These data demonstrate that a physiological [Hb] improves, but does not normalize, exercise performance in end-stage renal failure. Both younger and older patients appear to benefit similarly from the enhanced oxygen transport. Impaired K+ regulation is apparently related to [Hb] and could well contribute to the observed limitations in performance.

These data suggest there may be a significant haemodynamic and symptomatic advantage in maintaining a physiological [Hb] in haemodialysis patients. Although untoward effects were not identified in this study at [Hb](14), a substantially higher dose of epoetin is required to maintain this level.

Patients with a laparoscopic hernia repair had significantly less pain postoperatively than those with standard open hernia repairs.

This study was designed to assess the effect of different prime solution compositions on a patient's fluid balance, transfusion requirements, renal function and haemodynamic stability over the first 24 hours postbypass. Ninety-three patients presenting for first-time coronary artery bypass graft (CABG) surgery were randomly allocated to receive one of three prime solutions for the CPB pump: albumin (4.6%) + Plasmalyte (Group A, n = 32), polygeline (Hemaccel) + Plasmalyte (Group P, n = 29), or crystalloid (Plasmalyte) alone (Group C, n = 32). Patients, anaesthetists, surgeons and intensive care unit (ICU) staff were all blinded as to the solution type. The groups were demographically and haemodynamically similar. There were no differences between the groups with respect to white cell or platelet counts during the study. There was a significant difference in haemoglobin levels between the groups on weaning from CPB and on arrival in the ICU (Group C > Groups P and A, p < 0.001 for both times). There was no difference in blood transfusion requirements between any of the groups. During CPB, Group C required significantly more crystalloid than the other groups (p < 0.001). Urine output was significantly higher in Group C compared with Groups P and A at all time periods up to and including ICU 12 hours (p < 0.05). The use of frusemide was significantly higher in the ICU in Groups P and A (p < 0.01). There was a net gain of 3132 +/- 412 ml in Group C in 24 hour fluid balance, which was significantly higher than Group A (2166 +/- 223 ml, p = 0.04). Our results show that, in this patient population, there is no advantage in using a colloid-based prime solution over a purely crystalloid solution from a haemotologic or haemodynamic point of view for the first 24 hours after CPB. There appears to be an increase in extracellular fluid (ECF) retention in Group C, but this caused no related problems in the study period. On the other hand, diuretics (frusemide) needed to be given significantly less often in these patients to offset oliguria.

Heterotrimeric guanine nucleotide-binding proteins (G-proteins) are transducers in many cellular transmembrane signaling systems where regulators of G-protein signaling (RGS) act as attenuators of the G-protein signal cascade by binding to the Galpha subunit of G-proteins (G(i)(alpha)(1)) and increasing the rate of GTP hydrolysis. The high-resolution solution structure of free RGS4 has been determined using two-dimensional and three-dimensional heteronuclear NMR spectroscopy. A total of 30 structures were calculated by means of hybrid distance geometry-simulated annealing using a total of 2871 experimental NMR restraints. The atomic rms distribution about the mean coordinate positions for residues 5-134 for the 30 structures is 0.47 +/- 0.05 A for the backbone atoms, 0. 86 +/- 0.05 A for all atoms, and 0.56 +/- 0.04 A for all atoms excluding disordered side chains. The NMR solution structure of free RGS4 suggests a significant conformational change upon binding G(i)(alpha)(1) as evident by the backbone atomic rms difference of 1. 94 A between the free and bound forms of RGS4. The underlying cause of this structural change is a perturbation in the secondary structure elements in the vicinity of the G(i)(alpha)(1) binding site. A kink in the helix between residues K116-Y119 is more pronounced in the RGS4-G(i)(alpha)(1) X-ray structure relative to the free RGS4 NMR structure, resulting in a reorganization of the packing of the N-terminal and C-terminal helices. The presence of the helical disruption in the RGS4-G(i)(alpha)(1) X-ray structure allows for the formation of a hydrogen-bonding network within the binding pocket for G(i)(alpha)(1) on RGS4, where RGS4 residues D117, S118, and R121 interact with residue T182 from G(i)(alpha)(1). The binding pocket for G(i)(alpha)(1) on RGS4 is larger and more accessible in the free RGS4 NMR structure and does not present the preformed binding site observed in the RGS4-G(i)(alpha)(1) X-ray structure. This observation implies that the successful complex formation between RGS4 and G(i)(alpha)(1) is dependent on both the formation of the bound RGS4 conformation and the proper orientation of T182 from G(i)(alpha)(1). The observed changes for the free RGS4 NMR structure suggest a mechanism for its selectivity for the Galpha-GTP-Mg(2+) complex and a means to facilitate the GTPase cycle.