Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the last 10 years 63 courses (283 infusions) of porcine FVIII were given to 25 hemophiliacs with high titer alloantibodies and to 5 patients with autoantibodies to factor VIII. Although the product was in general clinically efficacious, adverse effects of treatment were more frequent and severe than previously reported. After 63 courses there was a median percentage fall in baseline platelet count of 54% (range 8-86%); for 10 courses (16%), thrombocytopenia was severe or moderately severe (less than 100 x 10(9)/l), with nadirs of platelet count ranging from 10 to 99 x 10(9)/l (median 67). Allergic reactions were seen in 15 of 30 patients (50%), in 20 of 63 courses (32%), more frequently but not exclusively after the first infusion. Relatively mild symptoms (fever, flushing, urticaria, shivering) occurred in 15 courses; 5 courses, however, were accompanied by more severe anaphylactoid reactions, 2 of which required resuscitation therapy. Allergic reactions were observed both in patients pretreated with steroids or anti-histamines (in 7 of 18 courses, 39%) and in nonpretreated patients (in 13 of 45 courses, 29%). In conclusion, adverse reactions are frequent after porcine FVIII (in 30 of 63 courses, 47%), and can occur also with infusions subsequent to the first. Hence, the recently proposed use of porcine FVIII as home treatment should be implemented with caution.
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PMID:Adverse effects of treatment with porcine factor VIII. 190 52

DDAVP was administered at 0.4 microgram kg-1 intravenous (i.v.) and subcutaneous (s.c.) routes to 6 healthy subjects in a double blind crossover study. Both study treatments were well tolerated. Flushing occurred after both treatments but was more prominent after i.v. than after s.c. DDAVP. Mild transient local discomfort at the s.c. injection site occurred in 5 of 6 subjects. The mean peak factor VIII (FVIII) response was 369% and 247% of baseline after i.v. and s.c. DDAVP respectively and the maximum increase in FVIII occurred earlier with the i.v. route. Changes in FVIII antigen (FVIII:Ag) and von Willebrand factor antigen (vWF:Ag) were also monitored. Tissue-type plasminogen activator (t-PA) activity measured by a chromogenic assay employing soluble fibrin had a median peak value of 2.9 IU ml-1 at 20 min after i.v. and of 1.9 IU ml-1 at 60 min after s.c. DDAVP. t-PA antigen was also measured so that the specific activity of circulating t-PA could be determined. Preinjection median values of 14,650 and 13,700 IU mg-1 increased to peak median values of 236,200 IU mg-1 at 20 min after i.v. and 202,400 IU mg-1 at 60 min after s.c. DDAVP. Plasminogen activator inhibitor (PAI) activity fell following DDAVP and became undetectable in some subjects during the sampling period. The ratio of maximum fibrinolytic response was similar to the ratio of maximum haemostatic responses obtained by two routes of injection. Our results indicate that s.c. DDAVP might successfully replace i.v. DDAVP in several applications such as confirmation of haemostatic or fibrinolytic responsiveness in patient groups; for obtaining FVIII enriched plasma; as well as its obvious potential usefulness in home treatment of haemophilia A and von Willebrand's disease.
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PMID:Fibrinolytic and haemostatic responses to desamino-D-arginine vasopressin (DDAVP) administered by intravenous and subcutaneous routes in healthy subjects. 312 7

Direct seeding of endothelial cells onto synthetic vascular prostheses has become the subject of increasing surgical research during the last 5 to 7 years. The currently employed cell harvest techniques are inefficient, resulting in cell counts far below the number of cells calculated to be present on the original donor vein. We have compared two methods of enzymatic endothelial cell harvest: cannulation with flushing and eversion over a stainless steel rod. Harvested cells were plated onto tissue culture plastic and counted after 24 hours of incubation. The methods ensured that only those cells viable and functional enough to adhere to the plastic were being considered. Cells were identified as endothelial by immunohistochemical techniques applying antisera to factor VIII-related antigen. Segments of normal vein and of veins treated by each technique were viewed with a scanning electron microscope. Cannulation was the superior method, providing greater numbers of viable, functional cells. The eversion technique was unreliable and probably injurious to endothelial cells.
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PMID:Endothelial cell harvest for seeding vascular prostheses: the influence of technique on cell function, viability, and number. 352 33

Autogenous endothelial seeding (AES) of vascular prostheses (VP) using venous endothelial cells (EC) reduces platelet-VP interactions and improves patency rates in small caliber VP in dogs. To conserve patients' veins for use in coronary or limb bypass surgery, human trials of AES should require proof that adequate numbers of EC with the growth capacity to cover VP can be harvested from acceptably small pieces of peripheral vein. EC were isolated from excess saphenous vein segments remaining after coronary bypass surgery by filling veins with 0.1% CLS II collagenase at 37 degrees C for 15 min and removing EC by flushing the veins with culture medium. EC were cultured on fibronectin-coated dishes in medium 199 with 30% human serum and 300 micrograms/ml of endothelial cell growth factor. These cells grew to form confluent monolayers, and were identified as EC by tests for factor VIII antigen. Veins from 53 patients with a mean age of 55.8 +/- 9.8 (SD) years yielded vein segments with an average area of 1.9 +/- 0.6 cm2, from which an average of 5.3 +/- 2.8 X 10(4) cells were removed per cm2 of vein area. EC in culture underwent 14.3 +/- 1.4 population doublings with an average population doubling time of 1.8 +/- 0.3 days (N = 14 cultures), which allowed an 100-fold increase in cell number to occur in 11 to 12 days. These data suggest that the EC available from small vein segments in adult humans have the growth capacity to cover areas comparable in size to the luminal areas of VP commonly used in arterial surgery.
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PMID:Adult human saphenous vein endothelial cells: assessment of their reproductive capacity for use in endothelial seeding of vascular prostheses. 632 16

Des-amino-D-arginine vasopressin (DDAVP) stimulates the release of factor VIII and plasminogen activator from the vascular endothelium. An infusion of exogenous factor VIII given to haemophiliacs causes an increase in platelet activation. This activation does not occur after stimulating a rise in the patient's own factor VIII level caused by DDAVP infusion. We hypothesised therefore that DDAVP could also cause the endothelial release of prostacyclin (PGI2), a potent anti-platelet agent which would counteract the aggregating effect of factor VIII. To examine this possibility we studied the effect of DDAVP on prostacyclin release, as measured by its stable metabolite 6-oxo-PGF1 alpha, in vitro and in vivo. Rabbit aortic rings were incubated with different concentrations of DDAVP using saline as control. The supernatant was assayed for 6-oxo-PGF1 alpha by radioimmunoassay. All concentrations of DDAVP gave a significant release of 6-oxo-PGF1 alpha. Vasopressin was much less potent. When DDAVP was infused into haemophilic patients there was a significant increase in circulating 6-oxo-PGF1 alpha levels immediately after the infusion. The facial flushing observed as a side-effect of DDAVP could therefore be prostacyclin-mediated. We confirmed this by abolishing the DDAVP induced flushing seen in normal subjects by prior treatment with aspirin which inhibits PGI2 formation.
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PMID:DDAVP stimulates prostacyclin production. 680 93

Intravenous infusion of desmopressin (DDAVP, 0.4 micrograms/kg b.w. in 12') causes an increase in the level of extrinsic plasminogen activator, measured in plasma euglobulin fractions with added C1-inactivator on fibrin plates. A poor response or no response at all was elicited in two out of 21 patients with spontaneous thrombosis, 18/38 with hyperlipoproteinaemia and 10/14 with terminal renal insufficiency requiring haemodialysis. Haemodilution during the first 30' after starting the DDAVP-infusion occurred both in responders and in non-responders; so did haemodynamic reactions: increase in heart rate, drop in diastolic blood pressure, facial flushing. The rise of fibrinolytic activity was shown not to be associated with decreased hepatic blood flow. Normal factor VIII-rises in "non-responders" indicate the responsiveness of the receptive organs, including the hypothalamus, to DDAVP. Despite a normal baseline level of fibrinolytic activity in the blood, as occurs for instance in terminal renal insufficiency, the vascular endothelium may be refractory to stimulation. In some patients especially in type IV hyperlipoproteinaemia, a selective defect of the release of plasminogen activator is postulated. In subjects with low fibrinolytic activity at rest, as observed in spontaneous thromboembolism and in hypertriglyceridaemia, the failure to release plasminogen activator upon stimulation with DDAVP might be a consequence of an impairment of synthesis as well.
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PMID:The use of desmopressin acetate (DDAVP) as a test of the fibrinolytic capacity of patients--analysis of responders and non-responders. 681 44

We describe a case of a novel mutant vasopressin 2 receptor (V2R)-dependent nephrogenic diabetes insipidus (NDI) with bilateral non-obstructive hydronephrosis in a middle aged man. This could be distinguished from aquaporin 2 (AQP2)-dependent NDI by the response of factor VIII and von Willebrand factor (vWF) to 1-deamino-8-D-arginine vasopressin (DDAVP) administration. A 47-year-old man was admitted to hospital because of polyuria, which had been present from infancy and was suspected of causing non-obstructive hydronephrosis. His mother's father, the older brother of his mother and his second daughter also all had polyuria. Sodium concentration, osmolality and vasopressin in blood were high, while sodium concentration and osmolality in urine were low. There were no changes in urine osmolality, factor VIII and vWF in response to DDAVP infusion. Neither was heart rate, diastolic blood pressure nor facial flushing affected. These findings suggested this case was V2R-dependent NDI rather than AQP2-dependent NDI. Molecular genetic analysis demonstrated that the patient had a V2R missense mutation involving a substitution of cysteine for arginine at position 104 (R104C) located in the first extracellular loop of the V2R. It was also found that the patient's mother and his second daughter were heterozygous for this R104C mutation.
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PMID:A case of a novel mutant vasopressin receptor-dependent nephrogenic diabetes insipidus with bilateral non-obstructive hydronephrosis in a middle aged man: differentiation from aquaporin-dependent nephrogenic diabetes insipidus by response of factor VII and von Willebrand factor to 1-diamino-8-arginine vasopressin administration. 1470 55