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S Harley

Publications and source records attributed to S Harley.

5 recordsLinked to original sources

A new look at nevus-associated melanomas.

The frequency with which malignant melanomas arise in association with preexisting melanocytic nevi has been studied extensively. We opted to evaluate new aspects of this association. In particular, we addressed the relative proportions of acquired versus congenital nevi involved and categorized the acquired nevi according to morphological type. Approximately 23% of the melanomas (29 of 124) in this group arose in association with preexisting nevi of which 55% (n = 16) were acquired and 28% (n = 8) were congenital (small). In 17% (n = 5) a distinction could not confidently be made. Of the acquired nevi, the vast majority were of Clark's type. It is clear that a relatively small proportion of melanomas as a whole are associated with preexisting nevi, and this number should be kept in perspective in devising strategies for early detection and prevention. The involvement of Clark's nevi in this regard is known, but to date the role of small congenital nevi has been underrecognized.

Adult↗

Cyclosporine and cremaphor modulate von Willebrand factor release from cultured human endothelial cells.

Cyclosporine has been associated with microangiopathic hemolysis (MAHA) and other thrombotic complications of bone marrow and renal transplantation. MAHA is characterized by intravascular platelet aggregation, which, in some situations, is thought to be mediated by hyperactive high molecular weight von Willebrand factor (vWF). We have hypothesized that transplant-related MAHA may be caused by CsA-mediated release of von Willebrand factor from endothelial cells. This hypothesis was tested by studying vWF release from human umbilical vein endothelial cells primed with either CsA or cremophor EL. CsA and cremophor alone did not increase vWF release until toxic concentrations were reached (50-100 micrograms/ml). However, at therapeutic concentrations (0.1-5 micrograms/ml) vWF release by cells stimulated with thrombin, histamine, PMA, and the calcium ionophore A23187 was enhanced by both CsA and cremophor in a concentration-dependent manner. In single isolated endothelial cells, the thrombin-induced increase in cytosolic free calcium was enhanced by both CsA and cremophor. Preincubation for 24 hr with CsA but not cremophor suppressed vWF release after thrombin stimulation. These observations were mirrored by a concentration-dependent suppression of [3H]thymidine uptake by CsA. We conclude that CsA vehicle, cremophor, enhances stimulated vWF release in vitro, probably by processes dependent upon increased cytosolic free calcium. This suggests a possible mechanism for thrombotic transplant complications.

Calcium↗

Efficacy and safety of intravenous tocainide compared with intravenous lidocaine for acute ventricular arrhythmias immediately after cardiac surgery.

In this double-blind parallel study, 99 patients with acute ventricular tachyarrhythmias after open-heart surgery were given either tocainide (50 patients) or lidocaine (49 patients) intravenously as 2 bolus injections 15 minutes apart, plus a fixed-rate infusion that started at the first bolus. If needed, a third bolus was administered and simultaneously the infusion rate was doubled. The boluses and initial infusion rate for tocainide treatment were, respectively, 250, 250 and 125 mg and 1.04 mg/min, and for lidocaine treatment, 100, 50 and 50 mg and 2.08 mg/min. When efficacy was defined as 80% or greater reduction in single ventricular premature complexes (VPCs) or complete abolition of ventricular couplets or ventricular tachycardia, no difference in efficacy between the 2 treatments was found by bedside electrocardiographic monitoring. By computer analysis of 24-hour taped electrocardiograms and a regression analysis of the proportion of patients responding favorably to treatment, it was estimated that an 80% or greater reduction of single VPCs occurred in 55% of patients during tocainide treatment and in 48% of patients during lidocaine treatment; abolition of couplets occurred in 74% and 68% of patients, respectively; and abolition of ventricular tachycardia in 87% and 73% of patients, respectively. These treatment-related differences were different (p less than 0.004). Adverse reactions occurred in 5 patients (10%) given tocainide (hypotension in 4; junctional rhythm in 1 patient; and nausea-vomiting in 1) and led to discontinuation of treatment in 3 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗