Dennis P. West

Topical Capsaicin in Dermatologic and Peripheral Pain Disorders

Topical capsaicin has been introduced in the U.S. and Canada as a cream indicated for temporary relief of neuralgia following episodes of herpes zoster infections and in the treatment of diabetic neuropathy. Although capsaicin is clinically used as an external analgesic for temporary relief of neuralgia, it has also been widely used as a research tool to study peripheral pain. Capsaicin apparently works to release substance P from sensory nerve fibers and after repeated applications, depletes neurons of substance P. Clinical investigations of topical capsaicin include trials in chronic pain syndromes such as postherpetic neuralgia, postmastectomy neuroma, reflex sympathetic dystrophy syndrome, diabetic neuropathy, rheumatoid arthritis, psoriasis, hemodialysis-associated itching, and vulvar vestibulitis. In addition, therapeutic benefits of capsaicin cream on apocrine chromhidrosis have been described. Further clinical studies are warranted in several of these conditions to establish the efficacy of topical capsaicin. Serious or unexpected adverse reactions from clinical use have not been reported to date. Considering the paucity of safe and effective treatments for the conditions mentioned above, capsaicin cream appears to warrant further clinical investigations to establish its efficacy in a variety of chronic pain syndromes.

Panniculitis associated with cutaneous T‐cell lymphoma and cytophagocytic histiocytosis

A 36‐year‐old woman had a 6‐year history of recurrent panniculitis with development of an angiocentric and angiodestructive cutaneous T‐cell lymphoma (CTCL) of the helper cell phenotype. She subsequently developed a rapidly progressive fatal syndrome characterized by cytophagocytic histiocytosis and hyperlipidaemia. Cytophagocytic histiocytosis has previously been reported in association with panniculitis, malignancy and infection, but not with CTCL and the precise relationship between panniculitis, CTCL, cytophagocytic histiocytosis and hyperlipidemia is unclear.

Evaluation of topical metronidazole gel in acne rosacea.

Topical metronidazole gel (0.75%) was compared to placebo gel in a randomized, double-blind, placebo-controlled, split-face clinical trial for the treatment of 59 patients with acne rosacea. Statistically significant differences in inflammatory lesions, erythema, and global assessments were seen at three, six, and nine weeks post-baseline in favor of the active treatment side. It did not, however, alter the telangiectatic component of the disease. No known drug-related side effects were detected, and the low topical dose along with low serum levels of metronidazole indicate a high safety profile for this therapeutic agent. This work suggests that metronidazole gel, as specifically formulated, is safe and effective in reducing the symptomatology of acne rosacea.

Chronic active hepatitis associated with etretinate therapy.

Acute hepatitis developed in a patient taking etretinate for severe psoriasis. Discontinuation of therapy was followed by progression of the histological changes to chronic active hepatitis, despite improvement of his clinical and laboratory status. This is the third reported case of chronic active hepatitis associated with etretinate therapy, and the second patient in our group of twenty‐two etretinate‐treated patients with severe psoriasis to develop clinically significant hepatic disease. Immunological evaluation revealed a marked increase in the patients OKMI‐staining population of peripheral mononuclear cells and augmentation of Con A‐induced lymphocyte blastogenesis in the presence of etretinate.

In vitro percutaneous absorption evaluation of phenobarbital through hairless mouse, adult and premature human skin

Abstract In vitro phenobarbital flux through newborn (preterm and full-term) infant, hairless mouse and adult human skin was determined using both Franz cells and flow-through diffusion cells. The phenobarbital flux value through preterm infant skin was significantly higher than that obtained through full-term infant skin which, in turn, was close to that measured for adult human skin. No significant difference was observed between phenobarbital flux values through preterm infant skin and hairless mouse skin using flow-through diffusion cells: this result suggests that hairless mouse skin can be successfully used as a model to study in vitro percutaneous absorption of phenobarbital through preterm infant skin. Phenobarbital flux through preterm infant skin was affected by the gestational age since flux decreased as the gestational age increased and from 37 weeks gestation onward (full-term infants) flux values were similar to those determined for adult human skin. Since by using the flux value from the in vitro experiments on preterm infant skin a steady state plasma concentration close to the therapeutic level can be predicted, phenobarbital transdermal delivery in preterm infants could be regarded as feasible.

Altered erythrocyte membrane phosphorylation in psoriasis

Autophosphorylation by [y‐32P]ATP of erythrocyte membranes from controls, psoriatic patients and patients with skin disorders other than psoriasis was compared by polyacrylamide gel electrophoresis. Compared with controls, membranes from psoriatic patients showed significantly less 32P incorporation in the band 2 region (nomenclature of Fairbanks et al., 1971). In addition, psoriasis and some of the other skin diseases examined displayed decreased phosphorylation in the region of bands 2.9‐3 and 4.5‐4.8. A new polypeptidc band in the 18‐20,000 dalton region was also observed in the diseases examined. Altered epidermal plasma membranes have been implicated in the pathogenesis of psoriasis, and our findings suggest the defective plasma membranes may be a generalized phenomenon in this disorder.

Erythrocyte membrane phosphorylation in untreated and in etretinate-treated psoriatic patients*

Levels of phosphorylation were decreased in bands 2 to 2.1, 2.9 to 3 and 4‐5 to 4‐8 of erythrocyte membranes from psoriatic patients compared with control values. In addition, higher than control levels of 32P were incorporated into a new polypeptide hand (mol. wt. 18‐20,000 daltons) of red cell membranes from patients. Uptake of 32P by these bands returned towards normal after the patients received oral etretmate treatment. These results suggest there is a gcneralixed plasma membrane defect in psoriasis and that ctretinate may affect the metabolism of red cell membrane proteins.

Evaluation of Transdermal Theophylline Pharmacokinetics in Neonates

Theophylline may be administered by several routes, but problems are associated with neonatal dosing. The transdermal route may provide a safer and noninvasive method of administration, yet produce therapeutic concentrations in a consistent and reliable manner. To study the feasibility of this in the apnea of prematurity, stable neonates were administered a subtherapeutic transdermal dose for 24 hours in order to assess pharmacokinetics and bioavailability. This was followed with routine intravenous theophylline therapy according to institutional policy. Six of nine neonates had detectable serum theophylline concentrations that increased slowly after patch application. Mean (± SD) maximum serum concentration was 2.4 ± 1.3 μg/ml, mean time to maximum serum concentration was 22 ± 8.2 hours, and mean latency period was 8.0 ± 4.9 hours. Mean total amount of theophylline delivered to the skin was 18.6 ± 4.1 mg. Mean fractional absorption at 30 hours was 0.25 ± 0.12. These data demonstrate that it is possible to produce systemic theophylline concentrations with a transdermal patch in preterm infants sufficient to study pharmacokinetics and bioavailability, and that transdermal delivery of therapeutic doses is technologically feasible.

NMR Assignments of Cis- and Trans-Capsaicin

Abstract The spectral properties of trans-capsaicin, the principal pungent ingredient in many Capsicum species and varieties, and its synthetic cis-isomer were assigned unambiguously by a combination of COSY, HMQC, and HMBC NMR techniques.

Effectiveness of a dapsone compliance program in leprosy

Background. Long‐term effectiveness of a dapsone compliance program was assessed in patients with leprosy.