Evaluating the effects of hypoxic storage on platelet function and health using a novel storage system.

BACKGROUND: Thousands of units of whole blood (WB) and blood components are transfused daily to treat trauma patients. Improved methods for blood storage are critical to support trauma-related care. The Hemanext ONE® system offers a unique method for hypoxic storage of WB, with successfully demonstrated storage of clinically viable RBCs. This work evaluated the system for the storage of WB, focusing on platelet health and function. STUDY DESIGN AND METHODS: WB was collected from healthy donors and processed through the Hemanext ONE® system. Hemoglobin oxygen saturation (HbSO2) levels of WB were depleted to 10%, 20%, or 30% of total HbSO2 and then stored in PVC bags sealed in oxygen-impermeable bags (except for normoxic control) with samples collected on days 1, 7, and 14 post-processing. Flow cytometry assessed the activation and apoptosis of platelets. Clot dynamics were assessed based on aggregometry and thromboelastography assays, as well as thrombin generation using a calibrated-automated thrombogram method. RESULTS: Hypoxic storage conditions were maintained throughout the storage period. Hypoxia triggered increased lactate production, but pH changes were negligible compared to normoxic control. Storage at 10% HbSO2 had a significant impact on platelet function, resulting in increased activation and reduced clot formation and aggregation. These effects were less significant at 20% and 30% HbSO2. DISCUSSION: This study indicates that platelets are sensitive to hypoxic storage and suffer significant metabolic and functional deterioration when stored at or below 10% HbSO2.

Pharmacokinetic and pharmacodynamic studies of glibenclamide in non-insulin dependent diabetes mellitus.

1. The pharmacokinetic and pharmacodynamic properties of oral glibenclamide have been studied in 31 hospitalised in-patients and 79 ambulant out-patients with diabetes mellitus. 2. Breakfast was found to have no significant influence on the kinetic behaviour of glibenclamide or on the effect of this drug on blood glucose utilisation. 3. The time course of glibenclamide kinetics after 20 mg dosing was adequately described by a two-compartment open model, yielding mean half-lives of 3.3 +/- 1.5 h (t1/2, lambda 1) and 9.7 +/- 1.2 (t1/2, z) for the initial and terminal elimination phases respectively. 4. No significant accumulation or change in kinetic profile occurred in patients who had normal renal and hepatic function, were treated continuously with glibenclamide, and then rechallenged after 8-12 weeks. 5. Despite inter-individual variations in drug absorption, peak plasma concentrations (Cmax) and the area under the plasma concentration-time curve (AUC(0-24] were dose-dependent over the dose range 5-20 mg. No significant dose-response behaviour was observed in respect of glucose utilisation, suggesting that there is little clinical benefit in using doses of glibenclamide above 5 mg day-1. 6. Comparison of plasma glibenclamide concentrations at different time-bands following doses of 5 and 10 mg showed a wider range in ambulant out-patients than in age-, sex-matched in-patients treated with the same dosages of drug. Mean plasma drug concentrations attained at all time bands up to 8 h after dosing were higher in out-patients than in in-patients, suggesting a tendency to 'over-compliance' by patients in anticipation of attendance at clinic.

Mixed connective tissue disease with associated glomerulonephritis and hypocomplementaemia.

Mixed connective tissue disease is an increasingly recognized entity in which renal disease is thought to be unusual and associated hypocomplementaemia even more uncommon. A patient is described who had both these features and who also illustrates many of the characteristic features of this syndrome. The response to steroids of the systemic sclerosis component is well shown and an additional feature of interest is the family history of other connective tissue diseases.

A comparison of the clearance of urographic contrast medium (sodium diatrizoate) by peritoneal and haemodialysis.

1. The clearance of isotopically labelled sodium diatrizoate by haemodialysis was measured in vitro, with simulated extracellular fluid, and in vivo in eleven patients, at varying rates of fluid or plasma flow. Clearance was also measured in five patients undergoing peritoneal dialysis. In all instances simultaneous measurements of urea clearance were made and the diatrizoate/urea clearance ratio was calculated. 2. In haemodialysis studies, diatrizoate and urea clearances showed a linear increase with increasing 'extracellular fluid' or plasma flow through the dialyser diatrizoate/urea clearance ratio fell. 3. The clearance of diatrizoate in vivo was slightly less than clearance in vitro at corresponding flow rates, but the diatrizoate/urea clearance ratio showed no significant difference. 4. Diatrizoate and urea clearances during peritoneal dialysis were very much lower than during haemodialysis but the diatrizoate/urea clearance ratios were within the same range. 5. The rapid removal of diatrizoate in patients with renal failure requires haemodialysis.

Excretion urography toxicity studies in experimental acute renal failure.

Studies have been carried out on the toxicity of large doses of contrast medium (Hypaque 45%) given to rats with acute renal failure induced both by mercuric chloride and by glycerol. No increase in the expected mortality of the experimental models was observed following infusion of twice the maximum clinical dose of contrast medium.

Excretion urography in acute renal failure.

High-dose excretion urography has been carried out in 32 patients presenting with non-obstructive acute oliguric or non-oliguric renal failure. An early, dense, persisting nephrogram has been observed in all patients with acute uncomplicated tubular necrosis and in patients with acute oliguric pyelonephritis. This appearance is modified by the presence of pre-existing renal disease. Different patterns have been observed in patients with acute glomerular disease, severe renal ischaemia, and chronic glomerular disease. The study demonstrates that careful analysis of the evolution of the nephrogram in patients with acute renal failure provides valuable information as to the nature of the parenchymal disease.

Maintenance of silastic-teflon shunts for intermitten haemodialysis.

The occurrence of infection in the tissues surrounding external arteriovenous shunts was studied and die important relationship of pyogenic infection to clotting was confirmed. The local application of fusidic add tulle and lanolin greatly reduced the occurrence of both infection and clotting and the need for cannula replacement.Urokinase used for declotting shunts when standard procedures had failed, restored blood flow whether dotting was related to infection or to local vascular factors. This treatment is not advised when clotting is associated with a local abscess, as it may make cannula replacement necessary. Severe local vascular factors, such as metastatic calcification, Raynaud's phenomenon, and venous stenosis, may lead to poor blood flow, so that despite clot lysis elective cannula replacement or the creation of a subcutaneous arteriovenous fistula is required.