ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1991.tb09884.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract——In this overview, a number of the major current, and possible future developments in laser medicine are explored. In therapeutic applications, particular emphasis is given to obtaining selectivity in tissue targets and interaction mechanisms in order to achieve specific biological effects. This includes spatial confinement of thermal damage by pulsed laser irradiation and targetting by exogenous photothermal or photochemical chromophores. The potential for diagnostic applications of lasers in medicine is illustrated primarily by various in vivo spectroscopic techniques. Both therapeutic and diagnostic applications will rely increasingly on the development of total systems in which lasers will form only one, albeit an essential, part. Numerous scientific and technical problems need to be solved in order to realize the full clinical potential of the many new concepts in laser medicine. The impetus for such progress will come from integrated, multidisciplinary collaborations between medical, scientific and industrial gro

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1991.tb09885.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract——The threshold for photokeratitis at 193 nm was obtained for the rabbit cornea using an ArF excimer laser. Because ablation occurs at a level below that for photokeratitis, it was necessary to expose the cornea to a lengthy series of low‐energy exposures. It is concluded that the 193 nm photons have such a shallow penetration depth, being limited to the outermost epithelial cells, that classical photokeratitis occurs from the fluorescence emitted at the corneal epithelial absorption site. An intact tear film may help to protect the cornea from low‐level, scattered 193 nm laser ra

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1991.tb09886.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract——We have previously reported photodynamic therapy of normal rat colon using aluminium sulphonated phthalocyanine (AlSPc). In that study, the AlSPc used was a mixture of phthalocyanines of different degrees of sulphonation. Phthalocyanines of defined degrees of sulphonation have recently become available and we compared the distribution of the di‐ and tetra‐sulphonates (AlS2Pc and AlS4Pc) in rat colon and colon wall structures employing both chemical extraction and fluorescence photometry using a charge coupled device imaging system. Also, the photodynamic effects produced by these components in rat colon were compared at various times after photosensitization. After intravenous photosensitizer administration using equimolar doses, the concentration of AlS2Pc in colon fell off more rapidly with time than AlS4Pc. Differences were noted in the microscopic distribution of these compounds, with the di‐sulphonate exhibiting peak fluorescence in colon wall structures by 1 h after photosensitization, while mucosal fluorescence with the tetra‐sulphonate peaked at 5 h. Fluorescence was also lost from the colon wall much more slowly with the tetra‐sulphonate, which tended to be retained in the submucosa. Maximum photosensitizing capability was seen at 1 h with AlS2Pc and no lesions could be produced with photodynamic therapy at 1 week, with up to 5.65 μmol/kg. With AlS4Pc (5.65 μmol/kg), while no lesions could be produced with light treatment at 1 h, photodynamic therapy at 1 week produced lesions only slightly smaller than those produced with treatment at 48 h (the time of maximum effect), and significant photosensitization was present at 2 weeks. It is proposed that differences between AlS2Pc and AlS4Pc with respect to pharmacokinetics, microscopic distribution and qualitative (related to the timing) and quantitative differences in photodynamic effects in normal rat colon are related to physico‐chemical characteristics of the phthalocyanines used, particularly lipid solubility. Similar studies are now required on tumou

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1991.tb09887.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract——Radioprotective agents have been found to protect normal tissues during photodynamic therapy (PDT). We have investigated a phosphorylated thiol protectant WR‐77913 (W7) with the photosensitizer aluminium sulphonated phthalocyanine (AlSPc). We compared the effects of PDT on normal and tumour tissue in the rat colon, with and without this protectant. In normal colon no necrosis was seen in sites treated after administration of the W7. Necrosis of mean diameter 4.2 mm was seen in those given the protectant after light exposure. At tumour sites the area of necrosis was similar after light exposure before and after the administration of the protective agent. These results suggest a possible role for W7 in enhancement of selectivity of PDT action. Several mechanisms of protection against porphyrin phototoxicity by these drugs have been proposed, including acceleration of photobleaching. We used fluorescence to detect AlSPc in strips of rat colon before and after laser treatment, with and without W7. However, a primary role for the photobleaching of AlSPc as the mechanism for the protection shown is not supported by these observa

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1991.tb09888.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract——Threshold radiant exposures for grossly apparent immediate whitening and ultrastructural alterations of melanosomes in black guinea pig skin were determined for a series of red visible laser pulses ranging from 4 × 10−4to 6.5 × 10−14s. Threshold exposures for melanosomal injury were found to be independent of pulsewidth when the pulsewidths were below the estimated thermal relaxation time of melanosomes. Threshold radiant exposures for melanosomal injury were found to increase when the pulsewidths were approximately equal to or above the thermal relaxation time of melanosomes. At longer pulse durations, fracturing of melanosomes was not observed despite the longer exposures necessary for injury. Instead, perimelanosomal vacuoles were noted. These findings are consistent with the theory of selective photothermolysis and provide evidence for the thermal initiation of melanosomal d

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1991.tb09889.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract——This study has examined the changes in tumor interstitial pressure exhibited during and after photodynamic therapy (PDT). The kinetics of these changes are marked by an initial decrease, followed by a rapid rise in tumor interstitial pressure. We have also employed two inhibitory agents to evaluate the different components of the pressure curve. Specially designed pressure chambers were seeded with chondrosarcoma and implanted subcutaneously in rats. Animals were injected with 0–50 mg/kg Photofrin II (i.v.) 7 days post‐implantation and tumors were exposed to 0–540 J/cm2630 nm 24 h later. Interstitial pressure was monitored via a transducer connected to the implanted chamber. Additional groups of animals were injected with either indomethacin (an inhibitor of thromboxane synthesis) or Ketanserin (a serotonin antagonist) before light treatment. Porphyrin doses of 10 mg/kg and above (135 J/cm2), or light doses of 135 J/cm2and above (25 mg/kg Photofrin II) were effective in modifying interstitial pressure. Porphyrin doses greater than 25 mg/kg, or light doses greater than 270 J/cm2produced no further increases in interstitial pressure. Animals given indomethacin (10 mg/kg i.p.) exhibited the initial decrease in pressure during light treatment, but showed no increase past baseline levels. Animals given Ketanserin (10 mg/kg i.p.) demonstrated no decrease in pressure during PDT, but showed the same elevations in pressure as controls. This suggests that two independent mechanisms account for the different components of the pressure curve, and that serotonin release may occur d

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1991.tb09890.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract——The explosive vaporization of melanosomes in situ in skin during pulsed laser irradiation (pulse duration<1 μs) is observed as a visible whitening of the superficial epidermal layer due to stratum corneum disruption. In this study, the ruby laser (694 nm) was used to determine the threshold radiant exposure, H0(J/cm2), required to elicit whitening for in vitro black (Negroid) human skin samples which were pre‐equilibrated at an initial temperature, Ti, of 0, 20, or 50°C. A plot of H0vs Tiyields a straight line whose x‐intercept indicates the threshold temperature of explosive vaporization to be 112 ± 7°C (SD, N = 3). The slope, ∂H0/∂Ti, specifies the internal absorption coefficient, μa, within the melanosome: μa= −ρC/(slope(1 + 7.1Rd)), where ρCis the product of density and specific heat, and Rdis the total diffuse reflectance from the skin. A summary of the absorption spectrum (μafor the melanosome interior (351–1064 nm) is presented based on H0data from this study and the literature. The in vivo absorption spectrum (380–820 nm) for human epidermal melanin was measured by an optical fiber spectrophotometer and is compared wi

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1991.tb09891.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract——We have developed a method for defining diagnostic algorithms for pathologic conditions based on fluorescence spectroscopy. We apply this method to human colon tissue and show that fluorescence can be used to diagnose the presence or absence of colonic adenoma. This method uses fluorescence excitation–emission matrices (EEM) to identify optimal excitation regions for obtaining fluorescence emission spectra which can be used to differentiate normal and pathologic tissues. In the case of normal and adenomatous colon tissue, these were found to be: 330, 370, and 430 nm ± 10 nm. At these excitation wavelengths, emission wavelengths for use in diagnostic algorithms are identified from average difference and ratio of the spectra from normal and pathologic tissues. In colon tissue, at 370 nm excitation, 404, 480, and 680 nm were found to be useful emission wavelengths for diagnosing the presence of adenoma in vitro. The basis of colon tissue autofluorescence was investigated using EEM of pure molecules and relevant excitation–emission maxima in the li

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1991.tb09892.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract——Laser and fluorescence light distributions with applications for photodynamic therapy were measured in mouse tumors using a non‐invasive electronic optical imaging system. The system consists of a liquid‐nitrogen‐cooled, charge‐coupled‐device (CCD) array camera under computer control with 576 × 384 detection elements having dimensions of 23 μm × 23 μm. The available dynamic range of the array is approx. 103, and the effective wavelength range is 400–1000 nm. An interstitially placed cylindrical diffusing optical fiber was used to provide tumor illumination. The light distribution pattern from the fiber was determined by immersing the cylindrical diffusing tip in a fluorescing solution and recording the emission image. Fluorescence imaging facilitates an accurate measurement of light intensity distribution while avoiding problems associated with the directional nature of other detection methods used with diffusing fibers. Radiation‐induced fibrosarcoma tumors on C3H mice were grown to about 1 cm diameter for in vivo recording of light distribution from the tumor volume and for determination of effective light penetration distance at 18 wavelengths in the range 458–995 nm. Endogenous tumor fluorescence and Photofrin II fluorescence intensity were measured over the wavelength range 585–725 nm to investigate the possible application of CCD imaging technology for drug distribution measurements. Model experiments were begun to evaluate the relative importance of potential distortions of light distribution measure

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1991.tb09893.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY