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Biomedical subjects

N Levine

Publications and source records attributed to N Levine.

At least 163 records · Page 9Linked to original sources

Risk factors for dental fluorosis in a fluoridated community.

We conducted a case-control study to determine the sources of fluoride which are particular risk factors to dental fluorosis. Cases and non-cases were identified by the screening of 8-, 9-, and 10-year-old schoolchildren in the fluoridated community of East York, Ontario. Parents were interviewed about the child's first five years of residence and about diet and preventive caries practices. The Mantel-Haenszel odds ratio and associated chi-square tests were used to assess the association of fluorosis with several potential sources, controlling for other sources of fluoride and mother's education. The prevalence of mild fluorosis [1-4 on the Thylstrup and Fejerskov (1978) Index] was 13%. Those who brushed their teeth before the age of 25 months had 11 times the odds of fluorosis compared with those beginning toothbrushing later; prolonged use of infant formula (greater than or equal to 13 months) was associated with 3.5 times the risk of fluorosis, compared with no, or shorter duration of, formula use. We estimate that these factors were responsible for 72% and 22%, respectively, of the cases in our population. Dental fluorosis is not a public health problem in East York, but parents should be advised to supervise toothbrushing by children under 2 years of age.

Child↗

Growing pains.

Explore the source record for details and available documents.

Forecasting↗

Topical application of a melanotropic peptide induces systemic follicular melanogenesis.

We determined the relative effectiveness of alpha-MSH and a highly potent melanotropin analogue, [Nle4, D-Phe] - alpha-MSH, in stimulating a shift from pheomelanogenesis to eumelanogenesis within hair bulbs of mice. The analogue proved to be at least a hundred times more effective than the native hormone when injected subcutaneously. The two melanotropins were then incorporated into an ointment base and topically applied to a shaved area of the skin on the back of a yellow strain of mice (C57BL/6JAY). Within 24-48 hours eumelanin production was visible within hair bulb melanocytes in both treated and untreated areas of animals. The presence of melanized organelles (eumelanosomes) within melanocytes was confirmed by electron microscopy. These results document the delivery of a peptide hormone through the skin and into the systemic circulation. This is the first demonstration of the delivery of a peptide hormone by percutaneous absorption and may provide a model for a similar route of delivery of other peptide hormones. The hormone analogue has also been delivered across human skin in vitro. Delivery of a melanotropin by a transdermal route may prove to be clinically useful in the treatment of some integumental hypopigmentary disorders in humans.

Administration, Topical↗

Capacitive radiofrequency hyperthermia in the treatment of cutaneous murine melanoma.

We have evaluated localized capacitive radiofrequency hyperthermia in the treatment of murine S91 melanoma. Two hundred and ten DBA/2J male mice were implanted with 1 X 10(6) S91 murine melanoma cells innoculated into a noninflammatory upper dermal suction blister cavity. Two tumors were implanted per animal, so that each animal served as its own control in evaluating the effects of temperature, treatment duration, and tumor size on tumor growth following radiofrequency hyperthermia treatment. The data supported the following conclusions: (1) capacitive radiofrequency hyperthermia is effective in the treatment of murine S91 melanoma; (2) duration of treatment between 10 and 60 seconds at 52 degrees C does not influence effectiveness; and (3) treatment temperatures greater than 49 degrees C are needed for maximal effectiveness in the treatment of these tumors. Based on these preliminary findings, high temperature, short duration capacitive radiofrequency hyperthermia may prove to be a useful modality in the treatment of certain cutaneous malignancies.

Animals↗

Stimulation of follicular melanogenesis in the mouse by topical and injected melanotropins.

The effects of melanocyte-stimulating hormone (alpha-MSH) and related analogs on follicular melanogenesis in the mouse (C57BL/6JA gamma) were studied. [Nle4, D-Phe7]-alpha-MSH and the related fragment analogues Ac-[Nle4, D-Phe7]-alpha-MSH4-11-NH2 and Ac-[Nle4, D-Phe7]-alpha-MSH4-10-NH2, stimulated the conversion of pheomelanogenesis to eumelanogenesis when subcutaneously injected at concentrations 100-fold lower than the native hormone, alpha-MSH. In addition, the melanotropin analogs stimulated follicular eumelanogenesis when applied topically to the skin of mice. The melanotropins were transdermally delivered to the systemic circulation as evidenced by the fact that eumelanogenesis was stimulated in hair follicles in areas distant from the site of topical application. These results demonstrate that peptide hormone analogs can be transported across the skin. The unique actions of the melanotropin analogs may relate to the fact that these peptides are nonbiodegradable and thus exert prolonged actions on melanocytes. These compounds may prove important for studies on normal integumental melanogenesis and for the treatment of hypopigmentary disorders in humans.

Administration, Topical↗

Effect of aerobic training on forced expiratory airflow in exercising asthmatic humans.

Pulmonary function after exercise was evaluated in 22 asthmatic subjects before and after a 36-session training sequence of aerobic exercise. Training did not change pulmonary function values, except for a small increase in maximal voluntary ventilation (P less than 0.02), which was attributed to respiratory muscle training. After aerobic training, both external work at a given heart rate and peak O2 consumption increased by 30 and 15%, respectively. At the same minute ventilation (VE), immediate postexercise forced expiratory airflow was higher after training (P less than 0.02), and reduction in forced expiratory airflow during the first 9 min postexercise was less after training (P less than 0.01). The posttraining airflow response to the pretraining work load was, as expected, less than the pretraining response (P less than 0.02). Although the difference in maximal-to-minimal airflow at the same VE was similar before and after training, the airflow increase accounted for 50% of the response after training compared with 16% of the pretraining response. Furthermore the strong negative correlation (P less than 0.01) between maximal and minimal airflow both pre- and posttraining indicates that exercise-induced bronchospasm (EIB) severity is, in part, determined by the degree of exercise-induced bronchodilation. We conclude that aerobic training significantly increases exercise-induced bronchodilation and diminishes EIB.

Aerobiosis↗

Isotretinoin and cutaneous helper T-cell lymphoma (mycosis fungoides).

Retinoids, including isotretinoin, have demonstrated antiproliferative and antineoplastic activity in laboratory and clinical trials. In a phase II trial, 25 patients with extensive mycosis fungoides were evaluated for response to isotretinoin. There was a 44% (11 patients) objective clinical response rate with three clinical complete responses without concomitant evidence of pathologic clearing of the disease. An additional 24% (six patients) showed a minor degree of clinical improvement. The median time to response was two months (range, 0.5 to eight months) and the median response duration was eight months or longer (range, one to 25 months). Chronic toxic reactions consisted primarily of drying of the skin and mucous membranes and resulted in dose reduction in the majority of patients. It is concluded that isotretinoin produces significant clinical benefit to some patients with mycosis fungoides.

Adult↗

Effect of intralesional alpha 2-interferon on actinic keratoses.

The effect of intralesional alpha 2-interferon (IFN) on actinic keratoses was examined in this two-part study. In phase I, 11 of 12 lesions cleared following nine injections of IFN (5 X 10(5) IU per dose) compared with none of 12 keratoses injected with placebo. Smaller doses of IFN (1 X 10(5) IU and 1 X 10(4) IU per injection) produced clearing of 42% and 58% of lesions, respectively. The second phase, which was designed to investigate the optimum schedule for treatment with IFN, showed that a minimum of six injections of IFN (5 X 10(5) IU per injection) was necessary to clear 14 of 15 actinic keratoses. Although this mode of delivery is not practical for clinical use, intralesional alpha 2-IFN demonstrates biologic activity against actinic keratoses.

Adult↗

Effects of topical retinoic acid on intracutaneously implanted S91 melanoma in mice.

Previous studies have demonstrated that retinoids possess antineoplastic properties against melanoma. The purpose of this study was to determine whether topically applied retinoic acid could prevent melanoma development in syngeneic mice after intracutaneous cell inoculation. Trans-retinoic acid in DMSO was applied daily for 28 days after melanoma implantation and tumor growth was quantitated by the uptake of [14C]thiouracil, a tracer compound specific for melanoma which is incorporated linearly according to the weight of the tumor. Marked reduction in tumor growth was noted at the highest concentration (0.1%) tested and lesser but significantly decreased tumor growth patterns were also realized at lower concentrations in a dose-dependent manner. Thus, topically applied retinoic acid is capable of inhibiting S91 melanoma growth in vivo.

Administration, Topical↗

Clobetasol propionate versus fluocinonide creams in psoriasis and eczema.

A double-blind, parallel comparison was made of the short-term efficacy and safety of three times daily regimens of 0.05% clobetasol propionate cream and 0.05% fluocinonide cream in 114 adolescent and adult patients with psoriasis and 113 with eczema. After 2 weeks of topical applications, patients were assessed according to (1) investigators' overall judgment of clinical response, (2) degree of severity of specific signs and symptoms, and (3) patients' evaluation of improvement. In all three response categories in psoriasis, and in two of three in eczema, clobetasol was statistically significantly superior to fluocinonide (p less than 0.05-p less than 0.001). Healing commenced more rapidly with clobetasol and there was no indication of tachyphylaxis. In contrast, the healing rate with fluocinonide slowed noticeably after the first week, and there was a greater tendency to relapse following fluocinonide treatment. Both regimens were safe: drug-related side effects were generally mild and occurred most commonly with fluocinonide therapy in eczema patients. Overall, drug-related effects occurred in 4% of patients receiving clobetasol and 12% receiving fluocinonide (p less than 0.05). Transient morning plasma cortisol reductions below 5 micrograms/dl occurred in 6% of clobetasol-treated patients, reverting to normal within 1 week of the end of treatment.

Administration, Topical↗

Effect of castration on prostaglandin-mediated changes in membrane potential and prostaglandin synthesis in guinea-pig seminal vesicle tissue.

Arachidonic acid stimulated an increase in transmural electrical potential difference (p.d.) in guinea-pig seminal vesicle tissue in vitro. Pretreatment with indomethacin abolished this response. Indomethacin pretreatment did not prevent the p.d. from increasing in response to theophylline. Changes in p.d. in response to arachidonic acid were greatly attenuated, and the response to theophylline was abolished in seminal vesicle tissue taken from castrated guinea-pigs. Seminal vesicles, aorta and ileum taken from castrated guinea-pigs synthesized and released more prostaglandins than did those from control animals. It is concluded that the effects of arachidonic acid on p.d. are mediated by its metabolism to prostaglandins; the inability of seminal vesicles from castrated animals to respond to arachidonic acid is not a result of a decrease in prostaglandin production, but is more likely a result of other degenerative changes attendant upon castration; and androgens appear to have some regulatory function on prostaglandin synthesis in a variety of tissues.

Animals↗

Inhibition by retinoic acid of murine retrovirus-induced cellular transformation and tumor formation.

The effect of all-trans-retinoic acid (RA) on cellular transformation and on tumorigenicity of retrovirally transformed cells was investigated. RA treatment of NRK and NIH/3T3 cells transformed by BALB/c murine sarcoma virus (MuSV), Kirsten murine sarcoma virus (K-MuSV), and simian sarcoma virus resulted in a significant reduction in anchorage-dependent growth of only K-MuSV-transformed NRK cells. A 62% reduction in cell number was observed at 10(-5) M RA. In contrast, anchorage-independent growth induced by each of the viruses tested was suppressed by RA. Balb/cMSV3T3 cells showed the greatest level of sensitivity with a significant reduction in anchorage-independent growth occurring at 10(-9) M RA. The level of cytoplasmic retinoic acid-binding protein (CRABP) was determined in both parent and transformed cell lines. CRABP was present at a high level in all 3T3 cell types but was absent in all NRK cell lines. For testing the antineoplastic activity of RA in vivo, Balb/cMSV3T3 cells were injected intradermally into nude mice. Subsequent treatment of the tumor sites of these animals by topical application of RA resulted in a significant reduction in both tumor incidence and tumor size, confirming the in vitro results. Analysis of the level of v-onc mRNA revealed that inhibition of retroviral transformation by RA was not due to a decrease in transcription of the v-onc genes.

Animals↗

Management of life-threatening dermatoses.

The notion of life-threatening dermatoses may seem to be a contradiction in terms, but in fact there are a number of serious dermatologic conditions that require prompt attention to prevent fatal consequences. This article will review four such diseases, for which prompt recognition and treatment will be emphasized.

Adult↗