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Biomedical subjects

R W Gange

Publications and source records attributed to R W Gange.

At least 19 recordsLinked to original sources

Treatment of telangiectases and other benign vascular lesions with the 577 nm pulsed dye laser.

BACKGROUND: This study was undertaken to evaluate the effectiveness and safety of the 577 nm pulsed dye laser in the treatment of various vascular lesions of the face. OBJECTIVE: Our purpose was to make observations on the effects of different variables that could affect response. METHODS: Ninety-two adults with telangiectases of the face were sequentially selected for treatment according to a protocol previously established. Evaluation consisted of visual inspection by two investigators, and before and after photographs at 2-months intervals. A few patients with other vascular lesions were also treated and reported. RESULTS: Ninety-one percent of the patients (84 of 92) showed good to excellent response after a single treatment. Recurrence occurred in 2%. Atrophy of the skin occurred in 2%. Venous lakes, pyogenic granulomas, and mucosal vascular malformations showed significant improvement. CONCLUSION: The 577 nm pulsed dye laser is effective and safe for vascular lesions of the face.

Adult

Human thermoregulatory responses during heat exposure after artificially induced sunburn.

Thermoregulatory responses in the heat (ambient temperature 49 degrees C, 20% relative humidity, 1 m/s wind) were investigated in 10 unacclimated men during 50 min of cycle ergometer exercise (approximately 53% of maximal aerobic power) after a 10-min rest before as well as 24 h and 1 wk after twice the minimal erythemal dose of UV-B radiation that covered approximately 85% of the body surface area. In 7 subjects esophageal temperature (Tes) was recorded while in all 10 subjects five-site skin and rectal temperatures, heart rate, and back, left forearm, and shielded (12 cm2 area) right forearm sweating rates (msw) were recorded at 15-s intervals. Venous blood was collected before and after exercise-heat stress. Mean skin temperature, Tes, rectal temperature, heart rate, and total body sweating rate were not significantly (P greater than 0.05) affected by sunburn. Pre- and postexercise values of hematocrit, hemoglobin, plasma protein, plasma volume, and plasma osmolality were also not affected (P greater than 0.05) by sunburn. Analysis of presunburn and post-sunburn data showed that the Tes intercept for sweating (degrees C) was unaffected (P greater than 0.05), but msw/Tes and final msw from the left forearm (msw/Tes 0.24 +/- 0.02 vs. 0.17 +/- 0.01 mg.cm-2.min-1. degrees C-1, P less than 0.05; msw 0.60 +/- 0.05 vs. 0.37 +/- 0.02, mg.cm-2.min-1, P less than 0.05) and back (msw/Tes 0.43 +/- 0.03 vs. 0.36 +/- 0.01 mg.cm-2.min-1. degrees C-1, P = 0.052; msw 1.08 +/- 0.09 vs. 0.74 +/- 0.05 mg.cm-2.min-1, P less than 0.05) were significantly reduced 24 h postsunburn.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Human thermoregulatory responses during cold water immersion after artificially induced sunburn.

Thermoregulatory responses during cold-water immersion (water temperature 22 degrees C) were compared in 10 young men before as well as 24 h and 1 wk after twice the minimal erythemal dose of ultraviolet-B radiation that covered approximately 85% of the body surface area. After 10 min of seated rest in cold water, the mean exercised for 50 min on a cycle ergometer (approximately 51% of maximal aerobic power). Rectal temperature, regional and mean heat flow (hc), mean skin temperature from five sites, and hearrt rate were measured continuously for all volunteers while esophageal temperature was measured for six subjects. Venous blood samples were collected before and after cold water immersion. The mean skin temperature was higher (P less than 0.05) throughout the 60-min cold water exposure both 24 h and 1 wk after sunburn compared with before sunburn. Mean hc was higher (P less than 0.05) after 10 min resting immersion and during the first 10 min of exercise when 24 h postsunburn was compared with presunburn, with the difference attributed primarily to higher hc from the back and chest. While rectal temperature and heart rate did not differ between conditions, esophageal temperature before immersion and throughout the 60 min of cold water immersion was higher (P less than 0.05) when 24 h postsunburn was compared with presunburn. Plasma volume increased (P less than 0.05) after 1 wk postsunburn compared with presunburn, whereas plasma protein concentration was reduced (P less than 0.05). After exercise cortisol was greater (P less than 0.05) 24 h postsunburn compared with either presunburn or 1 wk postsunburn.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Temperature

Effect of glutathione depletion on sunburn cell formation in the hairless mouse.

Cutaneous protection against ultraviolet B (UVB) radiation damage by endogenous glutathione (GSH) was evaluated in the epidermis of the hairless mouse by measuring the influence of GSH depletion on sunburn cell (SBC) formation. Cellular GSH exerts antioxidant effects and recent studies have suggested a role for oxygen radicals in the production of SBC. Hairless mice (Skh/h 1) received oral treatment with buthionine S,R-sulfoximine (BSO), an irreversible inhibitor of gamma-glutamylcysteine synthetase, to deplete cutaneous GSH; 4 d later their ears were exposed to UVB radiation. BSO treatment significantly reduced GSH levels in the epidermis to 10-15% of control levels. Twenty-four hours after UVB exposure, SBC counts in the ears of animals with and without BSO treatment were measured, and those exposed to UVB were found to have increased. Greater numbers of SBC were found in the ears of BSO-treated mice exposed to 15 or 20 mJ/cm2 UVB, than in non-BSO-treated mice exposed to the same UVB doses. At higher UVB doses, there were no statistically significant differences between the groups. The results show that endogenous GSH provides the epidermis with measurable protection against injury by low or moderate UVB doses.

Animals

Light and electron microscopic analysis of tattoos treated by Q-switched ruby laser.

Short-pulse laser exposures can be used to alter pigmented structures in tissue by selective photothermolysis. Potential mechanisms of human tattoo pigment lightening with Q-switched ruby laser were explored by light and electron microscopy. Significant variation existed between and within tattoos. Electron microscopy of untreated tattoos revealed membrane-bound pigment granules, predominantly within fibroblasts and macrophages, and occasionally in mast cells. These granules contained pigment particles ranging from 2-in diameter. Immediately after exposure, dose-related injury was observed in cells containing pigment. Some pigment particles were smaller and lamellated. At fluences greater than or equal to 3 J/cm2, dermal vacuoles and homogenization of collagen bundles immediately adjacent to extracellular pigment were occasionally observed. A brisk neutrophilic infiltrate was apparent by 24 h. Eleven days later, the pigment was again intracellular. Half of the biopsies at 150 d revealed a mild persistent lymphocytic infiltrate. There was no fibrosis except for one case of clinical scarring. These findings confirm that short-pulse radiation can be used to selectively disrupt cells containing tattoo pigments. The physial alteration of pigment granules, redistribution, and elimination appear to account for clinical lightening of the tattoos.

Biopsy

Long persistence of monofunctional 8-methoxypsoralen-DNA adducts in human skin in vivo.

Human skin can be persistently photosensitized by topical application of aqueous 8-methoxypsoralen plus immediate irradiation with a non-erythemogenic dose of wavelengths above 380 nm. Re-exposure of skin thus sensitized to broadband UV-A produces phototoxic erythema 72-120 h later. The persistence of the photosensitization was demonstrated by phototoxic erythema after re-exposure up to 15 days after the first sensitizing irradiation. According to the concept that the first exposure induces primarily psoralen monoadducts, we consider this an investigation of psoralen monoadduct persistence. In contrast to several earlier studies, this sensitive method indicates that psoralen monoadducts may remain in human skin in vivo for more than 2 weeks after formation.

DNA

Do pyrimidine dimer yields correlate with erythema induction in human skin irradiated in situ with ultraviolet light (275-365 nm)?

Ultraviolet radiation produces erythema in human skin, and damages the DNA of living cells in skin. Previous work showed that broad-band UV-B (290-320 nm) radiation produced higher levels of cyclobutyl pyrimidine dimers in DNA of individuals with high UV-B sensitivity (low minimal erythema dose) than in subjects of low UV-B sensitivity [Freeman et al. (1986) J. Invest. Dermatol., 86, 34-36]. We examined the relationship between erythema induction and dimer yields in DNA of human skin irradiated in situ with narrow band radiation spanning the wavelength range 275-365 nm. We find that, in general, higher dimer yields are produced per incident photon in volunteers with higher susceptibility to erythema induced by radiation of the same wavelength.

Adult

Protective effects of cadmium chloride against UVB injury in mouse skin and in cultured human cells: a possible role of cadmium-induced metallothionein.

Metallothionein (MT) is a cysteine-rich protein with antioxidant and metal-chelating activities that is readily inducible by exposure to a variety of stimuli including heavy metals such as cadmium (Cd2+). We have investigated the protective effects of Cd2+ treatment on sunburn cell (SBC) induction in mouse skin in vivo and human cell survival in vitro after UVB exposure. The number of SBC in mouse ear skin was significantly reduced in Cd(2+)-treated mice (10 mumol CdCl2/kg) with each UVB dose (25, 50 and 100 mJ/cm2) compared with controls. Delay of UVB exposure after Cd2+ administration (24 h) and higher doses of CdCl2 (10-30 mumol/kg) were more efficient in reducing SBC formation. Human bladder cancer cells (MGH-U1) made tolerant to Cd2+ by repeated low dose exposure, or cells acutely exposed to high Cd2+ concentration showed increased tolerance (cell survival) to UVB injury. Electrophoretic-autoradiographic analysis of [35S]-cysteine-labeled protein synthesized by cultured cells after Cd2+ treatment revealed increased MT-like protein content. These results suggest that MT is inducible by exposure to Cd2+ in our system and may be a photoprotective agent against UVB-induced oxidative damage in mammalian skin.

Animals

Investigations of a manganese-containing mimic of superoxide dismutase in riboflavin phototoxicity in human cells in vitro.

The activity and specificity of a manganese-containing low molecular weight mimic of superoxide dismutase (manganese desferioxamine (Mndf)) were investigated in riboflavin (Rf) photosensitization in solution and cell culture. In addition to the very high superoxide dismutase-like activity of Mndf at micromolar concentrations, photochemical studies in solution indicated that it could quench excited singlet and triplet states at millimolar concentrations. Human erythrocytes, human lymphocytes and a human bladder carcinoma cell line were used to evaluate the potential of Mndf for in vivo use. The efficacy and toxicity of Mndf in the protection against Rf photoxicity varied between the different cell types.

Deferoxamine

An action spectrum for the elicitation of erythema in skin persistently sensitized by photobound 8-methoxypsoralen.

Human skin can be rendered persistently photosensitive by topical application of aqueous 8-methoxypsoralen (8-MOP) and exposure to a suberythemogenic dose of more than 380 nm radiation. We report an action spectrum for the elicitation of phototoxic erythema induced by a second exposure of skin pretreated in this way. After correction for unsensitized skin erythema this action spectrum resembles the absorption spectrum of the 4',5'-monoadduct of 8-MOP to DNA. This suggests that the monoadduct is the chromophore for erythema elicited by the second irradiation, and supports the DNA crosslink as the crucial photoproduct causing phototoxic erythema due to 8-MOP in human skin.

Differential Threshold

Immediate pigment darkening: visual and reflectance spectrophotometric analysis of action spectrum.

Immediate pigment darkening (IPD) occurs in human skin upon exposure to ultraviolet-A and visible radiation. The spectral changes that occur during IPD were measured with a rapid scanning reflectance spectrophotometer (RS) which employs optical fiber bundles for delivery and detection of light between 400 and 750 nm. The radiation dose dependence and wavelength dependence (334-549 nm irradiation) of IPD were studied by both the classical visual grading method and by spectrophotometric scoring using the RS system. The spectral changes that occur at long wavelengths with IPD mimic the natural absorption spectrum of melanin. Therefore, the IPD was scored in terms of the apparent change in melanin optical density, using the method Kollias and Baqer [Photochem. Photobiol. 43, 49-54 (1986)], based on reflectance in the 620-720 nm range. The nonlinearity of the visual grading method is demonstrated. The degree of IPD is first-order with respect to delivered dose and saturates after high doses. The maximum amount of IPD attained at saturation is greater for shorter wavelengths. Extrapolation of the reflectance data suggests the longest wavelength capable of eliciting IPD is about 470 nm.

Adult

Does exposure of human skin in situ to 385 or 405 nm UV induce pyrimidine dimers in DNA?

A previous report [Freeman et al. (1986) Photochem. Photobiol. 43S, 93S] indicated that irradiation of human skin in situ with 385 or 405 nm radiation produced detectable levels of pyrimidine dimers in DNA. Since these wavelengths are absorbed poorly by DNA, these results suggested that DNA damage was sensitized by other absorbing molecules present in skin. Examination of two experimental aspects of the previous work indicates that (1) the static gel electrophoresis method for DNA dispersion used in lesion determination gave accurate values of the levels of induced dimers, and (2) the DNA damage apparently induced by 385 nm was actually induced by shorter wavelength UV present in the 20 nm bandpass beam of the monochromator. The current results indicate that monochromatic 385 and 405 nm radiation are ineffective in dimer production in human skin in situ.

Adult

Treatment of tattoos by Q-switched ruby laser. A dose-response study.

Tattoo treatment with Q-switched ruby laser pulses (694 nm, 40 to 80 nanoseconds) was studied by clinical assessment and light and electron microscopy. Fifty-seven blue-black tattoos or portions thereof (35 amateur and 22 professional) were irradiated with 1.5 to 8.0 J/cm2 at a mean interval of 3 weeks. Substantial lightening or total clearing occurred in 18 (78%) of 23 amateur tattoos and 3 (23%) of 13 professional tattoos in which the protocol was completed. Response was related to exposure dose. Scarring occurred in one case, and persistent confettilike hypopigmentation was frequent. Optimal fluence was 4 to 8 J/cm2. Clinicohistologic correlation was poor. Q-switched ruby laser pulses can provide an effective treatment for tattoos.

Adult

Wavelength dependence of pyrimidine dimer formation in DNA of human skin irradiated in situ with ultraviolet light.

The UV components of sunlight are believed to be a major cause of human skin cancer, and DNA is thought to be the principal molecular target. Alterations of the intensity and wavelength distribution of solar UV radiation reaching the surface of the earth, for example by depletion of stratospheric ozone, will change the effectiveness of solar radiation in damaging DNA in human skin. Evaluation of the magnitude of such effects requires knowledge of the altered sunlight spectrum and of the action spectrum for damaging DNA in human skin. We have determined an action spectrum for the frequency of pyrimidine dimer formation induced in the DNA of human skin per unit dose of UV incident on the skin surface. The peak of this action spectrum is near 300 nm and decreases rapidly at both longer and shorter wavelengths. The decrease in our action spectrum for wavelengths less than 300 nm is attributed to the absorption of the upper layers of the skin, an in situ effect that is inherently included in our measurements. Convolution of the dimer action spectrum with the solar spectra corresponding to a solar angle of 40 degrees under current levels of stratospheric ozone (0.32-cm O3 layer) and those for 50% ozone depletion (0.16-cm O3 layer), indicate about a 2.5-fold increase in dimer formation. If the action spectrum for DNA damage that results in skin cancer resembles that for dimer induction in skin, our results, combined with epidemiological data, suggest that a 50% decrease in stratospheric ozone would increase the incidence of nonmelanoma skin cancers among white males in Seattle, Washington, by 7.5- to 8-fold, to a higher incidence than is presently seen in the corresponding population of Albuquerque, New Mexico.

Adult

Longwave ultraviolet radiation (UVA, 320-400 nm)-induced tan protects human skin against further UVA injury.

The protective effect of a UVA (320-400 nm) induced tan against cutaneous injury by further UVA-irradiation was studied by evaluating the histopathologic changes in tanned and untanned normal human buttock skin 24 h after exposure to 2 and 4 minimal erythema doses of UVA. In each subject there were fewer polymorphonuclear leukocytes and less endothelial cell prominence and vessel wall necrosis in the UVA tanned skin than in the untanned UVA-irradiated skin. In the tanned control and tanned UVA-irradiated skin there was a prominent mononuclear cell inflammatory infiltrate that was much greater than in untanned skin. In immunoperoxidase stained tissue sections, the mononuclear cells were predominantly T cells, and in all of the specimens the number of phenotypic helper/inducer cells exceeded the phenotypic cytotoxic/suppressor cells. This demonstrates that a UVA tan provides photoprotection against acute UVA exposure. In addition, tanning, with or without further UVA-irradiation, was associated with a mononuclear cell inflammatory infiltrate.

Adult

An action spectrum for photoinduction of prolonged cutaneous photosensitivity by topical 8-MOP.

Suberythemogenic exposure of human skin treated with aqueous 8-MOP to radiation greater than 380 nm prolongs photosensitization to subsequent UVA from 6 to 24-72 h. One hypothesis for prolonged photosensitization is that greater than 380 nm irradiation forms 8-MOP-DNA monoadducts, which are removed more slowly than free 8-MOP and serve as a substrate for crosslinking by further UVA exposure. Sufficient DNA crosslinking results in erythema. We have examined this hypothesis by measuring the action spectrum for induction of prolonged photosensitization. Skin of normal volunteers was treated with aqueous 8-MOP (0.003%) and immediately received suberythemogenic monochromatic exposures between 334 and 430 nm. twenty-four hours later, the presence of prolonged sensitization was tested by small exposures of UVA. Erythema was evaluated 3 and 5 d later, and an action spectrum for prolonged sensitization was determined. The minimum phototoxic dose (MPD) was also determined at each wavelength. The action spectrum for prolonged photosensitization declined gradually between 334 and 425 nm. The action spectrum for delayed erythema induced by a single exposure of 8-MOP-treated skin declined rapidly from 334-390 nm. These findings are consistent with prolonged binding of 8-MOP in the skin by an initial exposure, possibly as 8-MOP-DNA monoadducts, allowing the second exposure to induce an erythemogenic event, possibly crosslinking of DNA.

Cross-Linking Reagents