Thirty-two untrained men [mean (SD) age 22.5 (5.8) years, height 178.3 (7.2) cm, body mass 77.8 (11.9) kg] participated in an 8-week progressive resistance-training program to investigate the "strength-endurance continuum". Subjects were divided into four groups: a low repetition group (Low Rep, n = 9) performing 3-5 repetitions maximum (RM) for four sets of each exercise with 3 min rest between sets and exercises, an intermediate repetition group (Int Rep, n = 11) performing 9-11 RM for three sets with 2 min rest, a high repetition group (High Rep, n = 7) performing 20-28 RM for two sets with 1 min rest, and a non-exercising control group (Con, n = 5). Three exercises (leg press, squat, and knee extension) were performed 2 days/week for the first 4 weeks and 3 days/week for the final 4 weeks. Maximal strength [one repetition maximum, 1RM), local muscular endurance (maximal number of repetitions performed with 60% of 1RM), and various cardiorespiratory parameters (e.g., maximum oxygen consumption, pulmonary ventilation, maximal aerobic power, time to exhaustion) were assessed at the beginning and end of the study. In addition, pre- and post-training muscle biopsy samples were analyzed for fiber-type composition, cross-sectional area, myosin heavy chain (MHC) content, and capillarization. Maximal strength improved significantly more for the Low Rep group compared to the other training groups, and the maximal number of repetitions at 60% 1RM improved the most for the High Rep group. In addition, maximal aerobic power and time to exhaustion significantly increased at the end of the study for only the High Rep group. All three major fiber types (types I, IIA, and IIB) hypertrophied for the Low Rep and Int Rep groups, whereas no significant increases were demonstrated for either the High Rep or Con groups. However, the percentage of type IIB fibers decreased, with a concomitant increase in IIAB fibers for all three resistance-trained groups. These fiber-type conversions were supported by a significant decrease in MHCIIb accompanied by a significant increase in MHCIIa. No significant changes in fiber-type composition were found in the control samples. Although all three training regimens resulted in similar fiber-type transformations (IIB to IIA), the low to intermediate repetition resistance-training programs induced a greater hypertrophic effect compared to the high repetition regimen. The High Rep group, however, appeared better adapted for submaximal, prolonged contractions, with significant increases after training in aerobic power and time to exhaustion. Thus, low and intermediate RM training appears to induce similar muscular adaptations, at least after short-term training in previously untrained subjects. Overall, however, these data demonstrate that both physical performance and the associated physiological adaptations are linked to the intensity and number of repetitions performed, and thus lend support to the "strength-endurance continuum".

Junctional epidermolysis bullosa (JEB) is a severe and often lethal genetic disease caused by mutations in genes encoding the basement membrane component laminin-332. Surviving patients with JEB develop chronic wounds to the skin and mucosa, which impair their quality of life and lead to skin cancer. Here we show that autologous transgenic keratinocyte cultures regenerated an entire, fully functional epidermis on a seven-year-old child suffering from a devastating, life-threatening form of JEB. The proviral integration pattern was maintained in vivo and epidermal renewal did not cause any clonal selection. Clonal tracing showed that the human epidermis is sustained not by equipotent progenitors, but by a limited number of long-lived stem cells, detected as holoclones, that can extensively self-renew in vitro and in vivo and produce progenitors that replenish terminally differentiated keratinocytes. This study provides a blueprint that can be applied to other stem cell-mediated combined ex vivo cell and gene therapies.

607 ALI = acute lung injury; ARDS = acute respiratory distress syndrome; ARDSexp = extrapulmonary ARDS; ARDSp = pulmonary ARDS; C CW = chest wall compliance; CHF = congestive heart failure; C L = lung compliance; COPD = chronic obstructive pulmonary disease; CPAP = continuous positive airway pressure; ESPVR = end-systolic pressure-volume relationship; FRC = functional residual capacity; IAP = intra-abdominal pressure; ITP = intrathoracic pressure; LV = left ventricular; PaCO2 = arterial carbon dioxide partial pressure; Palv = avleolar pressure; Paw = airway pressure; P CRIT = critical closing pressure; PEEP = positive end-expiratory pressure; Pes = esophageal pressure; Pms = mean systemic pressure; Ppc = pericardial pressure; Ppl = pleural pressure; PVR = pulmonary vascular resistance; RAP = right atrial pressure; RV = right ventricular; SV = stroke volume.Available online http://ccforum.com/content/9/6/607 AbstractIn patients with acute lung injury, high levels of positive endexpiratory pressure (PEEP) may be necessary to maintain or restore oxygenation, despite the fact that 'aggressive' mechanical ventilation can markedly affect cardiac function in a complex and often unpredictable fashion. As heart rate usually does not change with PEEP, the entire fall in cardiac output is a consequence of a reduction in left ventricular stroke volume (SV). PEEP-induced changes in cardiac output are analyzed, therefore, in terms of changes in SV and its determinants (preload, afterload, contractility and ventricular compliance). Mechanical ventilation with PEEP, like any other active or passive ventilatory maneuver, primarily affects cardiac function by changing lung volume and intrathoracic pressure. In order to describe the direct cardiocirculatory consequences of respiratory failure necessitating mechanical ventilation and PEEP, this review will focus on the effects of changes in lung volume, factors controlling venous return, the diastolic interactions between the ventricles and the effects of intrathoracic pressure on cardiac function, specifically left ventricular function. Finally, the hemodynamic consequences of PEEP in patients with heart failure, chronic obstructive pulmonary disease and acute respiratory distress syndrome are discussed.

No abstract

Increased abdominal pressure is common in intensive care unit patients. To investigate its impact on respiration and hemodynamics we applied intraabdominal pressure (aIAP) of 0 and 20 cm H 2 O (pneumoperitoneum) in seven pigs. The whole-lung computed tomography scan and a complete set of respiratory and hemodynamics variables were recorded both in healthy lung and after oleic acid (OA) injury. In healthy lung, aIAP 20 cm H 2 O significantly lowered the gas content, leaving the tissue content unchanged. In OAinjured lung at aIAP 0 cm H 2 O, the gas content significantly decreased compared with healthy lung. The excess tissue mass (edema) amounted to 30 Ϯ 24% of the original tissue weight (455 Ϯ 80 g). The edema was primarily distributed in the base regions and was not gravity dependent. Heart volume, central venous, pulmonary artery, wedge, and systemic arterial pressures significantly increased. At aIAP 20 cm H 2 O in OA-injured lung, the central venous and pulmonary artery pressures further increased. The gas content further decreased, and the excess tissue mass rose up to 103 Ϯ 37% (tissue weight 905 Ϯ 134 g), with homogeneous distribution along the cephalocaudal and sternovertebral axis. We conclude that in OAinjured lung, the increase of IAP increases the amount of edema.Keywords: intraabdominal pressure; acute respiratory distress syndrome; pulmonary edema; lung mechanics; computed tomography scanThe importance of intraabdominal pressure (IAP) in acute lung injury and acute respiratory distress syndrome has been recently suggested (1). For a long time any change in respiratory mechanics in patients with acute lung injury/acute respiratory distress syndrome was attributed to lung mechanics, whereas chest wall mechanics was assumed to be normal. However, few studies in which chest wall elastance was actually measured have showed that it was abnormal in a substantial proportion of patients with acute lung injury/acute respiratory distress syndrome (2-4). We (5) and others (6) have described different chest wall mechanics in patients with pulmonary and extrapulmonary acute respiratory distress syndrome, mainly due to different IAP values.However, apart from respiratory mechanics, the increased intrathoracic pressure caused by chest wall impairment may have important consequences on hemodynamics (7). We investigated the effect of changing IAP during controlled mechanical ventilation in healthy and diseased lungs. Surprisingly, the increase of IAP had an unexpected impact on lung edema, likely related to its formation and clearance. We wish to report our findings and METHODS(Additional details about Methods are provided in an online supplement.)The study group consisted of seven anesthetized and paralyzed domestic pigs (41 Ϯ 4 kg) ventilated throughout the experiment in supine position, with a Vt of 12 ml/kg, respiratory rate of 12-14 breaths/minute, positive end-expiratory pressure of 5 cm H 2 O, and Fi O 2 of 1.0. The animals were fully instrumented for hemodynamic monitoring (carotid artery, right atrium, mea...

The Castang Foundation, Bath Unit for Research in Paediatrics, National Institute of Health Research, the Royal United Hospitals Bath NHS Foundation Trust, BRONNER-BENDER Stiftung/Gernsbach, University Children's Hospital Zurich.

Given the poor prognosis of UCD with conservative therapy, LCT caused considerable beneficial effects. Periods of hyperammonemia and clinically relevant crises could be reduced during an observation period of up to 13 months. Though cell therapy is not a permanent therapeutic option, bridging to liver transplantation may be substantially improved.

IntroductionTo investigate haemodynamic and respiratory changes during lung recruitment and decremental positive end-expiratory pressure (PEEP) titration for open lung ventilation in patients with acute respiratory distress syndrome (ARDS) a prospective, clinical trial was performed involving 12 adult patients with ARDS treated in the surgical intensive care unit in a university hospital.MethodsA software programme (Open Lung Tool™) incorporated into a standard ventilator controlled the recruitment (pressure-controlled ventilation with fixed PEEP at 20 cmH2O and increased driving pressures at 20, 25 and 30 cmH2O for two minutes each) and PEEP titration (PEEP lowered by 2 cmH2O every two minutes, with tidal volume set at 6 ml/kg). The open lung PEEP (OL-PEEP) was defined as the PEEP level yielding maximum dynamic respiratory compliance plus 2 cmH2O. Gas exchange, respiratory mechanics and central haemodynamics using the Pulse Contour Cardiac Output Monitor (PiCCO™), as well as transoesophageal echocardiography were measured at the following steps: at baseline (T0); during the final recruitment step with PEEP at 20 cmH2O and driving pressure at 30 cmH2O, (T20/30); at OL-PEEP, following another recruitment manoeuvre (TOLP).ResultsThe ratio of partial pressure of arterial oxygen (PaO2) to fraction of inspired oxygen (FiO2) increased from T0 to TOLP (120 ± 59 versus 146 ± 64 mmHg, P < 0.005), as did dynamic respiratory compliance (23 ± 5 versus 27 ± 6 ml/cmH2O, P < 0.005). At constant PEEP (14 ± 3 cmH2O) and tidal volumes, peak inspiratory pressure decreased (32 ± 3 versus 29 ± 3 cmH2O, P < 0.005), although partial pressure of arterial carbon dioxide (PaCO2) was unchanged (58 ± 22 versus 53 ± 18 mmHg). No significant decrease in mean arterial pressure, stroke volume or cardiac output occurred during the recruitment (T20/30). However, left ventricular end-diastolic area decreased at T20/30 due to a decrease in the left ventricular end-diastolic septal-lateral diameter, while right ventricular end-diastolic area increased. Right ventricular function, estimated by the right ventricular Tei-index, deteriorated during the recruitment manoeuvre, but improved at TOLP.ConclusionsA standardised open lung strategy increased oxygenation and improved respiratory system compliance. No major haemodynamic compromise was observed, although the increase in right ventricular Tei-index and right ventricular end-diastolic area and the decrease in left ventricular end-diastolic septal-lateral diameter during the recruitment suggested an increased right ventricular stress and strain. Right ventricular function was significantly improved at TOLP compared with T0, although left ventricular function was unchanged, indicating effective lung volume optimisation.