Reduced Toxicity Conditioning with Busulfan, Fludarabine, Alemtuzumab and Allogeneic Stem Cell Transplantation From HLA-Matched Sibling Donors in Children with High Risk Sickle Cell Disease Results in Long Term Donor Chimerism and Low Incidence of aGVHD

Purpose It is still equivocal whether oxygen uptake recovery kinetics are limited by oxygen delivery and can be improved by supplementary oxygen. The present study aimed to investigate whether measurements of muscle and pulmonary oxygen uptake kinetics can be used to assess oxygen delivery limitations in healthy subjects. Methods Sixteen healthy young adults performed three sub-maximal exercise tests (6 min at 40% Wmax) under hypoxic (14%O2), normoxic (21%O2) and hyperoxic (35%O2) conditions on separate days in randomized order. Both Pulmonary VO2 and near infra red spectroscopy (NIRS) based Tissue Saturation Index (TSI) offset kinetics were calculated using mono-exponential curve fitting models. Results Time constant τ of VO2 offset kinetics under hypoxic (44.9 ± 7.3s) conditions were significantly larger than τ of the offset kinetics under normoxia (37.9 ± 8.2s, p = 0.02) and hyperoxia (37±6s, p = 0.04). TSI mean response time (MRT) of the offset kinetics under hypoxic conditions (25.5 ± 13s) was significantly slower than under normoxic (15 ± 7.7, p = 0.007) and hyperoxic (13 ± 7.3, p = 0.008) conditions. Conclusion The present study shows that there was no improvement in the oxygen uptake and muscle oxygenation recovery kinetics in healthy subjects under hyperoxic conditions. Slower TSI and VO2 recovery kinetics under hypoxic conditions indicate that both NIRS and spiro-ergometry are appropriate non-invasive measurement tools to assess the physiological response of a healthy individual to hypoxic exercise

Dynamical structure factor of the anisotropic Heisenberg chain in a transverse field

We consider the anisotropic Heisenberg spin-1/2 chain in a transverse magnetic field at zero temperature. We first determine all components of the dynamical structure factor by combining exact results with a mean-field approximation recently proposed by Dmitriev {\it et al}., JETP 95, 538 (2002). We then turn to the small anisotropy limit, in which we use field theory methods to obtain exact results. We discuss the relevance of our results to Neutron scattering experiments on the 1D Heisenberg chain compound ${\rm Cs_2CoCl_4}$.Comment: 13 pages, 14 figure

Limitations of skeletal muscle oxygen delivery and utilization during moderate-intensity exercise in moderately impaired patients with chronic heart failure

The extent and speed of transient skeletal muscle deoxygenation during exercise onset in patients with chronic heart failure (CHF) are related to impairments of local O2 delivery and utilization. This study examined the physiological background of submaximal exercise performance in 19 moderately impaired patients with CHF (Weber class A, B, and C) compared with 19 matched healthy control (HC) subjects by measuring skeletal muscle oxygenation (SmO2) changes during cycling exercise. All subjects performed two subsequent moderate-intensity 6-min exercise tests (bouts 1 and 2) with measurements of pulmonary oxygen uptake kinetics and SmO2 using near-infrared spatially resolved spectroscopy at the vastus lateralis for determination of absolute oxygenation values, amplitudes, kinetics (mean response time for onset), and deoxygenation overshoot characteristics. In CHF, deoxygenation kinetics were slower compared with HC (21.3 ± 5.3 s vs. 16.7 ± 4.4 s, P <0.05, respectively). After priming exercise (i.e., during bout 2), deoxygenation kinetics were accelerated in CHF to values no longer different from HC (16.9 ± 4.6 s vs. 15.4 ± 4.2 s, P = 0.35). However, priming did not speed deoxygenation kinetics in CHF subjects with a deoxygenation overshoot, whereas it did reduce the incidence of the overshoot in this specific group (P <0.05). These results provide evidence for heterogeneity with respect to limitations of O2 delivery and utilization during moderate-intensity exercise in patients with CHF, with slowed deoxygenation kinetics indicating a predominant O2 utilization impairment and the presence of a deoxygenation overshoot, with a reduction after priming in a subgroup, indicating an initial O2 delivery to utilization mismatch

Causes of nonlinearity of the oxygen uptake efficiency slope : a prospective study in patients with chronic heart failure

Background: The oxygen uptake efficiency slope (OUES) is an exercise parameter with strong prognostic value in the heart failure population. Yet, the optimal determination method of OUES remains unclear. The purpose of the present study was to investigate the influence of the ventilatory anaerobic threshold (VAT) and occurrence of a plateau in oxygen uptake (VO2) on determination of OUES from submaximal exercise data in patients with chronic heart failure (CHF). Methods and Results: Ninety-eight CHF patients (New York Heart Association class II–III) were included. All patients performed a symptom-limited exercise test with gas exchange analysis on a cycle ergometer. VAT was determined by the V-slope method and OUES was derived via least-squares linear regression using 100% (OUES100), 90% (OUES90), and 75% (OUES75) of exercise duration, and, in addition, by using only the first 50% of data points preceding VAT (OUES½VAT), all data preceding VAT (OUESVAT), and only data following VAT (OUESpostVAT). Whereas OUESVAT (1720¿±¿430¿ml/min/log(l/min)), OUES75 (1811¿±¿476¿ml/min/log(l/min)), and OUESpostVAT (1742¿±¿564¿ml/min/log(l/min)) were not significantly different from OUES100 (1767¿±¿542¿ml/min/log(l/min)), OUES½VAT (1500¿±¿314¿ml/min/log(l/min)) was significantly lower than all other values (p

The influence of adipose tissue on spatially resolved near-infrared spectroscopy derived skeletal muscle oxygenation: the extent of the problem

Objective. Near-infrared spectroscopy (NIRS) measurements of tissue oxygen saturation (StO2) are useful for the assessment of skeletal muscle perfusion and function during exercise, however, they are influenced by overlying skin and adipose tissue. This study explored the extent and nature of the influence of adipose tissue thickness (ATT) on StO2. Approach. NIR spatially resolved spectroscopy (SRS) derived oxygenation was measured on vastus lateralis in 56 patients with chronic heart failure (CHF) and 20 healthy control (HC) subjects during rest and moderate intensity exercise with simultaneous assessment of oxygen uptake kinetics (τ ). In vitro measurements were performed on a flow cell with a blood mixture with full oxygen saturation (100%), which was gradually decreased to 0% by adding sodium metabisulfite. Experiments were repeated with 2 mm increments of porcine fat layer between the NIRS device and flow cell up to 14 mm. Main results. Lower ATT, higher τ , and CHF were independently associated with lower in vivo StO2 in multiple regression analysis, whereas age and gender showed no independent relationship. With greater ATT, in vitro StO2 was reduced from 100% to 74% for fully oxygenated blood and increased from 0% to 68% for deoxygenated blood. Significance. This study shows that ATT independently confounds NIR-SRS derived StO2 by overestimating actual skeletal muscle oxygenation and by decreasing its sensitivity for deoxygenation. Because physiological properties (e.g. presence of disease and slowing of τ ) also influence NIR-SRS, a correction based on optical properties is needed to interpret calculated values as absolute StO2

Test–retest reliability of skeletal muscle oxygenation measurements during submaximal cycling exercise in patients with chronic heart failure

The potential purpose of near-infrared spectroscopy (NIRS) as a clinical application in patients with chronic heart failure (CHF) is the identification of limitations in O2 delivery or utilization during exercise. The objective of this study was to evaluate absolute and relative test–retest reliability of skeletal muscle oxygenation measurements in patients with CHF. Thirty patients with systolic heart failure (left ventricular ejection fraction 31 ± 8%) performed 6-min constant-load cycling tests at 80% of the anaerobic threshold (AT) with tissue saturation index (TSI) measurement at the vastus lateralis. Tests were repeated after 10 ± 5 days to evaluate reliability. Absolute reliability was assessed with limits of agreement (LoA, expressed as bias ± random error) and coefficients of variation (CV) for absolute values (LoA range: 0·4 ± 6·2% to 0·6 ± 7·9%; CV range: 4·7–7·1%), amplitudes (LoA range −0·5 ± 5·8% to −0·7 ± 6·8%; CV range: 26·2–42·1%), onset and recovery kinetics (mean response times; LoA 0·4 ± 9·5 s, CV 23·5% and LoA −5·8 ± 50·8 s, CV 67·4% respectively) and overshoot characteristics (CV range 45·7–208·6%). Relative reliability was assessed with intraclass correlation coefficients for absolute values (range 0·74–0·90), amplitudes (range 0·85–0·92), onset and recovery kinetics (0·53 and 0·51, respectively) and overshoot characteristics (range 0·17–0·74). In conclusion, absolute reliability of absolute values and onset kinetics seems acceptable for serial within-subject comparison, and as such, for evaluation of treatment effects. Absolute reliability of amplitudes and recovery kinetics is considered unsatisfactory. Relative reliability of absolute values and amplitudes is sufficient for purposes of physiological distinction between patients with CHF. Despite lower relative reliability, kinetics may still be useful for clinical application