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OBJECTIVE: The objective of this study was to investigate mechanisms underlying species specificity in particle-induced lung inflammation. METHODS: Rats, mice, and hamsters exposed to air, 1, 7, or 50 mg/m3 of carbon black for 13 weeks were killed at 1 day, 3 months, and 11 months after exposure. Bronchoalveolar lavage was performed and characterized for cell number, cell type, reactive oxygen and nitrogen species, and cytokine levels. Ex vivo mutational analysis of inflammatory cells was evaluated by coincubating with lung epithelial cells. Lung tissue was evaluated for gene expression of various antiinflammatory mediators. RESULTS: There was a dose- and time-related effect with all the parameters. Rats demonstrated greater propensity for generating a proinflammatory response, whereas mice and hamsters demonstrated an increased antiinflammatory response. CONCLUSIONS: These differences in pro- and antiinflammatory responses may contribute to the apparent species differences in inflammation and tumorigenesis. [ABSTRACT FROM AUTHOR]

PURPOSE AND METHOD: To investigate the possible role of carbohydrate (CHO) receptors in the mouth in influencing exercise performance, seven male and two female endurance cyclists (VO(2max) 63.2 +/- 2.7 (mean +/- SE) mL.kg*(-1).min(-1)) completed two performance trials in which they had to accomplish a set amount of work as quickly as possible (914 +/- 40 kJ). On one occasion a 6.4% maltodextrin solution (CHO) was rinsed around the mouth for every 12.5% of the trial completed. On the other occasion, water (PLA) was rinsed. Subjects were not allowed to swallow either the CHO solution or water, and each mouthful was spat out after a 5-s rinse. RESULTS: Performance time was significantly improved with CHO compared with PLA (59.57 +/- 1.50 min vs 61.37 +/- 1.56 min, respectively, P = 0.011). This improvement resulted in a significantly higher average power output during the CHO compared with the PLA trial (259 +/- 16 W and 252 +/- 16 W, respectively, P = 0.003). There were no differences in heart rate or rating of perceived exertion (RPE) between the two trials (P > 0.05). CONCLUSION: The results demonstrate that carbohydrate mouth rinse has a positive effect on 1-h time trial performance. The mechanism responsible for the improvement in high-intensity exercise performance with exogenous carbohydrate appears to involve an increase in central drive or motivation rather than having any metabolic cause. The nature and role of putative CHO receptors in the mouth warrants further investigation. [ABSTRACT FROM AUTHOR]

PURPOSE AND METHODS: To investigate the effect of glucose infusion on glucose kinetics and performance, six endurance cyclists (VO2max = 61.7 +/- 2.0 (mean +/- SE) mL x kg(-1) x min(-1)) completed two performance trials in which they had to accomplish a set amount of work as quickly as possible (991 +/- 41 kJ). Subjects were infused with either glucose (20% in saline; carbohydrate (CHO)) at a rate of 1 g x min(-1) or saline (0.9% saline; placebo (PLA)). It was hypothesized that time trial performance would be unaffected by the infusion of glucose, as endogenous stores of CHO would not be limiting in the PLA trial. RESULTS: Plasma glucose concentration increased from 4.8 +/- 0.1 mmol x L(-1) to 5.9 +/- 0.3 mmol x L(-1) during the PLA trial and from 4.9 +/- 0.1 mmol x L(-1) at rest to 12.4 +/- 1.1 mmol x L(-1) during the CHO trial. These values were significantly higher at all time points during the CHO trial compared with PLA (P < 0.001). In the final stages of the time trial, Rd in the PLA trial was 49 +/- 5 micromol x kg(-1) x min(-1) compared with 88 +/- 7 micromol x kg(-1) x min(-1) in the CHO trial (P < 0.05). Despite these differences, there was no difference in performance time between PLA and CHO (60.04 +/- 1.47 min, PLA, vs 59.90 +/- 1.49 min, CHO, respectively). Infused carbohydrate oxidation in the last 25% of the CHO trial was at least 675 +/- 120 micromol x kg(-1) and contributed 17 +/- 4% to total carbohydrate oxidation. CONCLUSION: The results demonstrate that glucose infusion had no effect on 1-h cycle time-trial performance, despite an increased availability of plasma glucose for oxidation and evidence of increased glucose uptake into the tissues. [ABSTRACT FROM AUTHOR]

Purpose: Large interindividual variation exists in maximal fat oxidation (MFO) rates and the exercise intensity at which it occurs (FATMAX). However, there are no data describing the shape of the fat oxidation curve or if individual differences exist when tested on separate occasions. Furthermore, there are limited data on fat metabolism in professional team sport athletes. Therefore, the aim of this study was to test-retest the concavity (shape) and intercept (height) of fat oxidation curves within a group of professional soccer players., Method: On two occasions, 16 professional male soccer players completed a graded exercise test in a fasted state (≥5 h). Rates of fat oxidation were determined using indirect calorimetry. Maximal oxygen uptake (V˙O2max) was measured to calculate FATMAX (%V˙O2max). The shape of the fat oxidation curves were modeled on an individual basis using third-degree polynomial. Test-by-test differences, in the shape and vertical shift of the fat oxidation curves, were established to assess within-individual variability., Results: Average absolute MFO was 0.69 ± 0.15 g·min (range, 0.45-0.99 g·min). On a group level, no significant differences were found in MFO between the two tests. No differences were found (P > 0.05) in the shape of the fat oxidation curves in 13 of 16 players (test 1 vs test 2). There were also no differences (P > 0.05) in the vertical shift of the fat oxidation curves in 10 players., Conclusions: In general, the shape of the fat oxidation curve does not change within an individual; however, the vertical shift is more susceptible to change, which may be due to training status and body composition. Understanding a player's metabolism may be of value to practitioners working within sport, with regard to personalizing nutrition strategies.

Purpose: Airway management in neonates with Pierre Robin sequence (PRS) can be challenging. The goal was to describe the algorithm developed by the authors over the past 8 years., Methods: A retrospective case series analyzing airway management in neonates with PRS admitted to the neonatal intensive care unit at a tertiary care pediatric hospital was performed. The utility of the proposed algorithm for airway management incorporating more consistent use of polysomnography (PSG), and airway assessment was assessed., Results: A total of 31 neonates with PRS (12 men, 19 women) with a mean gestational age of 38.2 weeks were analyzed. Thirteen (41.9%) patients had a named syndrome, chromosomal abnormality, or global delay. Twenty (64.5%) patients had pre-intervention PSG, and severe obstructive sleep apnea with an apnea-hypopnea index (AHI) ≥ 10 events/hour was identified in 19 (95.0%). Mandibular distraction osteogenesis was performed in 18 (58.1%) patients, and improved the AHI on post-operative PSGs. Direct assessment of the upper and lower airways was performed in 19 patients, and 13 (68.4%) were found to have secondary airway pathology. Presence of a concomitant syndrome was significantly associated with need for tracheostomy., Conclusion: The algorithm differs from previous ones in that it relies on rigorous pre- and post-intervention PSG (including with a nasopharyngeal airway), as well as that it allows flexibility between treatment options given the whole-patient clinical scenario and endoscopic findings. Results from these studies may be integrated to stratify patients into those who are most likely to benefit from conservative interventions or surgical procedures.

Introduction: The aim of this study was to describe maximal fat oxidation (MFO) rates in an athletic population., Method: In total, 1121 athletes (933 males and 188 females), from a variety of sports and competitive level, undertook a graded exercise test on a treadmill in a fasted state (≥5 h fasted). Rates of fat oxidation were determined using indirect calorimetry., Results: The average MFO was 0.59 ± 0.18 g·min, ranging from 0.17 to 1.27 g·min. Maximal rates occurred at an average exercise intensity of 49.3% ± 14.8% V˙O2max, ranging from 22.6% to 88.8% V˙O2max. In absolute terms, male athletes had significantly higher MFO compared with females (0.61 and 0.50 g·min, respectively, P < 0.001). Expressed relative to fat-free mass (FFM), MFO were higher in the females compared with males (MFO/FFM: 11.0 and 10.0 mg·kg·FFM·min, respectively, P < 0.001). Soccer players had the highest MFO/FFM (10.8 mg·kg·FFM·min), ranging from 4.1 to 20.5 mg·kg·FFM·min, whereas American Football players displayed the lowest rates of MFO/FFM (9.2 mg·kg·FFM·min). In all athletes, and when separated by sport, large individual variations in MFO rates were observed. Significant positive correlations were found between MFO (g·min) and the following variables: FFM, V˙O2max, FATMAX (the exercise intensity at which the MFO was observed), percent body fat, and duration of fasting. When taken together these variables account for 47% of the variation in MFO., Conclusion: MFO and FATMAX vary significantly between athletes participating in different sports but also in the same sport. Although variance in MFO can be explained to some extent by body composition and fitness status, more than 50% of the variance is not explained by these variables and remains unaccounted for.

Objective: Patients undergoing percutaneous coronary intervention (PCI) for acute myocardial infarction with cardiogenic shock (CS) are often treated with intra-aortic balloon pump counterpulsation (IABP), even though the evidence to support this is limited. We determined whether IABP as an addition to PCI-centered therapy ameliorates multiorgan dysfunction syndrome (MODS) in patients with acute myocardial infarction complicated by CS., Design: A prospective, randomized, controlled, open-label clinical trial recruiting patients between March 2003 and June 2004 (ClinicalTrials.gov ID NCT00469248)., Setting: Tertiary care university hospital., Patients and Interventions: Forty-five consecutive patients with AMI and CS undergoing PCI were randomized to treatment with or without IABP., Measurements and Main Results: Acute Physiology and Chronic Health Evaluation (APACHE) II scores (primary outcome measure), hemodynamic values, inflammatory markers, and plasma brain natriuretic peptide (BNP) levels (secondary outcomes) were collected over 4 days from randomization. The prospective hypothesis was that adding IABP therapy to "standard care" would improve CS-triggered MODS. The addition of IABP to standard therapy did not result in a significant improvement in MODS (measured by serial APACHE II scoring over 4 days). IABP use had no significant effect on cardiac index or systemic inflammatory activation, although BNP levels were significantly lower in IABP-treated patients. Initial and serial APACHE II scoring correlated with mortality better than cardiac index, systemic inflammatory state, and BNP levels in this group of patients. Nonsurvivors had significantly higher initial APACHE II scores (29.9 +/- 2.88) than survivors (18.1 +/- 1.66, p < .05). Nevertheless, discrepancies among patients within the groups cannot be ruled out and might interfere with our results., Conclusions: In this randomized trial addressing addition of IABP in CS patients, mechanical support was associated only with modest effects on reduction of APACHE II score as a marker of severity of disease, improvement of cardiac index, reduction of inflammatory state, or reduction of BNP biomarker status compared with medical therapy alone. However, the limitations of our present trial preclude any definitive conclusion, but request for a larger prospective, randomized, multicentered trial with mortality as primary end point.

Objectives: Levosimendan improves left ventricular hemodynamic function in patients with cardiogenic shock. However, its impact on right ventricular performance has not been determined. We compared the hemodynamic effects of levosimendan on left and right ventricular function in patients with intractable cardiogenic shock following myocardial infarction., Design: Observational hemodynamic study., Setting: Tertiary care center university hospital., Patients: Fifty-six patients with cardiogenic shock secondary to myocardial infarction were treated with percutaneous revascularization (including intra-aortic balloon pump when appropriate) and commenced on conventional inotropic therapy., Intervention: Twenty-five consecutive patients with cardiogenic shock due to myocardial infarction who had not improved sufficiently with conventional therapy (including dobutamine and norepinephrine) received levosimendan (as a bolus of 12 microg/kg per minute for 10 mins then 0.1 microg/kg per minute--0.2 mug/kg per minute) as "bail-out" therapy for 24 hrs while invasive hemodynamic parameters were recorded., Measurements and Main Results: Levosimendan therapy was associated with a significant increase in cardiac index from 2.1 +/- 0.1 to 3.0 +/- 0.2 L x min x m (p < .01). In addition, levosimendan enhanced right ventricular cardiac power index (0.14 +/- 0.19 to 0.18W +/- 0.12, p < .001), while pulmonary vascular resistance fell from 227.7 +/- 94.5 to 178.1 +/- 62.3 dyne x s x cm (p = .002). No significant change in central venous pressure or mean pulmonary artery pressure was observed. The observed hemodynamic improvement was sustained after the levosimendan infusion was stopped., Conclusions: Levosimendan infusion for cardiogenic shock following acute myocardial infarction improved hemodynamic parameters of right ventricular performance. Furthermore, we describe the use of right ventricular cardiac power index as a hemodynamic parameter of right ventricular performance.

Animal data strongly support a role for inflammation in myocardial ischemia reperfusion injury. Attempts at cardioprotection by immunomodulation (such as with the specific C5 antibody pexelizumab) in humans have been disappointing. We hypothesized that a broader spectrum antiinflammatory agent might yield successful cardioprotection. The serine protease inhibitor nafamostat (FUT-175), which is already in clinical use, is a potent antiinflammatory synthetic serine protease inhibitor with anticomplement activity that we tested in a well-established rabbit model of 1 hour of myocardial ischemia followed by 3 hours of reperfusion. Compared to vehicle-treated animals, nafamostat (1 mg/kg of body weight) administered 5 minutes before reperfusion significantly reduced myocardial injury assessed by plasma creatine kinase activity (38.1 +/- 6.0 versus 57.9 +/- 3.7I U/g protein; P < 0.05) and myocardial necrosis (23.6 +/- 3.1% versus 35.7 +/- 1.0%; P < 0.05) as well as myocardial leukocyte accumulation (P < 0.05). In parallel in vitro studies, Nafamostat was a significantly more potent broad spectrum complement suppressor than C1 inhibitor. Nafamostat appears to have capability as an inhibitor of both complement pathways and as a broad-spectrum antiinflammatory agent by virtue of its serine protease inhibition. Administration of nafamostat before myocardial reperfusion after ischemia produced significant, dose-dependent cardioprotection. Reduced leukocyte accumulation and complement activity seem involved in the mechanism of this cardioprotective effect.

Bacterial toxins cause cardiac dysfunction and death through an inflammatory process, but the mechanism remains unclear. Simvastatin is recognized as having anti-inflammatory properties beyond its lipid-lowering effects. We examined Staphylococcus aureus alpha-toxin in isolated heart and in vivo models and tested simvastatin's effects in sepsis. Isolated Langendorff-perfused rat hearts were exposed to a recirculating perfusate containing alpha-toxin (0.5 microg mL(-1)). Compared with controls, there was a significant increase in coronary perfusion pressure and fall in myocardial performance. Significant increases in p53 expression and apoptosis (1.3 +/- 0.5 to 7.1 +/- 1.4 terminal deoxynucleaotidyl transferase nick end labeling-positive cells; P < 0.05) compared with controls were observed, but markers of necrosis were similar. In parallel experiments, anaesthetized rats receiving alpha-toxin (40 microg kg(-1), i.v.) had in vivo hemodynamic parameters and serum markers of necrosis monitored for 4 h before the hearts were analyzed for histological change, p53 expression, and apoptosis. Over 4 h, alpha-toxin exposure produced substantial hemodynamic effects. In addition, p53 expression (0.2 +/- 0.2 to 7.1 +/- 0.5 p53-positive myocytes; P < 0.05), TNF-alpha levels, the degree of apoptosis, and markers of necrosis were all significantly increased compared with control animals. Pretreatment with simvastatin protected against alpha-toxin-induced sepsis associated with reduced p53, TNF-alpha, apoptosis, and necrosis. We found significant changes in systemic hemodynamics, coronary perfusion pressure, myocardial function, and increased p53 expression with apoptosis due to bacterial exotoxin. In vivo changes were significantly inhibited by pretreatment with simvastatin. We provide novel evidence for the mechanisms by which septicemia causes myocardial depression and hint at a potential role for simvastatin as an inhibitor of apoptosis in sepsis.

Unlabelled: Telemetric gastrointestinal (GI) temperature pills are now commonly used to measure core body temperature and could minimize the risk of heat illness while maximizing operational effectiveness in workers subject to high levels of thermal strain., Purpose: To quantify the effect of repeated cool water ingestion on the accuracy of GI pill temperature., Methods: Ten operational firefighters ingested a pill to measure GI temperature (T1int) before overnight sleep. Two hours following breakfast and 11.5 h after ingesting T1int, the firefighters ingested a second pill (T2int) before performing 8.5 h of intermittent activity (repetitive cycles of 30 min of seated rest followed by 30 min of general firefighter duties). During the first 2 min of each 30-min rest period, the firefighters consumed 250 mL of chilled water (5-8 degrees C)., Results: Water ingestion had a highly variable effect both within and between subjects in transiently (32 +/- 10 min) reducing the temperature of T2int in comparison with T1int. In general, this transient reduction in T2int became progressively smaller as time following ingestion increased. In some firefighters, the difference between T1int and T2int became negligible (+/- 0.1 degrees C) after 3 h, whereas in two others, large differences (peaking at 2.0 degrees C and 6.3 degrees C) were still observed when water was consumed 8 h after pill ingestion., Conclusion: These results show that a GI pill ingested immediately prior to physical activity cannot be used to measure core body temperature accurately in all individuals during the following 8 h when cool fluids are regularly ingested. This makes GI temperature measurement unsuitable for workers who respond to emergency deployments when regular fluid consumption is recommended operational practice.

Objectives: Levosimendan, a novel inodilator, has been shown to improve hemodynamic function in patients with acute exacerbation of congestive heart failure. We wanted to determine the hemodynamic effects of levosimendan following ineffective conventional therapy (with catecholamines) in patients with cardiogenic shock following myocardial infarction., Design: Observational hemodynamic study., Setting: Tertiary care center university hospital., Patients: Fifty-six patients with cardiogenic shock secondary to myocardial infarction were treated with percutaneous revascularization (intra-aortic balloon pump where appropriate) and commenced on conventional inotropic therapy., Interventions: Patients with persisting cardiogenic shock 24 hrs after revascularization were additionally treated with levosimendan (rapid bolus of 12 microg/kg for 10 mins, then 0.05-0.2 mug/kg/min for 24 hrs) (n = 25)., Measurements and Main Results: With conventional catecholamine therapy (norepinephrine and dobutamine), we observed only marginal improvement in mean arterial pressure or cardiac index. In contrast, the addition of levosimendan produced a significant increase in cardiac index (2.1 +/- 0.56 to 3.0 +/- 1.11 L/min/m2, p < .01) and cardiac power index (0.32 +/- 0.08 to 0.44 +/- 0.18 W, p < .01), whereas systemic vascular resistance decreased significantly (1208 +/- 333 to 858 +/- 299 dyne.sec.cm(-5), p < .01). There was no significant change in blood pressure during levosimendan treatment. Hemodynamic improvement was sustained after levosimendan infusion was stopped., Conclusions: Levosimendan infusion in cardiogenic shock following acute myocardial infarction improved cardiovascular hemodynamics without leading to hypotension.

Background: Reperfusion injury of ischemic myocardium has been attributed to neutrophil infiltration, inflammatory activation and cardiac necrosis/apoptosis. Serine protease inhibition with aprotinin is cardioprotective, but the mechanism is unknown., Methods and Results: We studied aprotinin in a rat model of myocardial ischemia for 20 minutes and reperfusion for 20 minutes, 8 hours or 24 hours. Aprotinin (20,000 IU/kg) given 5 minutes before reperfusion significantly reduced leukocyte accumulation (P<0.01), myocardial injury (determined by CK depletion, P<0.01) and myocyte apoptosis (P<0.05) compared with vehicle treated rats. Differential gene expression analysis showed myocardial ischemia plus reperfusion increased expression of proinflammatory genes like P-selectin, E-selectin, intercellular adhesion molecule, tumor necrosis factor-alpha, tumor necrosis factor-alpha receptor, interleukin-6, monocyte chemoattractant protein-1, p53, and Fas (CD59). Aprotinin before reperfusion suppressed expression of these inflammatory genes. Finally, differential protein expression analysis demonstrated increased intercellular adhesion molecule-1, tumor necrosis factor-alpha, and p53 after myocardial ischemia plus reperfusion, and this effect was diminished by aprotinin., Conclusions: We demonstrated myocardial ischemia plus reperfusion induced leukocyte accumulation, inflammation, gene expression, protein expression and finally tissue injury and showed aprotinin limiting reperfusion injury through each of these stages, even after 24 hours of reperfusion. This effect seems partly attributable to suppression of proinflammatory genes and leukocyte accumulation. This work casts further light on the complex signaling of ischemia and reperfusion.

The purpose of this study was to develop a method of defining, in mathematical terms, the interpositional relationships of the bones of the hindfoot complex in the idiopathic clubfoot and the neurogenic clubfoot. The neurogenic clubfoot and contralateral normal-appearing foot of a stillborn infant with myelomeningocele, and the normal foot of a 10-year-old were sectioned with a cryomicrotome. Magnetic resonance images (MRIs) of the clubfoot and the normal foot of a 3-month-old boy were obtained. Using a computer program, three-dimensional foot models were generated from the digitized cryomicrotome sections and from the MRIs. The central principal axes were determined for the talus and calcaneus. The long central principal axes of the talus and calcaneus were neutrally rotated with reference to the bimalleolar axis in the idiopathic clubfoot while in the neurogenic clubfoot the long central principal axis of the talus was medially rotated 52 degrees and that of the calcaneus 10 degrees. The talocalcaneal angles defined by the long central principal axes in the superior and medial views were 0 degree and 10 degrees, respectively, in the idiopathic clubfoot, and 42 degrees and 56 degrees, respectively, in the neurogenic clubfoot.

Eighteen neonates 33 to 42 wk gestational age with severe respiratory failure were referred for extracorporeal membrane oxygenation (ECMO). Sixteen ultimately met the ECMO criteria, of whom 15 were first offered high-frequency oscillatory ventilation (HFOV). Seven responded to HFOV alone and did not require ECMO treatment. Eight of the nine remaining patients were placed on ECMO support with HOFV. Infants who responded to HFOV alone tended to have pneumonia more than meconium aspiration, to be smaller and more immature, to have higher Apgar scores, and to have suffered severe hypoxia (alveolar-arterial oxygen pressure difference over 600 torr) for less time than the ECMO group. Although patient numbers are small, a trend is noted which favors HFOV treatment alone in terms of the duration of HFOV, the total duration of assisted ventilation, the rapidity with which extubation was accomplished, and the length of hospital stay.