. 95, No. 5Why is V˙o2 max after altitude acclimatization still reduced despite normalization of arterial O2 content?J. A. L. Calbet, R. Boushel, G. Rådegran, H. Søndergaard, P. D. Wagner, and B. Saltin1 February 2003 | American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, Vol. 284, No. 2Effect of blood haemoglobin concentration on V̇ o2,max and cardiovascular function in lowlanders acclimatised to 5260 m1 December 2002 | The Journal of Physiology, Vol. 545, No. 2Intermittent Hypoxic Training: Fact and FancyHigh Altitude Medicine & Biology, Vol. 3, No. 2Peak Heart Rate Decreases with Increasing Severity of Acute HypoxiaHigh Altitude Medicine & Biology, Vol. 2, No. 3Metabolic and thermodynamic responses to dehydration‐induced reductions in muscle blood flow in exercising humans7 September 2004 | The Journal of Physiology, Vol. 520, No. 2The role of the right ventricle during hypobaric hypoxic exercise: insights from patients after the Fontan operationMedicine & Science in Sports & Exercise, Vol. 31, No. 2O2 extraction maintains O2 uptake during submaximal exercise with β-adrenergic blockade at 4,300 mEugene E. Wolfel, Mark A. Selland, A. Cymerman, George A. Brooks, Gail E. Butterfield, Robert S. Mazzeo, Robert F. Grover, and John T. Reeves1 September 1998 | Journal of Applied Physiology, Vol. 85, No. 3Multiple variables explain the variability in the decrement in V??O2max during acute hypobaric hypoxiaMedicine & Science in Sports & Exercise, Vol. 30, No. 6Increasing maximal heart rate increases maximal O2 uptake in rats acclimatized to simulated altitudeNorberto C. Gonzalez, Richard L. Clancy, Yoshihiro Moue, and Jean-Paul Richalet1 January 1998 | Journal of Applied Physiology, Vol. 84, No. 1Skeletal muscle adaptations to training under normobaric hypoxic versus normoxic conditionsMedicine &amp Science in Sports &amp Exercise, Vol. 29, No. 2Factors limiting maximal oxygen consumption in humansRespiration Physiology, Vol. 80, No. 2-3Left ventricular function at high altitude examined by systolic time intervals and M-mode echocardiographyThe American Journal of Cardiology, Vol. 52, No. 7Model for capillary-alveolar equilibration with special reference to O2 uptake in hypoxiaRespiration Physiology, Vol. 46, No. 3Reduced physical work capacity at high altitude—a role for left ventricular dysfunctionInternational Journal of Cardiology, Vol. 1, No. 2Physiologic improvement following coronary artery bypass surgery.Circulation, Vol. 57, No. 4Maintained stroke volume but impaired arterial oxygenation in man at high altitude with supplemental CO2.Circulation Research, Vol. 38, No. 5Effects of acute through life-long hypoxic exposure on exercise pulmonary gas exchangeRespiration Physiology, Vol. 13, No. 1Morphometric estimation of pulmonary diffusion capacityRespiration Physiology, Vol. 11, No. 2 More from this issue > Volume 25Issue 4October 1968Pages 400-409 Copyright & PermissionsCopyright © 1968 the American Physiological Societyhttps://doi.org/10.1152/jappl.1968.25.4.400History Received 27 November 1967 Published online 1 October 1968 Published in print 1 October 1968 Metrics

Arthritis & RheumatismVolume 2, Issue 3 p. 224-249 ArticleFree to Read Steroid therapy and vascular lesions in rheumatoid arthritis Robert L. Johnson M.D., Robert L. Johnson M.D. Department of Medicine, Section of Rheumatic Diseases, University of Colorado School of Medicine, The Presbyterian Hospital of Denver, and the Denver Veterans Administration Hospital, Denver, Colo. Clinical Instructor in Medicine, University of Colorado School of Medicine, Denver, Colo.Search for more papers by this authorCharley J. Smyth M.D., Charley J. Smyth M.D. Associate Professor of Internal Medicine, University of Colorado School of Medicine, and Head of the Rheumatic Disease Section, Colorado General Hospital, Denver, Colo.Search for more papers by this authorGeorge W. Holt M.D., George W. Holt M.D. Clinical Instructor in Neurology, University of Colorado School of Medicine, Denver, Colo.Search for more papers by this authorAlexis Lubchenco M.D., Alexis Lubchenco M.D. Assistant Clinical Professor of Pathology, University of Colorado, Denver, Colo.; Pathologist, Presbyterian HospitalSearch for more papers by this authorEleanor Valentine M.D., Eleanor Valentine M.D. Associate Professor of Clinical Pathology, University of Colorado School of Medicine, Denver, Colo.; Pathologist, Denver Veterans Administration HospitalSearch for more papers by this author Robert L. Johnson M.D., Robert L. Johnson M.D. Department of Medicine, Section of Rheumatic Diseases, University of Colorado School of Medicine, The Presbyterian Hospital of Denver, and the Denver Veterans Administration Hospital, Denver, Colo. Clinical Instructor in Medicine, University of Colorado School of Medicine, Denver, Colo.Search for more papers by this authorCharley J. Smyth M.D., Charley J. Smyth M.D. Associate Professor of Internal Medicine, University of Colorado School of Medicine, and Head of the Rheumatic Disease Section, Colorado General Hospital, Denver, Colo.Search for more papers by this authorGeorge W. Holt M.D., George W. Holt M.D. Clinical Instructor in Neurology, University of Colorado School of Medicine, Denver, Colo.Search for more papers by this authorAlexis Lubchenco M.D., Alexis Lubchenco M.D. Assistant Clinical Professor of Pathology, University of Colorado, Denver, Colo.; Pathologist, Presbyterian HospitalSearch for more papers by this authorEleanor Valentine M.D., Eleanor Valentine M.D. Associate Professor of Clinical Pathology, University of Colorado School of Medicine, Denver, Colo.; Pathologist, Denver Veterans Administration HospitalSearch for more papers by this author First published: June 1959 https://doi.org/10.1002/1529-0131(195906)2:3<224::AID-ART1780020305>3.0.CO;2-ICitations: 69AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abstracten The clinical manifestations and pathology of diffuse vascular lesions, occurring in three patients with rheumatoid arthritis, are described. The possible significance of such lesions including their apparent relationship to corticosteroid therapy is discussed in detail. Abstractfr Es describite le manifestationes clinic e le pathologia de diffuse lesiones vascular, occurrente in tres patientes con arthritis rheumatoide. Es discutite in detalio le signification possibile de tal lesiones, incluse lor apparente relation con therapia corticosteroide. Citing Literature Volume2, Issue3June 1959Pages 224-249 RelatedInformation

ARTICLESDiffusing capacity of the lung in Caucasians native to 3,100 mA. C. DeGraff Jr, R. F. Grover, R. L. Johnson Jr, J. W. Hammond Jr, and J. M. MillerA. C. DeGraff Jr, R. F. Grover, R. L. Johnson Jr, J. W. Hammond Jr, and J. M. MillerPublished Online:01 Jul 1970https://doi.org/10.1152/jappl.1970.29.1.71MoreSectionsPDF (1 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByHuman genetic adaptation to high altitudes: Current status and future prospectsQuaternary International, Vol. 461Measuring high-altitude adaptationLorna G. Moore22 November 2017 | Journal of Applied Physiology, Vol. 123, No. 5Exercise Capacity and Selected Physiological Factors by Ancestry and Residential Altitude: Cross-Sectional Studies of 9–10-Year-Old Children in TibetHigh Altitude Medicine & Biology, Vol. 15, No. 2Improvement in lung diffusion by endothelin A receptor blockade at high altitudeClaire de Bisschop, Jean-Benoit Martinot, Gil Leurquin-Sterk, Vitalie Faoro, Hervé Guénard, and Robert Naeije1 January 2012 | Journal of Applied Physiology, Vol. 112, No. 1Alveolar diffusion-perfusion interactions during high-altitude residence in guinea pigsCuneyt Yilmaz, D. Merrill Dane, and Connie C. W. Hsia1 June 2007 | Journal of Applied Physiology, Vol. 102, No. 6Residence at 3,800-m altitude for 5 mo in growing dogs enhances lung diffusing capacity for oxygen that persists at least 2.5 yearsConnie C. W. Hsia, Robert L. Johnson, Paul McDonough, D. Merrill Dane, Myresa D. Hurst, Jennifer L. Fehmel, Harrieth E. Wagner, and Peter D. Wagner1 April 2007 | Journal of Applied Physiology, Vol. 102, No. 4Long-term enhancement of pulmonary gas exchange after high-altitude residence during maturationPaul McDonough, D. Merrill Dane, Connie C. W. Hsia, Cuneyt Yilmaz, and Robert L. Johnson1 February 2006 | Journal of Applied Physiology, Vol. 100, No. 2Upregulation of erythropoietin receptor during postnatal and postpneumonectomy lung growthDavid J. Foster, Orson W. Moe, and Connie C. W. Hsia1 December 2004 | American Journal of Physiology-Lung Cellular and Molecular Physiology, Vol. 287, No. 6Mechanisms and Limits of Induced Postnatal Lung GrowthAmerican Journal of Respiratory and Critical Care Medicine, Vol. 170, No. 3Effects of birthplace and individual genetic admixture on lung volume and exercise phenotypes of Peruvian Quechua7 July 2003 | American Journal of Physical Anthropology, Vol. 123, No. 4Recruitment of Lung Diffusing CapacityChest, Vol. 122, No. 5Pulmonary gas exchange and acid-base state at 5,260 m in high-altitude Bolivians and acclimatized lowlandersPeter D. Wagner, Mauricio Araoz, Robert Boushel, José A. L. Calbet, Birgitte Jessen, Göran Rådegran, Hilde Spielvogel, Hans Søndegaard, Harrieth Wagner, and Bengt Saltin1 April 2002 | Journal of Applied Physiology, Vol. 92, No. 4Invited Review: Pulmonary alveoli: formation, the “call for oxygen,” and other regulatorsDonald Massaro, and Gloria D. Massaro1 March 2002 | American Journal of Physiology-Lung Cellular and Molecular Physiology, Vol. 282, No. 3Chronic airway infection leads to angiogenesis in the pulmonary circulationNatalie Hopkins, Elaine Cadogan, Shay Giles, and Paul McLoughlin1 August 2001 | Journal of Applied Physiology, Vol. 91, No. 2Exercise performance of Tibetan and Han adolescents at altitudes of 3,417 and 4,300 mQiu-Hong Chen, Ri-Li Ge, Xiao-Zhen Wang, Hui-Xin Chen, Tian-Yi Wu, Toshio Kobayashi, and Kazuhiko Yoshimura1 August 1997 | Journal of Applied Physiology, Vol. 83, No. 2Greater maximal O2 uptakes and vital capacities in Tibetan than Han residents of LhasaRespiration Physiology, Vol. 79, No. 2Distribution of regional lung function during mild exercise in residents of 3100 mRespiration Physiology, Vol. 22, No. 3Diffusing capacity and over-all ventilation: Perfusion in asthmaThe American Journal of Medicine, Vol. 57, No. 5Effects of acute through life-long hypoxic exposure on exercise pulmonary gas exchangeRespiration Physiology, Vol. 13, No. 1 More from this issue > Volume 29Issue 1July 1970Pages 71-76 Copyright & PermissionsCopyright © 1970 the American Physiological Societyhttps://doi.org/10.1152/jappl.1970.29.1.71PubMed5425040History Published online 1 July 1970 Published in print 1 July 1970 Metrics

While searching for derivatives of d-tubocura- rine, Barlow and Ing (1) and Paton and Zaimis (2) independently synthesized a series of poly- methylene bistrimethylammonium salts.The lat- ter investigators demonstrated that the pharma- cological properties of this series were related to the length of the polymethylene chain; the deca- compound produced neuromuscular block while the penta and hexa-compounds prevented the transmission of impulses across the synapses in all autonomic ganglia.They also carried out pre- liminary trials in man (3) but Arnold and Rosen- heim were the first to use these agents in hy- pertension (4).Finally, Restall and Smirk demonstrated that it was possible to reduce blood pressure and obtain clinical improvement in hyper- tensive patients for long periods by the use of repeated parenteral doses of hexamethonium (5).Studies in this laboratory have confirmed the observations of Restall and Smirk and in addition have shown the potentiating effect of 1-hydrazinophthalazine (Apresoline) when alternated with doses of hexamethonium in patients with hypertension (6, 7).Our studies also suggested that hexamethonium may be useful in the treatment of

<h2>Abstract</h2> Observations from the electrocardiographic data of 350 subjects with first degree A-V block and from clinical studies of 139 subjects from this group are presented. First degree A-V block in a large, healthy population occurred at an incidence rate of 5.2 per thousand. A-V conduction time was greater than 0.24 second in 20 per cent of this group, indicating that a precise value which separates the normal from the abnormal A-V conduction time does not exist. Although the significance of the prolonged P-R interval can be determined only by individual clinical evaluation, there is no doubt that the P-R interval can be markedly prolonged in some subjects who are otherwise normal. In the present series only five of 139 were found to have evidence of organic disease. In the majority of subjects first degree A-V block was still present at the time of clinical evaluation several months after its discovery. Despite its tendency to persist, the prolonged P-R interval exhibited marked lability both spontaneously and during procedures that altered vagal and sympathetic influences. The effect of administration of atropine, standing and exercise on the A-V conduction time was compared. In nearly all, the P-R interval could be reduced to normal by one or more of these procedures. Instability of the A-V conduction mechanism was often demonstrable, particularly in those with the longest P-R intervals. Cardiac arrhythmias such as A-V dissociation, blocked sinus impulses, atrial rhythm, nodal escape beats and A-V dissociation could often be induced by stress. In three subjects, transient second degree A-V block with Wenckebach periods appeared either spontaneously or in response to respiratory maneuvers. While these changes could be related to alterations in vagal tone, individual responses were not always predictable and the response of the P-R interval to such alterations frequently seemed independent of the sinus node response. Observation of one case of second degree A-V block, apparently due to myocarditis, and one case of complete A-V block, presumably congenital, are included.

HomeCirculationVol. 5, No. 1The Treatment of Hypertension with Hexamethonium Free AccessResearch ArticlePDF/EPUBAboutView PDFSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBThe Treatment of Hypertension with Hexamethonium EDWARD D. FREIS, FRANK A. FINNERTYJR., HAROLD W. SCHNAPER and ROBERT L. JOHNSON EDWARD D. FREISEDWARD D. FREIS From The Cardiovascular Research Laboratory, Georgetown University Hospital and the Department of Medicine, Georgetown University School of Medicine, the Georgetown Medical Division, Gallinger Municipal Hospital, and the Veterans Administration Hospital, Washington, D. C. , FRANK A. FINNERTYJR.FRANK A. FINNERTYJR. From The Cardiovascular Research Laboratory, Georgetown University Hospital and the Department of Medicine, Georgetown University School of Medicine, the Georgetown Medical Division, Gallinger Municipal Hospital, and the Veterans Administration Hospital, Washington, D. C. , HAROLD W. SCHNAPERHAROLD W. SCHNAPER From The Cardiovascular Research Laboratory, Georgetown University Hospital and the Department of Medicine, Georgetown University School of Medicine, the Georgetown Medical Division, Gallinger Municipal Hospital, and the Veterans Administration Hospital, Washington, D. C. and ROBERT L. JOHNSONROBERT L. JOHNSON From The Cardiovascular Research Laboratory, Georgetown University Hospital and the Department of Medicine, Georgetown University School of Medicine, the Georgetown Medical Division, Gallinger Municipal Hospital, and the Veterans Administration Hospital, Washington, D. C. Originally published1 Jan 1952https://doi.org/10.1161/01.CIR.5.1.20Circulation. 1952;5:20–27AbstractHexamethonium by subcutaneous injection in doses of 10 to 75 mg. of the ion every 8 or 12 hours produced significant reductions of arterial pressure and symptomatic improvement in a high percentage of patients with benign or malignant hypertension. Methods for preventing tolerance and undesirable side effects are presented, and the advantages as well as the limitations of hexamethonium therapy are discussed. Previous Back to top Next FiguresReferencesRelatedDetailsCited By Skrzypecki J and Ufnal M (2015) Drug Resistant Hypertension - No SIMPLE Way Out, Kidney and Blood Pressure Research, 10.1159/000368483, 40:1, (66-76), . Sliskovic D (2013) Cardiovascular Drugs Drug Discovery, 10.1002/9781118354483.ch5, (141-204) Chast F (2008) A History of Drug Discovery The Practice of Medicinal Chemistry, 10.1016/B978-0-12-374194-3.00001-9, (1-62), . Chast F (2003) A BRIEF HISTORY OF DRUGS: FROM PLANT EXTRACTS TO DNA TECHNOLOGY The Practice of Medicinal Chemistry, 10.1016/B978-012744481-9/50005-2, (3-28), . Doyle A (1991) Sir Horace Smirk. Pioneer in drug treatment of hypertension., Hypertension, 17:2, (247-250), Online publication date: 1-Feb-1991. Erina E (1980) Ganglion-Blocking Agents in Internal Medicine Pharmacology of Ganglionic Transmission, 10.1007/978-3-642-67397-9_16, (417-438), . Sokolow M and Perloff D (1960) Five year survival of consecutive patients with malignant hypertension treated with antihypertensive agents, The American Journal of Cardiology, 10.1016/0002-9149(60)90285-X, 6:5, (858-863), Online publication date: 1-Nov-1960. Wollheim E and Moeller J (1960) Hypertonie Hypertonie · Hypotonie, 10.1007/978-3-662-38078-9_1, (1-776), . Wollheim E and Moeller J (1960) Hypertonie Herz und Kreislauf, 10.1007/978-3-642-94794-0_1, (1-776), . Lindauer M and Hafken Schiel J (2016) Hexamethonium Chloride With Reserpine in the Treatment of Severe Essential Hypertension, Angiology, 10.1177/000331975800900105, 9:1, (19-23), Online publication date: 1-Feb-1958. Grant A and Boyd J (1957) MECAMYLAMINE ILEUS AS A SURGICAL EMERGENCY, The Lancet, 10.1016/S0140-6736(57)91170-4, 269:6971, (713-715), Online publication date: 1-Apr-1957. Moffatt W and Grant A (1956) PARALYTIC ILEUS COMPLICATING MESENCEPHALITIS, The Lancet, 10.1016/S0140-6736(56)91440-4, 268:6956, (1290-1291), Online publication date: 1-Dec-1956. BARNETT A (2017) TREATMENT OF SEVERE ARTERIAL HYPERTENSION, Australasian Annals of Medicine, 10.1111/imj.1956.5.4.274, 5:4, (274-290), Online publication date: 1-Nov-1956. Moser R (1956) Diseases of Medical Progress, New England Journal of Medicine, 10.1056/NEJM195609272551306, 255:13, (606-614), Online publication date: 27-Sep-1956. Kleh J and Fazekas J (2015) EFFECTS OF HYPOTENSIVE AGENTS ON SUBJECTS WITH CEREBRAL VASCULAR INSUFFICIENCY†, Journal of the American Geriatrics Society, 10.1111/j.1532-5415.1956.tb01140.x, 4:1, (18-23), Online publication date: 1-Jan-1956. Schott J (2015) TREATMENT OF PRIMARY HYPERTENSION IN THE OLDER AGE GROUP, Journal of the American Geriatrics Society, 10.1111/j.1532-5415.1955.tb00945.x, 3:11, (910-921), Online publication date: 1-Nov-1955. Mader I and Iseri L (1955) The effect of oral 1-hydrazinophthalazine therapy on renal function in essential vascular hypertension, American Heart Journal, 10.1016/0002-8703(55)90301-X, 50:4, (556-566), Online publication date: 1-Oct-1955. RAST C, ORGAIN E, MULLER J, PRYOR W and SIEBER H (1955) Newer Drugs in the Treatment of Hypertension , Circulation, 12:3, (361-369), Online publication date: 1-Sep-1955. Moser M and Mattingly T (2016) I. Critical Evaluation of Drug Therapy of Hypertension, Postgraduate Medicine, 10.1080/00325481.1955.11708206, 17:5, (351-361), Online publication date: 1-May-1955. Grob D (1955) Management of the patient with primary "essential" hypertension, Journal of Chronic Diseases, 10.1016/0021-9681(55)90066-7, 1:5, (546-562), Online publication date: 1-May-1955. Page I (1955) Current treatment of arterial hypertension, Journal of Chronic Diseases, 10.1016/0021-9681(55)90065-5, 1:5, (536-545), Online publication date: 1-May-1955. King J (1955) Practical ambulatory therapy of functional constipation, The American Journal of Digestive Diseases, 10.1007/BF02895576, 22:4, (102-108), Online publication date: 1-Apr-1955. Smirk F (1954) Blood pressure reduction in arterial hypertension by hexamethonium and pentapyrrolidinium salts, The American Journal of Medicine, 10.1016/0002-9343(54)90228-4, 17:6, (839-850), Online publication date: 1-Dec-1954. K�hns K, Djuranovic R, Gehrs C and K�ppen K (1954) Vergleichende klinische Untersuchungen �ber die Blutdruckwirkung von Hydrazinophthalazin und dem Rauwolfia-Alkaloid Reserpin, Klinische Wochenschrift, 10.1007/BF01467155, 32:37-38, (930-935), Online publication date: 1-Oct-1954. Hoobler S (1954) Treatment of hypertension, The American Journal of Medicine, 10.1016/0002-9343(54)90263-6, 17:2, (259-270), Online publication date: 1-Aug-1954. Mottu T (1954) Artificial reduction of the heart effort, American Heart Journal, 10.1016/0002-8703(54)90254-9, 47:2, (270-281), Online publication date: 1-Feb-1954. SIEBER H, GRIMSON K and ORGAIN E (1953) Newer Drugs in the Treatment of Hypertension , Circulation, 8:6, (840-848), Online publication date: 1-Dec-1953.GROB D, SCARBOROUGH W, KATTUS A, LANGFORD H, ZIEGLER B, LORE S, SALTZER G and BIRMINGHAM M (1953) Further Observations on the Effects of Autonomic Blocking Agents in Patients with Hypertension , Circulation, 8:3, (352-369), Online publication date: 1-Sep-1953.GROB D, LANGFORD H and ZIEGLER B (1953) Further Observations on the Effects of Autonomic Blocking Agents in Patients with Hypertension , Circulation, 8:2, (205-223), Online publication date: 1-Aug-1953.SHAPIRO A and GROLLMAN A (1953) A Critical Evaluation of the Hypotensive Action of Hydrallazine, Hexamethonium, Tetraethylammonium and Dibenzyline Salts in Human and Experimental Hypertension, Circulation, 8:2, (188-198), Online publication date: 1-Aug-1953. Strang J and Gill R (2016) Current Therapy in Essential Hypertension, Postgraduate Medicine, 10.1080/00325481.1953.11711419, 14:1, (52-58), Online publication date: 1-Jul-1953. Schroeder H and Morrow J (1953) The Control of Arterial Hypertension by Hyphex: With an Evaluation of Other Methods of Therapy, Medical Clinics of North America, 10.1016/S0025-7125(16)34973-2, 37:4, (991-1008), Online publication date: 1-Jul-1953. Klayman M, Silberg N and Karlen W (1953) Death Associated with Hexamethonium and 1-Hydrazinophthalazine (Apresoline) Therapy, New England Journal of Medicine, 10.1056/NEJM195306252482606, 248:26, (1109-1111), Online publication date: 25-Jun-1953. Kuhn P (2016) The Use of Oral Hexamethonium Chloride (Methium in the Treatment of Hypertension, Angiology, 10.1177/000331975300400302, 4:3, (195-206), Online publication date: 1-Jun-1953. Cohen B (1953) Fatal reaction to 1-hydrazinophthalazine (Apresoline), American Heart Journal, 10.1016/0002-8703(53)90142-2, 45:6, (931-935), Online publication date: 1-Jun-1953. Meilman E (1953) The Medical Management of Arterial Hypertension, New England Journal of Medicine, 10.1056/NEJM195305282482205, 248:22, (936-943), Online publication date: 28-May-1953. Sadove M, Wyant G, Gittelson L and Bucy P Controlled Hypotension, Journal of Neurosurgery, 10.3171/jns.1953.10.3.0272, 10:3, (272-283) Schottstaedt M and Sokolow M (1953) The natural history and course of hypertension with papilledema (Malignant Hypertension), American Heart Journal, 10.1016/0002-8703(53)90147-1, 45:3, (331-362), Online publication date: 1-Mar-1953. Riven S, Pocock D, Kory R, Roehm D, Anderson R and Meneely G (1953) The control of hypertension with 1-hydrazinophthalazine (apresoline), The American Journal of Medicine, 10.1016/0002-9343(53)90015-1, 14:2, (160-167), Online publication date: 1-Feb-1953. Assali N and Suyemoto R (1952) The place of the hydrazinophthalazine and thiophanium compounds in the management of hypertensive complications of pregnancy, American Journal of Obstetrics and Gynecology, 10.1016/0002-9378(52)90364-5, 64:5, (1021-1036), Online publication date: 1-Nov-1952. Sutton G, Buckingham W, Brown R and Sutton D (1952) A clinical evualation of the treatment of hypertension with dihydrogenated ergotoxine alkaloids, American Heart Journal, 10.1016/0002-8703(52)90202-0, 44:4, (622-628), Online publication date: 1-Oct-1952. Palmer A (1952) THE MANAGEMENT OF HYPERTENSION WITH HEXAMETHONIUM BROMIDE, Medical Journal of Australia, 10.5694/j.1326-5377.1952.tb94562.x, 2:13, (428-435), Online publication date: 1-Sep-1952. JOHNSON R, FREIS E and SCHNAPER H (1952) Clinical Evaluation of 1-Hydrazinophthalazin (C-5968) in Hypertension , Circulation, 5:6, (833-841), Online publication date: 1-Jun-1952. January 1, 1952Vol 5, Issue 1 Advertisement Article InformationMetrics © 1952 American Heart Association, Inc.https://doi.org/10.1161/01.CIR.5.1.20 Originally publishedJanuary 1, 1952 PDF download Advertisement

The effect of 45 min of high- (80% VO2max) versus moderate- (50% VO2max) intensity treadmill exercise on circulating leukocyte and lymphocyte subpopulations, catecholamine and cortisol concentrations, and the mitogen-stimulated lymphocyte proliferative response was investigated in 10 well-conditioned (mean VO2max 66.0 +/- 1.9 ml/kg/min), young males (mean age 22.1 +/- 1.3 yrs). Blood samples were taken before and immediately after exercise, with three more samples taken during 3.5 h of recovery. Treatment order on the treadmill (graded walking at 7.3 +/- 0.1 km/h, 6.5 +/- 0.6% grade, versus level running at 16.1 +/- 0.3 km/h) was counterbalanced, with subjects acting as their own controls and results analyzed using a 2 x 5 repeated measures ANOVA. The concanavalin A- (Con A) stimulated lymphocyte proliferative response was decreased at 1 h and 2 h post-exercise relative to baseline levels following both exercise-intensity conditions. However, when adjusted on a per-T cell (CD3+) basis to account for the change in number of T cells in the in vivo assay, only the high-intensity exercise condition was associated with a 1-h post-exercise decrease (21%, p = 0.05) in the proliferative response relative to baseline. Exercise at 80% versus 50% VO2max resulted in significantly greater increases in cortisol and epinephrine concentrations, providing a physiological rationale for the immediate-post-exercise lymphocytosis, 1- to 3.5-h lymphocytopenia, and the decrease in Con A-stimulated lymphocyte proliferative response (per CD3+ cell) that occurred in greater measure following high-intensity exercise.

The purpose of this investigation was to study the efficacy of two dietary supplements on measures of body mass, body composition, and performance in 42 American football players. Group CM ( n = 9) received creatine monohy-drate, Group P ( n = 11) received calcium pyruvate. Group COM ( n = 11) received a combination of calcium pyruvate (60%) and creatine (40%), and Group PL received a placebo. Tests were performed before (Tl) and after (T2) the 5-week supplementation period, during which the subjects continued their normal training schedules. Compared to P and PL. CM and COM showed significantly greater increases for body mass, lean body mass, 1 repetition maximum (RM) bench press, combined 1 RM squat and bench press, and static vertical jump (SVJ) power output. Peak rate of force development for SVJ was significantly greater for CM compared to P and PL. Creatine and the combination supplement enhanced training adaptations associated with body mass/composition, maximum strength, and SVJ; however, pyruvate supplementation alone was ineffective.

To validate lung diffusing capacity for nitric oxide (DLNO) as an index of conductance of the alveolar-capillary membrane during exercise, we compared DLNO to lung diffusing capacity for carbon monoxide (DLCO) and pulmonary membrane diffusing capacity for carbon monoxide (DMCO), and compared pulmonary capillary blood volume (Vc) calculated by two methods.The study was performed at a university medical center involving 12 nonsmoking healthy volunteers (age range, 23 to 79 years). DLCO, DLNO, cardiac output (c), and lung volume were measured simultaneously at rest and during graded ergometer exercise by a rebreathing technique. Pulmonary membrane diffusing capacity and Vc were compared by (1) the classic technique of Roughton and Forster from DLCO measured at two alveolar oxygen tension (PAO(2)) levels, and (2) from DLNO and DLCO assuming negligible erythrocyte resistance to nitric oxide (NO) uptake, ie, DLNO approximately equal to pulmonary membrane diffusing capacity for nitric oxide.In all subjects, DLNO increased linearly from rest to exercise; age, c, and lung volume were the major determinants of DLNO by stepwise regression analysis. The DLNO/DLCO ratio averaged 3.98 +/- 0.38 (+/- SD) and the DLNO/DMCO ratio averaged 2.49 +/- 0.28 irrespective of exercise intensity. Changing PAO(2) did not alter DLNO. Brief exposure to 40 ppm of inhaled NO during 16 s of rebreathing did not alter either DLCO or c. Estimates of pulmonary membrane diffusing capacity and Vc by the two methods showed a strong correlation.Results support DLNO as a direct measure of pulmonary membrane diffusing capacity, allowing the estimation of Vc in a single rebreathing maneuver during exercise. The DLNO-DLCO rebreathing technique can be applied clinically in the investigation of pulmonary microvascular regulation.

NIEMAN, D. C., A. R. MILLER, D. A. HENSON, B. J. WARREN, G. GUSEWITCH, R. L. JOHNSON, J. M. DAVIS, D. E. BUTTER WORTH, and S. L. NEHLSEN-CANNARELLA. Effects of high vs moderate-intensity exercise on natural killer cell activity. Med. Sci. Sports Exerc., Vol. 25, No. 10, pp. 1126–1134, 1993. The effect of 45 min of high- (80% VO2max) vs moderate- (50% VO2max) intensity treadmill exercise on natural killer cell cytotoxic activity (NKCA) was investigated in 10 well-conditioned (66.0 ± 1.9 ml·kg−1. min−1), young males (22.1 ± 1.3 yr). Blood samples were taken before and immediately after exercise, with three more samples taken during 3.5 h of recovery, and analyzed for proportion of NK cells (CD3-CD16+CD56+) and NKCA. Exercise at 80% vs 50% VO2max resulted in a greater immediate postexercise increase in proportion of NK cells, followed by a 1-h and 2-h decrease below preexercise levels for both intensity conditions. NKCA rose significantly above preexercise levels following high- but not moderate-intensity exercise. For both exercise intensity conditions, NKCA tended to drop below preexercise levels by 1 h postexercise, rising back to preexercise levels by 3.5 h postexercise. When NKCA was expressed on a per-NK cell basis, however, no change relative to preexercise levels occurred following moderate-intensity exercise, while a significant increase occurred after 2-h recovery from high-intensity exercise. These data demonstrate that both high- and moderate-intensity exercise are associated with significant shifts in circulating proportions of NK cells which significantly influence interpretation of NKCA data based on assays using separated mononuclear cells.

Co-occurring diagnoses of substance abuse and mental disorders (e.g., schizophrenia, depression, or bipolar, anxiety, personality, conduct, or attention-deficit/hyperactivity disorders) are highly prevalent, often begin in youth, and place an immense burden on individuals, families, and society. Unchecked, co-occurring mental and substance use disorders represent a formula for troubled, unproductive, and foreshortened lives. Co-occurring mental and substance use disorders are associated with underachievement or failure at work and school, poor health, human immunodeficiency virus infection, hepatitis, difficulty fulfilling family responsibilities, abuse, violence, failed treatment attempts, incarceration, poverty, and homelessness ( Drake and Wallach 2000 Drake R.E. Wallach M.A. Dual diagnosis 15 years of progress. Psychiatr Serv. 2000; 51: 1126-1129 Crossref PubMed Scopus (137) Google Scholar ; Drake et al 2001 Drake R.E. Essock S.M. Shaner A. Carey K.B. Minkoff K. Kola L. et al. Implementing dual diagnosis services for clients with severe mental illness. Psychiatr Serv. 2001; 52: 469-476 Crossref PubMed Scopus (564) Google Scholar ; Gonzalez and Rosenheck 2002 Gonzalez G. Rosenheck R.A. Outcomes and service use among homeless persons with serious mental illness and substance abuse. Psychiatr Serv. 2002; 53: 437-446 Crossref PubMed Scopus (108) Google Scholar ; Mertens et al 2003 Mertens J.R. Lu Y.W. Parthasarathy S. Moore C. Weisner C.M. Medical and psychiatric conditions of alcohol and drug treatment patients in an HMO. Comparison with matched controls. Arch Gen Psychiatry. 2003; 163: 2511-2517 Google Scholar ). The risk of suicide is very high for persons with co-occurring mental and substance use disorders, especially for individuals with bipolar disorder ( Dalton et al 2003 Dalton E.J. Cate-Carter T.D. Mundo E. Parikh S.V. Kennedy J.L. Suicide risk in bipolar patients The role of co-morbid substance use disorders. Bipolar Disord. 2003; 5: 58-61 Crossref PubMed Scopus (248) Google Scholar ; Kelly et al 2002 Kelly T.M. Cornelius J.R. Lynch K.G. Psychiatric and substance use disorders as risk factors for attempted suicide among adolescents a case control study. Suicide Life Threat Behav. 2002; 32: 301-312 Crossref PubMed Scopus (63) Google Scholar ) and those who are lesbian, gay, transgender, or bisexual ( Botnick et al 2002 Botnick M.R. Heath K.V. Cornelisse P.G. Strathdee S.A. Martindale S.L. Hogg R.S. Correlates of suicide attempts in an open cohort of young men who have sex with men. Can J Public Health. 2002; 93: 59-62 PubMed Google Scholar ; Lebson 2002 Lebson M. Suicide among homosexual youth. J Homosex. 2002; 42: 107-117 Crossref PubMed Scopus (17) Google Scholar ; Wichstrom and Hegna 2003 Wichstrom L. Hegna K. Sexual orientation and suicide attempt A longitudinal study of the general Norwegian adolescent population. J Abnorm Psychol. 2003; 112: 144-151 Crossref PubMed Scopus (161) Google Scholar ).

The AIDS crisis has devastated segments of the population including the gay community and those who use intravenous drugs. HIV has spread to other groups including prostitutes and those with other sexually transmitted diseases. We have been studying adolescents in a major Northeast city where there is a major HIV/AIDS epidemic. Despite high levels of AIDS related knowledge, these adolescents reported high levels of sex risk behaviors. In addition, our data suggests that even moderate alcohol or marijuana use predicts high risk sexual behaviors. These data indicate the urgent need to develop prevention strategies for the spread of HIV among innercity youth based upon relevant predictors of risk behaviors. The coupling of HIV in inner-city populations with a high frequency of risk behaviors in adolescents demands an immediate public health response.

Controlled oxygen therapy may aggravate carbon dioxide retention during acute exacerbations of chronic obstructive pulmonary disease (COPD). Of 50 consecutive patients with COPD and acute respiratory failure, 13 required intubation because of carbon dioxide narcosis. With discriminant analysis of their arterial oxygen tension (PaO2) and pH on admission, a diagram separated patients into those at high risk and those at low risk for carbon dioxide narcosis. This diagram was then used to predict carbon dioxide narcosis in 73 patients with COPD and acute respiratory failure who were treated with controlled oxygen. In 16 of these patients carbon dioxide narcosis developed. Thirteen (81 per cent) were predicted by the diagram to be at high risk for this complication. Only two (4 per cent) patients judged by the diagram to be at low risk for carbon dioxide narcosis required mechanical ventilation. Utilizing an oxygen tension (PO2), carbon dioxide tension (PCO2) diagram a patient's ventilatory response was compared to that of ambulatory patients with COPD. These data suggest that hypoxemia and acidosis are more discriminatory for "carbon dioxide narcosis" than hypercapnia.

The early cardiovascular adaptation to zero gravity, simulated by head-down tilt at 5 degrees, was studied in a series of 10 normal young men. The validity of the model was confirmed by comparing the results with data from Apollo and Skylab flights. Tilt produced a significant central fluid shift with a transient increase in central venous pressure, later followed by an increase in left ventricular size without changes in cardiac output, arterial pressure, or contractile state. The hemodynamic changes were transient with a nearly complete return to the control state within 6 hr. The adaptation included a diuresis and a decrease in blood volume, associated with ADH, renin and aldosterone inhibition.

Colorectal cancer is a heterogeneous disease that afflicts a large number of people in the USA. The use of animal models has the potential to increase our understanding of carcinogenesis, tumor biology, and the impact of specific molecular events on colon biology. In addition, animal models with features of specific human colorectal cancers can be used to test strategies for cancer prevention and treatment. In this review, we provide an overview of the mechanisms driving human cancer, we discuss the approaches one can take to model colon cancer in animals, and we describe a number of specific animal models that have been developed for the study of colon cancer. We believe that there are many valuable animal models to study various aspects of human colorectal cancer. However, opportunities for improving upon these models exist.

Student evaluations should "be ethical, fair, useful, feasible, and accurate" [JCSEE (2003). The student evaluation standards. Arlen Gullickson, Chair. Thousand Oaks, CA: Corwin]. This study focuses on defining ethical behavior and examining educators' ethical judgments in relation to assessment. It describes the results from a web-based survey of educators in which they read a brief scenario and indicated whether the student evaluation practice in the depiction was ethical or unethical. Results showed strong agreement among the educators on fewer than half of the scenarios presented in this study. These findings suggest that assessment is currently an educational realm without professional consensus.

In normal subjects during 15-min positive-pressure ventilation with 10 cmH2O end-expiratory pressure (PEEP), cardiac output fell 19% due to a fall in stroke volume. Transmural mean right atrial pressure rose 3.1 cmH2O and right ventricular end-diastolic diameter increased 15%. Simultaneously, left ventricular end-diastolic diameter decreased 21%, ejection time increased 11%, and velocity of circumferential fiber shortening fell 30%. Thus, right ventricular filling increased and left ventricular filling decreased. The function of the right ventricle was impaired and the function of the left ventricle may have been impaired. Cardiac output gradually increased due to a 7% increase in heart rate as PEEP was continued for 1 h and transmural mean right atrial pressure also increased further by 2.4 cmH2O. Compensation for the reduced stroke volume occurred as filling pressures and heart rate rose, but ventricular function remained impaired for the entire duration of PEEP. On resuming spontaneous breathing, cardiac output and ventricular function returned to base-line levels. We conclude that the reduced cardiac output during PEEP is not due to a direct mechanical reduction in right ventricular filling.

The current spotlight on assessment in education raises ethical issues as practices evolve. This study documents ethical conflicts faced by teachers in the United States regarding assessment of students. Critical incidents generated by practising teachers revealed a majority of reported conflicts related to score pollution, and conflicts frequently arose between teachers' perceptions of institutional demands and the needs of students. The most frequently mentioned assessment topics causing conflict included grading, standardised testing, and special populations. These findings suggest that explicit guidelines for defining and avoiding unethical behaviour would be helpful to teachers in developing their assessment practices.

An animal model was developed to describe respiratory muscle work output, blood flow, and oxygen consumption during mechanical ventilation, resting spontaneous ventilation, and the increased unobstructed ventilatory efforts induced by CO2 rebreathing. Almost all of the work of breathing was inspiratory work at all ventilatory levels; thus, only blood flows to the diaphragm and external intercostals increased in the transition from mechanical to spontaneous ventilation, and they further increased linearly as ventilatory work was incrementally augmented ninefold by CO2 rebreathing. No other muscles of inspiration manifest increased blood flows. A small amount of expiratory work was measured at high ventilatory volumes during which two expiratory muscles (transverse abdominal and intercostals) had moderate increases in blood flow. Blood pressure did not change, but cardiac output doubled. Arterial-venous oxygen content difference across the diaphragm increased progressively, so oxygen delivery was augmented by both increased blood flow and increased oxygen extraction at all work loads. Oxygen consumption increased linearly as work of breathing increased, so efficiency did not change significantly. The mean efficiency of the respiratory muscles was 15.5%. These results differ significantly from the patterns previously observed by us during increased work of breathing induced by inspiratory resistance, suggesting a different distribution of work load among the various muscles of respiration, a different fractionation of oxygen delivery between blood flow and oxygen extraction, and a higher efficiency when shortening, not tension development, of the muscle is increased.

The cause of hypoxemia was studied in 21 patients with no previous heart or lung disease shortly after an episode of acute pulmonary embolism. The diagnosis was based on pulmonary angiography demonstrating distinct vascular filling defects or "cutoffs." It was found that virtually all of the hypoxemia in patients with previously normal heart and lungs could be accounted for on the basis of shunt-like effect. The magnitude of the shunting did not correlate with the percent of the pulmonary vascular bed occluded nor with the mean pulmonary artery pressure. The shunts tended to gradually recede over about a month after embolism. Patients without pulmonary infarction were able to inspire 80-111% of their predicted inspiratory capacities, and this maneuver temporarily diminished the observed shunt. Patients with pulmonary infarcts were able to inhale only to 60-69% of predicted inspiratory capacity, and this did not reverse shunting. These data suggest that the cause of right-to-left shunting in patients with pulmonary emboli is predominantly atelectasis. When the elevation of mean pulmonary artery pressure was compared to cardiac index per unit of unoccluded lung, it fell within the range of pulmonary hypertension predicted from published data obtained in patients with exercise in all except one case. This observation suggests that pulmonary vasoconstriction following embolism is not important in humans, although these data are applicable only during the time interval in which our patients were studied and in patients receiving heparin.

Fast vital capacity, 0.5-second, 0.75-second and 1.0-second timed expiratory capacities were measured with a Gaensler-Collins timed vitalometer in 153 healthy subjects, including equal numbers of males and females ranging in age from 20 through 60 years. The timed expiratory capacities (TEC) were found to constitute a fairly constant proportion of the vital capacity (VC) and the linear relationship of the TEC to the VC establishes the validity of using the ratio TEC/VC as a means of expressing this function for purposes of comparative analyses of function. The mean 0.5-second EC ratio was found to be 67.8%, the 0.75-second EC 77.3%, and the 1.0-second EC 83.9% with no variation between sexes and no significant age regression in the 0.5-second EC ratio. Values obtained by this method were comparable to those obtained by pneumotachographic and special spirometric techniques (Bernstein). Formulas for predicting the expected fast vital capacity for both males and females, using height and age as parameters, were calculated from these data to provide more accurate prediction of the VC in both sexes when the VC is measured by this commonly used method. A convenient nomogram was constructed for this purpose. Submitted on June 17, 1958

α Klotho ( α KL) regulates mineral metabolism, and diseases associated with α KL deficiency are characterized by hyperphosphatemia and vascular calcification (VC). α KL is expressed as a membrane-bound protein (mKL) and recognized as the coreceptor for fibroblast growth factor-23 (FGF23) and a circulating soluble form (cKL) created by endoproteolytic cleavage of mKL. The functions of cKL with regard to phosphate metabolism are unclear. We tested the ability of cKL to regulate pathways and phenotypes associated with hyperphosphatemia in a mouse model of CKD-mineral bone disorder and α KL -null mice. Stable delivery of adeno-associated virus (AAV) expressing cKL to diabetic endothelial nitric oxide synthase–deficient mice or α KL -null mice reduced serum phosphate levels. Acute injection of recombinant cKL downregulated the renal sodium-phosphate cotransporter Npt2a in α KL -null mice supporting direct actions of cKL in the absence of mKL. α KL -null mice with sustained AAV-cKL expression had a 74%–78% reduction in aorta mineral content and a 72%–77% reduction in mineral volume compared with control-treated counterparts ( P &lt;0.01). Treatment of UMR-106 osteoblastic cells with cKL + FGF23 increased the phosphorylation of extracellular signal–regulated kinase 1/2 and induced Fgf23 expression. CRISPR/Cas9-mediated deletion of fibroblast growth factor receptor 1 (FGFR1) or pretreatment with inhibitors of mitogen–activated kinase kinase 1 or FGFR ablated these responses. In summary, sustained cKL treatment reduced hyperphosphatemia in a mouse model of CKD-mineral bone disorder, and it reduced hyperphosphatemia and prevented VC in mice without endogenous α KL. Furthermore, cKL stimulated Fgf23 in an FGFR1-dependent manner in bone cells. Collectively, these findings indicate that cKL has mKL-independent activity and suggest the potential for enhancing cKL activity in diseases of hyperphosphatemia with associated VC.

Purpose: A systematic review was conducted to identify facilitators and barriers to movement integration (MI) in elementary school classrooms. Method: Online databases (Educational Resources Information Center, Google Scholar, PsycINFO, and PubMed) served as data sources for the study. Following the PRISMA guidelines, relevant published research on MI was identified and screened for inclusion in a qualitative synthesis. Content analysis of the included articles (N = 28) was used to identify themes of MI facilitators and barriers. Facilitators and barriers were then categorized using a social-ecological framework. Results: A total of 12 themes of MI facilitators and barriers were identified and categorized into two social-ecological levels: institutional factors (e.g., administrative support, resources) and intrapersonal factors (e.g., teacher confidence, ease of implementation). Conclusion: This review can inform research and practice aimed at supporting the implementation of MI in elementary classrooms.

Shortly after his move to the Veterans Administration Hospital and Georgetown University in Washington, DC, Freis and several colleagues tested theories about the hemodynamic effects of antihypertensive drugs, to better explain the drugs' actions.

Poor physical and mental health and substance use disorder can be causes and consequences of homelessness. Approximately 2.1 million persons per year in the United States experience homelessness. People experiencing homelessness have high rates of emergency department use, hospitalization, substance use treatment, social services use, arrest, and incarceration.A standard approach to treating homeless persons with a disability is called Treatment First, requiring clients be "housing ready"-that is, in psychiatric treatment and substance-free-before and while receiving permanent housing. A more recent approach, Housing First, provides permanent housing and health, mental health, and other supportive services without requiring clients to be housing ready. To determine the relative effectiveness of these approaches, this systematic review compared the effects of both approaches on housing stability, health outcomes, and health care utilization among persons with disabilities experiencing homelessness.A systematic search (database inception to February 2018) was conducted using 8 databases with terms such as "housing first," "treatment first," and "supportive housing." Reference lists of included studies were also searched. Study design and threats to validity were assessed using Community Guide methods. Medians were calculated when appropriate.Studies were included if they assessed Housing First programs in high-income nations, had concurrent comparison populations, assessed outcomes of interest, and were written in English and published in peer-reviewed journals or government reports.Housing stability, physical and mental health outcomes, and health care utilization.Twenty-six studies in the United States and Canada met inclusion criteria. Compared with Treatment First, Housing First programs decreased homelessness by 88% and improved housing stability by 41%. For clients living with HIV infection, Housing First programs reduced homelessness by 37%, viral load by 22%, depression by 13%, emergency departments use by 41%, hospitalization by 36%, and mortality by 37%.Housing First programs improved housing stability and reduced homelessness more effectively than Treatment First programs. In addition, Housing First programs showed health benefits and reduced health services use. Health care systems that serve homeless patients may promote their health and well-being by linking them with effective housing services.

ABSTRACTSome controversy exists concerning the “transfer of training effect” from different methods of resistance-training programs to various athletic performance variables. The purpose of this study was to examine the effects of 3 different resistance-training methods on a variety of performance v

Newborn screening programs for the detection of congenital hypothyroidism have dramatically shortened the time before treatment is begun. However, concern still exists about central nervous system sequelae which may persist due to a period of untreated intrauterine hypothyroidism. Presence of polyhydramnios led to the ultrasound diagnosis of a fetal goiter. Hypothyroidism was confirmed at 34 weeks gestation by percutaneous fetal blood sampling, which revealed an elevated TSH (186 mU/L) and a low T4 (19.3 nmol/L). Intraamniotic fluid injections of 500 micrograms levothyroxine sodium (T4) every 10-14 days increased fetal serum T4 (59.2 nmol/L), decreased fetal serum TSH (14 mU/L), decreased amniotic fluid TSH, and decreased the size of the fetal goiter. The infant was born at term without perinatal complications. Thyroid function studies on cord blood were normal (T4, 109.4 nmol/L; TSH, 1.3 mU/L), and the infant was discharged on oral T4. Follow-up examination at age 6 weeks revealed that the infant was developmentally normal and clinically and chemically euthyroid. Intrauterine T4 therapy can suppress fetal TSH and treat fetal hypothyroidism despite hypothyroid levels of serum T3. Highly sensitive TSH assays may allow the use of amniotic fluid TSH as a marker for fetal hypothyroidism.

Most information pertaining to male child sexual abuse victims is derived from cases presenting to the criminal-justice system, the mental-health system, hospital emergency rooms, and retrospective studies of college populations, all of which may be biased samples. This paper reports a six-year experience in an adolescent medicine clinic in which all medical interviews of adolescent males included questions about sexual molestation. Forty adolescent males reported sexual victimization during their preadolescent years. This study group of 40 was compared with a randomly selected age-matched group whose responses were negative to the same questions. None of the study group had previously been identified by medical or legal systems as having been molested. Twenty-five percent of the victimized males reported sexual dysfunction compared to 5% of the nonvictimized males, and 60% stated that the sexual abuse had a significant impact on their lives. Consequently, we conclude that questions about sexual molestation should be included as part of routine histories in adolescent clinics.

<h3>Abstract</h3> The independent, nonfederal Task Force on Community Preventive Services (Task Force), which directs development of the <i>Guide to Community Preventive Services</i> (<i>Community Guide</i>), has conducted a systematic review of published scientific evidence concerning the effectiveness of laws and policies that facilitate the transfer of juveniles to the adult criminal justice system, on either preventing or reducing violence (1) among those youth who experience the adult criminal system or (2) in the juvenile population as a whole. This review focuses on interpersonal violence. Violence may lead to the juvenile's initial arrest and entry into the justice system and, for those who are arrested, may be committed subsequent to exiting the justice system. Here transfer is defined as the placement of juveniles aged less than 18 years under the jurisdiction of the adult criminal justice system, rather than the juvenile justice system, following arrest. Using the methods developed by the <i>Community Guide</i> to conduct a systematic review of literature and provide recommendations to public health decision makers, the review team found that transferring juveniles to the adult justice system generally increases, rather than decreases, rates of violence among transferred youth. Evidence was insufficient for the Task Force on Community Preventive Services to determine the effect of such laws and policies in reducing violent behavior in the overall juvenile population. Overall, the Task Force recommends against laws or policies facilitating the transfer of juveniles from the juvenile to the adult judicial system for the purpose of reducing violence.

Intestinal hyperabsorption of calcium (Ca) is frequently observed in sarcoidosis and is characteristic of absorptive hypercalciuria (AH). The potential pathogenetic role of 1 alpha,25-dihydroxyvitamin D [1,25(OH)2D] in these two conditions was sought by a careful assessment of the circulating concentration of this vitamin D metabolite and various measures of Ca metabolism before and after prednisolone therapy. In eight patients with sarcoidosis, prednisolone treatment (50 mg/day for 8 days) produced a significant fall in serum 1,25(OH)2D [4.8 +/) 1.9 to 3.3 +/- 1.0 (SD) ng/dl; P less than 0.025], concomitant with a significant decrease in the fracitional intestinal Ca absorption (alpha) from 0.58 +/- to 0.14 to 0.46 +/- 0.13 (+/- SD; P less than 0.005). Urinary Ca and serum parathyroid hormone did not change significantly. However, in six patients with AH, prednisolone therapy resulted in a nonsignificant rise in serum 1,25(OH)2D from 3.6 +/- 0.7 to 4.4 +/- 1.0 ng/dl and no significant fall in alpha (from 0.73 +/- 0.08 to 0.70 +/- 0.10). Urinary Ca was significantly increased in AH patients from 230 +/- 35 to 343 +/- 74 (SD) mg/day (P less than 0.005), while serum parathyroid hormone rose slightly. Serum 1,25(OH)2D and alpha were significantly correlated (r = 0.543; P less than 0.05) for patients with sarcoidosis but not in AH patients. These results suggest that the hyperabsorption of calcium in sarcoidosis is dependent on the serum concentration of 1,25(OH)2D, while in AH it may result from additional vitamin D-independent processes.

Previous investigators have demonstrated that 5-10 min of fatiguing exercise would lead to respiratory muscle fatigue in normal subjects. The purpose of this study was to determine if there was a differential inspiratory pressure response to maximal cycle ergometer exercise in trained and untrained subjects. Six highly trained cross country skiers and five untrained college students were studied prior to and 10, 60, and 120 s postexercise (incremental VO2max to exhaustion). On each occasion, maximal inspiratory pressure (MIP) was measured at the mouth from residual volume. Prior to exercise, the two groups had similar MIP values. After exercise, the sedentary subjects experienced significant decreases in MIP compared to the preexercise values. These decreases averaged 10%, 17%, and 13% at 10, 60, and 120 s postexercise, respectively. The skiers, on the other hand, showed no evidence of a decrease in MIP postexercise, with the postexercise values being slightly, but not significantly, higher than the preexercise values. From these results, we conclude that maximal exercise results in inspiratory muscle dysfunction in normal subjects but not in athletes training at or near elite levels. Thus, it appears that endurance exercise training induces an adaptive change in the inspiratory muscles that protects them from the acute loss of strength seen following exercise in normal subjects.

We have examined whether lung hyperinflation in the anesthetized dog reflexly depresses cardiac output, stroke volume, heart rate, and blood pressure and whether these changes persist for more than a minute. To eliminate any mechanical restriction to venous return and pulmonary blood flow during lung hyperinflation, a model was developed in which all pulmonary artery blood flow and all ventilation were directed to the right lung in dogs with widely open chest and the left lung was hyperinflated before and after left cervical vagotomy. Heart rate, stroke volume, and blood pressure decreased by 24, 20, and 27%, respectively, within 15 s of left lung inflation to 30 cm H(2)O. Heart rate increased to preinflation levels by 1 min, but stroke volume and blood pressure remained depressed during lung hyperinflation for at least 15 min. Upon deflation, stroke volume and blood pressure returned to control levels within 1 min. Division of the left vagosympathetic trunk at the neck interrupted all autonomic afferent and efferent nerves of the left lung, but left intact the right vagal sympathetic and parasympathetic afferent and efferent nerves of the heart. After left cervical vagotomy the transient fall in heart rate, stroke volume, and blood pressure during left lung hyperinflation was greatly reduced or eliminated. These results suggest that unilateral lung hyperinflation reflexly depresses heart rate and blood pressure, which are partially compensated with time, and reflexly depresses stroke volume, which persists uncompensated until the lung is deflated. These findings may explain the depressed cardiovascular function observed during regional lung overdistention especially when it occurs during positive pressure ventilation.

Transient receptor potential cation channel, subfamily V, member 6 (TRPV6) is an apical membrane calcium (Ca) channel in the small intestine proposed to be essential for vitamin D-regulated intestinal Ca absorption. Recent studies have challenged the proposed role for TRPV6 in Ca absorption. We directly tested intestinal TRPV6 function in Ca and bone metabolism in wild-type (WT) and vitamin D receptor knockout (VDRKO) mice. TRPV6 transgenic mice (TG) were made with intestinal epithelium-specific expression of a 3X Flag-tagged human TRPV6 protein. TG and VDRKO mice were crossed to make TG-VDRKO mice. Ca and bone metabolism was examined in WT, TG, VDRKO, and TG-VDRKO mice. TG mice developed hypercalcemia and soft tissue calcification on a chow diet. In TG mice fed a 0.25% Ca diet, Ca absorption was more than three-fold higher and femur bone mineral density (BMD) was 26% higher than WT. Renal 1α hydroxylase (CYP27B1) mRNA and intestinal expression of the natural mouse TRPV6 gene were reduced to <10% of WT but small intestine calbindin-D(9k) expression was elevated >15 times in TG mice. TG-VDRKO mice had high Ca absorption that prevented the low serum Ca, high renal CYP27B1 mRNA, low BMD, and abnormal bone microarchitecture seen in VDRKO mice. In addition, small intestinal calbindin D(9K) mRNA and protein levels were elevated in TG-VDRKO. Transgenic TRPV6 expression in intestine is sufficient to increase Ca absorption and bone density, even in VDRKO mice. VDR-independent upregulation of intestinal calbindin D(9k) in TG-VDRKO suggests this protein may buffer intracellular Ca during Ca absorption. © 2012 American Society for Bone and Mineral Research.

Maximal oxygen intake (MOI) was determined according to the method of

2,460 (67) 2,830 (77) 1,000 (67) 635 (43) 2,180 (94) 2,100 (90) 3,460 (71) 3,465 (71) FC [6] 2,700 (83) 3,400 (105) 1,190 (66) 1,370 (77) 2,400 (86) 2,630 (94) 3,890 (81) 4,470 (93) MC [4] 2,480 (77) 3,160 (97) 2,430 (135) 1,390 (77) 3,400 (121) 2,390 (85) 4,960 (104) 4,650 (97) LF [5] 2,520 (81) 3,040 (97) 1,600 (104) 1,390 (90) 2,600 (116) 2,660 (118) 4,120 (93) 4,440 (101) SC [3] 2,420 (81) 2,600 (87) 850 (51) 890 (53) 1,920 (81) 1,380 (58) 3,270 (74) 3,490 (79) AT 2,230 (63) 1,235 (75) 1,870 (76) 3,465 (71) EL 3,090 (92) 1,070 (68) 2,480 (102) 4,160 (90) AL [3] 3,220 (122) 2,940 (111) 1,990 (120) 1,750 (106) 3,280 (100) 2,700 (88) 5,040 (123) 4,360 (107) HR 2,590 (83) 1,590 (95) 2,590 (108) 4,180 (92) MB 4,625 (95) 1,945 (74) 2,685 (72) 6,570 (93) EM [3] 2,640 (100) 3,240 (123) 2,290 (129) 1,315 (74) 2,690 (80) 2,340 (69) 4,940 (118) 4,690 (112) EQ 3,080 (95) 1,330 (85) 2,460 (106) 4,410 (97) Mean 2,820 (87) 3,030 (100) 1,540 (90) 1,250 (74) 2,500 (95) 2,315 (85) 4,380 (93) 4,220 (94) * Per cent of predicted values in parentheses.Since the predicted values of Needham, Rogan and McDonald (20) were measured at ATPSand the measured values in our subjects were corrected to BTPS, 9% has been added to the predicted figures.t Number of months between studies in brackets.

The tissue distribution and excretion of radioactive digitoxin and its metabolites were studied in normal rats and cats and in rats with dietary induced myocardial lesions. The prolonged cardiac and renal retention of digitoxin and its derivatives, associated with the persistence of these substancces in the excreta of sensitive animals, supports the concept of storage as an explanation for the cumulative action of certain of the cardiac glycosides. There is a suggestive increase in digitoxin metabolism in heart failure.

Abstract When the raters of constructed-response items, such as writing samples, disagree on the level of proficiency exhibited in an item, testing agencies must resolve the score discrepancy before computing an operational score for release to the public. Several forms of score resolution are used throughout the assessment industry. In this study, we selected 4 of the more common forms of score resolution that were reported in a national survey of testing agencies and investigated the effect that each form of resolution has on the interrater reliability associated with the resulting operational scores. It is shown that some forms of resolution can be associated with higher reliability than other forms and that some forms may be associated with artificially inflated interrater reliability. Moreover, it is shown that the choice of resolution method may affect the percentage of papers that are defined as passing in a high-stakes assessment.

Lung diffusing capacity for carbon monoxide (DLco) and its components, membrane diffusing capacity (Dmco) and capillary blood volume (Vc), as well as pulmonary blood flow (Qc), were measured at rest at several lung volumes and during treadmill exercise by a rebreathing technique in four adult dogs after right pneumonectomy (R-PNX) and in six matched control dogs (Sham) 6–12 mo after surgery. In both groups, lung inflation at rest was associated with a small increase in DLco and Dmco but not in Vc. After R-PNX, total DLco was lower by 30% at peak exercise compared with control values. When compared with DLco in a normal left lung, DLco in the remaining lung continued to increase along the normal relationship with respect to Qc up to a cardiac output equivalent to 34 l/min through both lungs of the Sham dog. There was no evidence of an upper limit of DLco being reached. The augmentation of DLco from rest to exercise was associated with corresponding increases in Dmco and Vc; after R-PNX, both Dmco and Vc continued to increase with respect to Qc along similar relationships as in control dogs without reaching an upper limit, suggesting a much larger alveolar-capillary reserve for gas exchange by diffusion than previously recognized. At higher levels of blood flow through the remaining lung, DLco was greater in adult dogs after R-PNX than after left pneumonectomy (Carlin et al. J. Appl. Physiol. 70: 135–142, 1991), suggesting that additional sources of compensation, e.g., lung growth, exist after removal of &gt; 50% of lung.

To determine if the functional compensation in diffusing capac- ity of the remaining lung following pneumonectomy is due to structural growth, we performed morphometric analysis of the right lung in three adult foxhounds -2 yr after left pneumonectomy (removal of 42% of lung) and compared the results to those in normal adult dogs previously studied by the same tech- niques.Diffusing capacity was calculated by an established mor- phometric model and compared to physiologic estimates at peak exercise in the same dogs after pneumonectomy.The ma- jor structural changes after left pneumonectomy are hyperinfla- tion of the right lung, alveolar enlargement, and thinning of the alveolar-capillary tissue barrier.These changes confer significant functional compensation for gas exchange by reducing the overall resistance to 02 diffusion.The magnitude of compensa- tion in diffusing capacity estimated either morphometrically or physiologically is similar.In spite of morphometric and physio- logic evidence of functional compensation, there is no evidence of significant growth of structural components.After pneumo- nectomy, morphometric estimates of diffusing capacity are on average 23% higher than physiologic estimates in the same dogs at peak exercise.We conclude that the previously re- ported large differences between morphometric and physiologic estimates of diffusing capacity reflects the presence of large physiologic reserves available for recruitment. (

Some controversy exists concerning the “transfer of training effect” from different methods of resistance-training programs to various athletic performance variables. The purpose of this study was to examine the effects of 3 different resistance-training methods on a variety of performance variables representing different portions of the force velocity curve, ranging from high force to high speed movements. Forty-two previously trained men (1 repetition maximum [RM] squat kg per kg body mass ≥ 1.4) served as subjects. After a 4-week high-volume training period and the pretests, the subjects were randomly assigned to 1 of 3 groups. The groups were high force (HF; n = 13), high power (HP; n = 16), and a combination training group (COM; n = 13); each group trained 4 d·wk−1 for 9 weeks. Group HF trained using 80–85% of their 1RM values. Group HP trained at relative intensities approximating 30% of peak isometric force. Group COM used a combination training protocol. Variables measured pre-and posttraining were the 1RM parallel squat, 1RM 1/4 squat, 1RM midthigh pull, vertical jump (VJ), vertical jump power, Margaria-Kalamen power test (MK), 30-m sprint, 10-yd shuttle run (10-yd), and standing long jump (SLJ). Data were analyzed within groups with t-tests, and the between-group analysis used a group χ trials analysis of variance test. The HF group improved significantly in 4 variables (p ≤ 0.05 for squat, 1/4 squat, midthigh pull, MK), the HP group in 5 variables (p ≤ 0.05 for 1/4 squat, midthigh pull, VJ, MK, SLJ), and the COM group in 7 variables (p ≤ 0.05 for squat, 1/4 squat, midthigh pull, VJ, VJP, 10-yd). These results indicate that when considering the improvement of a wide variety of athletic performance variables requiring strength, power, and speed, combination training produces superior results.

We measured diffusing capacities for carbon monoxide (DLCO) and nitric oxide, lung volume, and cardiac output by a rebreathing technique at two alveolar O2 tensions (PAO2) at rest and exercise. Membrane diffusing capacity for CO (DMCO) and VC were estimated from DLCO by the Roughton-Forster (RF) method and also from simultaneous lung diffusing capacity for NO and DLCO measured at one O2 tension (modified RF method). Estimates by these methods agreed closely in normal subjects (Tamhane et al., Chest 2001;120:1850-1856). Using these methods, we studied patients with stages II-III pulmonary sarcoidosis to determine (1) whether the modified RF method accurately estimates DMCO and VC in parenchymal disease and (2) whether sarcoidosis alters recruitment of diffusing capacity with respect to cardiac output. In patients, DMCO and VC estimated by the two methods agreed closely. DMCO was disproportionately reduced relative to VC at any given cardiac output, and the slope of the relationship between DLCO and cardiac output was moderately, though significantly, below normal. We conclude that in sarcoidosis (1) the modified RF method provides comparable estimates of DMCO and VC as the standard RF method and (2) the limitation to diffusive gas transport resides primarily in the membrane barrier, although recruitment of microvascular reserves is also modestly impaired.

Genetically modified mice have been used for colon cancer research, but findings from these models are confounded by expression of cancer in multiple organs. We sought to create a transgenic mouse with Cre recombinase (Cre) expression limited to the epithelial cells of the large intestine and used this model to study colon cancer driven by adenomatosis polyposis coli (APC) gene inactivation. A promoter/enhancer from the mouse carbonic anhydrase I gene was used to generate a Cre-expressing transgenic mouse (CAC). After characterizing transgene expression and distribution, CAC mice were crossed to APC(580S) mice to generate mice with APC inactivation at one (CAC;APC(580S/+)) or both alleles (CAC;APC(580S/580S)). Transgene expression was limited to the epithelial cells of the cecum and colon, extended from the crypt base to the luminal surface, and was expressed in approximately 15% of the crypts. No abnormal gross phenotype was seen in 3- or 6-week-old CAC;APC(580S/+) mice, but CAC;APC(580S/580S) mice had significant mucosal hyperplasia in the colon at 3 weeks, which developed into tumors by 6 weeks. By 10 weeks, 20% of CAC;APC(580S/+) mice developed adenomatous lesions in the distal colon (3.0 +/- 0.4 mm; 1.1 per mouse). Dextran sulfate sodium treatment increased the incidence and number of tumors, and this occurred predominantly in distal colon. Our new model has improved features for colon cancer research, that is, transgene expression is limited to the epithelium of the large bowel with normal cells found next to genetically modified cells.

This study correlated levels of activated fibrinolysis with the presence, extent, and rate of resolution of angiographically documented pulmonary emboli. Pulmonary emboli demonstrable by angiography were associated with detectable fibrin split products in the serum of 24 of 25 patients. In the absence of increased fibrin split products, pulmonary emboli large enough to be demonstrated by angiography were found in only 2 of 25 positive pulmonary angiograms. Spontaneous resolution of pulmonary emboli could not be correlated with the the concentration or persistence of fibrin split products but did correlate well with the presence of a reversible precipitating cause. Thrombophlebitis in the absence of clinical evidence of pulmonary embolism was not associated with increased concentrations of fibrin split products in eight of nine patients. The one patient with increased fibrin split product concentration had evidence on lung scan of silent pulmonary embolism.

Proton pump inhibitor-responsive oesophageal eosinophilia (PPI-REE) is a recently described entity which resembles oeosinophilic oesophagitis (EoE), yet responds to acid suppressive treatment.To determine whether EoE shares similar staining features with PPI-REE or with gastro-oesophageal reflux disease (GERD).This retrospective study consisted of patients with an established diagnosis of EoE, PPI-REE, or GERD identified from a database during a 1-year period. Immunohistochemistry (IHC) analysis was performed specifically targeting eotaxin-3 antibodies. All sections were qualitatively (intensity) and quantitatively (percentage of cells stained) assessed independently by two blinded pathologists.The cohort consisted of three groups of patients: EoE (n = 22), PPI-REE (n = 23) and GERD (n = 23) for a total of 68 patients. Study demographics included mean age 39 (14) years, 75% male and 77% Caucasian. There was a significant difference in the eotaxin-3 staining among EoE, PPI-REE and GERD groups [mean score (s.d.): 1.2 (1.2), 0.8 (1.0), 0.3 (0.7), P = 0.006]. Staining scores of EoE patients were significantly higher compared with GERD (P = 0.002) and a trend towards significance was seen between EoE and PPI-REE (P = 0.054). There was also a significant difference in EoE staining intensity score among the three groups (P = 0.006). Intensity scores of EoE were significantly higher compared with GERD [1.0 (0.9) vs. 0.22 (0.52), P < 0.001]. There was no significant difference between EoE and PPI-REE groups [1.0 (0.0) vs. 0.52 (0.75) P = 0.094].A difference in eotaxin-3 staining was seen in the three groups of patients with oesophageal eosinophilia. Eotaxin-3 can distinguish EoE from GERD, but not from proton pump inhibitor responsive-oesophageal eosinophilia.

During exercise pulmonary diffusing capacity for carbon monoxide and oxygen increases because the pulmonary capillary bed expands (1).It seems reasonable that there should be an upper limit to this expansion at which the diffusing ca- pacity reaches maximum.The apparent oxygen diffusing capacity (DLO2) has been noted to ap- proach a plateau or upper limit as the work load increases (2, 3), but a similar plateau for CO dif- fusing capacity has never been clearly demon- strated (1, 4) perhaps because it has not been measured at heavy enough work loads.Thus our purpose was to determine how high CO diffusing capacity can go as exercise work load increases and to see whether it reaches a plateau before the maximal tolerated work load is achieved.To accomplish this we measured apparent CO diffusing capacity (DLco) and pulmonary blood flow simultaneously in five normal adults, five normal children, and in three adult patients with mitral stenosis.Measurements were made at rest and at increasing treadmill work loads up to and beyond that causing maximal oxygen con- sumption.At rest and at maximal oxygen con- sumption the true membrane diffusing capacity for CO (DMco) and the pulmonary capillary blood volume (Vc) were estimated by the Roughton- Forster method (5).

Complete right bundle branch block was noted in 106 subjects in a survey of 67,375 apparently healthy men. The rate per thousand below the age of forty was 1.5 contrasted to a rate of 2.9 per thousand past the age of forty. Complete right bundle branch block could not be correlated with an increase in clinical factors thought to be associated with an increased incidence of coronary artery disease. The body weight, blood cholesterol and phospolipid levels and blood pressure were similar in the normal group as compared to the subjects with complete right bundle branch block. The initial 0.08 second QRS vector was more often normally oriented even in the presence of complete right bundle branch block, suggesting that the initial events of ventricular excitation are relatively unaltered in the presence of uncomplicated right bundle branch block. The T waves were normal in all, suggesting that the presence of right bundle branch block does not significantly alter the order of ventricular recovery. S-T segment changes were noted infrequently after a double Master exercise test. The significance of these findings should be evaluated in terms of anticipated long term follow-up studies. In contradistinction to left bundle branch block, right bundle branch block is frequently seen in apparently healthy persons and unless other evidence of heart disease is present or the subject is in the older age group with a previously normal electrocardiogram it should not be accepted as diagnostic evidence of significant underlying heart disease.

Context: Children in low-income and racial and ethnic minority families often experience delays in development by 3 years of age and may benefit from center-based early childhood education. Design: A meta-analysis on the effects of early childhood education by Kay and Pennucci best met Community Guide criteria and forms the basis of this review. Results: There were increases in intervention compared with control children in standardized test scores (median = 0.29 SD) and high school graduation (median = 0.20 SD) and decreases in grade retention (median = 0.23 SD) and special education assignment (median = 0.28 SD). There were decreases in crime (median = 0.23 SD) and teen births (median = 0.46 SD) and increases in emotional self-regulation (median = 0.21 SD) and emotional development (median = 0.04 SD). All effects were favorable, but not all were statistically significant. Effects were also long-lasting. Conclusions: Because many programs are designed to increase enrollment for high-risk students and communities, they are likely to advance health equity.

NAMPT, an enzyme essential for NAD+ biosynthesis, has been extensively studied as an anticancer target for developing potential novel therapeutics. Several NAMPT inhibitors have been discovered, some of which have been subjected to clinical investigations. Yet, the on-target hematological and retinal toxicities have hampered their clinical development. In this study, we report the discovery of a unique NAMPT inhibitor, LSN3154567. This molecule is highly selective and has a potent and broad spectrum of anticancer activity. Its inhibitory activity can be rescued with nicotinic acid (NA) against the cell lines proficient, but not those deficient in NAPRT1, essential for converting NA to NAD+ LSN3154567 also exhibits robust efficacy in multiple tumor models deficient in NAPRT1. Importantly, this molecule when coadministered with NA does not cause observable retinal and hematological toxicities in the rodents, yet still retains robust efficacy. Thus, LSN3154567 has the potential to be further developed clinically into a novel cancer therapeutic. Mol Cancer Ther; 16(12); 2677-88. ©2017 AACR.

Context High school completion (HSC) is an established predictor of long-term morbidity and mortality. U.S. rates of HSC are substantially lower among students from low-income families and most racial/ethnic minority populations than students from high-income families and the non-Hispanic white population. This systematic review assesses the effectiveness of programs to increase HSC and the potential of these programs to improve lifelong health among at-risk students. Evidence acquisition A search located a meta-analysis (search period 1985–2010/2011) on the effects of programs to increase HSC or General Educational Development (GED) diploma receipt; the meta-analysis was concordant with Community Guide definitions and methodologic standards. Programs were assessed separately for the general student population (152 studies) and students who were parents or pregnant (15 studies). A search for studies published between 2010 and August 2012 located ten more recent studies, which were assessed for consistency with the meta-analysis. Analyses were conducted in 2013. Evidence synthesis The review focused on the meta-analysis. Program effectiveness was measured as the increased rate of HSC (or GED receipt) by the intervention group compared with controls. All assessed program types were effective in increasing HSC in the general student population: vocational training, alternative schooling, social–emotional skills training, college-oriented programming, mentoring and counseling, supplemental academic services, school and class restructuring, multiservice packages, attendance monitoring and contingencies, community service, and case management. For students who had children or were pregnant, attendance monitoring and multiservice packages were effective. Ten studies published after the search period for the meta-analysis were consistent with its findings. Conclusions There is strong evidence that a variety of HSC programs can improve high school or GED completion rates. Because many programs are targeted to high-risk students and communities, they are likely to advance health equity. High school completion (HSC) is an established predictor of long-term morbidity and mortality. U.S. rates of HSC are substantially lower among students from low-income families and most racial/ethnic minority populations than students from high-income families and the non-Hispanic white population. This systematic review assesses the effectiveness of programs to increase HSC and the potential of these programs to improve lifelong health among at-risk students. A search located a meta-analysis (search period 1985–2010/2011) on the effects of programs to increase HSC or General Educational Development (GED) diploma receipt; the meta-analysis was concordant with Community Guide definitions and methodologic standards. Programs were assessed separately for the general student population (152 studies) and students who were parents or pregnant (15 studies). A search for studies published between 2010 and August 2012 located ten more recent studies, which were assessed for consistency with the meta-analysis. Analyses were conducted in 2013. The review focused on the meta-analysis. Program effectiveness was measured as the increased rate of HSC (or GED receipt) by the intervention group compared with controls. All assessed program types were effective in increasing HSC in the general student population: vocational training, alternative schooling, social–emotional skills training, college-oriented programming, mentoring and counseling, supplemental academic services, school and class restructuring, multiservice packages, attendance monitoring and contingencies, community service, and case management. For students who had children or were pregnant, attendance monitoring and multiservice packages were effective. Ten studies published after the search period for the meta-analysis were consistent with its findings. There is strong evidence that a variety of HSC programs can improve high school or GED completion rates. Because many programs are targeted to high-risk students and communities, they are likely to advance health equity.

Low vitamin D status potentiates experimental colitis, but the vitamin D-responsive cell in colitis has not been defined. We hypothesized that vitamin D has distinct roles in colonic epithelial cells and in nonepithelial cells during colitis. We tested this hypothesis by using mice with vitamin D receptor (VDR) deletion from colon epithelial cells (CEC-VDRKO) or nonintestinal epithelial cells (NEC-VDRKO). Eight-week-old mice were treated with 1.35% dextran sulfate sodium (DSS) for 5 days and then euthanized 2 or 10 days after removal of DSS. DSS induced body weight loss and increased disease activity index and spleen size. This response was increased in NEC-VDRKO mice but not CEC-VDRKO mice. DSS-induced colon epithelial damage and immune cell infiltration scores were increased in both mouse models. Although the epithelium healed between 2 and 10 days after DSS administration in control and CEC-VDRKO mice, epithelial damage remained high in NEC-VDRKO mice 10 days after removal of DSS, indicating delayed epithelial healing. Gene expression levels for the proinflammatory, M1 macrophage (Mɸ) cytokines tumor necrosis factor-α, nitric oxide synthase 2, and interleukin-1β were significantly elevated in the colon of NEC-VDRKO mice at day 10. In vitro experiments in murine peritoneal Mɸs demonstrated that 1,25 dihydroxyvitamin D directly inhibited M1 polarization, facilitated M2 polarization, and regulated Mɸ phenotype switching toward the M2 and away from the M1 phenotype. Our data revealed unique protective roles for vitamin D signaling during colitis in the colon epithelium as well as nonepithelial cells in the colon microenvironment (i.e., modulation of Mɸ biology).

Single oral doses of 1-hydrazinophthalazine frequently lowered blood pressure particularly diastolic pressure in hypertensive patients. Prolonged therapy was less successful, apparently as a result of development of tolerance or side effects. The best long-term results were obtained when l-hydrazinophthalazine was alternated with hexamethonium.

The pattern of recovery of renal function following two hours of complete ischemia was studied in a series of dogs. A marked functional ischemia persisted for several hours after release of the clamp, but restoration of blood flow was substantially complete in 24 hours. Other renal functions returned slowly over a period of weeks, reflecting the rate of repair of damaged tubules. Two important phases of recovery are thus to be considered: (a) a brief but significant period of continuing ischemia immediately following the trauma, and (b) a period of slow repair of those nephrons damaged but not destroyed in the first phase of the insult.

HomeCirculationVol. 103, No. 7Gas Exchange Efficiency in Congestive Heart Failure II Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBGas Exchange Efficiency in Congestive Heart Failure II Robert L. JohnsonJr Robert L. JohnsonJrRobert L. JohnsonJr From the Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas. Search for more papers by this author Originally published20 Feb 2001https://doi.org/10.1161/01.CIR.103.7.916Circulation. 2001;103:916–918It has become increasingly apparent that congestive heart failure (CHF) affects not only the cardiovascular system, but every organ system involved with oxygen transport, including the respiratory system, skeletal muscles, and the hormonal and neural feedback control systems for breathing, cardiac output, blood pressure, blood volume, and distribution of blood flow. One segment of this transport system cannot be isolated from the rest. The ventilatory response to exercise in patients with CHF is augmented despite normal arterial O2 saturation and a normal or low end-tidal Pco2.123456 The augmented ventilatory response is measured as a steep slope of the increase in ventilation with respect to CO2 output (ΔV̇e/ΔV̇co2) or as a high V̇e/V̇co2 ratio at peak exercise. The source of this ventilatory augmentation has been controversial, but its pathophysiological significance is clear. A high slope at submaximal exercise or a high V̇e/V̇co2 ratio at peak exercise is a powerful index of poor prognosis in patients with CHF.47 As indicated by Ponikowski et al8 in the current issue of Circulation, this prognostic power is retained in patients with CHF, even when the maximal O2 uptake (V̇o2 max) is near the normal range.A high V̇e/V̇co2 ratio has 2 possible sources: (1) increased ventilation, which is required to overcome a large dead space to maintain a normal arterial CO2 tension (Paco2), or (2) increased central drive to ventilation, which drives the Paco2 below what is normally expected. Ponikowski et al8 present convincing evidence that the augmented ventilatory response to exercise in CHF is significantly correlated with other markers of abnormal cardiorespiratory reflex control (ie, central and peripheral chemoreceptor control of ventilation, ergoreceptor drive to ventilation, and both autonomic and baroreceptor control of the circulation). Thus, the high V̇e/V̇co2 seems related to altered chemoreceptor gain and ergoreceptor drive to ventilation, as well as to impaired reflex control of the heart and circulation. Impaired autonomic and baroreceptor control become manifest in severe heart failure by an abnormally reduced variability in heart rate and an increased variability in blood pressure, with predisposition to arrhythmias and sudden death.910 These observations provide a major link between augmented exercise ventilation in CHF and poor prognosis.Is the augmented ventilation during exercise an integral part of the deranged cardiorespiratory reflex controls in CHF or a manifestation of structural changes in the lung that impair ventilation/perfusion matching, as I suggested in a previous editorial?11 Ponikowski et al8 and others612 from the same laboratory provide indirect support for a high ventilatory drive related to increased chemoreceptor gain and ergoreceptor drive in skeletal muscle. However, if present, such an increased ventilatory drive should force the Paco2 below expected levels during exercise and generate a negative correlation between Paco2 and V̇e/V̇co2 at peak exercise. No convincing data from arterial blood gases indicate that this occurs. Wasserman et al5 provided comprehensive data on alveolar arterial blood gas exchange in 130 patients with CHF and 52 normal controls. They concluded that “the increase in ventilatory response in CHF is due primarily to 2 mechanisms: (1) the increased CO2 output relative to V̇o2, owing to bicarbonate buffering of accumulating lactic acid, and (2) the increase in Vd/Vt ratio due to reduced perfusion of ventilated lung.” Arterial Pco2 was not depressed from rest to heavy exercise, although end-tidal Pco2 was depressed because of a high alveolar dead space. There was no evidence for increased central or peripheral drive to ventilation.Franciosa et al2 reported both arterial blood gas and hemodynamic data at rest and peak exercise in 28 patients with CHF. They concluded that “exercise intolerance in patients with severe CHF is associated with marked elevation of pulmonary capillary wedge pressure and anaerobic metabolism without hypoxemia or altered carbon dioxide tension.” The mean Paco2 (35±7 mm Hg) was the same at rest and peak exercise; hence, similar to the data from Wasserman et al,5 there was no evidence suggesting a high ventilatory drive. Fortunately, however, Franciosa et al2 provided the blood gas and hemodynamic data on each subject in a table, which allowed a more comprehensive analysis. Both the V̇e/V̇co2 and dead-space gas volume to tidal gas volume (Vd/Vt) ratios can be calculated at peak exercise from the tabulated data and plotted with respect to Paco2 (Figure 1). This yields a highly significant inverse correlation between V̇e/V̇co2 and Paco2 (Figure 1A) that supports Ponikowski et al’s8 hypothesis. There is also a highly significant, direct correlation between V̇e/V̇co2 and the Vd/Vt ratio (Figure 1B), confirming an uneven distribution of ventilation with respect to perfusion in the lung. Thus, the Paco2 is driven to low levels during peak exercise in CHF, despite inefficient gas exchange from a high Vd/Vt ratio.From whence might this increased drive arise? Ponikowski et al8 show high chemoreceptor gains for Po2 and Pco2 in CHF that positively correlate with a high V̇e/V̇co2 slope. Normal individuals who have high chemoreceptor gain also have an augmented ventilatory response to exercise.131415 In Figure 2, I compare the relationship between V̇e/V̇co2 and Paco2 at peak exercise in the CHF patients studied by Franciosa et al2 with that in the normal subjects studied by Martin et al.15 The normal subjects had different chemoreceptor gains for Po2 and Pco2 at rest, which were augmented at exercise; those normal subjects with high chemoreceptor gains had higher ratios of V̇e/V̇co2 and a lower Paco2. The point of the graph is to illustrate from the regression lines that that ventilation had to be about twice that in the normal subjects to achieve the same Paco2 because of the inefficient gas exchange (ie, the high Vd/Vt ratio). This means that ventilatory drive had to be, on average, twice as high in the CHF patients than in the normal subjects studied by Martin et al.15 It is hard to explain this increased drive by a simple increase in chemoreceptor gain, however, because chemoreceptor gain does not represent a unidirectional drive; rather, it represents the strength of feedback control to minimize any deviation of arterial Po2 and Pco2 in either direction from their respective set points. This is like the gain of the thermostat in a home air-conditioning system. Exercise must alter the set point of the control system, perhaps by increased sympathetic stimulation or from increased stimulation from skeletal muscle ergoreceptors, both of which are augmented in CHF. A high chemoreceptor gain would then tighten the control and ensure a smaller error signal at full response. It would be of interest to know whether normal subjects who have a high chemoreceptor gain and a high ventilatory response to exercise also have a high ergoreceptor drive from skeletal muscle.The augmented ventilatory response to exercise in CHF correlates with control and reflex abnormalities and with hemodynamic alterations. The latter relationships can also be illustrated from the data of Franciosa et al2 (Figure 3). There is a strong inverse correlation of V̇e/V̇co2 with cardiac index (Figure 3A) and with pulmonary artery pressure (Figure 3B). Hence, there are multiple reasons why this simple ratio of V̇e/V̇co2, or the slope of the increase in V̇e with respect to V̇co2 during exercise, provides a powerful prognostic index in heart failure. It seems to reflect the severity of derangement in almost all aspects of CHF; it is also an objective measurement that can be made easily.The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.Download figureDownload PowerPoint Figure 1. Relationship of augmented ventilation with respect to CO2 output (V̇e/V̇co2) to arterial CO2 tension (Paco2) and to dead-space ventilation (Vd/Vt) at peak exercise in patients with CHF, derived from data of Franciosa et al.2 Averaged data from Clark et al6 fall within same range. Results indicate that augmented ventilatory response in patients with heart failure is a consequence of both an increase in ventilatory drive and a corresponding increase in dead-space ventilation.Download figureDownload PowerPoint Figure 2. Data from Franciosa et al2 plotted in Figure 1A is compared with similar data in normal subjects studied by Martin et al,15 who also showed a positive correlation between chemoresponsiveness to hypoxia and hypercapnia similar to that in patients with CHF. Normal subjects with high chemosensitivity had a lower Paco2 and higher V̇e/V̇co2 than subjects with low chemosensitivity, but ventilation at same CO2 output in patients must be, on average, twice that in normal subjects to achieve same Paco2 as a consequence of inefficient gas exchange.Download figureDownload PowerPoint Figure 3. High V̇e/V̇co2 ratio in CHF also correlates significantly with hemodynamic abnormalities, as demonstrated here using data of Franciosa et al2 for cardiac index at peak exercise and for resting pulmonary artery (PA) pressure.FootnotesCorrespondence to Robert L. Johnson, Jr., MD, Pulmonary and Critical Care Division, Department of Internal Medicine, 5323 Harry Hines Blvd, Dallas, TX 75390-9034. 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Ponomarev D, Kamenskaya O, Klinkova A, Loginova I, Lomivorotov V, Kornilov I, Shmyrev V, Chernavskiy A, Landoni G and Karaskov A (2017) Prevalence and Implications of Abnormal Respiratory Patterns in Cardiac Surgery: A Prospective Cohort Study, Journal of Cardiothoracic and Vascular Anesthesia, 10.1053/j.jvca.2016.12.005, 31:6, (2010-2016), Online publication date: 1-Dec-2017. Dubé B, Agostoni P and Laveneziana P (2016) Exertional dyspnoea in chronic heart failure: the role of the lung and respiratory mechanical factors, European Respiratory Review, 10.1183/16000617.0048-2016, 25:141, (317-332), Online publication date: 1-Sep-2016. Jiang R, Wang L, Zhu C, Yuan P, Pudasaini B, Zhao Q, Gong S, He J, Liu J and Hu Q (2015) Comparative effectiveness of sildenafil for pulmonary hypertension due to left heart disease with HFrEF, Hypertension Research, 10.1038/hr.2015.73, 38:12, (829-839), Online publication date: 1-Dec-2015. 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Olson T, Denzer D, Sinnett W, Wilson T and Johnson B (2013) Prognostic Value of Resting pulmonary Function in Heart Failure, Clinical Medicine Insights: Circulatory, Respiratory and Pulmonary Medicine, 10.4137/CCRPM.S12525, 7, (CCRPM.S12525), Online publication date: 1-Jan-2013. Poon C and Tin C (2013) Mechanism of augmented exercise hyperpnea in chronic heart failure and dead space loading, Respiratory Physiology & Neurobiology, 10.1016/j.resp.2012.12.004, 186:1, (114-130), Online publication date: 1-Mar-2013. Poole D, Hirai D, Copp S and Musch T (2012) Muscle oxygen transport and utilization in heart failure: implications for exercise (in)tolerance, American Journal of Physiology-Heart and Circulatory Physiology, 10.1152/ajpheart.00943.2011, 302:5, (H1050-H1063), Online publication date: 1-Mar-2012. Apostolo A, Giusti G, Gargiulo P, Bussotti M and Agostoni P (2012) Lungs in Heart Failure, Pulmonary Medicine, 10.1155/2012/952741, 2012, (1-9), . 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BELOKA S, GUJIC M, DEBOECK G, NISET G, CIARKA A, ARGACHA J, ADAMOPOULOS D, VAN DE BORNE P and NAEIJE R (2008) β-Adrenergic Blockade and Metabo-Chemoreflex Contributions to ExerciseCapacity, Medicine & Science in Sports & Exercise, 10.1249/MSS.0b013e31817fbe11, 40:11, (1932-1938), Online publication date: 1-Nov-2008. Guazzi M, Casali M, Berti F, Rossoni G, D'Gennaro Colonna V and Guazzi M (2007) Endothelium-mediated Modulation of Ergoreflex and Improvement in Exercise Ventilation by Acute Sildenafil in Heart Failure Patients, Clinical Pharmacology & Therapeutics, 10.1038/sj.clpt.6100306, 83:2, (336-341), Online publication date: 1-Feb-2008. Jankowska E, Witkowski T, Ponikowska B, Reczuch K, Borodulin-Nadzieja L, Anker S, Piepoli M, Banasiak W and Ponikowski P (2007) Excessive ventilation during early phase of exercise: A new predictor of poor long-term outcome in patients with chronic heart failure, European Journal of Heart Failure, 10.1016/j.ejheart.2007.07.001, 9:10, (1024-1031), Online publication date: 1-Oct-2007. Poon C, Tin C and Yu Y (2007) Homeostasis of exercise hyperpnea and optimal sensorimotor integration: The internal model paradigm, Respiratory Physiology & Neurobiology, 10.1016/j.resp.2007.02.020, 159:1, (1-13), Online publication date: 1-Oct-2007. Ravipati G, McClung J, Aronow W, Peterson S and Frishman W (2007) Type 5 Phosphodiesterase Inhibitors in the Treatment of Erectile Dysfunction and Cardiovascular Disease, Cardiology in Review, 10.1097/01.crd.0000233904.77128.49, 15:2, (76-86), Online publication date: 1-Mar-2007. Brozhaitene J and Žiliukas G (2006) Characteristics of ventilatory control during exercise in coronary heart disease patients, Human Physiology, 10.1134/S0362119706040037, 32:4, (394-397), Online publication date: 1-Jul-2006. Wolfel E (2006) Exercise testing with concurrent beta-blocker usage: Is it useful? What do we learn?, Current Heart Failure Reports, 10.1007/s11897-006-0006-x, 3:2, (81-88), Online publication date: 1-Jun-2006. Guazzi M, Reina G, Tumminello G and Guazzi M (2004) Exercise ventilation inefficiency and cardiovascular mortality in heart failure: the critical independent prognostic value of the arterial CO2 partial pressure, European Heart Journal, 10.1093/eurheartj/ehi060, 26:5, (472-480), Online publication date: 1-Mar-2005. Guazzi M, Tumminello G, Di Marco F, Fiorentini C and Guazzi M (2004) The effects of phosphodiesterase-5 inhibition with sildenafil on pulmonary hemodynamics and diffusion capacity, exercise ventilatory efficiency, and oxygen uptake kinetics in chronic heart failure, Journal of the American College of Cardiology, 10.1016/j.jacc.2004.09.041, 44:12, (2339-2348), Online publication date: 1-Dec-2004. Guazzi M, Tumminello G, Matturri M and Guazzi M (2003) Insulin ameliorates exercise ventilatory efficiency and oxygen uptake in patients with heart failure–type 2 diabetes comorbidity, Journal of the American College of Cardiology, 10.1016/S0735-1097(03)00914-8, 42:6, (1044-1050), Online publication date: 1-Sep-2003. Kim H, Park S, Cho B, Hong S, Park P and Hong K (2003) The Role of Cardiopulmonary Exercise Test in Mitral and Aortic Regurgitation: It Can Predict Post-Operative Results, The Korean Journal of Internal Medicine, 10.3904/kjim.2003.18.1.35, 18:1, (35-39) Guazzi M, De Vita S, Cardano P, Barlera S and Guazzi M (2003) Normalization for peak oxygen uptake increases the prognostic power of the ventilatory response to exercise in patients with chronic heart failure, American Heart Journal, 10.1016/S0002-8703(03)00321-1, 146:3, (542-548), Online publication date: 1-Sep-2003. Robertson H (2011) Gas Exchange Consequences of Left Heart Failure Comprehensive Physiology, 10.1002/cphy.c100010, (621-634) Chen S, Wang L, Wu P, Liaw M, Chen Y, Chen A, Tsai T, Hang C and Lin M (2020) The Interrelationship between Ventilatory Inefficiency and Left Ventricular Ejection Fraction in Terms of Cardiovascular Outcomes in Heart Failure Outpatients, Diagnostics, 10.3390/diagnostics10070469, 10:7, (469) Mélot C and Naeije R (2011) Pulmonary Vascular Diseases Comprehensive Physiology, 10.1002/cphy.c090014, (593-619) Phillips D, Collins S and Stickland M (2020) Measurement and Interpretation of Exercise Ventilatory Efficiency, Frontiers in Physiology, 10.3389/fphys.2020.00659, 11 February 20, 2001Vol 103, Issue 7 Advertisement Article InformationMetrics Copyright © 2001 by American Heart Associationhttps://doi.org/10.1161/01.CIR.103.7.916 Originally publishedFebruary 20, 2001 Keywordsheart failureEditorialsventilationPDF download Advertisement

HomeCirculationVol. 101, No. 24Gas Exchange Efficiency in Congestive Heart Failure Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBGas Exchange Efficiency in Congestive Heart Failure Robert L. JohnsonJr Robert L. JohnsonJrRobert L. JohnsonJr From the Division of Pulmonary and Critical Care, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Tex. Originally published20 Jun 2000https://doi.org/10.1161/01.CIR.101.24.2774Circulation. 2000;101:2774–2776The lungs and heart are irrevocably linked in their oxygen and CO2 transport functions. Functional impairment of the lungs often affects heart function, and functional impairment of the heart often affects lung function. In patients with chronic congestive heart failure (CHF), exertional dyspnea is a common symptom, and ventilatory effort is increased at a given exercise workload despite normal arterial blood gases. In this issue of Circulation, the increased exercise ventilation in CHF is reported to contain prognostic information that extends beyond that provided by maximal oxygen uptake (V̇o2max), left ventricular ejection fraction, or the NYHA functional classification.1 Their data indicate that the steepness with which ventilation increases relative to CO2 production during incremental exercise, either alone or in combination with V̇o2max, left ventricular ejection fraction, and NYHA classification, can be a sensitive tool for predicting event-free survival of patients with CHF. Such a tool can be important for evaluating the need for heart transplantation or for following the efficacy of therapeutic measures; it can be evaluated at submaximal work loads and is easier to measure than V̇o2max.The high ventilation (V̇e) with respect to CO2 production (V̇co2) in CHF is not a new observation,23456 but its potential usefulness as a prognostic tool to evaluate the severity of CHF is relatively new. Perhaps even more important, however, is what the studies of Kleber et al,1 using this tool, tell us about impaired gas exchange in CHF and its relationship to impaired gas exchange in lung disease.Because the high level of ventilatory drive in heart failure can predict survival, it must contain important information on how left ventricular dysfunction affects either the lung or ventilatory control. The first thing that we need to examine, then, is what basic information is contained in the slope of the relationship between ventilation (V̇e) and CO2 production (V̇co2). The modified alveolar equation7 concisely describes the determinants of the steepness with which V̇e rises with respect to V̇co2: The relationship between V̇e and V̇co2 by Equation 1 is linear over a wide range, and its slope is determined by just 2 factors: (1) behavior of arterial CO2 tension during exercise and (2) the Vd/Vt ratio. If Paco2 is driven down by a high ventilatory drive from peripheral chemoreceptors or by ergoreceptors in skeletal muscle, the slope of the V̇e/V̇co2 relationship will increase, or if Vd/Vt is high, the V̇e/V̇co2 slope will increase. Increased chemoreceptor gain is often seen in severe CHF,8 eg, in patients with Cheyne-Stokes breathing, but increased chemoreceptor gain alone will not drive the Paco2 down unless the set point about which Paco2 is controlled is depressed or unless hypoxic drive or ergoreceptor drive is high. Most studies suggest that blood gases are normal in patients with CHF4 and that Paco2 either stays the same or declines modestly from rest to peak exercise, no differently than in normal controls. There are 2 potential sources for a high Vd/Vt ratio: (1) a low tidal volume (Vt) with respect to a normal anatomic dead space or (2) an abnormally high physiological dead space. Patients with CHF often have a reduced tidal volume at heavy exercise, which would increase the Vd/Vt ratio; however, it has been estimated that only ≈33% of the increased dead space ventilation in CHF can be explained by a low Vt.25Current information suggests that the major source for an abnormally steep V̇e/V̇co2 slope in CHF is increased nonuniformity of ventilation-perfusion ratios (V̇/Q̇), causing inefficient gas exchange. However, a word of caution is still necessary. The above conclusion is based on indirect evidence. No direct comparisons have been made of Paco2 and dead space ventilation in CHF patients with and without a high V̇e/V̇co2 slope during exercise. Such comparisons are needed.What might be the source of an increased nonuniformity of pulmonary V̇/Q̇ ratios in CHF and why would it provide prognostic information not provided by V̇o2max? Lung volumes and ventilatory function in the CHF patients studied by Kleber et al1 were relatively normal, and arterial blood oxygen saturation at peak exercise was normal, as is generally the case in CHF in the absence of coexisting lung disease. This pattern of a high Vd/Vt ratio with normal arterial blood gases suggests that nonuniformity of V̇/Q̇ ratios in the lung is more likely caused by increased nonuniformity of perfusion than of ventilation. When ventilatory capacity remains normal, inefficient gas exchange caused by abnormal distribution of perfusion usually can be well compensated during exercise by raising ventilation enough to maintain a normal Paco2 and normal arterial blood O2 saturation. This is not true in severe chronic obstructive lung disease, in which not only are ventilation and perfusion poorly matched, but also, compensatory increases in ventilation are restricted by the high resistance to air flow; during exercise, Paco2 rises and arterial blood O2 saturation falls. In the CHF patients studied by Kleber et al1 with high V̇e/V̇co2 slopes, mean total lung capacity (TLC), vital capacity (VC), and lung diffusing capacity (Dlco) were significantly lower than in patients with a normal V̇e/V̇co2 slope, yet arterial O2 saturation remained normal at peak exercise. Dlco is usually reduced in severe CHF9101112 and correlates significantly with V̇o2max. A modest reduction in Dlco may reflect a more severe reduction of true membrane diffusing capacity (Dmco), because the low Dmco in CHF can be counterbalanced by a high pulmonary capillary blood volume (Vc). In patients with severe CHF (NYHA class III) studied by Puri et al,9 Dmco was 35% of control, whereas Dlco was reduced only to 55% of control because of a high Vc (144% of control). The low Dmco implies that oxygen diffusing capacity (Dlo2) is correspondingly reduced, which in turn will reduce the rate of oxygenation of blood perfusing the lungs, and if the cardiac output is high enough, will cause oxygen saturation of blood leaving the lung to fall during exercise. Some of these changes in diffusing capacity and dead space ventilation are reversible with ACE inhibitors and diuretics, reflecting subclinical interstitial pulmonary edema.513 However, persistence of a low Dlco after heart transplantation14 implies additional structural changes in microvasculature, which is confirmed by morphological studies. Muscular arteries and arterioles show medial hypertrophy and intimal and adventitial fibrosis with narrowing vascular lumens.15 Matrix proteins are increased in the alveolar walls, and capillary basement membranes are thickened1617 ; these changes probably begin very early in response to a chronic increase in pulmonary capillary blood pressure from any cause.18In the face of an abnormally high Vd/Vt ratio and a significant reduction of Dlo2 in patients with severe CHF, why is maximal oxygen transport not partially limited by impaired gas exchange associated with a rise in Paco2 and fall in arterial O2 saturation during exercise, as usually occurs in lung disease with similar abnormalities? There are 2 reasons: (1) Maximal ventilatory capacity is well maintained in CHF and can compensate for the high Vd/Vt, bringing the Paco2 down to normal levels at peak exercise and maintaining a normal or high alveolar oxygen tension. (2) Maximal cardiac output (Q̇max) in CHF is reduced more than is the Dlo2; hence, the ratio of Dlo2/Q̇ never falls low enough during exercise to cause a fall of O2 saturation of blood leaving the lung.7It is the low maximal cardiac output and impaired peripheral O2 extraction that primarily impairs oxygen transport in CHF,419 not pulmonary gas exchange; arterial blood gases remain normal. However, the reduced efficiency of gas exchange in CHF reflected by the steep relationship between V̇e and V̇co2 is probably a major source of the exertional dyspnea with normal arterial blood gases.Thus, left ventricular heart failure has important effects on lung function, just as lung disease has important effects on cardiovascular function. The application of a measurement that quantifies efficiency of gas exchange during exercise as an index of the severity of CHF and life expectancy in CHF emphasizes the important functional linkage between the heart and the lungs. The measurement used is simple and can be applied even at low levels of exercise. It must be emphasized, however, that the measurement, ie, the slope of the relationship between V̇e and V̇co2 during exercise, is nonspecific and is frequently abnormally steep in primary lung disease as well as in CHF, although usually associated with abnormal arterial blood gases in lung disease. Hence, the measurement used by Kleber et al1 must be interpreted in context. To emphasize this, a comparison of the primary determinants of impaired gas exchange in CHF, chronic obstructive lung disease, and interstitial lung disease with alveolar capillary block20 are shown in the Table.In the Table, the arrows, pointing either up or down, indicate the change in direction of the key determinants at each step in oxygen transport for each condition. The Table is oversimplified but is conceptually useful. In CHF, the primary impairment of oxygen transport is imposed by a reduced maximal cardiac output (Q̇max), indicated by a boldface arrow pointing down. In patients with chronic obstructive pulmonary disease, primary impairment of oxygen transport is imposed by a reduced maximal ventilation (V̇emax) with inefficient gas exchange, and in patients with interstitial lung disease with alveolar capillary block, the primary impairment is imposed by a reduced Dlo2. In all of these disorders, uneven V̇/Q̇ matching increases the Vd/Vt ratio and impairs the efficiency of CO2 excretion from the lung; if ventilation can be increased enough during increasing exercise to prevent the Paco2 from rising, the V̇e/V̇co2 slope will be steeper than normal in lung disease as well as in CHF, as indicated by the bracketed term in Equation 1. In severe chronic obstructive pulmonary disease, Paco2 will rise as exercise load increases, and the V̇e/V̇co2 slope may become low even though Vd/Vt is high.19 Coexistent lung disease can significantly alter the expected pattern of gas exchange in CHF. Thus, it must be cautioned that if a patient with CHF has significant coexistent lung disease, application of the V̇e/V̇co2 slope to predict survival, as proposed by Kleber et al,1 becomes invalid.In summary, available data suggest that chronic CHF induces structural changes as well as interstitial pulmonary edema in the lungs, which impair the efficiency of gas exchange; the extent of these changes reflects the severity of the CHF and probably its duration. Physiologically, these structural changes are manifested by an increased ratio of dead space to tidal volume (Vd/Vt), which causes an abnormally high ventilation during exercise. They are also usually manifested by a reduction in diffusing capacity of the lung (Dlco), which varies with the severity of CHF. Although the magnitude of these physiological changes in lung function can reflect the severity of CHF and be an important predictor of survival, inefficiency of gas exchange is not the primary cause of impaired exercise capacity. Reduced maximal oxygen transport in CHF is caused by a low maximal cardiac output and perhaps impaired peripheral oxygen extraction; arterial Paco2 and arterial O2 saturation at peak exercise remain normal. Even though arterial blood gases remain normal, inefficient gas exchange can be a major source of exertional hyperpnea and dyspnea. The pattern of abnormal gas exchange during exercise in CHF clearly differs from that in primary lung disease; problems of interpretation arise when CHF and primary pulmonary disease coexist.The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association. Table 1. Determinants of Gas Exchange at Maximal Exercise in Patients With CHF and With Primary Lung Disease Q̇ max V̇ emaxDlo2Vd/VtV̇e/V̇co2 SlopeDlo2/Q̇Paco2Sao2CHF ⬇ N↓↑↑NNNCOPD↓ ⬇ ↓↑V↓V↓IPF↓↓ ⬇ ↑↑ ⬇ ↓ ⬇ COPD indicates chronic obstructive lung disease; IPF, interstitial pulmonary fibrosis; V, variable (can be high, normal, or low); N, normal; ↓, decreased; ↑, increased; and boldface arrow, a primary change. In CHF, the primary determinant of V̇o2max is a low Q̇max; in COPD, the primary determinant is V̇emax; and in IPF with alveolar capillary block, the primary determinant of V̇o2max is a low Dlo2.FootnotesCorrespondence to Robert L. 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References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate. Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page. Sign In to Submit a Response to This Article Previous Back to top Next FiguresReferencesRelatedDetailsCited By Dempsey J and Welch J (2023) Control of Breathing, Seminars in Respiratory and Critical Care Medicine, 10.1055/s-0043-1770342, 44:05, (627-649), Online publication date: 1-Oct-2023. Eser P, Marcin T, Prescott E, Prins L, Kolkman E, Bruins W, van der Velde A, Gil C, Iliou M, Ardissino D, Zeymer U, Meindersma E, Van't Hof A, de Kluiver E and Wilhelm M (2023) Breathing pattern and pulmonary gas exchange in elderly patients with and without left ventricular dysfunction—modification with exercise-based cardiac rehabilitation and prognostic value, Frontiers in Cardiovascular Medicine, 10.3389/fcvm.2023.1219589, 10 Omar M, Omote K, Sorimachi H, Popovic D, Kanwar A, Alogna A, Reddy Y, Lim K, Shah S and Borlaug B (2023) Hypoxaemia in patients with heart failure and preserved ejection fraction, European Journal of Heart Failure, 10.1002/ejhf.2930, 25:9, (1593-1603), Online publication date: 1-Sep-2023. Ashikaga K, Itoh H, Maeda T, Itoh H, Tanaka S, Ichikawa Y, Nagayama M, Akashi Y and Isobe M (2022) Usefulness of the predicted percentage ventilatory efficiency for carbon dioxide output during exercise in patients with chronic heart failure, Heart and Vessels, 10.1007/s00380-022-02132-w, 38:1, (56-65), Online publication date: 1-Jan-2023. Schulz A and Schuster A (2022) Visualizing diastolic failure: Non-invasive imaging-biomarkers in patients with heart failure with preserved ejection fraction, eBioMedicine, 10.1016/j.ebiom.2022.104369, 86, (104369), Online publication date: 1-Dec-2022. Cuocolo A and Petretta M (2021) Ventilation/perfusion SPECT: One more promising resource to fight the medical Hydra, Journal of Nuclear Cardiology, 10.1007/s12350-021-02846-w, 29:6, (2984-2987), Online publication date: 1-Dec-2022. Neder J, Phillips D, O'Donnell D and Dempsey J (2022) Excess ventilation and exertional dyspnoea in heart failure and pulmonary hypertension, European Respiratory Journal, 10.1183/13993003.00144-2022, 60:5, (2200144), Online publication date: 1-Nov-2022. Huang J, McDonnell B, Lawley J, Byrd J, Stöhr E and Cornwell W (2022) Impact of Mechanical Circulatory Support on Exercise Capacity in Patients With Advanced Heart Failure, Exercise and Sport Sciences Reviews, 10.1249/JES.0000000000000303, 50:4, (222-229), Online publication date: 1-Oct-2022. Neder J, Berton D, Phillips D and O'Donnell D (2021) Exertional ventilation/carbon dioxide output relationship in COPD: from physiological mechanisms to clinical applications, European Respiratory Review, 10.1183/16000617.0190-2020, 30:161, (200190), Online publication date: 30-Sep-2021. Nishizaki M, Ogawa A and Matsubara H (2020) Response to exercise in patients with pulmonary arterial hypertension treated with combination therapy, ERJ Open Research, 10.1183/23120541.00725-2020, 7:1, (00725-2020), Online publication date: 1-Jan-2021. Santoso A, Maulana R, Alzahra F, Prameswari H, Ambari A, Hartopo A, Arso I and Radi B (2020) The Effects of Aerobic Exercise on N-terminal Pro-B-type Natriuretic Peptide and Cardiopulmonary Function in Patients With Heart Failure: A Meta-Analysis of Randomised Clinical Trials, Heart, Lung and Circulation, 10.1016/j.hlc.2020.05.098, 29:12, (1790-1798), Online publication date: 1-Dec-2020. Cundrle I, Johnson B, Rea R, Scott C, Somers V and Olson L (2020) Mitigation of Exercise Oscillatory Ventilation Score by Cardiac Resynchronization Therapy, Journal of Cardiac Failure, 10.1016/j.cardfail.2020.03.006, 26:10, (832-840), Online publication date: 1-Oct-2020. Chen S, Wang L, Wu P, Liaw M, Chen Y, Chen A, Tsai T, Hang C and Lin M (2020) The Interrelationship between Ventilatory Inefficiency and Left Ventricular Ejection Fraction in Terms of Cardiovascular Outcomes in Heart Failure Outpatients, Diagnostics, 10.3390/diagnostics10070469, 10:7, (469) Nayor M, Xanthakis V, Tanguay M, Blodgett J, Shah R, Schoenike M, Sbarbaro J, Farrell R, Malhotra R, Houstis N, Velagaleti R, Moore S, Baggish A, O'Connor G, Ho J, Larson M, Vasan R and Lewis G (2020) Clinical and Hemodynamic Associations and Prognostic Implications of Ventilatory Efficiency in Patients With Preserved Left Ventricular Systolic Function, Circulation: Heart Failure, 13:5, Online publication date: 1-May-2020. Thompson R, Chow K, Pagano J, Sekowski V, Michelakis E, Tymchak W, Haykowsky M, Ezekowitz J, Oudit G, Dyck J, Kaul P, Savu A and Paterson D (2019) Quantification of lung water in heart failure using cardiovascular magnetic resonance imaging, Journal of Cardiovascular Magnetic Resonance, 10.1186/s12968-019-0567-y, 21:1, Online publication date: 1-Dec-2019. Kampouras A, Hatziagorou E, Avramidou V, Georgopoulou V, Kirvassilis F, Hebestreit H and Tsanakas J (2019) Ventilation efficiency to exercise in patients with cystic fibrosis, Pediatric Pulmonology, 10.1002/ppul.24438, 54:10, (1584-1590), Online publication date: 1-Oct-2019. Cundrle I, Olson L and Johnson B (2019) Pulmonary Limitations in Heart Failure, Clinics in Chest Medicine, 10.1016/j.ccm.2019.02.010, 40:2, (439-448), Online publication date: 1-Jun-2019. Schure A and DiNardo J (2019) Cardiac Physiology and Pharmacology A Practice of Anesthesia for Infants and Children, 10.1016/B978-0-323-42974-0.00018-5, (424-457.e17), . Kato Y, Suzuki S, Uejima T, Semba H, Nagayama O, Hayama E, Arita T, Yagi N, Kano H, Matsuno S, Otsuka T, Oikawa Y, Kunihara T, Yajima J and Yamashita T (2018) Relationship between the prognostic value of ventilatory efficiency and age in patients with heart failure, European Journal of Preventive Cardiology, 10.1177/2047487318758775, 25:7, (731-739), Online publication date: 1-May-2018. Ponomarev D, Kamenskaya O, Klinkova A, Loginova I, Lomivorotov V, Kornilov I, Shmyrev V, Chernavskiy A, Landoni G and Karaskov A (2017) Prevalence and Implications of Abnormal Respiratory Patterns in Cardiac Surgery: A Prospective Cohort Study, Journal of Cardiothoracic and Vascular Anesthesia, 10.1053/j.jvca.2016.12.005, 31:6, (2010-2016), Online publication date: 1-Dec-2017. Tipton M, Harper A, Paton J and Costello J (2017) The human ventilatory response to stress: rate or depth?, The Journal of Physiology, 10.1113/JP274596, 595:17, (5729-5752), Online publication date: 1-Sep-2017. Mezzani A (2017) Cardiopulmonary Exercise Testing: Basics of Methodology and Measurements, Annals of the American Thoracic Society, 10.1513/AnnalsATS.201612-997FR, 14:Supplement_1, (S3-S11), Online publication date: 1-Jul-2017. Mezzani A, Giordano A, Komici K and Corrà U (2017) Different Determinants of Ventilatory Inefficiency at Different Stages of Reduced Ejection Fraction Chronic Heart Failure Natural History, Journal of the American Heart Association, 6:5, Online publication date: 5-May-2017. Cundrle I, Somers V, Singh P, Johnson B, Scott C and Olson L (2017) Sex differences in leptin modulate ventilation in heart failure, Heart & Lung, 10.1016/j.hrtlng.2017.01.008, 46:3, (187-191), Online publication date: 1-May-2017. Malhotra R, Bakken K, D'Elia E and Lewis G (2016) Cardiopulmonary Exercise Testing in Heart Failure, JACC: Heart Failure, 10.1016/j.jchf.2016.03.022, 4:8, (607-616), Online publication date: 1-Aug-2016. Chase S, Wheatley C, Olson L, Beck K, Wentz R, Snyder E, Taylor B and Johnson B (2016) Impact of chronic systolic heart failure on lung structure-function relationships in large airways, Physiological Reports, 10.14814/phy2.12867, 4:13, (e12867), Online publication date: 1-Jul-2016. Warriner D, Sheridan P and Lawford P (2015) Heart failure: not a single organ disease but a multisystem syndrome, British Journal of Hospital Medicine, 10.12968/hmed.2015.76.6.330, 76:6, (330-336), Online publication date: 2-Jun-2015. Cundrle I, Johnson B, Rea R, Scott C, Somers V and Olson L (2015) Modulation of Ventilatory Reflex Control by Cardiac Resynchronization Therapy, Journal of Cardiac Failure, 10.1016/j.cardfail.2014.12.013, 21:5, (367-373), Online publication date: 1-May-2015. SHEN Y, ZHANG X, MA W, SONG H, GONG Z, WANG Q, CHE L, XU W, JIANG J, XU J, YAN W, ZHOU L, NI Y, LI G, ZHANG Q and WANG L (2015)(2015) VE/VCO2 slope and its prognostic value in patients with chronic heart failure, Experimental and Therapeutic Medicine, 10.3892/etm.2015.2267, 9:4, (1407-1412), Online publication date: 1-Apr-2015. Houstis N and Lewis G (2014) Causes of Exercise Intolerance in Heart Failure With Preserved Ejection Fraction: Searching for Consensus, Journal of Cardiac Failure, 10.1016/j.cardfail.2014.07.010, 20:10, (762-778), Online publication date: 1-Oct-2014. Thomsen L, Karbing D, Smith B, Murley D, Weinreich U, Kjærgaard S, Toft E, Thorgaard P, Andreassen S and Rees S (2013) Clinical refinement of the automatic lung parameter estimator (ALPE), Journal of Clinical Monitoring and Computing, 10.1007/s10877-013-9442-9, 27:3, (341-350), Online publication date: 1-Jun-2013. Poon C and Tin C (2013) Mechanism of augmented exercise hyperpnea in chronic heart failure and dead space loading, Respiratory Physiology & Neurobiology, 10.1016/j.resp.2012.12.004, 186:1, (114-130), Online publication date: 1-Mar-2013. Olson T, Denzer D, Sinnett W, Wilson T and Johnson B (2013) Prognostic Value of Resting pulmonary Function in Heart Failure, Clinical Medicine Insights: Circulatory, Respiratory and Pulmonary Medicine, 10.4137/CCRPM.S12525, 7, (CCRPM.S12525), Online publication date: 1-Jan-2013. Ramos R, Alencar M, Treptow E, Arbex F, Ferreira E and Neder J (2013) Clinical Usefulness of Response Profiles to Rapidly Incremental Cardiopulmonary Exercise Testing, Pulmonary Medicine, 10.1155/2013/359021, 2013, (1-25), . Schwaiblmair M, Faul C, von Scheidt W and Berghaus T (2012) Ventilatory efficiency testing as prognostic value in patients with pulmonary hypertension, BMC Pulmonary Medicine, 10.1186/1471-2466-12-23, 12:1, Online publication date: 1-Dec-2012. Corrà U, Mezzani A, Giordano A, Caruso R and Giannuzzi P (2011) A new cardiopulmonary exercise testing prognosticating algorithm for heart failure patients treated with beta-blockers, European Journal of Preventive Cardiology, 10.1177/1741826710396625, 19:2, (185-191), Online publication date: 1-Apr-2012. Poole D, Hirai D, Copp S and Musch T (2012) Muscle oxygen transport and utilization in heart failure: implications for exercise (in)tolerance, American Journal of Physiology-Heart and Circulatory Physiology, 10.1152/ajpheart.00943.2011, 302:5, (H1050-H1063), Online publication date: 1-Mar-2012. Apostolo A, Giusti G, Gargiulo P, Bussotti M and Agostoni P (2012) Lungs in Heart Failure, Pulmonary Medicine, 10.1155/2012/952741, 2012, (1-9), . Robertson H (2011) Gas Exchange Consequences of Left Heart Failure Comprehensive Physiology, 10.1002/cphy.c100010, (621-634) Methvin A, Owens A, Emmi A, Allen M, Wiegers S, Dries D, Margulies K and Forfia P (2011) Ventilatory Inefficiency Reflects Right Ventricular Dysfunction in Systolic Heart Failure, Chest, 10.1378/chest.10-0318, 139:3, (617-625), Online publication date: 1-Mar-2011. Woods P, Bailey K, Wood C and Johnson B (2014) Submaximal exercise gas exchange is an important prognostic tool to predict adverse outcomes in heart failure, European Journal of Heart Failure, 10.1093/eurjhf/hfq187, 13:3, (303-310), Online publication date: 1-Mar-2011. Tang W and Francis G (2011) Clinical Evaluation of Heart Failure Heart Failure: A Companion to Braunwald's Heart Disease, 10.1016/B978-1-4160-5895-3.10035-X, (511-525), . Woods P, Olson T, Frantz R and Johnson B (2010) Causes of Breathing Inefficiency During Exercise in Heart Failure, Journal of Cardiac Failure, 10.1016/j.cardfail.2010.05.003, 16:10, (835-842), Online publication date: 1-Oct-2010. Elliott A and Grace F (2010) An examination of exercise mode on ventilatory patterns during incremental exercise, European Journal of Applied Physiology, 10.1007/s00421-010-1541-4, 110:3, (557-562), Online publication date: 1-Oct-2010. Olson T, Joyner M, Dietz N, Eisenach J, Curry T and Johnson B (2010) Effects of respiratory muscle work on blood flow distribution during exercise in heart failure, The Journal of Physiology, 10.1113/jphysiol.2009.186056, 588:13, (2487-2501), Online publication date: 1-Jul-2010. Mezzani A, Agostoni P, Cohen-Solal A, Corrà U, Jegier A, Kouidi E, Mazic S, Meurin P, Piepoli M, Simon A, Laethem C and Vanhees L (2009) Standards for the use of cardiopulmonary exercise testing for the functional evaluation of cardiac patients: a report from the Exercise Physiology Section of the European Association for Cardiovascular Prevention and Rehabilitation, European Journal of Cardiovascular Prevention & Rehabilitation, 10.1097/HJR.0b013e32832914c8, 16:3, (249-267), Online publication date: 1-Jun-2009. Moesgaard J, Kristensen J, Malczynski J, Holst-Hansen C, Rees S, Murley D, Andreassen S, Frokjaer J and Toft E (2009) Can new pulmonary gas exchange parameters contribute to evaluation of pulmonary congestion in left-sided heart failure?, Canadian Journal of Cardiology, 10.1016/S0828-282X(09)70042-X, 25:3, (149-155), Online publication date: 1-Mar-2009. Ukkonen H, Burwash I, Dafoe W, de Kemp R, Haddad H, Yoshinaga K, Davies R, Gannon E, DaSilva J and Beanlands R (2008) Is ventilatory efficiency (VE/VCO 2 slope) associated with right ventricular oxidative metabolism in patients with congestive heart failure? , European Journal of Heart Failure, 10.1016/j.ejheart.2008.08.010, 10:11, (1117-1122), Online publication date: 1-Nov-2008. ARENA R, OWENS D, AREVALO J, SMITH K, MOHIDDIN S, MCAREAVEY D, ULISNEY K, TRIPODI D, FANANAPAZIR L and PLEHN J (2008) Ventilatory Efficiency and Resting Hemodynamics in Hypertrophic Cardiomyopathy, Medicine & Science in Sports & Exercise, 10.1249/MSS.0b013e31816459a1, 40:5, (799-805), Online publication date: 1-May-2008. Olson L, Arruda-Olson A, Somers V, Scott C and Johnson B (2008) Exercise Oscillatory Ventilation, Chest, 10.1378/chest.07-2146, 133:2, (474-481), Online publication date: 1-Feb-2008. Milani R, Lavie C, Mehra M and Ventura H (2006) Understanding the Basics of Cardiopulmonary Exercise Testing, Mayo Clinic Proceedings, 10.4065/81.12.1603, 81:12, (1603-1611), Online publication date: 1-Dec-2006. Wolfel E (2006) Exercise testing with concurrent beta-blocker usage: Is it useful? What do we learn?, Current Heart Failure Reports, 10.1007/s11897-006-0006-x, 3:2, (81-88), Online publication date: 1-Jun-2006. Davis J, Sorrentino K, Ninness E, Pham P, Dorado S and Costello K (2006) Test–retest reliability for two indices of ventilatory efficiency measured during cardiopulmonary exercise testing in healthy men and women, Clinical Physiology and Functional Imaging, 10.1111/j.1475-097X.2006.00674.x, 26:3, (191-196), Online publication date: 1-May-2006. Olson L, Snyder E, Beck K and Johnson B (2006) Reduced Rate of Alveolar-Capillary Recruitment and Fall of Pulmonary Diffusing Capacity During Exercise in Patients With Heart Failure, Journal of Cardiac Failure, 10.1016/j.cardfail.2006.01.010, 12:4, (299-306), Online publication date: 1-May-2006. Davis J, Tyminski T, Soriano A, Dorado S, Costello K, Sorrentino K and Pham P (2006) Exercise test mode dependency for ventilatory efficiency in women but not men, Clinical Physiology and Functional Imaging, 10.1111/j.1475-097X.2006.00657.x, 26:2, (72-78), Online publication date: 1-Mar-2006. Murley D, Rees S, Rasmussen B and Andreassen S (2005) Decision support of inspired oxygen selection based on Bayesian learning of pulmonary gas exchange parameters, Artificial Intelligence in Medicine, 10.1016/j.artmed.2004.07.012, 34:1, (53-63), Online publication date: 1-May-2005. Guazzi M (2003) Alveolar-Capillary Membrane Dysfunction in Heart Failure, Chest, 10.1378/chest.124.3.1090, 124:3, (1090-1102), Online publication date: 1-Sep-2003. Tabet J, Beauvais F, Thabut G, Tarti??re J, Logeart D and Cohen-Solal A (2003) A critical appraisal of the prognostic value of the VE/VCO2 slope in chronic heart failure, European Journal of Cardiovascular Prevention & Rehabilitation, 10.1097/00149831-200308000-00008, 10:4, (267-272), Online publication date: 1-Aug-2003. Rees S, Malczynski J, Korup E, Kjaergaard S, Thorgaard P, Andreassen S and Toft E Assessing pulmonary congestion in left sided heart failure using pulmonary gas exchange parameters 25th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, 10.1109/IEMBS.2003.1279703, 0-7803-7789-3, (435-438) Murley D, Rees S, Rasmussen B and Andreassen S (2003) Bayesian Learning of the Gas Exchange Properties of the Lung for Prediction of Arterial Oxygen Saturation Artificial Intelligence in Medicine, 10.1007/978-3-540-39907-0_37, (264-273), . Crapo R, Jensen R and Wanger J (2001) SINGLE-BREATH CARBON MONOXIDE DIFFUSING CAPACITY, Clinics in Chest Medicine, 10.1016/S0272-5231(05)70057-5, 22:4, (637-649), Online publication date: 1-Dec-2001. Lauer M and Snader C (2001) USING EXERCISE TESTING TO PROGNOSTICATE PATIENTS WITH HEART FAILURE, Cardiology Clinics, 10.1016/S0733-8651(05)70244-7, 19:4, (573-581), Online publication date: 1-Nov-2001. June 20, 2000Vol 101, Issue 24 Advertisement Article Information Metrics Copyright © 2000 by American Heart Associationhttps://doi.org/10.1161/01.CIR.101.24.2774PMID: 10859280 Originally publishedJune 20, 2000 KeywordsEditorialsexercisedyspneahyperpneablood gasesPDF download Advertisement

ABSTRACTThis study examined the effects of a single set of weight training exercise to failure and 2 multiple-set protocols (not to failure) on the 1-RM parallel squat. Forty-three men were randomly assigned to 1 of 3 weight training protocols emphasizing leg and hip strength: SS = single set to fai

Ventilation-perfusion relationships, diffusing capacity for O2, and hemodynamic response were measured at rest and during exercise while five adult dogs breathed air and 15% O2 2 mo (Pnx-A, n = 2) or 12 mo (Pnx-B, n = 3) after right pneumonectomy (removal of 58% of lung tissue). Results were compared with those in five sham-operated controls. The multiple inert gas elimination technique was employed. Maximal O2 uptake was reduced by 50% in Pnx-A and by 15% in Pnx-B. Ventilation-perfusion matching was impaired in Pnx-A but not in Pnx-B. The increase in O2 diffusing capacity during exercise was significantly restricted in Pnx-A but was partially restored in Pnx-B. Mean pulmonary arterial pressure at a given blood flow through the remaining lung was normal in Pnx-A but lower than normal in Pnx-B compared with control values for a single lung. Stroke volume and cardiac output were lower in both Pnx-A and Pnx-B than in controls at a given exercise level. All functional abnormalities were more severe at 2 mo than at 12 mo postpneumonectomy. Gas phase diffusion resistance was present in both Pnx-A and Pnx-B but not in controls. We conclude that physiological compensation postpneumonectomy is progressive. Inability to recruit pulmonary vascular bed with incremental perfusion pressure or flow appears to be the major pathophysiological process that limits early functional capacity after right pneumonectomy.

A two-stage process by which a holistic rubric is applied to the assessment of open-ended items, such as writing samples, is defined. The first stage involves scoring a performance by the assignment of an integer rating that is congruent with the proficiency level that is exhibited in the performance. The second stage is the subsequent assignment by the rater of an augmentation that indicates whether or not the writing competency reflected in the paper is a bit higher or lower than the competency level reflected in the benchmark paper for the given proficiency level. If the rater feels that the paper represents benchmark proficiency for the given level, no augmentation is assigned to the rating. The results of this study indicate that the use of rating augmentation can improve the inter-rater reliability of holistic assessments, as indicated by generalizability phi coefficients, correlation coefficients, and percent agreement indices. Implications and suggestions for follow-up research are discussed.

Abstract Many studies have indicated that at least 2 raters should score writing assessments to improve interrater reliability. However, even for assessments that characteristically demonstrate high levels of rater agreement, 2 raters of the same essay can occasionally report different, or discrepant, scores. If a single score, typically referred to as an operational score, is to be reported to the examinee, then a method of resolving those differences must be applied to the ratings. Many score resolution methods are available to assessment practitioners, and the choice of resolution method might affect the reliability and the validity of the resulting operational scores. This study investigates the accuracy of scores when based on either (a) averaging the 2 discrepant ratings or (b) using discussion to obtain a consensus score. Two questions guided our investigation. First, when 2 raters disagree, does discussion improve the accuracy of the reported scores as compared to averaging the original scores? Second, is there evidence that raters are equally engaged in the resolution process, or does the use of discussion as a form of resolution allow the opportunity for one rater to dominate, or defer, to the other rater?

ARTICLESEfficiency, maximal blood flow, and aerobic work capacity of canine diaphragmM. B. Reid, and R. L. Johnson JrM. B. Reid, and R. L. Johnson JrPublished Online:01 Mar 1983https://doi.org/10.1152/jappl.1983.54.3.763MoreSectionsPDF (2 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited BySupraspinal fatigue in human inspiratory muscles with repeated sustained maximal effortsBilly L. Luu,* Julian P. Saboisky,* Janet L. Taylor, Robert B. Gorman, Simon C. Gandevia, and Jane E. Butler11 December 2020 | Journal of Applied Physiology, Vol. 129, No. 6Respiratory muscle blood flow during exercise: Effects of sex and ovarian cycleJoshua R. Smith, K. Sue Hageman, Craig A. Harms, David C. Poole, and Timothy I. Musch5 April 2017 | Journal of Applied Physiology, Vol. 122, No. 4Human diaphragm efficiency estimated as power output relative to activation increases with hypercapnic hyperpneaKevin E. Finucane, and Bhajan Singh1 November 2009 | Journal of Applied Physiology, Vol. 107, No. 5Canine Locomotive BehaviorEfficiency of the normal human diaphragm with hyperinflationKevin E. Finucane, Janine A. Panizza, and Bhajan Singh1 October 2005 | Journal of Applied Physiology, Vol. 99, No. 4Midazolam-Induced Muscle Dysfunction and Its Recovery in Fatigued Diaphragm in DogsAnesthesia & AnalgesiaFlumazenil Recovers Diaphragm Muscle Dysfunction Caused by Midazolam in DogsAnesthesia & Analgesia, Vol. 95, No. 4The Dose-Related Efficacy of Diltiazem for Enhancing Diaphragmatic Fatigability in DogsAnesthesia & Analgesia, Vol. 95, No. 1Inhaled olprinone improves contractility of fatigued canine diaphragmBritish Journal of Anaesthesia, Vol. 88, No. 3Adaptation of respiratory muscle perfusion during exercise to chronically elevated ventilatory workConnie C. W. Hsia, Shin-Ichi Takeda, Eugene Y. Wu, Robb W. Glenny, and Robert L. Johnson1 November 2000 | Journal of Applied Physiology, Vol. 89, No. 5Respiratory muscle blood flows during physiological and chemical hyperpnea in the ratDavid C. Poole, William L. Sexton, Bradley J. Behnke, Christine S. Ferguson, K. Sue Hageman, and Timothy I. Musch1 January 2000 | Journal of Applied Physiology, Vol. 88, No. 1Propofol Decreases Diaphragmatic Contractility in DogsAnesthesia & Analgesia, Vol. 89, No. 6The Effect of Olprinone Compared with Milrinone on Diaphragmatic Muscle Function in DogsAnesthesia & Analgesia, Vol. 89, No. 3Regulation of ventilatory muscle blood flowSabah N. A. Hussain1 October 1996 | Journal of Applied Physiology, Vol. 81, No. 4Effect of inhibition of nitric oxide release on the diaphragmatic oxygen delivery-consumption relationshipJournal of Critical Care, Vol. 9, No. 2Recovery from fatigue of human diaphragm and limb musclesRespiration Physiology, Vol. 84, No. 1Diaphragmatic fatigue and its recovery are influenced by cardiac outputJournal of Anesthesia, Vol. 5, No. 1Blood flow to the respiratory muscles during hypercapnic hyperpnoea in the newborn lambRespiration Physiology, Vol. 76, No. 1Origins and regional distribution of blood flow to the respiratory muscles in conscious sheepRespiration Physiology, Vol. 67, No. 3 More from this issue > Volume 54Issue 3March 1983Pages 763-772 Copyright & PermissionsCopyright © 1983 the American Physiological Societyhttps://doi.org/10.1152/jappl.1983.54.3.763PubMed6841221History Published online 1 March 1983 Published in print 1 March 1983 Metrics

Single-breath diffusing capacity of the lung for carbon monoxide (DLCO) increases as lung volume increases above functional residual capacity (FRC). However, the physiological mechanism responsible for this increase remains controversial. This volume dependence of diffusing capacity could reflect changing regional distribution of inspired air as lung volume increases rather than a change in capillary blood volume or surface area for gas exchange. We measured DLCO during breath holding and during rebreathing with a technique employed to mix respired gases throughout the lung thereby minimizing regional distribution differences. Measurements were made 1,500 ml above FRC and near total lung capacity (TLC). Breath holding DLCO was 18% higher near TLC than at 1,500 ml above FRC (P less than 0.05). Rebreathing DLCO was 16% higher near TCL than at 1,500 ml above FRC (P less than 0.01). Equality of results by the two techniques indicates that changes in DLCO with lung volume are not a consequence of the changing distribution of inspired air. Our results are compatible with the hypothesis that effective surface area of the lung increases as lung volume expands.

A theoretical model for oxygen transport assuming a series linkage of ventilation, diffusion, oxygen uptake by erythrocytes, cardiac output, and oxygen release was used to calculate expected values for maximal oxygen intake (VO2max) of patients with various pulmonary disorders 22 patients with either restrictive or obstructive ventilatory impairment were studied at rest and maximal exercise. When exercise measurements of maximal pulmonary blood flow (QCmax), oxygen capacity, membrane diffusing capacity for CO, pulmonary capillary blood volume, alveolar ventilation, and mixed venous oxygen saturation were employed as input values, predictions of VO2max from the model correlated closely with measured values (r = 0.978). Measured VO2max was 976+/-389 ml/min (45.3+/-13% of predicted normal), and VO2max predicted from the model was 1,111+/-427 ml/min. The discrepancy may in part reflect uneven matching of alveolar ventilation, pulmonary capillary blood flow, and membrane diffusing capacity for CO within the lung; uniform matching is assumed in the model so that mismatching will impair gas exchange beyond our predictions. Although QCmax was less than predicted in most patients (63.6+/-19.6% of predicted) the model suggests that raising QCmax to normal could have raised VO2max only 11.6+/-8.8% in the face of existent impairment of intrapulmonary gas exchange. Since pulmonary functions measured at rest correlated well with exercise parameters needed in the model to predict VO2max we developed a nomogram for predicting VO2max from resting CO diffusing capacity, the forced one second expired volume, and the resting ratio of dead space to tidal volume. The correlation coefficient between measured and predicted VO2max, by using this nomogram, was 0.942.

Diffusing capacity of the lungs imposes a theo- retical limit to oxygen consumption, causing oxy- gen saturation of arterial blood to fall sharply if this limit is approached (1).The diffusing surface of the normal lung is so large, however, that at sea level oxygen capacity of the blood and the cardiac output rather than diffusing capacity create the major bottleneck to oxygen transport (2).Diffusion becomes an important limit only at high altitudes (3) or when diffusing capacity is reduced sufficiently by disease to cause alveolar capillary block (4).Diffusing capacity of the lungs usually is meas- ured with respect to CO (DLco) rather than oxygen (DLO2).Yet little information exists regarding how low DLCO must be before alveolar capillary block is manifest.Recent work of Roughton and Forster (5) and of Staub, Bishop, and Forster (6) defines the theoretical relation- ship between DLco and DLO2 allowing translation of CO diffusing capacity into terms of oxygen transport.Thus we should be able to state more explicitly the functional significance of a low CO diffusing capacity.Our purpose has been to pre- dict the restriction in maximal oxygen transport implied by a low DLco and then to check the pre- diction by experimental measurement. MethodsTheory.The reciprocals of DLco and DLO2 are specific resistances in millimeters Hg per milliliter per minute to CO *

Maximal breathing capacity (MBC) and timed expiratory capacity (TEC) measurements are estimates of voluntary ventilatory capacity. The MBC embodies certain disadvantages and is dependent on coordination, endurance, learning, motivation, breathing rate and pulmonary mid-position at which breathing is performed. Correlations (R = &gt; +0.91) were found for the relationship 0.5, 0.75 and 1.0 second TEC and the MBC in 153 normal subjects and 100 patients with ventilatory insufficiency. The MBC can be conveniently estimated from any of the TEC values with essentially equal reliability. This is only an approximation since expiratory flow rate is only one of the many variables determining the MBC. Aside from the effects of maximal inspiratory and expiratory flow rate on the determined MBC, the breathing rate must exceed 65/min. and the steepest slope of the expiratory flow curve must be repetitiously utilized, otherwise maximal ventilation is not achieved. The forced expiratory vital capacity and timed expiratory capacities are not merely convenient substitutes for the MBC, but deserve investigation as potentially valuable reflections of muscular and visco-elastic properties of the pulmonary apparatus.

Blood flow was measured in the left foot using the venous occlusion plethysmograph described by Abramson (10), but with certain modifications. These changes were introduced because of the necessity of removing the foot from the plethysmograph at the time of the regional block and then replacing it rapidly to avoid delaying the determinations of blood flow. Therefore, instead of cementing the edge of a thick rubber sheeting to the ankle, a thin rubber boot was prepared, the edges of which were everted and sealed permanently to the inlet of the plethysmograph in a manner similar to that described by Krogh, Landis and Turner (11) for use with the limb segment plethysmograph. The boot was made of rubber thin and pliable enough for the pressure of the water filling the plethysmograph to press the rubber membrane snugly against the contours of the foot.4 Since an air pocket usually formed at the upper end of the boot, the air was removed by means of small-bore plastic tubing leading from the toe of the boot to one of the two outlets of the plethysmograph. The trapped air could then be removed by applying suction to the plastic tube with a syringe. By means of this device, the foot could be sealed quickly

We determined the overall pulmonary diffusing capacity (DL) and the diffusing capacities of the alveolar membrane (Dm) and the red blood cell (RBC) segments (De) of the diffusional pathway for O2 by using a two-dimensional finite-element model developed to represent the sheet-flow characteristics of pulmonary capillaries. An axisymmetric model was also considered to assess the effect of geometric configuration. Results showed the membrane segment contributing the major resistance, with the RBC segment resistance increasing as O2 saturation (SO2) rises during the RBC transit: RBC contributed 7% of the total resistance at the capillary inlet (SO2 = 75%) and 30% toward the capillary end (SO2 = 95%) for a 45% hematocrit (Hct). Both Dm and DL increased as the Hct increased but began approaching a plateau near an Hct of 35%, due to competition between RBCs for O2 influx. Both Dm and DL were found to be relatively insensitive (2-4%) to changes in plasma protein concentration (28-45%). Axisymmetric results showed similar trends for all Hct and protein concentrations but consistently overestimated the diffusing capacities (approximately 2.2 times), primarily because of an exaggerated air-tissue barrier surface area. The two-dimensional model correlated reasonably well with experimental data and can better represent the O2 uptake of the pulmonary capillary bed.

We present a simple geometric model of a pulmonary capillary segment containing a variable number of red blood cells. The pattern of CO transfer from alveolar air to capillary red blood cells in this model is accurately computed by a finite element method and used to explore conceptual flaws in the Roughton-Forster (RF) and morphometric methods of estimating pulmonary diffusing capacity for CO. The CO uptakes calculated by the finite element method at two alveolar O2 tensions are introduced into the RF model to determine whether the anatomically defined membrane component of diffusing capacity for CO (DmCO) and pulmonary capillary blood volume (Vc) are recovered. The same capillary model is also subjected to standard morphometric analysis. Results are compared at different levels of capillary hematocrit (Hct). The RF method accurately recovers DmCO and Vc at a low Hct but modestly overestimates DmCO and underestimates Vc at higher Hct; errors arise because conductance of the tissue-plasma membrane for CO varies with alveolar O2 tension. The morphometric method seriously overestimates DmCO because the true tissue-plasma resistance to diffusion is underestimated and the effective membrane utilized for diffusion is overestimated; these errors are accentuated by a low Hct.

Mammals native to high altitude (HA) exhibit larger lung volumes than their lowland counterparts. To test the hypothesis that adaptation induced by HA residence during somatic maturation improves pulmonary gas exchange in adulthood, male foxhounds born at sea level (SL) were raised at HA (3,800 m) from 2.5 to 7.5 mo of age and then returned to SL prior to somatic maturity while their littermates were simultaneously raised at SL. Following return to SL, all animals were trained to run on a treadmill; gas exchange and hemodynamics were measured 2.5 years later at rest and during exercise while breathing 21% and 13% O 2 . The multiple inert gas elimination technique was employed to estimate ventilation-perfusion (V̇a/Q̇) distributions and lung diffusing capacity for O 2 (Dl O 2 ). There were no significant intergroup differences during exercise breathing 21% O 2 . During exercise breathing 13% O 2 , peak O 2 uptake and V̇a/Q̇ distributions were similar between groups but arterial pH, base excess, and O 2 saturation were higher while peak lactate concentration was lower in animals raised at HA than at SL. At a given exercise intensity, alveolar-arterial O 2 tension gradient (A-aDo 2 ) attributable to diffusion limitation was lower while Dlo 2 was 12–25% higher in HA-raised animals. Mean systemic arterial blood pressure was also lower in HA-raised animals; mean pulmonary arterial pressures were similar. We conclude that 5 mo of HA residence during maturation enhances long-term gas exchange efficiency and Dl O 2 without impacting V̇a/Q̇ inequality during hypoxic exercise at SL.

We (42) previously reported differential regulation of hypoxia-inducible factors (HIF-1alpha, -2alpha, and -3alpha) mRNA in canine lungs during normal maturation and postpneumonectomy (PNX) compensatory growth in the absence of overt hypoxia. To test the hypothesis that lung expansion activates HIF signaling, we replaced the right lung of six adult foxhounds with inflated custom-shaped silicone prosthesis to keep the mediastinum in the midline and minimize lateral expansion of the remaining lung. After 3 wk of recovery and stabilization of perfusion, the prosthesis was acutely deflated in three animals, causing the remaining lung to expand by 114%. In three other animals, the prosthesis remained inflated. Three days following deflation, we observed significant elevation in the mRNA and nuclear protein levels of HIF-1alpha ( approximately 60%) as well as activation of its transcriptional regulator, the serine/threonine protein kinase B (phospho-Akt-to-total Akt ratio, 124%), and the mRNA and protein levels of its downstream targets, erythropoietin receptor (71-183%) as well as VEGF (33-58%) compared with the pre-PNX control lung from the same animal. The mRNA of HIF-2alpha, HIF-3alpha, and VEGF receptors did not change with acute deflation. We conclude that in vivo lung expansion by post-PNX deflation of space-occupying prosthesis elicits coordinated activation of HIF-1alpha signaling in adult lungs. This pathway could play an important role in mediating lung growth and remodeling during maturation and post-PNX compensation.

Patrolling behaviour, an adaptation bringing the sexes together for copulation, is defined as the flight movements of male ants as they leave their nests in search of reproductive females, and involves flight across wind until perceiving the presence of a female. Once sex attraction has occurred, males fly directly upwind to the general location of the female, and make rapid flitting and crawling movements up and down plant stems until contact is made with the female. This phenomenon has been observed of F. montana and F. pergandei and may be common to other species of Formica, even other genera of ants. The most plausible explanation of this attraction is that the males are responding to a pheromone released by a female. The attractant is apparently wind-borne, and males are able to determine the direction of its source by antennal movements. The immediate vicinity of a female may become so saturated with attractant that males are unable to find her directly, either by chemical or visual means, but must explore each specific area of vegetation until physical contact between them is made. Male attraction may be illustrative of the mechanism used by males of many ant species to locate mates during nuptial flights. In the absence of specialized mating aggregations such as swarms, an odour stimulus would probably be a more effective attractant than auditory or visual stimulation. That this mechanism may be used by other species of ants is suggested by the discovery that females of F. ulkei, which are reproductively unattractive on the vegetation surrounding a nest, later became attractive after flying a short distance and landing in a tree.

The field of literacy education has long been concerned with the question of how to help classroom teachers improve their practices so that students will improve as readers. Although there is consensus on what characterizes effective professional development, the reading research on which this consensus is based most often is small scale and involves direct support provided by university faculty. The South Carolina Reading Initiative is an exception: It is a statewide, site-based, large-scale staff development effort led by site-selected literacy coaches. Although university faculty provide long-term staff development to the coaches, the faculty are not directly involved with the professional development provided to teachers. In this study we sought to understand whether site-based, site-chosen literacy coaches could help teachers’ beliefs and practices become more consistent with what the field considers to be best practices. To understand teacher change, we used two surveys (Theoretical Orientation to Reading Profile, n = 817; South Carolina Reading Profile, n = 1,005) and case study research ( n = 39) to document teachers’ beliefs and practices. We also had access to a state department survey ( n = 1,428). Across these data, we found that teachers’ beliefs and practices became increasingly consistent with best practices as defined by standards set by the South Carolina State Department of Education, standards that were consistent with national standards. This suggests that large-scale staff development can affect teachers when the providers are site-based, site-selected literacy coaches.

The purpose of this study was to investigate the perceptions of pre-service teachers in the United States and China about ethics of classroom assessment practices. To investigate pre-service teachers’ perceptions, we developed 36 scenarios that described teachers’ actions or thoughts related to ethics and assessment practices. Participants were 173 pre-service teachers in the U.S. and 174 pre-service teachers in China. Overall, the perceptions of Chinese and American respondents were divided within countries on different scenarios. In addition, chi-square analyses contrasting Chinese responses with American responses indicated that the pre-service teachers had statistically significant differences in their opinions on 22 out of 36 scenarios, but only 13 had practical significance (effect size ≥ .3). Chinese and American pre-service teachers had similar perceptions on 14 scenarios. In some instances, respondents’ perceptions of the ethics of assessment practices depicted in the scenarios did not agree with the literature on classroom assessment. The findings offer insights for developing ethical guidelines in classroom assessment in both cultures. In addition, we recommend that cultural issues as related to ethics should be included in assessment courses for pre-service teachers.

This paper surveys macroeconomic and microeconomic perspectives on the role of international trade in structural transformation.We start by describing canonical frameworks that have been used to quantify how trade influences sectoral shares of employment and value added.We then pivot to survey micro-empirical evidence on the impact of changes in trade on the allocation of labor across sectors and productivity at the firm level.In this, we put special emphasis on the role of participation in global value chains and inward foreign direct investment in mediating these effects.Next, we evaluate evidence on the barriers to trade faced by low-income countries, with special attention to recent work that measures these costs taking firm dynamics into account.We conclude by discussing how these micro-perspectives can be integrated into macro-models to advance our understanding of structural change.

Objective. On February 1, 1997, new pediatric Residency Review Committee guidelines became effective. Eighteen months later, pediatric residency program directors were queried regarding the implementation of these guidelines. Because both the challenge to implement these guidelines and the opportunities to shape pediatric graduate medical education rest with the program directors, obtaining the feedback and suggestions from this group is seen as the keystone of future planning endeavors. Methods. A 20-question multiple-choice/opened-ended questionnaire was sent to the 201 members of the Association of Pediatric Program Directors in 2 mailings in August and September 1998. Results. A final response rate of 70% was achieved. Very few program directors reported difficulties in instituting the new residency review committee requirements. The exceptions to this pattern were those requirements pertaining to limitations on time spent in intensive care experience and in the neonatal intensive care unit, wherein 34% of the respondents identified barriers. Although the majority of respondents regarded these requirements as very good or sufficient, some program directors expressed concern regarding insufficient amounts of time available for preparation in intensive care (18%), neonatal intensive care unit (22%), behavioral/developmental pediatrics (16%), and in adolescent medicine (13%). In general, programs have been more successful in defining new competencies than in developing curricula to teach them. The majority of respondents also indicated that their residents' exposure was excellent or satisfactory in all 6 of the following practice settings: private office-based practice for continuity clinic, private office-based practice for outpatient rotation, predominately managed care practice, community clinics for continuity clinic, community clinics for outpatient rotation, and hospital-based practice for continuity clinic. They also indicated that they had no serious concerns about the types of career development assistance offered to residents and the types of follow-up tracking of residents. Conclusion. The findings from this survey have reaffirmed the merit of the current system of pediatric residency education. They have also revealed the commitment of program directors to address the complex issues generated by the evolution of health care delivery, and thereby contribute to the optimal provision of pediatric health care now and in the future.

The assessment of students' writing skills through essays is a common practice in educational institutions. Scoring of essays requires considerable judgment on the part of those who rate the response. When raters assign different scores to an essay, testing practitioners must resolve the discrepancy before computing an operational score to report to the examinee. This study investigated five forms of score resolution that were reported in a national survey of state department of education-testing agencies. The study examined the effect that each form of resolution has on the reliability of the resulting operational scores. It is shown that some methods of resolution can be associated with higher interrater reliability than can others. It is also shown that the choice of resolution can affect the magnitude of the reported score as well as the final passing rate of an assessment.

After pneumonectomy (PNX), mechanical strain on the remaining lung is greatly increased. To assess whether remaining lobes expand uniformly after left or right PNX (removing 42 and 58% of lung mass, respectively), we performed high-resolution computed tomography (CT) scans at 45 ml/kg above end-expiratory lung volume on adult male foxhounds after left or right PNX, which were compared with adult Sham controls. Air and tissue volumes were separately measured in each lobe. After left PNX, air and tissue volumes in the right upper and cardiac lobes increased approximately 2.2-fold above and below the heart, whereas volumes in right middle and lower lobes did not change significantly. After right PNX, air and tissue volumes in the left upper and middle lobes increased 2.3- to 2.7-fold across the midline anterior to the heart, whereas the left lower lobe expanded approximately 1.9-fold posterior to the heart. Regional changes in volume density of tissue post-PNX estimated by CT scan parallel postmortem estimates by morphometric analyses. Data indicate heterogeneous regional distribution of mechanical lung strain, which could influence the differential cellular compensatory response following right and left PNX.

Maximal exercise performance was evaluated in four adult foxhounds after right pneumonectomy (removal of 58% of lung) and compared with that in seven sham-operated control dogs 6 mo after surgery. Maximal O2 uptake (ml O2.min-1.kg-1) was 142.9 +/- 1.9 in the sham group and 123.0 +/- 3.8 in the pneumonectomy group, a reduction of 14% (P less than 0.001). Maximal stroke volume (ml/kg) was 2.59 +/- 0.10 in the sham group and 1.99 +/- 0.05 in the pneumonectomy group, a reduction of 23% (P less than 0.005). Lung diffusing capacity (DL(CO)) (ml.min-1.Torr-1.kg-1) reached 2.27 +/- 0.08 in the combined lungs of the sham group and 1.67 +/- 0.07 in the remaining lung of the pneumonectomy group (P less than 0.001). In the pneumonectomy group, DL(CO) of the left lung was 76% greater than that in the left lung of controls. Blood lactate concentration and hematocrit were significantly higher at exercise in the pneumonectomy group. We conclude that, in dogs after resection of 58% of lung, O2 uptake, cardiac output, stroke volume, and DL(CO) at maximal exercise were restricted. However, the magnitude of overall impairment was surprisingly small, indicating a remarkable ability to compensate for the loss of one lung. This compensation was achieved through the recruitment of reserves in DL(CO) in the remaining lung, the development of exercise-induced polycythemia, and the maintenance of a relatively large stroke volume in the face of an increased pulmonary vascular resistance.

To demonstrate that whereas all HIV-infected youth evidence complex factors that challenge retention in care and adherence to treatment, HIV-infected females have additional issues that are gender-specific.Preliminary data from a subset of 21 adolescent/young women under age 25 from the Whole Life mental health-perinatal HIV care project were analyzed to illustrate the needs of these patients.Of the 21 young women assessed, all but one was of minority background, and a sizeable majority had limited education (<high school diploma) and were quite poor (incomes <$500/mo.). Nearly 67% first learned of their HIV status between ages 16 and 19 years. More than three-fourths were pregnant and, of these, more than one-third entered prenatal care in the last trimester. More than half had responsibility for one to two other children. Two-thirds reported having unprotected sex in the prior 6 months. Nearly 43% had CD4 counts of 500 or below. About one-third screened positive for a mental health problem, and the majority reported a striking frequency of exposure to abusive events and traumatic losses across their short lifetimes.Adolescent girls and young women have unique needs for developmentally appropriate medical and psychosocial approaches to promote retention and adherence.