The effects of minoxidil, 1% pyrithione zinc and a combination of both on hair density: a randomized controlled trial.

BACKGROUND: Recent studies of antidandruff shampoos or tonics containing antifungal or antibacterial agents produced effects suggestive of a potential hair growth benefit. OBJECTIVES: The purpose of this 6-month, 200-patient, randomized, investigator-blinded, parallel-group clinical study was to assess the hair growth benefits of a 1% pyrithione zinc shampoo. The efficacy of a 1% pyrithione zinc shampoo (used daily), was compared with that of a 5% minoxidil topical solution (applied twice daily), a placebo shampoo and a combination of the 1% pyrithione zinc shampoo and the 5% minoxidil topical solution. METHODS: Two hundred healthy men between the ages of 18 and 49 years (inclusive) exhibiting Hamilton-Norwood type III vertex or type IV baldness were enrolled. Total hair counts, the primary efficacy measure, were obtained using fibre-optic microscopy and a computer-assisted, manual hair count method. Secondary measures of efficacy included assessments of hair diameter, as well as patient and investigator global assessments of improvement in hair growth. These were based on photographs of the scalp using both midline and vertex views. RESULTS: Hair count results showed a significant (P < 0.05) net increase in total visible hair counts for the 1% pyrithione zinc shampoo, the 5% minoxidil topical solution, and the combination treatment groups relative to the placebo shampoo after 9 weeks of treatment. The relative increase in hair count for the 1% pyrithione zinc shampoo was slightly less than half that for the minoxidil topical solution and was essentially maintained throughout the 26-week treatment period. No advantage was seen in using both the 5% minoxidil topical solution and the 1% pyrithione zinc shampoo. A small increase in hair diameter was observed for the minoxidil-containing treatment groups at week 17. Assessments of global improvements by the patients and investigator generally showed the benefit of 5% minoxidil. The benefit of the 1% pyrithione zinc shampoo used alone tended (P < 0.1) to be apparent only to the investigator. CONCLUSIONS: Hair count results show a modest and sustained improvement in hair growth with daily use of a 1% pyrithione zinc shampoo over a 26-week treatment period.

Intralesional interferon therapy for basal cell carcinoma.

In a clinical trial of 172 patients at four medical centers, interferon alfa-2b (1.5 x 10(6) IU) or a placebo was injected directly into biopsy-proved noduloulcerative or superficial basal cell carcinomas three times weekly for 3 weeks, for a cumulative dose of 13.5 million IU. Efficacy of treatment was determined at 16 to 20 weeks by examination of biopsy specimens that demonstrated cure of lesions in 86% of interferon-treated patients and in only 29% of placebo-treated patients. During the treatment course and follow-up, an initial inflammatory response was observed at the treatment sites, followed by diminished erythema, improvement in overall appearance, and a decrease in size of lesions. Side effects of treatment, mainly flu-like symptoms, were usually mild and transient and occurred more commonly in the interferon-treated group. Only three patients, all in the interferon-treated group, discontinued therapy because of side effects. One year after initiation of therapy, 81% of interferon recipients and 20% of those given the placebo remained tumor free. Noduloulcerative and superficial lesions were equally responsive to treatment with interferon. For some patients with noduloulcerative or superficial basal cell carcinomas, intralesional interferon alfa-2b may be an alternative, effective treatment.

The effect of an intralesional sustained-release formulation of interferon alfa-2b on basal cell carcinomas.

Intralesional interferon alfa-2b has been proven effective in the treatment of basal cell carcinomas. Because nine injections over a 3-week period have been necessary to produce clinically significant cure rates, a sustained-release protamine zinc chelate interferon formulation has been developed. In this study, 65 basal cell carcinomas were treated in one of two dosing schedules with intralesional sustained release interferon alfa-2b (10 million IU per injection). Thirty-three patients received a single injection and 32 patients received one injection per week for 3 weeks. At study week 16, 80% of evaluable tumors treated with three injections and 52% treated with one injection were cured histologically. Two patients discontinued injections because of side effects. A sustained-release protamine zinc preparation of interferon alfa-2b shows promise as a practical, effective, and cosmetically elegant treatment for basal cell carcinoma.

The effect of topical interferon alpha 2b on actinic keratoses.

As a result of the known effects of intralesional interferon alfa 2b (Intron A) on actinic keratoses, we have now examined the effects of topical interferon alfa 2b gel on actinic keratoses. Twenty-four subjects each treated three actinic keratoses with either interferon gel 30 million IU/gm or a placebo preparation applied topically 4 times a day for 4 weeks. Although more lesions treated with the active interferon showed clinical improvement, this difference was not statistically significant.

The effect of intralesional interferon gamma on basal cell carcinomas.

This open label study evaluated the effect of nine intralesional injections of two different doses of interferon gamma on basal cell carcinomas in 29 patients. One group of 15 patients received interferon gamma, 0.01 mg (20,000 IU), intralesionally three times a week for 3 weeks. Fourteen patients received interferon gamma, 0.05 mg (100,000 IU), intralesionally in the same dosage schedule. Excisional biopsy specimens 12 weeks after therapy showed no evidence of tumor remaining in 7 of 14 patients (50%) treated with the higher dose of interferon gamma, whereas only 1 of 15 patients (7%) treated with low-dose interferon gamma was cured according to histologic criteria (p = 0.025). Seventy-six percent of patients reported at least one adverse reaction, but most were considered mild by the patient and the investigator.

Intralesional interferon alfa-2b for the treatment of genital warts.

A randomized, double-blind, placebo-controlled study has been conducted, and intralesional interferon alfa-2b was tested in the treatment of genital warts. This study design was to give 1 million units interferon alfa-2b intralesionally into the base of each of five external genital warts per patient, on a Monday-Wednesday-Friday treatment schedule for 3 weeks (total of nine injections). Forty-two patients were entered (20 randomized to receive interferon and 22 placebo injections). There were 43.8% of patients on the interferon treatment arm of the double-blind portion of the study who had complete disappearance of all warts, with an additional 25% of patients showing greater than 50% shrinkage of visible warts. On the placebo arm 14.3% showed a complete response, with an additional 14.3% showing greater than 50% shrinkage. This difference between interferon and placebo treatment was statistically significant (p less than 0.03). We conclude that intralesional interferon alfa-2b has significant activity in the treatment of genital warts.

Recombinant interferon alfa-2b in plaque-phase mycosis fungoides. Intralesional and low-dose intramuscular therapy.

A two-part clinical trial was conducted to determine the therapeutic efficacy of recombinant interferon alfa-2b in plaque-phase mycosis fungoides. In an initial randomized double-blind study, each of six patients had two representative plaques injected intralesionally with 1 X 10(6) U of recombinant interferon alfa-2b per site and two control plaques injected with placebo three times weekly for four consecutive weeks. Complete clinical regression of disease was observed at ten of 12 recombinant interferon alfa-2b sites compared with one of 12 placebo-treated sites four weeks after treatment with injections was stopped. Subsequently, in an open-labeled study, five of these patients were treated intramuscularly with 5 X 10(6) U of recombinant interferon alfa-2b three times weekly for four weeks and two patients were treated with a second, more extended course of therapy lasting 12 to 16 weeks. Three of the five patients treated systemically showed some improvement overall, but the responses were judged not to be clinically significant. The differential response observed from intralesional and intramuscular injections may be related to differences in concentration of recombinant interferon alfa-2b achieved in lesional skin by the two methods of administration.

Intralesional interferon in the treatment of early mycosis fungoides.

Twelve patients with early mycosis fungoides were enrolled in a randomized, double-blind, placebo-controlled study. Isolated plaques were injected three times a week with recombinant alpha 2-interferon in nine patients and with the vehicle in three patients. Two additional plaques were evaluated in each patient; one was left untreated, and another was treated topically with either placebo ointment or betamethasone ointment. Biopsies were taken from an untreated, representative plaque prior to treatment and from all test sites following treatment for light microscopy and T lymphocyte subsets. Three of the nine lesions injected with interferon cleared, and all showed improvement. Thirteen of eighteen noninjected lesions improved in patients who received interferon, showing a systemic effect. In the control group, none of the injected lesions improved and only two of the noninjected lesions showed any change. Histopathologic changes confirmed the clinical impression. This study shows that intralesional interferon may be given safely and has a beneficial effect, both locally and systemically.

Sweating responses during changes of hypothalamic temperature in the rhesus monkey.

A technique is presented for preparing a durable thermode implant in the hypothalamus of the rhesus monkey. In unanesthetized monkeys implanted with thermodes in the anterior hypothalamic area of the brain, a linear relation was found between local sweat rates on the general body surface and clamped hypothalamic temperature. Changes in skin temperature were found to shift the hypothalamic set-point temperature at which sweating began but did not alter the gain of the hypothalamic temperature-sweat rate relationship. This study provides direct support for the concept that central brain temperature and skin temperature interact additively in the control of sweating in higher primates. Due to the very close similarity between these responses and those seen with indirect measurements of brain temperature in men, the rhesus monkey is seen as an excellent experimental analogue for studying human thermoregulation.

Effect of labyrinthectomy on the dynamic vestibulo-ocular counterrol reflex in the rhesus monkey.

Timeline records of eyeball counterrotation to constant speed rotations about the line of sight were examined in the Rhesus monkey via a linear transformer measurement system using a contact lens. Normal monkeys exhibited a decrease in the amplitude ratio of eye-to-chair motion and an increasing phase lag between eye and chair as the frequency of the motion platform increased. Bilateral labyrinthectomy or prolonged dosage with streptomycin was found to nearly abolish the counterroll reflex. Unilateral damage to the vestibular system resulted in a decrease in the amplitude ratio of the eye-to-chair motion by approximately 50% 1 month after surgery.