A prospective audit of hospital-acquired deep vein thrombosis and pulmonary embolism.

The incidence of symptomatic deep vein thrombosis and pulmonary embolism acquired in hospital was studied, and the effectiveness of current thromboprophylaxis was assessed in an open study of 8648 admissions to the Doncaster Royal Infirmary between April and July 1994. On admission, all patients were assessed for their likely risk of thromboembolic problems according to THRIFT criteria. Treatment, prophylaxis, complications and outcome were recorded on discharge. A high risk sub-group was followed up for up to 42 days after discharge. The overall rate of clinically apparent hospital-acquired thromboembolic complications was 0.4% (n = 35). The rate of clinically apparent thromboembolic disease in the high risk group was 2.1% (n = 17). The incidence of thromboembolic problems appeared not to be reduce by prophylaxis apparently even when stratified by risk group. These findings suggest that thromboembolic complications may be less common than would be expected from published literature. Thromboprophylaxis as currently practised within our institution does not seem to affect the incidence of deep vein thrombosis or pulmonary embolism, and these results would appear to argue against a 'blanket' policy for pharmacological thromboprophylaxis.

Antiproliferative effects on keratinocytes of a range of clinically used drugs with calmodulin antagonist activity.

Thirty-two drugs, including some in use for a variety of clinical disorders, were examined for their ability to inhibit calmodulin activity in vitro. From these, 10 drugs were selected for their inhibition of calmodulin activity and examined for their ability to inhibit proliferation of rapidly dividing human keratinocytes. A significant correlation between antiproliferative activity and calmodulin antagonist potency was found. Of these drugs there were several, including miconazole, dequalinium chloride, bromocriptine and tamoxifen, whose use is well established and well documented. The potential use of these drugs (and others identified in this way) as antipsoriatic agents is discussed.

1 alpha,25(OH)2 vitamin D3 increases intracellular calcium in human keratinocytes.

Vitamin D3 metabolites have been found to improve psoriasis but their mechanism of action is not clear. Keratinocyte proliferation and differentiation are known to be dependent on calcium concentrations in vitro. The aim of this study was to examine whether 1 alpha,25(OH)2 vitamin D3 had any direct effect on intracellular free calcium concentrations in cultured keratinocytes. A response to 1 alpha,25(OH)2 vitamin D3 was seen in 88% of monolayers of normal human keratinocytes attached to glass coverslips. An increase in intracellular free calcium was seen in 80% of the reactive cultures, with over half the responses occurring within 30 s of exposure to 1 alpha,25(OH)2 vitamin D3 and the remainder occurring within minutes. Responses could be seen at physiological concentrations of 1 alpha,25(OH)2 vitamin D3 and were not blocked by the protein synthesis inhibitor cycloheximide. The response to 1 alpha,25(OH)2 vitamin D3 took the form of rapid transient increases in intracellular free calcium in 29 out of 59 coverslips. The basal intracellular free calcium was calculated to be 245 +/- 47 nM rising to a maximum of 834 +/- 267 nM (mean +/- SEM; n = 20) following exposure to 1 alpha,25(OH)2 vitamin D3. We conclude that 1 alpha,25(OH)2 vitamin D3 acts directly on keratinocytes to increase intracellular free calcium and that this may be relevant to its mechanism of action in psoriasis.