Head pre-cooling improves 5-km time-trial performance in male amateur runners in the heat.

This study aimed to evaluate the effect of head pre-cooling on the 5-km time-trial performance of amateur runners in the heat. In a counterbalanced design, 15 male amateur runners (22.6 ± 3.5 y; VO2 max in heat 42.3 ± 4.4 mLO2 /kg/min) completed two 5-km time trials performed in the heat (35°C, 50% relative humidity). In one trial (HCOOL), participants underwent 20 min of head cooling in a temperate environment (23°C, 70% relative humidity) prior to exercise. In another trial (CON), exercise was preceded by 20 min of rest under the same temperature conditions. Exercise time was shorter in HCOOL (25 min and 36 s ± 3 min) compared to CON (27 ± 3 min; p = 0.02). Rectal temperature was reduced during the pre-exercise intervention in HCOOL (p < 0.001), but not in CON (p = 0.55). Relative changes in rectal temperature and mean head temperature were lower throughout HCOOL when compared with CON condition (p = 0.005 and p = 0.022, respectively). Mean skin temperature, heart rate, and rating of perceived exertion did not differ between HCOOL and CON conditions throughout exercise (p = 0.20, p = 0.52 and 0.31, respectively). Thermal comfort was lower in HCOOL condition in pre-exercise (p = 0.014) with no differences observed throughout exercise (p = 0.61). 5-km running performance in a hot environment was improved after a 20-min head cooling intervention, suggesting that this method may be practical as pre-cooling strategy and easily administered to both professional and amateur runners alike.

Correction: The influence of a hot environment on physiological stress responses in exercise until exhaustion.

[This corrects the article DOI: 10.1371/journal.pone.0209510.].

The influence of a hot environment on physiological stress responses in exercise until exhaustion.

Exhaustive exercise in a hot environment can impair performance. Higher epinephrine plasma levels occur during exercise in heat, indicating greater sympathetic activity. This study examined the influence of exercise in the heat on stress levels. Nine young healthy men performed a maximal progressive test on a cycle ergometer at two different environmental conditions: hot (40°C) and normal (22°C), both between 40% and 50% relative humidity. Venous blood and saliva samples were collected pre-test and post-test. Before exercise there were no significant changes in salivary biomarkers (salivary IgA: p = 0.12; α-amylase: p = 0.66; cortisol: p = 0.95; nitric oxide: p = 0.13; total proteins: p = 0.07) or blood lactate (p = 0.14) between the two thermal environments. Following exercise, there were significant increases in all variables (salivary IgA 22°C: p = 0.04, 40°C: p = 0.0002; α-amylase 22°C: p = 0.0002, 40°C: p = 0.0002; cortisol 22°C: p = 0.02, 40°C: p = 0.0002; nitric oxide 22°C: p = 0.0005, 40°C: p = 0.0003, total proteins 22°C: p<0.0001, 40°C: p<0.0001 and; blood lactate 22°C: p<0.0001, 40°C: p<0.0001) both at 22°C and 40°C. There was no significant adjustment regarding IgA levels between the two thermal environments (p = 0.74), however the levels of α-amylase (p = 0.02), cortisol (p<0.0001), nitric oxide (p = 0.02) and total proteins (p = 0.01) in saliva were higher in the hotter conditions. Blood lactate was lower under the hot environment (p = 0.01). In conclusion, enduring hot temperature intensified stressful responses elicited by exercise. This study advocates that hot temperature deteriorates exercise performance under exhaustive stress and effort conditions.

Long-term safety and efficacy of recombinant factor VIII Fc fusion protein (rFVIIIFc) in subjects with haemophilia A.

INTRODUCTION: The safety, efficacy and prolonged half-life of recombinant factor VIII Fc fusion protein (rFVIIIFc) in previously treated patients with severe haemophilia A was demonstrated in the phase 3 A-LONG and Kids A-LONG studies. Here, we report interim safety and efficacy data from the rFVIIIFc extension study, ASPIRE (ClinicalTrials.gov #NCT01454739). METHODS: Eligible subjects could enrol in ASPIRE upon completing A-LONG or Kids A-LONG. There were four treatment groups: individualized prophylaxis; weekly prophylaxis; modified prophylaxis (for subjects in whom optimal treatment could not be achieved with individualized or weekly prophylaxis); and episodic treatment. The primary endpoint was development of inhibitors. RESULTS: A total of 150 A-LONG subjects and 61 Kids A-LONG subjects enrolled in ASPIRE. As of the interim data cut (6 January 2014), the median time on study was 80.9 (A-LONG) and 23.9 (Kids A-LONG) weeks. The majority of subjects (A-LONG, 92.0%; Kids A-LONG, 57.4%) had ≥100 cumulative rFVIIIFc exposure days. No inhibitors were observed. Adverse events were generally consistent with those expected in the general haemophilia A population. Median annualized bleeding rates (ABRs) were low with individualized [A-LONG: 0.66; Kids A-LONG: 0.00 (<6 years old), 1.54 (6 to <12 years old)], weekly (A-LONG: 2.03) and modified (A-LONG: 1.97) prophylaxis. There was no change in prophylactic infusion frequency or total weekly prophylactic dose in the majority of subjects from A-LONG and Kids A-LONG. CONCLUSION: Interim data from ASPIRE confirm the long-term safety of rFVIIIFc and the maintenance of a low ABR with extended-interval prophylactic dosing in patients with severe haemophilia A.

Recombinant factor VIII Fc fusion protein for the prevention and treatment of bleeding in children with severe hemophilia A.

BACKGROUND: Prophylactic factor replacement, which prevents hemarthroses and thereby reduces the musculoskeletal disease burden in children with hemophilia A, requires frequent intravenous infusions (three to four times weekly). OBJECTIVE: Kids A-LONG was a phase 3 open-label study evaluating the safety, efficacy and pharmacokinetics of a longer-acting factor, recombinant factor VIII Fc fusion protein (rFVIIIFc), in previously treated children with severe hemophilia A (endogenous FVIII level of < 1 IU dL(-1) [< 1%]). METHODS: The study enrolled 71 subjects. The starting rFVIIIFc regimen was twice-weekly prophylaxis (Day 1, 25 IU kg(-1) ; Day 4, 50 IU kg(-1) ); dose (≤ 80 IU kg(-1) ) and dosing interval (≥ 2 days) were adjusted as needed. A subset of subjects had sequential pharmacokinetic evaluations of FVIII and rFVIIIFc. The primary endpoint was development of inhibitors (neutralizing antibodies). Secondary endpoints included pharmacokinetics, annualized bleeding rate (ABR), and number of infusions required to control a bleed. RESULTS: No subject developed an inhibitor to rFVIIIFc. Adverse events were typical of a pediatric hemophilic population. The rFVIIIFc half-life was prolonged relative to that of FVIII, consistent with observations in adults and adolescents. The median ABR was 1.96 overall, and 0.00 for spontaneous bleeds; 46.4% of subjects reported no bleeding episodes on study. Ninety-three per cent of bleeding episodes were controlled with one to two infusions. The median average weekly rFVIIIFc prophylactic dose was 88.11 IU kg(-1) . At study end, 62 of 69 subjects (90%) were infusing twice weekly. Among subjects who had been previously receiving FVIII prophylaxis, 74% reduced their dosing frequency with rFVIIIFc. CONCLUSION: Twice-weekly infusions with rFVIIIFc were well tolerated and yielded low bleeding rates in children with severe hemophilia A.

Public health concerns about lung cancer: a case report.

An illustrative clinical case is presented and important features are highlighted regarding public health concerns about risk factors for lung cancer, lung cancer in women, and lung cancer screening.

Effect of chest wall vibration on dyspnea during hypercapnia and exercise in chronic obstructive pulmonary disease.

Vibration of chest wall inspiratory muscles during inspiration (in-phase) reduces breathlessness associated with hypercapnia and resistive loading in normal subjects and in patients with chronic obstructive pulmonary disease (COPD) at rest. To evaluate further the effect of chest wall vibration on breathlessness ("breathing discomfort") in patients, we studied 10 subjects 52 to 79 yr of age with severe dyspnea (mean FEV1, 0.75 L, 27% predicted). On a single day, we used two separate stimuli to produce mild to moderate breathlessness (BR): Protocol 1, steady-state hypercapnia; Protocol 2, exercise with a lower extremity ergometer. During each protocol, we applied in-phase chest wall vibration (CW) randomly alternating with one of two controls: deltoid vibration (DV) or no vibration (NV). During hypercapnia, CW significantly reduced BR (DV, 2.9 +/- 2.1; CW, 2.3 +/- 1.4; p < 0.05; NV, 3.3 +/- 2.1; CW, 2.6 +/- 2.0; p < 0.01) without significant changes in ventilation. During exercise, CW did not significantly alter BR relative to controls. These findings may be explained by the effect of vibration on the sense of respiratory effort and/or by improvement of the match between efferent motor commands and afferent information from the respiratory system. The lack of effect during exercise on BR suggests there may be a "therapeutic window" or range of conditions within which CW is effective in reducing dyspnea in patients with COPD.

Air trapping in the lungs during cardiopulmonary resuscitation in dogs. A mechanism for generating changes in intrathoracic pressure.

To test the hypothesis that during cardiopulmonary resuscitation, chest compression with an unobstructed trachea raises and maintains intrathoracic pressure by collapsing airways and trapping air in the lung, we studied 11 dogs (20-32 kg). An inflatable vest compressed the thorax after induction of ventricular fibrillation. First, tracheal airflow was measured by a pneumotachometer during vest inflation and deflation in nine of the dogs. As expected, during the initial phase of vest inflation of cycles after ventilation, air moved out of the lungs, but then airflow stopped. After vest deflation, however, more air moved out of the lungs in eight of the nine dogs; this occurrence indicated that a portion of the inspired tidal volume was trapped during vest inflation. During cycles without prior ventilation, the amount of air expired by chest compression decreased, paradoxically, at higher peak vest pressure (p less than 0.002); this occurrence indicated that air was trapped at the higher vest pressures. The change in right atrial pressure was higher on cycles after ventilation than on cycles without prior ventilation (79 +/- 12 vs. 67 +/- 12 mm Hg [mean +/- SEM], p less than 0.005), and lung volume was higher on cycles after ventilation (p less than 0.001). Next, a 5-Fr micromanometer was advanced down the airway in eight of the dogs. With the tip of the micromanometer 5-8 cm distal to the carina, a zone of high pressure was noted in seven dogs; this high pressure suggested a zone of airway collapse distal to the carina.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute non-dilating obstructive renal failure in a patient with AIDS.

A 30-year-old male who presented with acute renal failure was found to have acquired immunodeficiency syndrome (AIDS). Although sonography and computerized tomography did not show urinary tract dilatation, obstructive renal failure was demonstrated by retrograde pyelography. Relief of obstruction(s) due to encasement of the renal pelves and ureters with histiocytic lymphoma led to immediate return of normal renal function. Although the etiology of renal failure in this patient is highly unusual, the high incidence of lymphoma in patients with AIDS should make tumor-related renal disease a consideration in all such patients with renal dysfunction.