The spectroscopic properties and the sensitizing efficiency of phthalocyanine derivatives as photosensitizers were investigated to performe for photodynamic therapy(PDT) with a ruby laser.
In the results, the absorbances at longer wavelength corresponded to the monomer increased in order of PcS<Zn-Pc<Al-Pc. The Fluorescence intensity increased as following order: PcS<Zn-Pc<Al-Pc. The fluorescence lifetime in 10mM-CTAB were long as following order: Zn-Pc<PcS<Al-Pc. The delay of tumor growth was observed in either group of laser treatment with or without photosensitizer, but its tendency was remarkable in groups of laser treatment with photosensitizers, especially with Zn-Pc or Al-Pc. The histological changes of tumor by PDT were severe edema and bleeding immediately after irradiation and necrosis expanded gradually.
It is considered that phthalocyanine can be useful sensitizer of ruby laser treatment.

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We subcutaneously transplanted colon 26 cells into mice to producea tumorl cm in diameter. Next, we intravenously administered PH-1126 to the cancer-bearing mice at dose levels of 5 mg/kg, 10 mg/kg, and 20 mg/kg, then observed the degree of distribution and accumulation of PH-1126 at the tumor sites and the individual normal intestial sites 24, 48, and 72 hours after administration. In a comparative study on the accumulation of PH-1126 in the skin, duodenum, ileum, rectum, and colon 26-induced tumor, we noted accumulations in the small intestine and colon, and to a small degree, in the rectum. The greatest accumulation was in the colon 26-induced tumor.
Next, we intravenously administered PH-1126 to mice bearing 1cm-diameter tumor at dose levels of 5 mg/kg and 10 mg/kg. 48 hours after the administration, we carried out P.D.T. using a krypton-ion lasr. We observed the changes in mice over time after the laser radiation. We then made a comparison between the P. D. T. group and the control group. As a result, we were able to obtain the antitumoral and survival effects of PH-1126 and P. D. T. These results suggest that P. D. D.·P. D. T. together with the administration of PH-1126 is useful in treating cancer of the rectum.

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The effect of Excimer Dye Laser (EDL) on photodynamic therapy (PDT) for brain tumor has been investigated in glioma model, established by implanting C6 cells in Wistar male rat and induced by ENU. The anti-tumor effects were studied histologically and evaluated measuring the size of tumor necrosis (depth×width) after the therapy in comparison with concentration of HpD (2, 5, 10mg/kg), frequency of repetition (30, 40, 60Hz), and pulse energy (0.5, 1.0, 2.0, 4.0mJ). Consequently, EDLPDT resulted in as follows; the size of tumor necrosis was closely correlated with concentration of HpD and total light dose, while it was inversely correlated with pulse energy. The histological examination suggested that EDL has higher selection to tumor tissues rather than normal brain tissues. Especially, in border zone between tumor and normal brain tissues 1.0-2.0mJ of pulse energy seemed to be more favorable to the tumor selection. There were no severe adverse effects in EDL-PDT.

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Recently, new photosensitizers which have a greater affinity for malignant tissue, longer absorption wavelength bands, and that hold hope for deeper effects by PDT than with HpD or PHE (Photofrin). We report the effect of such a new photosensitizer, ATX-S10 and a new laser equipment, Nd: YAG-OPO laser, which is a tunable laser.
Meth-A sarcomas were transplanted on the back of 20 BALB/C mice. When the tumors growth to 1.5 or 2.0 cm in diameter, we divide the mice into Photofrin injected group and ATX-S10 injected group. Laser equipment for excitation light was Nd: YAG-OPO tunable laser. We chose a wavelength 630 nm to excite Photofrin and 670 nm for ATX-S10. The energy density was constant at 50 joules for cm2. We ecaluate the effect of PDT to measure the depth of the tumor necrosis.
The result of this study shows that ATX-S10 had a deeper effect (more than 5 mm deeper) by PDT than Photofrin.

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The optical parametric oscillator(OPO), which employed a BBO crystal as a nonlinear optical frequency conversion medium pumped at 355nm, could be tuned in the wavelengths from 400 to 2550nm continuously by rotating the crystal. The output energy was obtained to be more than 6mJ from 620 to 680nm, and approximately 1mJ at 405nm. We investigated the combination effectivity of photosensitizers and radiation wavelengths in the PDT researches. After two photosensitizers of Pheophorbide a(Phd) and Photosan-3(Ph-3, hematoporphyrin-derivative) were injected to Wister rat livers respectively, the output beams from the OPO at 670nm and 630nm with the energy of 25, 50, and 100J/cm2 were irradiated to the liver tissues. The liver under the combination of Phd and 670nm was observed to be necrosed more deeply than the combination of Ph-3 and 630nm. In another experiment, the combined cytodamage-effect of CPT-11 and light against HeLa cells was examined by radiation of wavelengths from 355nm to 680nm in vitro. Remarkable combined effect in the radiation at 540nm was observed. The PDT and CPT-11 combined therapy used by HeLa cell tumors in BALB/c nude mice was remarkably effective in vivo. The result was expected to demonstrate Yoshida's MAT theory(1985).

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We have developed new high power red(664nm) laser diode and its system. This system has a wavelength of 664nm and a power output of 600mW(CW) to tissue. Its features are listed as follows;
1) Small, lightweight and portable.
·The size is 490 (W)×200 (H)×400 (D)mm and the weight is 20kg.
2) Easy to operate and reliable.
·Needs only 100VAC·3A power supply.
·The laser power is easily controled.
·The wavelength is stable (less than 1120.2nm).
·Coupled to quartz fiber for delivery of light.
3) Narrow FWHM (full width at half maximum).
·The full width at half maximum is less than 2nm.
4) Free of maintenance.
We beleive that this laser diode system and the support from medical specialists will contribute to the spread of photodynamic therapy.

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We studied the effectiveness of the Q-switched ruby laser (QRL), RD-1200 (694nm, 20ns), Spectrum Corporation, by treating 86 cases of nevus Ota.
The results of the total 86 cass were excellent in 10 cases(12%), good in 64 cases (74%), fair in 5 cases(6%), poor in 7 cases(8%). Satisfactory results (excellent or good) were achieved in 86% of total cases. Those treated once or twice showed the less satisfactory results as fair and poor, while those treated more than three times showed the satisfactory results. No side effects, such as scar formation, abnormal hyper or hypopigmentation, was noted on any case.
Histological changes caused by laser irradiation were limited to that of melanosomes and melanin containing cells, other tissue being kept normal. In Practical irradiations no special skill was required, the post-operative treatment being simple. From these findings, it appeared that the QRL was highly effective and safe in the treatment of nevus Ota and repeated multiple treatments to the same site at regular intervals could attain high efficacy.

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A short pulse duration ruby laser with pulse duration of 200-400 microsec, was applied for treatment of nevus spilus. Nine out of twenty three cases of nevus spilus (40%) were effective after one or several shot. Six cases (26%) were not effective after one shot and 8 cases (35%) were not effective even after several shots,although the exanthema became lighter before irradiation. Histlogically the epidermal basal cells were damaged and “craster-like degeneration” was also observed in the incontinent areas in the upper dermis.

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Since early 1980's, an excellent effect of the dye laser treatment for portwine stain and other superficial hemangiomatous lesions has been aware of and, nowadays, it has been a main method for the treatment for these lesions.
We have had a chance to use the Japan Laser Systems' model KDL-102 dye laser system for the treatment of thirty cases of portwine stain and other lesions. These were twenty eight cases of portwine stain. Thirteen cases of them were superficial located type and fifteen cases of them were fully located type. The other two cases were telangiectasia and angiokeratoma.
Evaluation was made at the time of two or three months after one dye laser treatment and based on the degree of blanching and scar formation as side effect of the treatment. The degree of blanching was divided into three steps: Excellent means remarkable blanching: Good means still existing reddish coloring of the skin; and Poor means almost no change in the portwine stain.
The evaluation of blanching was that one superficially located portwine stain resulted in Excellent, twenty six cases of which ten cases of superficially located portwine stain, fourteen cases of fully located portwine stain, telangiectasia and angiokeratoma., resulted in Good, three cases of which two cases of superficially located portwine stain and one case of fully located portwine stain resulted in Poor. Post operative scar formation as side effect occurred in two cases, telangiectasia and fully located portwine stain, but both were not serious.
This result was almost as same as the result of another system that has been used in our unit now.

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Dye laser irradiation therapy is gradually being recognized as an effective treatment for portwine stain nevus (PWS) because of its selective destruction of abnormal vessels in the nevus. The laser therapy is, however, not always effective, leaving the results unsatisfactory, which is suggesting that something special be added to plain (conventional) dye laser therapy. Having carried out therapeutical studies of 60 patients with PWS, 138 lesions, the authors discuss the results of their methods with dye laser including“marginal compression method”(MC) and“subcutaneous dissecting method”(SD), which are newly devised curative means. Principles of the procedure of MC are compression with a ring-like device at the lesional margin and dye laser irradiation during the compression. The effective rate of the conventional laser was remarkably affected by the histopathological types (superficial type: 75%, diffuse type: 20%) and the lesional sites (neck: 65%, face: 53%, trunk, limbs: less than 20-30%). The difference in the effectiveness between the histological types is due to the limitations of the photological character of the laser beam and its external approach on the skin surface; the deeper the lesional vessels located, the less sensitive are they to the laser. The difference in the effectiveness among the lesional sites is due to that in skin thickness, epidermal melanin contents, etc. In multiple application of dye laser, the conversion rate of ineffective into effective was significantly made up by MC method, which was recognized to make the lesional vessels much more dilated, leading them to be more sensitive to the laser (conventional laser : 29%, MC method: 42%). SD method also impressed its effectiveness in suppressing the recurrence of PWS.

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Dye laser therapy is appeared to be the first choice for the treatment of port wine stain. However it is safe to say that many patients with port wine stain are used to recieved several times of this therapy until they were satisfied with their results. On the other hand, the effect of dye laser therapy on the leasions of extremities is not reliable yet. This paper would report about a new approach to improve those results following the dye laser therapy.
What we name the negative pressure method is that a laser ray is shot at the spot which is conditioned with the negative pressure (300 torr under the atmosphere pressure). The status of dye laser rays are as follows: 1. Wavelength is 575nm. 2.Pulse duration is 300msec. 3.Laser ray energy is 6.0J/cm2 4. Spot size is 5mm in diameter.
Our new method provided appearently better results in comparison with those of conventional method. Those will be reported in detail and also their histological findings will be discussed.

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We have developed a new laser flowmeter, which can measure and visualize blood flows of a skin in non contact. Present instrument comprises a laser diode, scanner mirrors and photo-diode. The output signal from the Photo-diode is analyzed by a personal computer and a map of blood flows is visualized in a display of the computer. The method of calculate blood flows in the instrument is similar in to the commercial laser flowmeter's. So the instrument can evaluate the blood flows quantitatively.
Skin blood flows in the test of allergic and irritant reaction were measured by present instrument. Change in blood flows after 24 hours from application correlated with visual scores, but erythema was different from the increased of blood flow itself.

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Optimization of therapeutic conditions of a pulsed laser for pigmented lesions is discussed herein from the standpoint of the fundamental interactions of laser light with pigmented cells. Among the important mechanisms leading to cell damage is thermal in nature. This laser therapy is a process for damaging pigmented lesions in tissue by absorption of pulsed laser light. First, the wavelength must be selected in considering preferential absorption in target cells, which relate closely to the penetration depth of laser light and effectiveness for removing pigmented cells. The second thing we consider is thermal confinement. The pulse duration must be shorter than the time for thermal relaxation of the pigmented cells, and the energy delivered must be sufficient to cause irreversible thermal damage. The thermal damage is associated with the denaturation of proteins and the inactivation of enzymes. Accordingly, we consider that the models must include not only the solution of the heat conduction equation but also the Arrhenius equation for the inactivation process. Energy absorption and heat transfer processes occuring during the interaction of laser light pulses with pigmented lesions in tissues is investigated theoretically. As a result, the relation between the target size and the thermal relaxation time is formulated. Ideal therapy is defined as minimal heating of the epidermis and dermis, but with irreversible damage to the pigmented cells. By applying the Arrhenius equation for the inactivation process, we obtain the variation of the temperature rise as a function of the time required to give the same survival ratio. The possibility for selective interaction between short laser light pulses and pigmented cells is shown, resulting in the formation of thermo-denaturation of microregions near the pigmented granules.

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Pulse ruby laser is presently used in the treatment of superficial pigmented lesions such as nevus spilus and senile lentigo. However, irradiation of a laser beam with the appropriate output density is required for such treatment. It is difficult to accurately measure the laser output under the treatment. Futhermore, it is much more difficult to measure the laser output density, because the measurement of irradiation area is involved in the measurement of output density. In the treatment of nevus, the laser beam providing uniform intensity output distribution of approximately 20 Joules/ is used. However, it is also difficult to simply measure this output density. In order to solve these problems, we have devised the method to determine the laser output density from the degree of discoloration caused by irradiation of the laser beam onto the color paper with a fixed reflectivity. We measured the reflectivity of many color papers by a photospectrometer, arranged them in order of reflectivity with wavelength of 694nm, and irradiated a ruby laser beam onto them. As a result, we confirmed that the laser output density could be determined by the degree of discoloration of these color papers. Now, we are effectively using this paper for checking the output density before operating equipment in practical use.

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The blood velocity pattern near the cranial wall at the renal ostia, where atherosclerotic lesions are prone to develop, are characterized by 1) slow time-averaged shear rate, 2) separation of the flow, and 3) a time-varying oscillation of the flow (Arterioscler Thromb 1992; 12: 626-632). To elucidate the relation between the velocity pattern and localization of development of atherosclerosis, we analyzed the fine structure and function of the vascular wall by using laser scanning confocal microscope. In a Wistar rat the renal artery was perfusion fixed at a pressure of 75 mmHg. F-actin and DNA in nuclei were stained with rhodamine phalloidin and bisBenzimide, respectively. Low density lipoprotein (LDL) scavenger transport was investigated by injection of DiI-Ac-LDL before sacrificed. At the cranial wall, where atherosclerotic lesions as prone to develop, the shapes of endothelial cells and nuclei were relatively round, comparing to the caudal wall or the distal portion of renal artery, where atherosclerotic lesions hardly develop. The orientation of nuclei and stress fibers at the cranial wall was relatively random. With ten minutes incubation, Ac-LDL were observed in the endothelial cell and smooth muscle cell with higher density in the former. The density of Ac-LDL in vascular media at the cranial wall was much higher than that the caudal wall. In conclusion, the velocity pattern localizes the development of atherosclerosis via the change in the endothelial cell structure and Ac-LDL transport within the vascular wall.

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A new laser flowgraphy system is developed to visualize in real time the blood flow map in capillary network. A newly designed hardware logic is used to calculate the blur rate (BR) distribution in the image speckle field. The data analysis with a new system is 50 times as fast as the old system using a software. Some results of the real time measurement of blood flow are demonstrated.

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Real-time measurement of blood flow in retina is achieved by developing a hardware-logic board for the Laser Flowgraphy system. The retina is illuminated by a diode laser through a fundus camera and the spot is imaged onto the area sensor. The speckle field is scanned for certain numbers of time, and the blur rate of the speckles is calculated by the logic board. The maps of blood flow are obtained in every 120 msec and are displayed successively in the color CRT screen of a personal computer. The time varying blood flow in arterioles, as well as in veinules is clearly observed; which is synchronized to the heart pulse

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This study was designed to investigate a combination treatment of Diode laser (wavelength: 808nm) with Indocyanine green (ICG), as an photoenhancement dye. Three different concentrations of ICG (0.5, 3.0, 10.0mg/ml) and three different staining periods (20sec, 1min, 5min) were applied to stain the fresh human aorta after endarterectomy to find out an optimal condition. Spectrophotometric and histological examinations revealed that the optimal parameter for tissue staining was 3.0mg/ml of ICG concentration and five minutes of staining period at 37°C.
Diode laser was applied for the previously stained and the non-stained aortic media in four different laser energy (4.7, 9.3, 18.6 and 27.9w/cm2) for five seconds. Thermal camera showed a real-time change of surface temperature. The peak temperature for the stained specimen at 27.9w/cm2 was 219±15°C, and the peak temperature for the non-stained one was 26±1°C at the same energy. In conclusion, the combination treatment of Diode laser with Indocyanine green participates to absorb and localize laser energy, that is, minimizing thermal injury.

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Recently, a surgical procedure has been employed for treatment of ventricular tachycardia, that paroxysmal supraventricular tachycardia due to atrio-ventricular (A-V) nodal reentry is refractry to medical therapy. We have studied for inducing the complete A-V block with application of Argon-laser and Nd-YAG laser without extracorporeal circulation.[Methods]Twenty mongorel dogs were used in this study. Under general anesthesia, the laser-probe was guided to the A-V node from their right auricule, with monitoring electrogram of His bundle. Laser power was set up from 6W to 10W, and the time of ablation between 3 and 5 secs. Therafter, the laser-ablation was initiated, and its hemodinamics were observed and recorded.[Results]The complete A-V block was produced in all dogs. Total laser energy for inducing of the complete A-V block by Nd-YAG-laser was in average of 68.2 J. And, in case of Argon-laser it was 224 J in average. In this study it could be recognized that, Nd-YAG-laser reached more deeper region of myocardium than that of Argon-laser. The histological findings at the site of the endocardium induced by laser ablation showed the coaglation necrosis with vacuolization, and the borderline between the coagulation necrosis and the native myocardium was completely demarcated.
[Conclusions]1) The complete A-V block could be easily achieved by laser ablation without extracorporeal circulation. 2) Nd-YAG-laser was more effect to induce the complete A-V block than Argon-laser.

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The chronic response of novel hot balloon catheter using laser energy as a heating source was evaluated in vivo animal experiment. Our laser hot balloon catheter was characterized by short-period heating with sufficient temperature uniformity throughout the balloon. The temperature rize and fall times were 2-3s. The laser energy was converted to heat in the metal mesh tube, then transfer to contrast medium. The heated contrast medium was irrigated in the balloon.
The severe stenosis model had been made by Chitin tube insertion at femoral arteries of mongorel dogs. Conventional balloon angioplasty and hot balloon angioplasty were applied to the model stenosis in sequence. The balloon temperature, duration, and pressure were 60-80 deg., 15s, and 3 atoms, respectively. The lumen diameters of pre- and post- of each precedures were measured by angiography. We also measured the lumen diameter after 2 month from the precedures. The restenosis in chronic phase was not found in 5 cases of procedure success. We think short duration heating may restrict temperature elevation within the vascular wall, so that good chronic response might be given. This idea was confirmed by heat conduction calculation.

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A new catheter combined with endoscope and intravascular ultrasound (CVIS) was developed for laser mitral valve commissurotomy. The catheter also had the lumen for laser fiber and the mitral guide wire for toucing the laser tip to the commissure. In the animal experiment, after the left thoracotomy, the catheter was inserted from the left atrium. Scanning the leaflet of the mitral valve with the CVIS, the laser tip was guided to the commissure. After reaching the commissure, the position of the laser tip was confirmed by both endoscope and CVIS. At this point, the laser ablation to the commissure was performed under the observation of the endoscope. The pathological finding showed that the commissure was correctly ablated and there were no thermal damage to the commissure and coronary artery and veins. In conclusion, this newly developed catheter considered to have a remarkable ability to make the stenotic valve area wider safely and correctly.

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The primary aim of this research study was to dertermine the wound healing process in femoral arteries of rabbits dissected with LBD in compared to the heat conduction and ligation threads. At the cut end of vessels using LBD, both vessel wall were conjuncted and welded. The wound healing process after LBD dissection was characterized by welding of internal elastic laminas without fragmentation and proliferation of smooth muscle cells in the medial layer.
After dissection of vessels by heat conduction, severe thermal coaglative changes, necrosis, and vacuoles which results partial rupture of media after few days and the retarded healing, were present in the medial layer at the cut end. No smooth muscle proliferation was observed. Ligation thread resulted in the foreign body reaction at the cut end of vessels.

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Recently, clinical study on percutaneous translumial laser coronary angioplasty (PTLCA) has been started and cases of vascular perforation were seen among the reports pointing out necessities of detailed preoperative diagnosis of arteriosclerosis and monitoring of intraoperative state of ablation. we applied a newly developed coronary endoscopic fluorescence spectrum analyser (exciting light: mercury-xenon lamp filtered light 405nm wavelength) to clinical uses and examined its usefulness together with the result obtained in the heart of a dead body.
First of all, as a basic study, we analyzed spectra using non-arteriosclerotic and arteriosclerotic rabbits. after excision of the aorta out of the respective rabbits, autofluorescence spectrum was determined in the arteriosclerotic and normal regions using a fluorescence spectrum analyser. then, the same arterial specimens were incubated in a doxycyclin solution for 15 minutes and fluorescence spectrum was measured again from the same regions. Thereafter, the regions where spectrum was measured were examined histologically. Next, 30 sites in the coronary artery of a dead body were classified into normal regions, white atheroma and yellow atheroma and autofluorescence was determined, respectively. Further, these specimens were processed with doxycycline similarly as in the case of rabbits and fluorescence was measured again for histological examination. In 30 cases of ischemic heart diseases with 90% or more coronary stenosis, coronary endoscopy was performed according to the double guiding catheter method and analyzed the spectrum in the observation sites. In 10 cases out of these, 200mg doxycycline were administered after observation by coronary endoscopy and similar measurements were made. In the result, autofluorescence of 540nm peak was obtained in the tunica media in the healthy regions of the rabbits and coronary artery of a dead body while the height of this wave was reduced in the arteriosclerotic regions. After doxycycline processing, the spectrum peak shifted from 540 to 560nm and augumented in the arteriosclerotic regions. In clinical applications, a flurorescence spectrum was clearly measurable in coronary arteriosclerotic lesions. In the cases given doxycycline, a unique spectrum with its peak at 560nm was observed in the arteriosclerotic lesion.In the present study, it was confirmed clinically that doxycyclin flurorescence was measurable as a photosensitizer. When this method is employed as an intraoperative monitoring during PTLCA, the doxycyclin peak height is considered to indicate the depth of ablation and is expected to serve as a meansto prevent vascular perforation.

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In rabbits, the abdominal aorta was subjected to balloon abrasion injury and atherosclerosis was produced by feeding with a high-cholesterol diet. The vessel wall reaction was studied just after, 3 days after, and 1, 2, and 4 weeks after injury. Rabbits in each group were injected intravenously with 5mg/kg of a hematoporphorin derivative (HpD) and were sacrificed after 24 hours. The tissues were studied by light and fluorescence microscopy. In addition, the effect of photodynamic therapy (PDT) was evaluated 1 hour, 3 days, and 1 and 2 weeks after balloon injury. PDT was performed after HpD injection and the animals were sacrificed 2 weeks later for histological examination. Migration of smooth muscle cells at the site of vascular injury was revealed by the accumulation of HpD. It started in the media about 3 days after balloon injury and reached a peak after 1 week. After 2-3 weeks, smooth muscle cell proliferation shifted from the media to the intima, and the media returned to normal after 3-4 weeks. When PDT was done 3 days or 1 and 2 weeks after balloon injury, it had a significant inhibitory effect on intimal smooth muscle hyperplasia. PDT at 1 week had the strongest inhibitory effect on smooth muscle proliferation, but PDT at 2 weeks caused the least medial necrosis.

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The authors have evaluated the possibility of tetracycline derivatives-doxycycline (DC), minocycline (MINO), oxytetracycline (OTC), rolitetracycline phosphate (NPRMTC), and rolitetracycline (PRMTC) as the photosensitizer for PDT. Exicitation source used is third harmonic beam (355nm) of a Nd; YAG laser. The evaluation of intensity ratio indicated that DC had the best selectivity for the atheromatous plaque.
In order to define the acceptable laser power for PDT, we examined previously the acute efect of laser irradiation to resected plaques that induced rabitts' abdominal aorta treated with or without those photosensitizer. The laser was radiated in the power of 0.5, 1, 2, 3, or 6W/cm2, and the effects was evaluated as “vapolization time”. Based on this result, we decided to try the PDT to the rabbits models with degree of the power without acute effect. In result, the effect of PDT at two month follow up indicated DC was the most effective photosensitizer for PDT. Atheromatous plaque was disappeared without acute damage. DC was thought to be one of the useful drug as the photosensitizer for PDT of atherosclerosis.

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(Introduction) Recently considerable attention is focused on the diagnosis of atheromatous lesion using laser induced fluorescense spectra. But stronger the laser power is, more quickly the intensity of fluorescense spectra falls down (bleaching phenomenon). So we examined the relationship between the intensity of laser power and the pattern of fluorescense spectra in this study. (Methods) The fluorescense spectra was obtained from the normal intima of postmortem aorta using helium-cadmium laser (wave length; 325nm). The intensity of laser power, 9mW, 4.5mW, 1.8mW, 0.5mW, and 0.1mW were used. Constant irradiation was made and the fluorescense spectra was measured at 280msec interval. From the selected spectra, peak intensities of wave length at 390nm (I³⁹⁰) and 450nm (I⁴⁵⁰) were measured, and its ratio, I³⁹⁰/I⁴⁵⁰ (plaque index: PI), was devised. (Results) The fluorescense spectra was not recorded at laser power 0.1mW. The intensity of fluorescense spectra fell down with time, and the ratio of fluorescence intensity decrease was bigger as the laser power increased. The values of PI were almost constant through recording at each intensity power. As the laser power was bigger, the coefficient of variation (CV) was smaller. CV were 11%, 8%, 4.8%, and 4.1% at laser power 0.5mW, 1.8mW, 4.5mW, and 9mW, respectively. (Conclusion) At the strong excitation laser output, quick fall of fluorescense spectra occured. The diagnosis of atheromatous lesion, using the fluorescence intensity at one wave length seemed to be quite difficult, but the rario of two peak fluorescence intensities is a feasible index because of its less fluctuation.

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We perfomed photorefractive keratectomy (PRK) since August 1990, with the use of 193nm excimer laser. The total number of the cases treated was 181 eyes of 105 patients. As the results, the predictability of low and moderate myopia was excel lent. And no significant changes could be seen in either corneal endothelium or epithelium to show that PRK is very safe procedure. But it is necessary to solve the ploblems of corneal haze and centration of irradiation.

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We report the clinical experience of middle ear surgery by the use of the KTP laser at the department of otolaryngology, Kobe City General Hospital. This laser gives new and broader applications to middle ear surgery which needs delicate operative manipulation (1. stapedotomy; 2. removal of affected tissues involving the ossicles, especially the stapes; 3. complete removal of cholesteatoma; 4. removal of affected tissues in the middle ear cavity; 5.tumor vaporization). No side effects were observed in 28 ears operated with this laser. The characteristics of this laser suitable for middle ear sugery are as follows. 1. This laser is excellently absorbed by damaged middle ear tissue with rich hemoglobin. 2. The aiming beam and the surgical beam are the same, providing superior target accuracy. 3. The small hand piece with the fine optical fiber makes easier delicate operative manipulation under the operative microscope. 4. The operator does not need to wear the special glasses, because his eyes are protected through the microscope with an automatic eye safety filter during operation.

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Two cases of severe bullous emphysema were treated by thoracoscopic lung surface coagulation with Nd: YAG laser. In case 1, a 68-year-old man was admitted to our hospital with 3-year history of shortness of breath on exertion. A CT scan revealed a large bulla of the right upper lobe and diffuse bullous emphysema of the both lobes. The large bulla was resected by liner stapler, and the other right lung surface was coagulated and shrunken by contact Nd: YAG laser (8-10W). In case 2, a 76-year-old man was admitted to our hospital with shortness of breath on exertion after preveous five times spontaneous pneumothorax. A CT scan revealed diffuse bullous emphysema of the both lobes. The right lung surface was coagulated and shrunken in the same manner as case 1. Air leakage persisted for 13 postoperative days in case 1 and for 10 postoperative days in case 2, but the postoperative course were uneventful in both cases. At 1 to 3 months postoperatively there was increase in forced expiratory volume in 1 second% (from 33.3% to 41.7% in case 1, from 32.2% to 46.6% in case 2), decrease in%residual volume (from 172.8% to 140% in case 1, from 162% to 149% in case 2), and the dyspneic symptoms were improved in both cases. Thoracoscopic lung surface coagulation with Nd: YAG laser is a possibility of an effective treatment of bullous emphysema.

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From March 1981 to June 1993, 5 cases of benign tracheobronchial neoplasms were treated with endoscopic Nd-YAG Laser therapy. The patients ranged in age from 17 to 60 years with an average of 36.7 years old and included 3 males and 2 females. Histologic type consisted of two leiomyomas, one papilloma, one schwannoma, and one granular cell tumor. Papilloma was located in the trachea. Leiomyomas were located in the left main stem bronchus and the right B3b. Schwannoma was located in the right upper bronchus. Granular cell tumor was located in the right lower bronchus. Papilloma was nodular type tumor and other tumors were polypoid type tumors.
Bronchofiberscopic polypectomy was performed before irradiation in the polypoid type tumors. We used power setting ranging from 30 to 40 W with pulse duration of 1s. Total joules ranged from 1222 to 5502 J (mean joules 2955. 6J).
In all cases, we treated the tumors safely by endoscopic surgery and the tumors were disappeared completely. There were no recurrence during the follow up intervals from 6 months to 77 months with an average of 30.8 months after the first endoscopic Nd: YAG Laser surgery. In polypoid type tumors, polypectomy was useful for the reduction of treatment time and joules. Endoscopic Nd: YAG Laser therapys considered to be a modality of curative treatment for the benign tracheobronchial neoplasms growing exclusively endoluminally or intraluminally within cartilageneous rings.

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Endscopic Nd: YAG laser therapy is useful for the treatment of tracheobronchial stenosis. However, in case of restenosis of airway caused by a regrowth of tumor or granulation, and a fragility in respiratory tract with destroyed cartilagious rings, insertion of stent tube is frequently required. We treated six patients by using Dumon tube or T tube in comination with Nd: YAG laser therapy, in four cases with stenosis of trachea or main bronchus due to malignant disease, consisting of advanced lung carcinomas, tracheal carcinoma, and esophagus carcinoma invading to trachea, and in two cases with extensive post-tracheostomy stenosis. In all cases, symptoms of airway stenosis and pulumonary function were improved remarkably after the procedure, especially in two cases of post-tracheostomy stenosis indwelled Dumon tube or T tube were achieved a good quality of life for long term, and experienced no complications secondary to the stent placement. Although, in four cases of advanced malignant disease, three cases were died within two months after insertion of stent tube, except for one case of lung cancer eighteen months alive, a remarkable improvement of stenosis in respirstory tract was temporally obtained. Dumon tube and T tube were useful in alleviating symptoms of tracheobronchial stenosis, and effective for compressive stenosis of trachea and bronchus caused by tumor.

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Me report a case of YAG Laser vaporization for residual endometrial ovarian cyst which had been treated by LH-RHa for 10 month.
The case was 37-years-old, P (1) G (1). She consulted our hospital because of severe algomenorrhea. By pelvic examination severe tenderness of Douglas pouch and left ovarian cyst was found out and bilateral ovarian cysts were revealed by CT, echo image. Serum level of CA-125 was 56U/ML, CA19-9 was 43U/ML. She had been treated by LH-RHa for 10 month on the diagnosis of bilateral ovarian chocolate cysts and pelvic endometriosis.
The size of ovarian cysts was redused and her complains of algomenorrhea was softened. But 4 month later algomenorrhea and tenderness of duoglas pouch recurred. After, successing of treatment by LH-RHa for 4 month laparoscopy was done.
By findings of pelvic cavity, left ovary was enlarged as over hens egg sized and adhered to douglas pouch. This adhesion was convinced as the cause of recurred algomenorrhea. After punctation of the surfase of the left ovary and absorption of the chocolate contents, latex balloon named. VP-16 was inserted and swelled by 15ml saline solution and was oppressed to the ovarian surface. YAG laser was irradiated through the balloon by output power of 10 watts for 5 minutes. The inner surface was degenerated evenly. Me incised a part of it and confirmed degeneration by microscopy. During all these procedure there was no apparent side effects.
After this procedure algomenorrhea was diminished and ovarian enlargement has not been observed.

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Seventy patients who underwent endoscopic Nd: YAG laser therapy for palliation of esophageal and cardiac cancer were evaluated in detail to define clinical characteristics suitable for laser therapy. In the 70 patients, 20 were esophageal cancer and 50 were cardiac cancer.
In cardiac cancer, 78.0%(39/50) showed the technical success, 78.0%(39/50) showed the functional success, and 59.2%(29/49) showed the complete functional success (discharge period of more than one month from the hospital). In esophageal cancer, on the other hand, the rates of the technical success, the functional success and the complete functional success were 55.0%(11/22),, 55.0%(11/22) and 40.0%(8/20), respectively.
The contact method was more effective than noncontact method, and the mean number of treatments required to alleviate symptoms and remove obstruction was 4.6 (range: 1-16). As to the patient's characteristics, good adaptability to laser therapy was noted for advanced age (more than 75 years), a performance status of grade 2 and under, and well differentiated adenocarcinomas (pap, tub1). Esophagial cancer with a length of 5 cm and under were well adapted to laser therapy. Limit or inadaptability to laser therapy was noted for a performance status of grade 3 and over, and an appearance of peritonitis cartinomatosa. Esophageal tumors located in the cervical region, those with a length of 8 cm and over, those with pulmonary metastasis, and those of re-stenosis after radio-therapy were limits to laser therapy.

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The clinical course and problem in laser treatment for inoperable case with early gastric cancer were studied. The reason why they were considered to be inoperable were severe heart failure (4cases), severe renal failure (4cases), liver cirrhosis with easy bleeding (3cases), case more than 85 years old (2cases), and pthers (3cases). Six cases had early gastric cancer with absolute indication for endoscopic therapy, that is IIa type and IIc type without ulcer less than 2 cm in size of differentiated adenocarcinoma. Nine cases had early gastric cancer with relative indication. Follow-up study by endoscopic biopsy for more than 6 months was performed in 12 cases out of 15 cases and showed recurrense or remnant in 2 cases. One was absolute indicative case and the other was relative indicative caseit seems that laser therapy is effective for relative indicative cases with early gastric cancer.

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To clarify the mechanism of signal transmission in nerve systems is one of the most important problems in both medicine and physiology. Until now, many studies and analyses have been done by means of electric circuit theory and cable theory, but the systematic electromagnetic characteristics are not clearly known. In synaptic transmission, electromagnetic and chemical phenomena are closely connected, but their relationship has not been completely explained. In this study, the electromagnetic characteristics of synaptic transmission are analyzed. Every phenomenon that has been explained separately, namely, the propagation of an action potential, the discharge of synaptic transmitter, the reaction of a receptor to transmitter, etc., are connected theoretically so that the characteristics of the spatiotemporal distribution of electric field and ion current are systematically clarified. A 3-dimensional model of single synapse having half-spherical synaptic knob and flat, parallel pre-and postsynaptic membranes is presented. The electric field is separated into three types-intracellular, extracellular and membrane field, and boundary conditions are regarded on the boundary area between which the material constants differ discontinuously. The analysis starts from the Maxwell's equations, to derive the expressions of the Hodgkin-Huxley's equations in vector field instead of scalar field. The cable equations in vector field are also derived from them, and they are connected to expresses the relationship between transmembrane current and propagation-directional current.

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An extremely weak light emission originating from the cells, tissues and organs of all living organisms is generally referred to as“biophoton emission”. This phenomenon is different from the well known bioluminescence, that is visible light emission from firefly and luminescent bacteria for example. Our earlier studies on biophoton emission from human body surface showed that the emission intensity is stronger in the index and middle fingers than the middle of the palm.
In the present study, we report the results of measurement of ultraweak biophoton emission from human body surface, especially at the acupuncture points on fingers.

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One of the most popular optical mode for monitoring membrane potential is fluorescence. In linear spectroscopic approach the fluorescence intensity is monitored as function of membrane potential. The purpose of this research is to develop a micro optical probe system for measuring membrane potential, in which fluorescent dye is used. This system has high spatial resolution for monitoring interaction between cells and is available for the analysis of functions and structures of the ion-channel. We measured the beamwaist of incident laser light, spectral properties of voltage-sensitive dye: NK2612 and temporal change of fluorescence intensity from cardiac cells stained with NK2612. The beamwaist of incident laser light is 1.5μm, the absorption maximum is 767nm and the fluorescent maximum is 843nm. Furthermore, we optimized the concentration of the voltage-sensitive dye: NK2612, confirmed fluorescence intensity is maximum when the concentration of the dye is 12.5μg/ml. Therefore, in our measurement the cardiac cells are stained with NK2612 solution of 12.5μg/ml. We observed the dependence of fluorescence intensity on the membrane potential and showed micro optical probe system is available for measuring membrane potential by fluorescence.

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This paper investigates an optical method which measures cytoplasmic membrane action potential and intercellular free calcium ion density at the same time and point. The measurement (simultaneous fluorescence measurement) is brought to realization with two kind of fluorescent dyes. The multi-dyeing of voltage-sensitive dye and fluorescent calcium indicator is considered, and spectrum characteristic of these dyes is examined.
The experiment is gone as follows. First, absorption spectrum of Rhod2 and Fluo3, which fluorescent calcium indicator can be pumped by visible light, is measured. These solutions are composed of distilled water, 5[μM] dye, and 50[mM] CaCl2. The result suggests that Rhod2 and Fluo3 can be pumped with Ar or Kr laser and Ar laser for high efficiency respectively. Second, Fluorescence spectrum of Rhod2 an.d Fluo3 is measured. Absorption spectrum and fluorescence spectrum of WW781, which voltage-sensitive dye can be pumped, is measured too. Rhod2 solution and Fluo3 solution are prepared as has been pointed out. WW781 solution is made up of ethanol and 0.025[mg/ml] WW781. These spectrums show that simultaneous fluorescence measurement of cytoplasmic membrane action potential and intercellular free calcium density with WW781 and Fluo3 is possible.

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The interaction of UV laser light with hard tissue has been investigated. Cow thighbone and teeth enamel were irradiated by excimer lasers; ArF (193nm) and KrF (248nm). Electron Probe Micro Analysis (EPMA) was used to know the ratio of Ca atoms and P atoms (Ca/P) on the irradiated surface.
In the case of cow thighbone, Ca/P ratio increased by ArF laser irradiation of low intensity comparing with that of the control. On the other hand, for KrF laser irradiation, the ratio slightly increased only at high intensity.
In the case of teeth enamel, the ratio is enhanced by KrF laser irradiation and no change was observed by ArF laser irradiation.
These results can be explained by the relation between bond strength of Ca-O and P-O and photon energy and the type of photon absorption.

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We have developed the fiber-optic probe method to monitor the ablation bubble which is generated at the fiber tip during Ho: YAG laser (λ=2.1μm) ablation. We performed comparative measurements by means of time-resolved photography and this probe method. The backscattered probe light, that was the probe method signal, which was simultaneously delivered together with Ho: YAG laser was measured at the incident end of the fiber. The ablation bubble volume at the end of laser output was about 10mm3 at 240J/cm2 in water by the time-resolved photography, but it didn't obey a liner relation to the backscatterd light intensity. The results from the water irradiation experiments explained that the probe method signal indicated the ablation bubble behavior because the observed signal was consisits of boundary reflection between bubble and water and debris scattering in the bubble. In the case of the agar experiments at 240J/cm2 in fluence, photographies and measured waveform corresponded to a ablation bubble behavior.. At 500J/cm2 in fluence, the cavitation which induced tissue dissection could be observed by photographies after ablation bubble collapse. The decay of meaured waveform was longer, which was influenced by the cavitation.We confirmed the possibility of monitoring tissue dissection from mesured waveform by the fiber-optic probe method.

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Ho: YAG laser has tissue cutting capability through silica glass fiber, so that it may become to be useful laser in gastroenterological therapy. We experimentally studied ablation characteristics of Ho: YAG laser. We used extracted fresh porcine gastric wall as a sample. Ho: YAG laser was deliverd by 400um i. d. silica glass fiber. The irradiation were performed by the contact method with 200 to 500J/cm2in fluences. One or two shots of Ho: YAG could ablation whole mucosal layer. At 200J/cm2 in fluence, the ablation hole was limited at mucosal muscular layer because of strong tensile strength of this layer. In case of 500J/cm2 the ablation hole was easily penetrated throug proper muscle layer.In some case of 500J/cm2 in fluence, a dissection on the submucosal layer was seen due to generation of the ablation bubble in front of the fiber tip. Ho: YAG laser ablation might be available not only for ablation/coagulation, but also atripping of submucosal using laser induced disection.

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We have been deveroping new laser device for orthopedic surgery. Although various kinds of laser have become to utilize to these devices, their reaction to the living tissue has not been clarified yet. The objective of this study is to compare the tissue reaction difference between high output diode laser, Erb: YAG laser, Nd: YAG laser and Electrocautery. Rat gluteal muscle was used for this study. Immediatly after cutting muscle with these instruments, specimens were treated for histological observation with light microscope and Scanning Electron Microscope (SEM). A fiber chip was used for tissue cutting with CW lasers. Four layers of heat influences were observed in very wide range with electrocautery cutting; from surface, char layer, necrotic layer, degeneration layer transient zone and normal layer. These four layers were also recognized on the tissue with CW laser cutting such as diode laser and Nd: YAG laser. On the other hand, the cutting surface by Erb: YAG laser with high peak power and few Hz of pulse rate condition, was very sharp, and almost normal tissue was naked under the microscopic and SEM observation. However, very thin layered heat influence appeared on the surface at the irradiating condition of low peak power and above several Hz of pulse rates.

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It is well known that alumina ceramics (Al₂O₃) is bio-inert material. We try to change this to bio-active material by laser irrdioation.
To improve a bio compatibility of alumina ceramics, it is necessary that there is Ca and P rich layer near surface of alumina ceramics. The alumina which has Ca-deposited layer or thin HAP layer was irraddiated with KrF laser light (248nm).
Depth profiles of Ca and P atoms were measured by Rutherford Backscattering Spectrometry (RBS) and Electron Spectroscopy for Chemical Analysis (ESCA).
The results indicate that Ca and P atoms are implanted into the alumina surface.

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Special probe for dentin hypersensitivity treatment was developed. The effects of the optical fiber carbon dioxide laser irradiation on the dentin hypersensitivity model were discussed with changing irradiation output power, time or irradiation mode.
The laser used is optical fiber carbon dioxide laser unit ZH-5 LM 10. (Matsushita Industrial Equipment.)
Dentinhypersensitivity model was made according to Nakamura's method.
The effects were observed as 2mm spot in diameter by a single irradiation.
The conditions were as follows; flowing quantity 21/min of the cooling gas, output power 3W, irradiation time 60 seconds at 0.01 seconds in the irradiation repetition time, total energy density 54 J/mm2.
As results of this study, irradiation was followed by melting of dentin and, then, sealing dental tubules was observed. However, carbonization, pigmentation or clacking were not noted on the irradiated dentin.

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In order to improve complications associated with conventional methods of neurotomy, a new method was proposed. In this method, nerve fiber is degenerated with a local heat generated by an irradiation of high power infra red light to a nerve fiber through an optical fiber with a needle in which the optical fiber is involved. As a basic study of this new method, tissue reaction with a light generated heat in nerve fiber was investigated pathologically, and the blockage of impulse in nerve fiber was investigated with somato-spinal evoked potential (SSEP) method, by using rabbits. A semiconductor laser with 810nm of wave length and 850mw of maximum power was used as a high power infra red light source. Total or partial thermal degeneration in nerve fiber were observed with all the nerve irradiated with 400-800mW of laser power and 2-10 seconds of irradiation. As the magnitude of degeneration in nerve fiber was higher in thin fiber, so it was considered that the selective blockage of pain would be possible by controlling the irradiate condition of laser. In the experiment of SSEP, the evoked potential was reduced with the procedure of laser irradiation. However, reduced potential was still remain by the irradiation with 400mw of laser power and 30 seconds of irradiation. It was considered that the magnitude of neurotomy could be controllable by controlling the irradiate condition of laser.

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The transmittance and delivery laser energy of KrF and ArF excimer lasers were improved through Hollow Light Guide with aluminum reflector. The hollow light guide uses thin polytetra-fluoroethylene (teflon) slab and polyolefin coat as its material. The size of the guide's hollow part is 8 mm width, 0.5 mm height, with 120 cm maximum length. The transmittance of KrF laser was 68%at 100 cm long. This value was higher than the previous value 50%. The maximum delivery laser energy was raised from 7 mJ to 90 mJ. In the case of ArF laser, transmittance and delivery energy was 50% per meter and 20 mJ, respectively. Their values were also higher than the previous data. The reason why the transmittance and the delivery laser energy were improved are that laser beam changed from non-polarization to linear polarization, the reflectance of aluminum reflector was high so as to devise the polishing technique, and the optimum of the coupling system were made.

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Power delivering of excimer lasers has been studied to a medical application. We adopt the quartz optical fiber for the application of laser scalpel and endoscopy. The transmittance of OH doped optical fiber was measured in excimer lasers. In the high OH doped fiber, transmittance was gradually reduced for increasing the number of laser shots due to the laser induced defect in a core material. On the other hand, transmittance of low OH doped fiber increased gradually, which is due to the extrication of the Oxygen deficient center. The delivering power for one shot base was 1 J/cm2 in KrF excimer laser. Furthermore, the possible approaches to obtain higher transmittance has been considered. Gradual index change of the fiber clad was quite effective for suppressing the induced defect, so that the reasonable transmittance would be obtained. From the experimental results, we have to consider that the coupling optics at the outlet of the optical fiber should be installed for a hard biotissue incision.

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We have developed a laser bone scalpel using an excimer laser. The laser bone scalpel consists of a monitor system which allows surgeons to control the depth of the incision during operation, a flexible manipulator which guides the ultraviolet laser beam, detachable laser handpieces which are fitted to operations in various affected areas, and a laser safety system for the excimer laser. These elements result in a safer, easier-to-use laser scalpel for bone surgery.

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The purpose of this study is to investigate the influence of low-power laser irradiations on the development of mouse embryos in vitro. We examined the percentage of the development up to the blastocyst stage of mouse embryos which were irradiated by various wavelengths and energy densities. The 1-cell mouse embryos superovulated from ICR female mice were cultured in BWW medium of 37°C under 5% CO₂ containing air. The energy densities which applied to the 1-cell mouse embryos were set to 1, 10, 100 and 500 kJ/m2. Each energy density corresponded to 0.05, 0.5, 5 and 20 folding to the actual light dose by microscope light source during in vitro fertilization (IVF). We used three kinds of irradiations of which wavelengths were located in the spectrum of the microscope light source. A red He-Ne laser with 632.8 nm radiation, the green He-Ne laser with 543 nm radiation and blue He-Cd laser with 442 nm radiation were employed for the light source. In case of 632.8 nm radiation with the energy density of 500 kJ/m2, the percentage of blastocyst was markedly suppressed to 3.1% comparing to 25.0% of the control. While the embryos which were irradiated below the energy density of 100 kJ/m2 did not show any inhibitory effect on their developments. In case of 543 nm and 442 nm radiations, no influence were observed in embryo development. These results suggest that light environment might affect on the development of mouse embryos.

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This experiment was designed to approach the bone regeneration effect of lasers from the viewpoint of the optical aspect. METHOD: The extracted leg bones of a pig was applied as the experimental model for a living body. Argon ion laser, HeNe laser and GaAlAs laser of low power level of the output were applied in this experiment. The surface of the bone model was exposed to each laser beam and the sectional aspect of the bone was observed by the CCD video camera during the laser irradiation. In addition to this, these VTR images were processed to the scanning profiles of the laser intensity. RESULTS OBTAINED: Every beam of the 3 kinds of lasers was diffusively transmitted the cortical bone and infiltrated into the bone-marrow effectively. Ar⁺ L. and GaAlAs L. beams were absorbed effectively in a bone-marrow (especially in a reddish bone-marrow) and did not infiltrat into the bone-marrow so deeply. HeNe L., however, was comparativiely infiltrative into the bone-marrow to the Ar⁺ L. and the GaAlAs L.. The laser beams were spattered more in a yellowish bone-marrow than a reddish bone-marrow. The periostium was proved not to intercept the laser beam so much. CONCLUSION: Ar⁺ L. and GaAlAs L. are comparatively absorbed in the surface of a bone. On the contrally HeNe L. is comparatively infiltrates diffusively into the bone-marrow. The results of this experiment fully suggests that Ar⁺ L. or GaAlAs L. may be suitable for a comparatively superficial bone focuses and HeNe L. may be suitable for a deep bone focuses.

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