Search PubMedSearch

Biomedical subjects

N Levine

Publications and source records attributed to N Levine.

At least 19 recordsLinked to original sources

Tretinoin emollient cream: a new therapy for photodamaged skin.

BACKGROUND: Tretinoin administered topically in 0.1% concentration has been shown to improve the wrinkling and irregular pigmentation of photoaged skin. OBJECTIVE: The purpose of this study was to assess the safety and efficacy of various concentrations of tretinoin in a new emollient cream base in the treatment of photoaged skin. METHODS: Three concentrations of tretinoin (0.05%, 0.01%, and 0.001%) in a new emollient cream formulation were compared with vehicle in a 24-week, double-blind, randomized, multicenter study of 296 subjects with photodamaged facial skin. RESULTS: Tretinoin emollient cream 0.05% gave a significantly better global response to therapy than vehicle (p less than 0.001), with 68% of subjects exhibiting improvement at the end of therapy, compared with 43% of subjects in the vehicle group. An excellent or good response was found in 26% of subjects treated with tretinoin emollient cream 0.05% versus 11% of vehicle-treated subjects. Fine wrinkling, mottled hyperpigmentation, and roughness were more improved in subjects who received tretinoin emollient cream 0.05% than in vehicle-treated subjects (p less than 0.05). No significant difference was found between vehicle and tretinoin emollient cream 0.01% or 0.001%. Histologic examination showed increases in epidermal and granular layer thickness, decreased melanin content and compaction of the stratum corneum after therapy with tretinoin emollient cream 0.05% or 0.01%. Mild to moderate skin reactions, such as erythema, peeling, and burning, were the most common side effects and, although most prevalent in the group using the 0.05% concentration, generally did not limit tretinoin use. CONCLUSION: Tretinoin emollient cream 0.05% appears to be safe and effective in the treatment of photodamaged skin.

Administration, Topical

Effects of a melanotropic peptide on melanoma cell growth, metastasis, and invasion.

Melanocyte stimulating hormone (alpha-MSH, alpha-melanotropin),Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Ly-Pro-Va l-NH2, regulates melanogenesis within epidermal melanocytes of many animals. An MSH analogue ([Nle4,D-Phe7]alpha-MSH) that exhibits superpotency and prolonged biological activity has been synthesized, biologically characterized, and is presently in clinical trials to determine its possible clinical use in tanning of the skin. It also has potential for the diagnosis, localization, and chemotherapy of melanoma. The effects of this analogue on the growth, metastatic behavior, and invasive potential of a melanotic variant of Cloudman S-91 murine melanoma are reported here. In an intracutaneous murine model of melanoma cell tumor growth, the analogue did not increase primary tumor growth (size) after the period of administration of the peptide hormone analogue and did not affect spontaneous lung metastases. Survival times for the control and melanotropin-treated groups were similar, suggesting that overall tumor burden was not affected by treatment with the hormone analogue. Last, melanoma cell invasion through a human amniotic basement membrane in vitro was not enhanced compared to untreated cells.

Amino Acid Sequence

Advances in the treatment of acquired and developmental defects of hard dental tissues.

With the decline in dental caries, the dental profession and the general public have become sensitized to the "new" specialty of cosmetic dentistry. As a consequence, research in the field of dental materials for the ideal, most natural restorative materials and techniques has become a primary focus and has had a profound influence on dental education and practice. This brief article will highlight some of these newer concepts.

Composite Resins

Controlled localized heat therapy in cutaneous warts.

BACKGROUND: Controlled localized heating as a method of superficial tissue destruction has been used in veterinary medicine for the treatment of benign and malignant tumors. The rationale for its use is that the diseased tissue being treated is more sensitive to the effects of heating than is normal tissue. This technology was applied to the treatment of common hand warts in a placebo-controlled study. OBSERVATIONS: Twenty-nine warts were treated one to four times (median, two times) at 50 degrees C for 30 to 60 seconds. Twenty-five (86%) of 29 treated verrucae regressed completely while seven (41%) of 17 control warts resolved during the course of the study. No wart that regressed regrew during the follow-up period (mean, 15.6 weeks). CONCLUSIONS: Controlled localized heating can cause the regression of hand warts. The 86% regression rate compares favorably with other wart treatment modalities. The mechanism of action and the effect of heat on these virally induced tumors is not known but may involve direct antiviral effects, physical destruction of the tumor, or the promotion of an inflammatory response that ultimately eradicates the lesion.

Adult

Induction of skin tanning by subcutaneous administration of a potent synthetic melanotropin.

UNLABELLED: OBJECTIVE--To determine the efficacy of short-term administration of a synthetic analogue of alpha-melanotropin, [Nle4D-Phe7] (NDP)-alpha-melanocyte-stimulating hormone (MSH), in darkening (tanning) human skin. DESIGN--Randomized, placebo-controlled, double-blind clinical trial. SETTING--Clinical research unit of a university medical center. SUBJECTS--Twenty-eight healthy white men with a history of either poor tanning (skin type I or II) or good tanning (skin type III or IV) recruited from advertisements and paid to participate in the study. METHODS--Each subject received 10 subcutaneous injections of either a purified NDP preparation or saline over 12 days. They were followed up for 7 weeks after therapy was completed. All subjects used a high-potency sunscreen during the trial. MAIN OUTCOME MEASURE--Skin darkening was quantified by serial chromaticity measurements prior to, during, and after therapy. RESULTS: -A significant parabolic curve of skin darkening activity was noted in subjects with skin type I or II (P less than .001) and with skin type III or IV (P much less than .001) who were given NDP. No darkening occurred in the subjects who were given a placebo. Peak changes were seen 1 to 3 weeks after therapy was completed. CONCLUSION--Human skin darkens as a response to a synthetic melanotropin given by subcutaneous injection. Skin tanning appears possible without potentially harmful exposure to ultraviolet radiation.

Adult

Controlled localized heating and isotretinoin effects in canine squamous cell carcinoma.

Controlled localized radiofrequency heating and systemic isotretinoin were used serially as therapy in a hairless dog that developed multiple cutaneous squamous cell carcinomas in chronically sun-damaged skin. During the course of therapy, four superficial tumors regressed completely, both clinically and histologically. Two larger, deeper tumors showed clinical signs of regression but histologic clearing did not occur. Both treatment modalities are known to have antitumor effects independently and may exert their effects in an additive fashion. However, it is also possible that heat-induced injury to tumor cells could lead to retinoid-mediated enhancement of an immunologic response to tumor antigens or some other process that might lead to regression.

Animals

In vitro transdermal delivery of a melanotropic peptide through human skin.

A superpotent analogue of alpha-MSH, (Nle4,D-Phe7)-alpha-MSH, when applied topically to mice induces darkening of follicular melanocytes throughout the skin. In vitro studies have demonstrated delivery of the peptide across mouse but not rat skin. This variation in permeability of skin of animal models prompted us to use human skin in vitro. The melanotropin was applied to the surface of human skin samples through a permeation apparatus and allowed to penetrate for 24 h at 36 degrees C. Passage of the analogue was shown by both bioassay and radioimmunoassay. These assays correlated well and demonstrated both the presence and the biologic integrity of the peptide after transdermal passage. Regional differences were noted in the degree of transdermal penetration. In addition, split thickness skin allowed greater penetration suggesting dermal binding of the hormone. This study is the first to show that a melanotropic peptide can be delivered transdermally through human skin in vitro. This has potential importance in the development of therapies for hypopigmentary disorders and for the stimulation of skin tanning without ultraviolet light.

Administration, Cutaneous

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.

Administration, Topical

A transition space maintainer for the adolescent dentition: a case report.

Premature loss of teeth in posterior segments of the primary, mixed or permanent dentition may lead to space loss in an anterior-posterior dimension. This article illustrates how a simple, aesthetic and effective space maintainer can be used to prevent space loss in the permanent dentition.

Adolescent

Effect of oral isotretinoin on dysplastic nevi.

We previously reported a favorable histologic response of dysplastic nevi to topical tretinoin in three patients. To investigate the anticancer and cancer preventive effects of retinoids we have examined the effect of systemic isotretinoin on dysplastic nevi. After confirmatory baseline biopsies, eleven patients with the dysplastic nevus syndrome were treated with oral isotretinoin, 40 mg twice a day for 4 months. At completion of therapy, at least three previously identified and photographed clinically typical dysplastic nevi were rephotographed and removed for histologic evaluation. Eight patients completed the full course of medication. There were no clinical changes in the dysplastic nevi in these patients. Posttherapy biopsy specimens in six volunteers revealed most of the remaining lesions to be dysplastic nevi. The majority of lesions biopsied in two subjects showed normal, benign nevi only. This proportion of clinically typical dysplastic nevi that prove to be normal nevi histologically (28%) is not significantly different from that reported by others. Oral isotretinoin does not appear to have a significant biologic effect on the clinical or histologic appearance of dysplastic nevi in the treatment schedule employed.

Administration, Oral

Radiofrequency hyperthermia and topical retinoic acid therapy in murine melanoma.

Malignant cells are known to be sensitive to increased temperature. The effects of hyperthermia (HT) on intradermally implanted S91 melanoma cells in syngeneic mice were investigated with a hand-held radiofrequency generator. The possible additive effects of topical retinoic acid (RA) in this system also were studied. Five millimeter diameter melanomas were treated with either HT alone, RA alone, or a combination of HT and RA and were then evaluated after 43 days and 59 days. Eighteen of 20 tumors treated with HT alone and all 20 melanomas treated with HT/RA were eradicated. RA alone caused complete regression in 11 of 19 treated tumors. It is concluded that radiofrequency HT is an effective treatment in intradermal murine melanoma and that the addition of RA does not significantly alter the outcome because of the extreme effectiveness of HT alone.

Administration, Cutaneous

Radiofrequency hyperthermia therapy of murine melanoma: a comparison of fractionated versus single-dose treatments.

The effects of single and fractionated doses of radiofrequency hyperthermia were investigated in the treatment of cutaneous murine melanoma. S91 murine melanoma cells were implanted into preformed intradermal blister cavities on the backs of DBA/2J mice. Evaluation of treatment response was undertaken after single and fractionated doses of hyperthermia. A single 60-second treatment at 46 degrees C did not result in any complete regressions, while 3 weekly 46 degrees C treatments produced a 40% incidence of tumor regression. Higher temperature therapy was associated with improved cure rates. A single treatment for 60 seconds at 50 degrees C resulted in a 25% complete response rate while 3 weekly 50 degrees C treatments resulted in the eradication of 92% of the treated tumors. In those tumors that responded only partially to hyperthermia, fractionated low- (46 degrees C) and (50 degrees C) high-dose regimens resulted in significantly smaller melanomas than single-treatment schedules at the same temperatures. It is concluded that fractionated hyperthermia is an effective modality in the control of intracutaneous murine melanoma. If other cutaneous malignancies are also sensitive to heat, this may provide a useful nonsurgical means of treating skin cancer.

Animals

The effects of bergapten and sunlight on cutaneous pigmentation.

The effects of bergapten-containing preparations in sunlight-induced skin pigmentation were evaluated. Oil and lotion vehicles with bergapten/UV-B sunscreen or sunscreen alone were applied to the backs of subjects twice weekly for 4 weeks and the subjects were exposed to gradually increasing doses of midday sunlight. The degree of skin darkening was assessed by clinical examination, reflectometry, and light microscopy of skin biopsy specimens. At 5 weeks, 1 week after the last sunlight exposure, the sites treated with either the bergapten/UV-B sunscreen lotion or the lotion vehicle were significantly darker than the sites treated with the sunscreen lotions without bergapten. Oil preparations produced less clearcut results, possibly because of a less potent sunscreen or because the bergapten did not leave the vehicle and absorb into the epidermis. In type I skin, the bergapten/sunscreen and the oil vehicle alone produced the same amount of tanning; both yielded more tanning than the sunscreen in oil by clinical examination. The findings were not confirmed by reflectometry or by light microscopy. Thus, we conclude that bergapten added to a UV-B sunscreen lotion preparation can increase skin pigmentation over the sunscreen alone when one is exposed to sunlight. The bergapten/UV-B sunscreen combination is a potentially useful product since one can develop a psoralen and UV-A-induced tan while being protected from UV-B-induced sunburn by the UV-B sunscreen incorporated into the formulation.

5-Methoxypsoralen

Facial swelling and asymmetry in children: systematic diagnosis and review.

This paper reviews a systematic approach which can be used to determine the diagnosis of a child who presents with a facial swelling or asymmetry. Once the most likely diagnosis is formulated then appropriate treatment can be initiated. Examples of some of the more common facial swellings within the listed differential diagnostic categories are also presented.

Child

Toxicologic studies of a superpotent alpha-melanotropin, [Nle4, D-Phe7]alpha-MSH.

A toxicology study was performed in mice given a superpotent alpha melanocyte stimulating hormone (MSH) analog. This 13 amino acid derivative, [Nle4, D-Phe7]alpha-MSH or NDP-MSH, is a melanotropin which is very slowly biodegraded in vivo and is active at 1/1,000 the concentration of natural alpha-MSH. Mice were administered up to 2 mg/kg of the analog daily and weekly over 4 or 12 weeks by both topical application (in 90% DMSO) or by IP injections (in physiologic saline). At the end of this period, no toxic effects were observed in various organs, on hematologic indices, or on weight gain. A slight increase in triglyceride and platelet levels were noted in mice given the analog weekly for 12 weeks. There was no evidence of an effect on behavior nor ACTH-like endocrine actions such as elevated serum cortisol levels. Transdermal drug delivery studies performed in vitro showed reproducible diffusion of the NDP-MSH analog through full-thickness mouse skin. Approximately 0.002% to 0.05% of a 10(-4) M preparation was transdermally delivered using a DMSO/water solution or a PEG/alcohol cream base, respectively. This superpotent analog is now entering a Phase I clinical trial with possible therapeutic applications for the treatment of hypomelanotic disorders such as vitiligo and for pharmacologic tanning without the need for sunlight exposure.

Administration, Cutaneous

Changes in serum K+ in healthy and in asthmatic subjects during exercise.

Adrenergic mechanisms modulate exercise-induced changes in blood serum K+ concentration ([K+]). Impairment of these same mechanisms may be associated with bronchial hyper-reactivity. If this is accurate, asthmatic subjects should show disturbed K+ regulation during exercise. We measured [K+] and FEV1 in 13 healthy control and in 13 asthmatic subjects pre-exercise, at peak exercise (within 1 min of stopping exercise), and 10 min postexercise. This was done on 2 separate days, one with and one without bronchodilator (BD) pretreatment. Both groups were equally fit, exercising to the same O2 consumption and heart rate. Resting [K+] was normal for both groups (two-day averages were 4.00 +/- 0.07 and 4.09 +/- 0.07 mmol/L, mean +/- SEM, in control and asthmatic subjects, respectively). Without BD pretreatment, at peak exercise, [K+] in control subjects rose by 0.56 +/- 0.08 compared with 0.96 +/- 0.09 in asthmatics (p less than 0.01). After exercise, [K+] returned to baseline (4.12 +/- 0.08) in control subjects but remained elevated in asthmatics (4.60 +/- 0.12, p less than 0.01). Although FEV1 was unchanged in control subjects, in asthmatics it fell after exercise (p less than 0.01). With BD pretreatment: peak exercise [K+] increased by 0.55 +/- 0.09 in control subjects, and by 0.49 +/- 0.01 in asthmatics (p less than 0.01). By 10 min postexercise, it returned to baseline in both groups (4.15 +/- 0.11 for control subjects and 4.32 +/- 0.07 for asthmatics). The asthma group's fall in FEV1 was also abolished. These data indicate that postexercise K+ remains elevated in asthmatics, supporting the suggestion that their adrenergic function is impaired.

Adult