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Biomedical subjects

G Rock

Publications and source records attributed to G Rock.

At least 73 records · Page 4Linked to original sources

DDAVP-induced release of von Willebrand factor from endothelial cells in vitro: the effect of plasma and blood cells.

The vasopressin analogue 1-deamino-8-D-arginine vasopressin (DDAVP) causes an immediate, transient rise in plasma levels of von Willebrand factor (vWF) after its administration. Although it is recognized that vascular endothelial cells play an essential role in this process, the molecular basis of the response is not understood. We have investigated the phenomenon using human umbilical vein endothelial cells as an in vitro model. When normal individuals were stimulated with DDAVP, plasma from blood samples collected subsequently caused the release of vWF from cultured endothelial cells over a 24 h period (22-46% increase over baseline), compared to control plasma (5-17%). DDAVP added directly to the endothelial cells produced no increase in vWF release. When whole blood was treated in vitro with DDAVP, and the plasma subsequently added to endothelial cells, a significant increase in vWF secretion was found. Peripheral blood mononuclear cells were then tested. In the presence of DDAVP, an increased response occurred. Further fractionation of these cells showed that monocytes were largely responsible, causing an increased vWF release of 162% at 2 h. These observations were reinforced by finding that the supernatants of monocytes incubated with DDAVP were also effective in causing increased vWF release (118% compared to 58% for the control sample). Our studies suggest that DDAVP plays an indirect role in causing the release of vWF from endothelial cells, and that peripheral blood monocytes may act as intermediary target cells, which then produce factor(s) acting directly on endothelial cells.

Cells, Cultured↗

A comparison of results obtained by two different chromium-51 methods of determining platelet survival and recovery.

A number of different methods exist that use chromium-51 to determine platelet survival and recovery. A 1986 article in TRANSFUSION described the recommended methods for conducting such studies in the hope of standardizing methodology and permitting interlaboratory comparison of results. The results obtained with the recommended method have been compared with those of our previous method. With the new method, recovery of fresh random-donor platelets prepared in polyolefin bags was 76 +/- 6 percent with a survival of 9.3 +/- 2.8 days (n = 4). After 5 days of storage, these values were 67 +/- 8 percent and 7.8 +/- 1.9 days. Similar values were obtained for fresh and stored platelets collected on automated cell separators. However, when our previous (pre-1986) method of evaluation was used, recovery of fresh platelets in the polyolefin bags was 56 +/- 11 percent, and survival was 8.6 +/- 1.3 days. The 5-day values were 36 +/- 5 percent and 6.9 +/- 2.7 days. These values are significantly lower (p less than 0.05) than those obtained with the newer method, but they are in agreement with those previously reported for other techniques. Thus, the new method consistently gives higher values, possibly as a result of a less harmful labeling procedure.

Blood Platelets↗

Studies on the prolonged bleeding time in von Willebrand's disease.

Ten studies of the effect of cryoprecipitate infusion in four patients with von Willebrand's Disease (vWD) are reported. The doses studied (4, 8 and in one case 10 bags of cryoprecipitate) were based on previous reports of correction of the bleeding time (BT) with such doses. A modest shortening of the BT was observed in only 2 studies and complete correction of the BT at 1 and 4 hours was observed in only one study. This latter result could not be reproduced in a subsequent study of the same patient. In all cases, the von Willebrand factor antigen (vWF:Ag) multimer patterns were normal in the infused cryoprecipitate and in the recipients' plasma post infusion with the presence of high molecular weight multimers demonstrated in all samples. These results contradict earlier reports of the effect on the BT of similar doses of cryoprecipitate and suggest that the presence of the high molecular weight forms of vWF:Ag does not necessarily correlate with the presence of the factor which corrects the bleeding time.

Adult↗

Epinephrine and dDAVP administration in patients with congenital nephrogenic diabetes insipidus. Evidence for a pre-cyclic AMP V2 receptor defective mechanism.

We recently showed that the administration of the antidiuretic V2 specific agonist, 1-desamino[8-D-arginine]vasopressin (dDAVP), to seven male patients with congenital nephrogenic diabetes insipidus (CNDI) did not cause a decrease in blood pressure nor an increase in plasma renin activity or factor VIIIc or von Willebrand factor release. In normal subjects, plasma renin activity, coagulation factors and plasma cyclic AMP are stimulated not only by dDAVP but also by the administration of epinephrine. In the present study, we measured tissue plasminogen activator (activity and antigenicity), von Willebrand factor multimers, plasma and urinary cyclic AMP concentrations following dDAVP or epinephrine administration. We infused epinephrine into three male patients with CNDI. Factor VIIIc and tissue plasminogen activator augmented by 75 to 100% and von Willebrand Factor multimers were increased; plasma renin activity and plasma cyclic AMP concentration increased by 200%. None of these values changed when the same subjects as well as eleven other male patients with CNDI received dDAVP. Furthermore, dDAVP administration increased plasma cyclic AMP concentrations in normal subjects, but not in 14 male patients with CNDI. These results demonstrate the specificity of the extrarenal V2 receptor defect expressed in our patients. The lack of a plasma cyclic AMP response to the administration of dDAVP would suggest an altered pre-cyclic AMP stimulation mechanism.

Adult↗

Complications of plasma exchange.

For the past few years, the Canadian Apheresis Study Group has collected data on most apheresis procedures carried out throughout the country. The information accumulated during calendar year 1985 has been reviewed, and the complications that occurred as a result of therapeutic plasma exchange (PE) have been assessed. There were side effects during 612 (12%) of the 5235 procedures done, involving 252 (40%) of the 627 patients treated. The most common reactions were fever, chills, urticaria, muscle cramps, or paresthesias; these reactions were encountered more frequently when plasma was used in the replacement fluid. Most reactions had little or no clinical significance. However, there were 28 severe complications, including one cardiac arrest and two respiratory arrests. Five late deaths occurred, but these were not related directly to PE. Although PE is relatively safe, life-threatening reactions do occur, and patients require careful observation during the procedure.

Adolescent↗

Formation of a cryogel during processing of cell-free plasma.

Automated plasmapheresis devices are being integrated into many modern plasma procurement programs. Owing to the use of a different concentration and type of anticoagulant, the recovered plasma differs in pH and citrate levels from that obtained by manual plasmapheresis or whole blood donation. Recently, fractionators noted the recovery of a sticky, gelatinous fraction (cryogel) during thawing of cell-free (CF) plasma, along with reduced recovery of factor VIII:C (FVIII:C) in the cryoprecipitate fraction. Following their manufacturing procedures, it was established that the cryogel fraction of CF plasma is enriched in FVIII:C, fibrinogen, and fibronectin, as compared to cryoprecipitate from CPDA-1 plasma. Cryogel formation was not significantly affected by pH or citrate adjustment of the recovered plasma, by the use of polycarbonate or nylon filter membranes, or by the filter wetting agent polyvinylpyrrolidone (PVP). Furthermore, passage of CPDA-1 plasma through the polycarbonate filter did not alter cryoprecipitate quality. However, cryogel formation from CF plasma was reduced significantly by 1) slow thawing at 4 degrees C rather than quick thawing at 20 and 0 or 20 and 4 degrees C, 2) the use of 1:16.6 sodium citrate rather than 1:12.5 ACD-A, or 3) the addition of intact platelets, platelet lysate, membranes, or cytosol to CF plasma before freezing. The data suggest an important and, indeed, essential role of platelet constituents in the formation of both cryoprecipitate and cryogel during the low-temperature purification of plasma proteins.

Blood Platelets↗