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Emphysema associated with intravascular leukocyte sequestration. Comparison with papain-induced emphysema.

The pulmonary effects of endotoxin-induced, repetitive, intravascular leukocyte sequestration were studied in dogs and were compared to the effects of intratracheal papain. Lung specimens from 7 animals receiving 20 to 23 weekly injections were histologically and physiologically similar to those from 10 control animals. Dogs receiving 50 injections of endotoxin during 17 wk developed histologic evidence of emphysema as seen on whole lung sections, a significant increase in mean linear intercept, and loss of elasticity at high lung volumes. The group of animals given intratracheal papain also developed histologic evidence of emphysema, with increased mean linear intercepts and loss of lung elasticity. However, the effects on lung elasticity were much greater in the papain group. Endotoxin-induced, repetitive leukocyte sequestration in the lungs results in mild emphysema; however, similar changes in alveolar size appear to cause less effect on the pressure-volume loop than does papain-induced emphysema.

Animals↗

Evaluation of the urinary desmosine radioimmunoassay as a monitor of lung injury after endobronchial elastase instillation in sheep.

Thirty male sheep were treated with varying doses of endobronchial elastase. Urinary excretion of elastin peptides was then measured by desmosine radioimmunoassay and compared with pre-enzyme values. Mean linear intercepts were measured in treated and untreated lobes 4 wk later, and in addition, lung perfusion, ventilation, and volume were measured before enzyme treatment and 4 wk later using radionuclide-imaging techniques. Most of the elevation in urinary desmosine excretion occurred in the first 48 h after elastase administration. The increase in desmosine excretion was positively correlated with: enzyme dose (r = 0.74, p less than 0.01), increase in mean linear intercept (r = 0.61, p less than 0.05), decrease in lung perfusion (r = 0.77, p less than 0.01), and decrease in ventilation (r = 0.58, p less than 0.05). These results demonstrate that the urinary desmosine radioimmunoassay is a reliable index of pulmonary elastin breakdown and of several resultant anatomic and physiologic stigmata of pulmonary emphysema.

Amino Acids↗

Long-term sequelae of bronchiolitis induced by nitrogen dioxide in hamsters.

The long-term consequences of acute lung injury during critical growth periods of the lung were evaluated by inducing mild bronchiolitis with nitrogen dioxide (NO2) in 3-day-old (newborn) and 21-day-old (young) hamsters. Hamsters were exposed to 30 ppm NO2 for 7 days. Age-matched animals exposed to room air served as controls. Lung volumes, static deflationary pressure-volume curves, mean linear intercept, and internal surface area were measured when the animals reached 1 yr of age. Newborns exposed to NO2 showed an increased volume at 25 cm H2O pressure (V25) adjusted for body weight, a decreased transpulmonary pressure at 60% of V25, and an increased mean linear intercept when compared with control animals. The internal surface area was less than that in the control animals; the difference approached significance. In the young exposed group there were no differences for any measurements when compared with the control group. These data indicate that a mild injury imposed during the newborn period may result in physiologic and morphometric changes that simulate mild emphysema in the mature animal.

Animals↗

Quantitative structural alterations in long-standing allergic asthma.

The lungs of 6 elderly nonsmoking persons with severe long-standing "allergic" asthma (mean duration, 45 yr), not dying in status asthmaticus, were examined quantitatively to characterize the structural alterations that would produce clinical chronic air-flow obstruction. The percent of bronchial smooth muscle was not significantly elevated in these asthmatics, compared with that in 7 control subjects. Two asthmatics had reduced small airway diameters, with histologic evidence of inflammation or fibrosis. Mean linear intercept (interalveolar distance) in asthmatics was not significantly elevated over that in control subjects, but one asthmatic had a clearly increased mean linear intercept and histologic evidence of very mild emphysema. Bronchial basement membrane thickness was 8.3 +/- 2.0 mu in asthmatics and 5.1 +/- 0.9 mu in control subjects (p less than 0.01), a measurement that discriminated best between asthmatics and nonasthmatics. Small airway narrowing may develop in long-standing asthma to explain the component of nonreversible air-flow obstruction that characterizes such patients.

Aged↗

A novel oral neutrophil elastase inhibitor (ONO-6818) inhibits human neutrophil elastase-induced emphysema in rats.

We investigated the effects of a novel oral neutrophil elastase inhibitor (ONO-6818) on acute lung injury and pulmonary emphysema induced by human neutrophil elastase (HNE). Young male Wistar rats were divided into four treatment groups: (1) control group (saline); (2) HNE group (HNE 200 U + 0.5% carboxymethyl-cellulose [solution for ONO-6818]); (3) low-dose ONO-6818 group (HNE 200 U + ONO-6818 10 mg/kg); and (4) high-dose ONO-6818 group (HNE 200 U + ONO-6818 100 mg/kg). Saline and HNE were applied via the trachea using a microsprayer. ONO-6818 was administered orally 1 hour before HNE application. Six hours after HNE application, neutrophil counts and hemoglobin concentration in bronchoalveolar lavage fluid and lung tissue myeloperoxidase activity were determined. Eight weeks after the application, FRC, TLC, lung compliance, and mean linear intercept were estimated. ONO-6818 attenuated dose-dependently HNE-induced increases in lung myeloperoxidase activity, hemoglobin, and neutrophil count in bronchoalveolar lavage fluid. Furthermore, it significantly attenuated HNE-induced increases in FRC, TLC, lung compliance, and mean linear intercept. ONO-6818 inhibited acute lung injury induced by HNE by minimizing lung hemorrhage and accumulation of neutrophils in the lung. ONO-6818 also inhibited the development of HNE-induced emphysematous changes including lung hyperinflation, degradation of elastic recoil, and airspace enlargement.

Administration, Oral↗

Alpha1-antitrypsin determines the pattern of emphysema and function in tobacco smoke-exposed mice: parallels with human disease.

Cigarette smoking in humans is associated with various patterns of emphysema and functional consequences. We tested the hypothesis that variations in alpha1-antitrypsin expression modulate the pattern of emphysema and functional consequences in cigarette smoke-exposed mice. We compared the effects of up to 6 months of cigarette smoke exposure in C57BL/6J (C57) mice and in low-alpha1-antitrypsin, C57BL/6J pa+/pa+ (pallid) mice. At the end of the experiment, we determined lung mechanical properties, the extent (mean linear intercept) and type of emphysema, and the cellular inflammatory response. After 4 months of cigarette smoking, pallid smoking mice, but not C57 smoking mice, had a significant increase in mean linear intercept. After 6 months of smoke exposure, C57 smoking mice and pallid smoking mice had similar degrees of emphysema. The pattern of emphysema in pallid smoking mice was more diffuse than in C57 smoking mice, affecting all airspaces. Pallid mice, but not C57 mice, developed a T cell inflammation in the alveolar wall after 6 months of smoking (p < 0.01). Although lung compliance was not changed in C57 smoking mice after smoke exposure, it increased significantly in pallid smoking mice over the 6 months of exposure (p < 0.0082). In summary, cigarette smoking induces emphysema in C57 and pallid mice, but the emphysema, inflammatory infiltrate, and resulting physiologic abnormalities were substantially different in the two strains, with the C57 and pallid mice exhibiting features similar to centrilobular and panlobular emphysema, respectively.

Animals↗

Noninvasive measurement of rodent intraocular pressure with a rebound tonometer.

PURPOSE: The present study evaluated the applicability of a rebound tonometer in measuring intraocular pressure (IOP) in rats and mice. METHODS: The accuracy of the TonoLab rebound tonometer was determined in cannulated mouse and rat eyes. IOP was manipulated by changing reservoir height, and tonometer pressure readings were recorded by an independent observer. IOP values were recorded in conscious Wistar rats and in four different strains of mice. The effects of anesthesia on IOP were evaluated in two different strains of mice. RESULTS: The IOP readings generated by the rebound tonometer correlated very well with the actual pressure in the eye. In rats, this linear correlation had a slope of 0.96 +/- 0.05 (mean +/- SEM, n = 4) and a Y-intercept of -2.1 +/- 1.2. In mice, the slope was 0.99 +/- 0.05 (n = 3), and the Y-intercept was 0.8 +/- 1.4. Using this method, the resting IOP of conscious male Wistar rats was observed to be 18.4 +/- 0.1 mm Hg (n = 132). In mice, strain differences in IOP were detected. Baseline IOP values in Balb/c, C57-BL/6, CBA, and 11- to 12-month-old DBA/2J mice were 10.6 +/- 0.6, 13.3 +/- 0.3, 16.4 +/- 0.3, and 19.3 +/- 0.4 mm Hg (n = 12), respectively. In separated studies, anesthesia lowered IOP from 14.3 +/- 0.9 to 9.2 +/- 0.5 mm Hg (n = 8) in C57-BL/6 mice, and from 16.6 +/- 0.4 to 9.4 +/- 0.6 mm Hg (n = 10) in CBA mice. CONCLUSIONS: The rebound tonometer was easy to use and accurately measured IOP in rats and mice. This technique, together with advances in genetic and other biological studies in rodents, will be valuable in the further understanding of the etiology and pathology of glaucoma.

Anesthesia, Local↗

Tear film osmolarity: determination of a referent for dry eye diagnosis.

PURPOSE: To determine new referents, or cutoff levels for tear film hyperosmolarity in the diagnosis of keratoconjunctivitis sicca (KCS) and to assess their effectiveness in independent patient groups. METHOD: A meta-analysis was performed on published data for tear osmolarity in samples of normal eyes and various subtypes of dry eye, and pooled estimates of the mean and standard deviations for normal and (all) dry eye subjects were determined. Diagnostic referents were derived from the intercept between the distributions of osmolarity in the two samples and from receiver operator characteristic (ROC) curves. This referent was tested for effectiveness of diagnosis in independent groups with normal and dry eyes. RESULTS: An osmolarity referent of 315.6 mOsmol/L was derived from the intercept of the distribution curves, and 316 mOsmol/L from the ROC curve. When applied to independent groups of normal and dry eye subjects a value of 316 mOsmol/L was found to yield sensitivity of 59%, specificity of 94%, and an overall predictive accuracy of 89% for the diagnosis of dry eye syndrome. CONCLUSIONS: Tear hyperosmolarity, defined by a referent of 316 mOsmol/L, was superior in overall accuracy to any other single test for dry eye diagnosis (Lactoplate, Schirmer test, and Rose Bengal staining), even when the other test measures were applied to a diagnosis within the sample groups from which they were derived. For overall accuracy in the diagnosis of dry eye, the osmolarity test was found to be comparable with the results of combined (in parallel or series) tests.

False Positive Reactions↗

Hypertonicity regulates the function of human neutrophils by modulating chemoattractant receptor signaling and activating mitogen-activated protein kinase p38.

Excessive neutrophil activation causes posttraumatic complications, which may be reduced with hypertonic saline (HS) resuscitation. We tested if this is because of modulated neutrophil function by HS. Clinically relevant hypertonicity (10-25 mM) suppressed degranulation and superoxide formation in response to fMLP and blocked the activation of the mitogen activated protein kinases (MAPK) ERK1/2 and p38, but did not affect Ca2+ mobilization. HS did not suppress oxidative burst in response to phorbol myristate acetate (PMA). This indicates that HS suppresses neutrophil function by intercepting signal pathways upstream of or apart from PKC. HS activated p38 by itself and enhanced degranulation in response to PKC activation. This enhancement was reduced by inhibition of p38 with SB203580, suggesting that p38 up-regulation participates in HS-induced enhancements of degranulation. HS had similar effects on the degranulation of cells that were previously stimulated with fMLP, but had no effect on its own, suggesting that HS enhancement of degranulation requires another signal. We conclude that depending on other stimuli, HS can suppress neutrophil activation by intercepting multiple receptor signals or augment degranulation by enhancing p38 signaling. In patients HS resuscitation may reduce posttraumatic complications by preventing neutrophil activation via chemotactic factors released during reperfusion.

Calcium-Calmodulin-Dependent Protein Kinases↗

Predicting the trajectory of will to live in terminally ill patients.

Will to live has been shown to vary considerably during the final course of a terminal illness. The goal of this study was to identify illness-related and demographic variables predicting will to live among dying patients. Subjects were 168 patients with cancer who were admitted for palliative care. Will to live was measured twice daily for the duration of hospitalization by using a self-report 100-mm visual analogue scale. Will-to-live data for each patient were summarized into two statistics, intercept and slope, by using simple linear regression analyses. Intercept-slope pairs for all patients were classified into the following five clusters by using spatial and conceptual criteria: patients with sustained high will to live (58%), patients with sustained moderate will to live (11%), patients with sustained low will to live (3%), will-to-live relinquishers (18%), and will-to-live acquirers (10%). Discriminant analyses revealed seven variables that accounted for 69% of the variance in cluster membership: anxiety, shortness of breath, nausea, length of survival from time of admission, having a diagnosis of colon cancer, having no religion, and living with a spouse.

Attitude to Death↗

A simple radioimmunoassay for plasma cortisol: comparison with the fluorimetric method of determination.

A quick and simple method for the radioimmunoassay of plasma cortisol is described. The mean morning plasma cortisol concentration in 43 normal subjects was 9.8 +/- 3.1 (S.D.) microgram/100 ml with a range of 5.0-19.5 microgram/100 ml. Mean midnight concentration in 24 normal subjects was 4.3 +/- 2.3 (S.D.) microgram/100 ml with a range of 1.4-9.6 microgram/100 ml. When compared with the fluorimetric method the mean results by radioimmunoassay of 154 routine specimens were 23% lower. In samples from unstimulated patients, regression analysis of results obtained by the two methods gave a correlation coefficient (r) of 0.93, regression line slope of 1.1, and intercept of 1.4 microgram. Mean radioimmunoassay results were 15% lower. When plasma cortisol concentration was above the normal range (greater than 30 microgram/100 ml) the regression line slope was 0.87, the intercept 17.9 microgram, r = 0.87 and mean radio immunoassay results were 37% lower. Plasma cortisol concentration in patients after insulin or Synacthen stimulation exhibited similar responses when measured by either method. Plasma cortisol concentration in normal subjects given metyrapone was lower when measured by radioimmunoassay (mean +/- S.D. = 8.7 +/- 2.7 microgram/100 ml) than when measured by fluorimetry (18.5 +/- 10.8 microgram/100 ml). The diagnostic usefulness of the two methods, ease of assay, and costs are compared.

Adrenal Glands↗

The effect of physician's explanations on patients' treatment preferences: five-year survival data.

OBJECTIVE: To evaluate the influence of physicians' explanations on patients' choices. SETTING: A university-based Department of Veterans Affairs Medical Center. PARTICIPANTS: 136 patients seen in a continuity-care general medicine clinic. MEASUREMENTS AND RESULTS: Patients were randomized to two groups [Limited Explanation (LE) and Extensive Explanation (EE)] and asked to choose between two alternative treatments (differing in short-term vs long-term survival benefits) for an unidentified medical condition, based on the information given in the explanations. LE consisted of a brief orientation to graphs summarizing the treatment results, while EE consisted of a detailed verbal description of the graphs. Significantly (p < 0.001) more patients receiving EE changed their preferences across the three pairs of five-year survival curves, compared with patients receiving LE. Of the patients receiving EE, 57% reported either medium-term (year 0-to-intercept or intercept-to-year 5) data or the average life expectancy for the five-year period contained in the curves (ALE-5) as most influencing their decision making; whereas 78% of patients receiving LE reported only endpoint (year 0 or year 5) data as most influencing their preferences. CONCLUSIONS: The patients' treatment preferences for long-term vs short-term survival benefits were influenced by the amounts of verbal explanation provided to them about five-year survival graphs summarizing treatment results. The patients appeared to minimize the importance of medium-range data when those data were not specifically pointed out to them.

Female↗

Helium-3 MRI diffusion coefficient: correlation to morphometry in a model of mild emphysema.

Hyperpolarised gases have been most recently used in magnetic resonance imaging to demonstrate new image-derived pulmonary function parameters. One of these parameters is the apparent diffusion coefficient, which reflects the sizes of the structures that compartmentalise gas within the lung (i.e. alveolar space). In the present study, noninvasive parameters were compared to microscopic measurements (mean linear intercept and mean alveolar internal area). Nonselective helium-3 gas density coronal ex vivo images and apparent diffusion maps were acquired in control and elastase-induced panacinar emphysema rats. Total lung capacity was considered the reference for both imaging experiments and lung fixation. A mild degree of emphysema was found based on mean linear intercept (134 +/- 25 microm) versus control (85 +/- 14 microm). The apparent diffusion coefficients were significantly different between the two groups (0.18 +/- 0.02 and 0.15 +/- 0.01 cm2 x s(-1) for elastase and control, respectively). A significant correlation between the apparent diffusion coefficient and corresponding morphometric parameters in mild emphysema was demonstrated for the first time. This study opens the possibility of estimating absolute airspace size using noninvasive techniques.

Animals↗

Severe traumatic brain injury and risk for osteoporosis: a Mendelian randomization study.

BACKGROUND: The influence of nervous system activity on bone remodeling has been widely reported. Patients with traumatic brain injury (TBI) exhibit a high incidence of osteoporosis (OP). Nevertheless, the relationship between severe TBI (sTBI) and OP remains unclear. We performed Mendelian randomization (MR) analysis to assess the potential causal relationship between sTBI and OP. METHODS: Data on exposure and outcomes were acquired from genome-wide association studies (GWAS). Data on OP was obtained from UK Biobank (5,266 cases of OP and 331,893 controls). Data on sTBI was obtained from FinnGen Consortium (6,687 cases and 370,590 controls). Single nucleotide polymorphisms (SNPs) that underwent strict screening were regarded as instrumental variables. We used the inverse variance weighted (IVW), constrained maximum likelihood and model averaging (CML-MA), MR-Egger, and weighted median methods for causal effect estimation. To test the reliability of the results, sensitivity analysis was performed using Cochran's Q, leave-one-out, MR-Egger intercept, and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) tests. RESULTS: The IVW analysis indicates that sTBI and OP have a suggestive association (odds ratio [OR]&#x2009;=&#x2009;1.004, 95% confidence interval [CI]&#x2009;=&#x2009;1.001,1.007; p&#x2009;=&#x2009;0.002), and no heterogeneity (Q&#x2009;=&#x2009;11.536, p&#x2009;=&#x2009;0.241) or directional pleiotropy was observed (egger_intercept&#x2009;=&#x2009;7.368&#x2009;&#xd7;&#x2009;10-&#x2009;5, p&#x2009;=&#x2009;0.870). The robustness of the results was validated using a leave-one-out sensitivity test. CONCLUSION: According to the MR analysis, sTBI and OP are likely suggestively related. This finding contributes to the prevention of OP in patients with sTBI and provides genetic evidence supporting the theory that the nervous system regulates bone remodeling.

Humans↗

Deviations from the population-averaged versus cluster-specific relationship for clustered binary data.

There has been much debate about the relative merits of mixed effects and population-averaged logistic models. We present a different perspective on this issue by noting that the investigation of the relationship between these models for a given dataset offers a type of sensitivity analysis that may reveal problems with assumptions of the mixed effects and/or population-averaged models for clustered binary response data in general and longitudinal binary outcomes in particular. We present several datasets in which the following violations of assumptions are associated with departures from the expected theoretical relationship between these two models: 1) negative intra-cluster correlations; 2) confounding of the response-covariate relationship by cluster effects; and 3) confounding of autoregressive relationships by the link between baseline outcomes and subject effects. Under each of these conditions, the expected theoretical attenuation of the population-averaged odds ratio relative to the cluster-specific odds ratio does not necessarily occur. In all cases, the naive fitting of a random intercept logistic model appears to lead to bias. In response, the random intercept model is modified to accommodate negative intra-cluster correlations, confounding due to clusters, or baseline correlations with random effects. Comparisons are made with GEE estimation of population-averaged models and conditional likelihood estimation of cluster-specific models. Several examples, including a cross-over trial, a multicentre nonrandomized treatment study, and a longitudinal observational study are used to illustrate these modifications.

Animals↗

Assessing NEO hazard mitigation in terms of astrodynamics and propulsion systems requirements.

Uncertainties associated with assessing valid near-Earth object (NEO) threats and carrying out interception missions place unique and stringent burdens on designing mission architecture, astrodynamics, and spacecraft propulsion systems. A prime uncertainty is associated with the meaning of NEO orbit predictability regarding Earth impact. Analyses of past NEO orbits and impact probabilities indicate uncertainties in determining if a projected NEO threat will actually materialize within a given time frame. Other uncertainties regard estimated mass, composition, and structural integrity of the NEO body. At issue is if one can reliably estimate a NEO threat and its magnitude. Parameters that determine NEO deflection requirements within various time frames, including the terminal orbital pass before impact, and necessary energy payloads, are quantitatively discussed. Propulsion system requirements for extending space capabilities to rapidly interact with NEOs at ranges of up to about 1 AU (astronomical unit) from Earth are outlined. Such missions, without gravitational boosts, are deemed critical for a practical and effective response to mitigation. If an impact threat is confirmed on an immediate orbital pass, the option for interactive reconnaissance, and interception, and subsequent NEO orbit deflection must be promptly carried out. There also must be an option to abort the mitigation mission if the NEO is subsequently found not to be Earth threatening. These options require optimal decision latitude and operational possibilities for NEO threat removal while minimizing alarm. Acting too far in advance of the projected impact could induce perturbations that ultimately exacerbate the threat. Given the dilemmas, uncertainties, and limited options associated with timely NEO mitigation within a decision making framework, currently available propulsion technologies that appear most viable to carry out a NEO interception/mitigation mission within the greatest margin of control and reliability are those based on a combined (bimodal) nuclear thermal/nuclear electric propulsion platform. Elements of required and currently available performance characteristics for nuclear and electric propulsion systems are also discussed.

Journal Article↗

Acceleration of blood flow velocity in the carotid artery and myocardial contractility in the newborn lamb.

We investigated the influence of quantitative changes in myocardial contractile state, reflected by changes in the end-systolic pressure-volume relationship (its slope and volume intercept) and by changes in the slope of the relationship between change in pressure per unit time and end-diastolic volume induced by beta-adrenergic stimulation or inhibition, on the Doppler derived blood flow velocity wave form of the carotid artery, using a newborn lamb model. Acceleration time of the velocity wave form was investigated during control state I, during 4 and 8 micrograms/kg/min dobutamine infusion, during control state II, and during 0.5 mg/kg propranolol infusion, respectively. Using multiple linear regression analysis with dummy variables, confounding effects such as interanimal variability were removed. Acceleration time showed a strong relationship to both the slope and the volume intercept of the end-systolic pressure-volume relationship and to the change in pressure per unit time-end-diastolic volume relationship. The relations appeared to be independent of aortic pressure and relative resistance in the vascular bed of the carotid artery. These results indicate that acceleration of cerebral blood velocity may prove to be useful in assessing changes in myocardial contractile state of the newborn.

Animals↗

Growth hormone treatment improves peripheral muscle oxygen extraction-utilization during exercise in patients with human immunodeficiency virus-associated wasting: a randomized controlled trial.

The arteriovenous oxygen difference (a-vO(2) difference), a measure of peripheral muscle oxygen extraction-utilization during exercise, is reduced in antiretroviral-treated patients with human immunodeficiency virus (HIV), thus causing a shift in the cardiac output-oxygen consumption (Q-VO(2)) relationship. We investigated the impact of recombinant human GH (rhGH) treatment on a-vO(2) difference and the Q-VO(2) relationship during submaximal exercise by randomizing 12 HIV-infected patients (mean +/- sem: age, 43.3 +/- 1.5 yr; body mass, 69.5 +/- 2.9 kg; body mass index, 22.4 +/- 0.9 kg/m(2); maximum oxygen consumption, 33.6 +/- 1.5 ml/kg x min), with documented unintentional weight loss (>or=10% within the preceding 12 months) despite antiretroviral therapy, to receive 3 months of rhGH (6 mg/d) in a double-blind, placebo-controlled, cross-over trial. We assessed Q (determined noninvasively using CO(2) rebreathing), and subsequently a-vO(2) difference, from Q-VO(2) relationships. At study entry, the mean slope (8.1 +/- 1.0 liters/min x 1-liter increase in VO(2)) and intercept (3.1 +/- 1.3 liters/min), generated from each patient's Q-VO(2) relationship, were greater and lower, respectively, than those reported for healthy individuals (6.0 and 4.0, respectively), thereby indicating a deficit in the a-vO(2) difference. After 3 months of rhGH treatment, the slope decreased to 7.0, and the intercept increased to 3.5. After 1 month of rhGH treatment, the a-vO(2) difference (at a VO(2) of 1250 ml/min) significantly (P < 0.05) increased (17.1 +/- 8.9%) from baseline (9.92 +/- 0.51 ml/dl) and remained elevated (10.39 +/- 0.48 ml/dl) after 3 months of treatment. No significant changes were seen with placebo. Therefore, treatment with rhGH leads to an improvement in peripheral muscle oxygen extraction-utilization and the Q-VO(2) relationship during exercise in patients with HIV-associated wasting despite antiretroviral therapy.

Adult↗