Effect of topical basic fibroblast growth factor on the healing of chronic diabetic neuropathic ulcer of the foot. A pilot,
randomized, double-blind, placebo-controlled study.
J L Richard ,
C ...Parer-Richard ,
J P Daures ,
S Clouet ,
D Vannereau ,
J Bringer ,
M Rodier ,
C Jacob and
M Comte-Bardonnet
Department of Dietetics and Diabetology, Centre Medical, Le Grau du Roi, France.
Abstract
OBJECTIVE--To assess the efficacy and safety of topical human recombinant basic fibroblast growth factor (bFGF) on the healing
of diabetic neurotrophic foot ulcers. RESEARCH DESIGN AND METHODS--Seventeen diabetic patients suffering from chronic neuropathic
ulcer of the plantar surface of the foot entered a pilot, randomized, double-blind study comparing local application of bFGF
with placebo. Main inclusion criteria were a typical neuropathic ulcer of Wagner grade I-III, more than 0.5 cm in the largest
diameter, with an abnormally high vibration perception threshold in the absence of significant peripheral vascular disease
or wound infection. bFGF or placebo was applied daily during the 6 weeks as inpatients then twice a week for 12 weeks. Evolution
of ulcer size was assessed through weekly clinical examination and computerized photographs. RESULTS--In the bFGF group, three
of nine ulcers healed compared with five of eight in the placebo group (NS). The weekly reduction in ulcer perimeter and area
was identical in both groups, as was the rate of linear advance from entry to the 6th week of treatment (bFGF: 0.053 +/- 0.048
mm vs. placebo: 0.116 +/- 1.129 mm): the same result was obtained at the 11th week. Moreover, percent healed area at the end
of the study did not differ significantly. No side effects were observed during bFGF application. CONCLUSIONS--Topical application
of bFGF has no advantage over placebo for healing chronic neuropathic diabetic ulcer of the foot. Because diabetes causes
significant wound-healing defects, we hypothesized that using a single growth factor might be insufficient to accelerate wound
closure of diabetic ulcers.
The effects of cyclosporine A treatment on arterial pressure and renal function were assessed in 11 young patients with type I diabetes of short duration. Cyclosporine was started at 7.5 mg/kg/day, ...progressively decreased to 63 mg/kg/day at 6 months, and then continued at a lower dose (4.1 mg/kg/day) for an additional 3 months in patients in whom remission of insulin dependency was obtained (n=6). After 3 months of cyclosporine, a slight but significant increase in arterial pressure (+5.2±1.5 mm Hg), a rise in renal vascular resistance (—20%), a decrease in glomerular filtration rate (—25%), and a fall in filtration fraction were observed. Such changes were sustained after 6 and eventually 9 months of therapy. The decrease in glomerular filtration rate observed during cyclosporine treatment contrasted with the lack of change in simultaneously estimated creatinine clearance; in fact, the creatinine clearance/ glomerular filtration ratio increased from 1.07±0.05% to 1.33±0.09% within 3 months of cyclosporine therapy, thus suggesting an enhanced tubular secretion of creatinine. Plasma renin activity and urinary excretion of kallikrein decreased significantly (—50%), whereas plasma aldosterone concentration remained unaltered and plasma concentration of potassium increased during cyclosporine therapy. These changes were observed in the presence of a constant urinary excretion of sodium and potassium and a constant body weight All parameters returned to pretreatment values within 3 months after cessation of cyclosporine. These results indicate that cyclosporine given for 6-9 months at a moderate dose causes a deleterious but reversible effect on arterial pressure and renal function in young diabetic patients.
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