Pool E diluted 1 : 3 with human serum albumin in saline Low Low ") For this purpose the freeze-dried renin was dissolved in 0.9% saline and added to the plasma at doc. This was then gently agitated by hand so as to achieve mixing without foaming.
Angiotensin II, infused intravenously, increased plasma aldosterone concentration in two of six anephric subjects taking their usual dietary quantities of sodium. After 3 days of dietary sodium restriction and weight-reducing hemodialysis, the aldosterone response to infused angiotensin II in the two previously reactive subjects was enhanced, while the four previously unreactive subjects also showed a rise in plasma aldosterone. Before and after sodium depletion the anephric subjects were less responsive than normal subjects. Even when sodium-depleted, the anephrics showed no further rise in plasma aldosterone when arterial plasma angiotensin II was increased by infusion to concentrations greater than 50-199pg/ml, in contrast to sodium-depleted normals who show progressive aldosterone responses with plasma angiotensin II concentrations up to at least 370pg/ml. Before the infusion of angiotensin II, arterial plasma renin, angiotensin II, and aldosterone were detectable in the anephrics, but were unchanged by dietary sodium restriction or weight-reducting hemodialysis. Sodium depletion caused significant falls in weight, plasma sodium, and blood pressure, but no changes in plasma potassium or cortisol. Increases in blood pressure in relation to increments of arterial plasma angiotensin II were unaffected by sodium depletion, as might be expected in the absence of a rise in endogenous angiotensin II.
SummaryAn International Collaborative Study was organized to establish a standard for factor IX. Two freeze-dried concentrate preparations, C1 and C2, and one freeze-dried plasma P were compared with each other, with fresh normal plasmas and with local standards in 13 laboratories. One of the concentrate preparations (C1) contained heparin and this gave rise to non-parallel assays in laboratories testing concentrate C1 in dilutions containing more than 0.05 i.u. of heparin per ml.Assays of factor IX showed good precision for both plasma and concentrate in all laboratories; no systematic effect of method, operator or day of assay was detected.The plasma preparation P and the concentrate preparation C2 were compared with 59 individual fresh normal plasma samples, and a mean potency ratio of 0.78 (95% confidence Hmits 0.73-0.84) for plasma and 5.62 (95 % confidence limits 5.13-6.16) for the concentrate C2 obtained. Only 21 estimates of concentrate C1 in terms of fresh plasma were obtained giving a mean potency ratio of 3.85 (95% confidence limits 1.87—7.92).The estimated loss of potency for freeze-dried plasma stored at — 20° C is approximately 0.4% per year. The concentrate C2 is apparently more stable and only very small losses occurred even at higher storage temperatures.All participants agreed that the preparation C2 would be suitable to serve as an International Standard for factor IX; they also agreed that the figure assigned for the unitage should be based on the number of ml of ‘average fresh normal plasma’ estimated to contain the factor IX activity of one ampoule of the preparation. It is proposed to recommend to the World Health Organization that the preparation of factor IX concentrate C2, in ampoules coded 72/32, be considered for establishment as the International Standard for factor IX, and that the international unit for factor IX be assigned on the basis of 5.62 units per ampoule of this preparation.
The activity and stability of factors X and VIII were studied in three ainpouled preparations of freeze-dried pooled human plasma.Factor-X activity in all three preparations decreased on storage. It was calculated that after 10 yr at -2o"C, between 37: and 8% of the original factor-X activity would be lost. If stored for the same period at 4°C and 2ooC the loss could be up to 54% and 90% respectively of the initial activity. If, however, factor VIII was added to restore the concentration of this factor to approximately normal level, the proportion of factor X available for activation via the intrinsic pathway remained the same irrespective of the temperaturc and length of storage.Factor-VIII activity was lost more readily. It was estimated that between 20% and 300/, of the activity would be lost in each of the preparations kept at -20°C in 10 years. This is in good agreement with the results of the international collaborative study carried out to establish the international standard for factor VIII.
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