Unfortunately, at present, it is difficult to name a distinctive use of laser in dentistry, as one could easily do for laser application in medicine. However, an improvement can be foreseen for the near future, since many investigators are conducting research on the applications in dentistry of the same kind of laser as in medicine, but also on distinctive applications of laser in dentistry, as well as on applications that can not be replaced by other methods. This investigation was based on the studies presented at the last four meetings of the Society of Laser in Dentistry and it reviews the applications of laser in the two major diseases of the oral cavity, namely dental caries and periodontal disease, the dental fields in which laser research is carried out, and the type of laser in use at present, as well as expectations for the future of laser in dentistry.

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As the Global levels on medical fields, the two points are expressed that are the medical demands and medical researches.
In the medical demands, in particular, in the developed countries, the mutual connections among health, medical and welfare cares, saving of medical cost, cares for agings, promotion of preventive medicine and home cares and enhancement of QOL of patients should be considered. In the medical researches, the various researches such as on brain, cancer, AIDS, genetic engineering, molecular bio-medicine, and interdisciplinary research between medicine and engineering have to be considered.
The application of lasers in these two fields are discussed in this paper.

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Lasers have contributed enormously to the advancement on evolution of medicine, taking another step in the march towards and improved therapeutic condition. The Argon and frequency-doubled YAG-KTP lasers both produce a green wavelength of light that can be delivered through an optical fiber. Recently some researchers use the Er: YAG laser for clinics. Short pulses from the Er: YAG have an ablative effect with little thermal damage. And also the Er: YAG offers a superior cutting tool when longer pulses are used. The Ho: YAG laser ablation with the contact irradiation method has been employed for laser angioplasty and various other clinical therapies due to the capability of the silica fiber delivery and tissue ablation. The remarkable advances and emerging technologies have been appeared in Research and developments of high-power dioed laser. They have already achieved the maximum output to approximately 60W by diode laser. Some manufactures developed the medical systems based on the tunable laser crystal, titanium-doped sapphire. This medium lasers in the range 850-1000nm. Frequency-conversion techniques, including a proprietary method of extending the range in the infrared, are expected to yield a device that tunes from 325-3000nm. This widely tunable laser may be the basis for a “universal” surgical tool that suits a variety of applications. The Japanese manufacturer (IHI Co.) developed new tunable laser consisting of YAG-OPO (Optical Prametric Oscillator) which could tune from 410-2650nm wavelength.

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Laser surgery in head and neck area was reviewed and the results of laser treatment were presented based on our experience. Laser surgery to allergic rhinitis was performed for 204 cases at our out-patient clinic. The therapy was effective in 91% of cases for nasal obstruction and 87%for nasal symptoms overall.
Seventy-five cases of glottic carcinoma were treated with laser surgery. The 3 year determinate survival rate was 100%, and the voice coservation rate was 91% (52/57) for Ti cases and 78% (14/18) for T2. About 90% of glottic T1 cases was cured by laser surgery alone and laser surgery followed by external radiotherapy for T2 cases improved the voice coservation rate. Seventeen patients with subglottic or tracheal stenosis were treated with laser surgery. Sixteen patients required emergency laser surgery due to severe dyspnea and satisfactory results were achieved in 12, who obtainedan adequate lumen for ventilation. Airway obstructions due to malignant tumor can be effectively reduced. Recently, the flexible endoscope has been used as one of the treatment technique and the concept of flexible endoscopic surgery is being established in the domain of otolaryngology. Flexible endoscopic laser surgery is minimally invasive and the surgery to larynx is very useful, if indications are selected properly. Laser assisted uvulopalatoplasty (LAUP) by KTP laser was performed for simple snoring patients. LAUP was safe, easy, reliable procedure, and could be done on outpatient basis.

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Lasers have contributed enormously to the advancement on evolution of medicine, taking another step in the march towards and improved therapeutic condition. Recently, the remarkable advances and emerging technologies have been appeared in research and developments not only for high-power diode laser. but also solidstate middle-infraredlight laser. Short pulses from the Er: YAG have an ablative effect with little thermal damage. And also the Er: YAG offers a superior cutting tool when longer pulses are used. Moreover, the 2.9μm output radiation can be delivered through optical fiber. The most applicable optical fiber for medical applications is the silica glass fiber. There are two other promising fibers. They are the chalcogenide glass fiber for 5μm band and fluoride glass fiber for 3μm band. The chalcogenide glass fiber has sufficient flexibility with small allowable bending radius despite the fluoride glass fiber has better mechanical properties than the chalcogenide in bulk glass. Furthermore, we shoule know the another important characteristics of tissue interactions to these infrared lasers. Ho: YAG laser ablation with the contact irradiation method has been employed for laser angioplasty and various other clinical therapies clue to the capability of the silica fiber delivery and tissue ablation.
Regard to the diode laser they have already achieved the maximum output to approximately 60W. Also some manufactures developed the medical systems based on the tunable laser crystal, titanium-doped sapphire. This medium lasers in the range 650-1000nm. The frequency-doubled YAG-KTP lasers both produce a green wavelength of light that can be delivered through an optical fiber. This advantage, along with the fact that these beams can be transmitted through fluids, has made them preferable to some surgeons. Frequency-conversion techniques, including a proprietary method of extending the range in the infrared, are expected to yield a device that tunes from 325-3000nm. This widely tunable laser may be the basis for a “universal” surgical tool that suits a variety of applications. The Japanese manufacturer (IHI Co.) developed new tunable laser consisting of YAG-OPO (Optical Prametric Oscillator) which could tune from 410-2650nm wavelength.

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In the urological field laser has been applied to the treatment of various disorders. Here I would like to demonstrate laser technology applicable to the malignancy, BPH and urolithiasis. Nd: YAG laser has been used for the treatment of bladder tumor, ureteral tumor and urethral stenosis. Bladder tumor was treated by Nd: YAG laser without severe complications. Benign prostatic hyperplasia was also treated with Nd: YAG laser using side firing fiber (UltraLine). Most of BPH were resected and coagulated with contact irradiation. Extracorporeal shock wave lithotripsy (ESWL) is the main stay in the treatment of urolithasis. Dye laser is also effective modality for ureteral stone. We attempted the destruction of ureteral stone with either dye laser or alexandrite laser, which proved to be useful and valuable method.

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In clinical cases, it was generally accepted that low level laser (LLL) irradiation is effective for pain relief of subjects with chronic pain. As one of neuronal mechanisms underlying the analgesic effects, a 'gating mechanism' in the spinal cord, which was caused by excitatory effects of LLL on large myelinated fibers, has been proposed. We have demonstrated that the analgesic effects of LLL was due to not only an increase of incoming inputs resulting a 'gating mechanism' within a spinal cord but also a decrease of incoming inputs caused by suppression of a nerve conduction. There has been reported a possibility that the laser beam had different effects upon neuronal membrane. However, it was unable to speculate the reason why the polarity of the effects, excitatory vs inhibitory, was reversed. Though further study will be necessary, there is an equally plausible possibility that LLL method may be developed to a new clinical analgesic method instead of anesthetic drugs.
The healing effect of He-Ne laser on skin ulcer was first reported by Mester et al.. Since then, the biostimulation of LLL has attracted various clinicians. In vivo study, the effect of the LLL on the inflammatory stage of wound healing was investigated using delayed wound healing animal model. Although many clinical studies have tested usefulness of LLL for the wound healing, the mechanism of the effects by LLL has not been fully elucidated. We demonstrated that the LLL enhanced effects to the procollagen product of the fibroblast might be directly occurred at the translational level not at t he pretranslational level of the m RNA synthesis. But, It is still not known what kinds of factors were concerned and how the process of the effect were underwent. Further study is needed.

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We analyzed the results of endoscopic mucosal resection (EMR) for early gastric cancer and of laser irradiation to the residuals after EMR. Between 1986 and April 1997, 248 lesions were performed EMR, in those 154 lesions were classified in a absolute indication group, 94 lesions in a relative indication group. In them 71 lesions were treated by a laser irradiation as a additional therapy after EMR. The curative rate of EMR was over 70% for lesions below 10 mm in size, and less than 50% for the size over 11 mm. The cure rate of EMR was 66.9% (103/154) for an absolute indication group and 39.4% (37/94) for a relative indication group.The cure rate of laser irradiation for the residual tumor after EMR was raised to 95.5% in the absolute indication group (n=44) and 70.4% in the relative indication group (n=27). Combination therapy of EMR and laser irradiation is a useful treatment to avoid a invasive treatment as operation for limited patients.

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For the purpose of diagnosis and treatment of early gastric cancer, we conduct endoscopic mucosal resection (EMR hereinafter) as the first choice of treatment. However, partial resection cases, remaining tumor cases due to the difficulty in complete resection and the cases to which EMR was inapplicable are indicated for laser therapy. We also conduct laser irradiation to those demonstrating ew (-) after EMR aggressively to allow surgical margin. The breakdown of early gastric cancer cases which underwent endoscopic treatment at Sakura National Hospital between April 1994 and August 1997 are sa follows: 52 lesions with gastric cancer (EMR only-15, EMR+laser-37, laser only-0). Of these patients, 6 with gastric cancer had surgical resection due to pathorogical (poor differential adenocarcinoma), depth sm2 or the remaining cancer. We report on the role of laser therapy in the endoscopic treatment against early gastric cancer based on our investigation.

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Combination therapy using a diode laser and indocyanine green (ICG) was evaluated for the endoscopic treatment of gastrointestinal disease. Approximately 10ml of ICG solution with the 1mg/ml concentration was administrated to canine esophageal and colonic submucosa to enhance the tissue absorption for 805nm laser light. We performed the 25W diode laser intermitted radiation with is duration until the mucosa was removed and the submucosa was exposed. In the case of esophagus, reliable irradiation was difficult owing to the narrow canal space and the heart beat. When the ablation reached to esophageal submucosa, thermal damage also occurred in the proper muscle. Coagulation with/without carbonization sometimes was induced by insufficient irradiation intensity. In this case the thermal damage also affected the proper muscle. We think by using the transparent food and decreasing the laser output, this method may be applicable for the treatment of esophageal cancer, Barret's esophagus and varices. In the case of the colon, the selective ablation and coagulation of the submucosa without proper muscle damage was obtained. This method might be useful for the vilous adenoma and carcinoid tumor as well as early colonic cancer. We think the diode laser therapy using ICG should be one of the useful alternatives for the gastrointestinal disease.

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Photodynamic therapy (PDT) is a new endoscopic method for treating malignant tumors using a photosensitizer and a laser. We employed a new pulse laser as the excitation light source for PDT to treat early gastric cancer, which is an optical parametric oscillator system pumped by a Q-switched Nd: YAG laser (YAG-OPO laser; Ishikawajima-Harima Heavy Industries, Tokyo, Japan). It has a high peak power of 700 kW and its average output is 250 mW. Because of the tunability of wavelength which is between 620-670 nm enables it to be used for various kinds of new photosensitizers.
From June 1995 until December 1997, we performed a cooperative clinical trial of PDT for early gastric cancer with Photofrin Injection^R and the YAG-OPO laser. Fifteen patients were enrolled and 12 were evaluable for response. Complete responses (CR) were obtained in 75% of twelve patients, including two cases that required the second session of PDT. According to the depth of the lesion, CR was observed in all cases with mucosal carcinoma and 63% with submucosal carcinoma One case, whose tumor was 19cm² in area, was ineligible because of its large size but the cancerous lesion was cured completely. Regarding toxicity, mild photosensitivity was seen in one case and it lasted several weeks. Another major side effect was the decrease of total protein, which was observed in six patients (40%) and it lasted several months. There were no serious abnormalities in symptoms or laboratory tests.
We conclude that YAG-OPO laser has the capability of acting as the excitation light source for PDT.

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Since 1982, we have performed endoscopic Nd: YAG laser therapy for palliation of cancerous stenosis of the upper gastrointestinal tract. In 115 patients suffering from malignant dysphagia, we used the Nd: YAG laser as a palliative therapy for stenosis relief and the improvement of dietary intake. The stenosis were lacated on the esophagus in 73 patients, on the other in 42 patients.
The patients were treated once to twice a week until luminal patency was achieved, and then thereafter, were maintained by treatment given at 2-to-4 week intervals.
Stenosis improvement was evaluated based on the following three definitions: Technical success, functional success, and clinical success. Luminal stenosis was graded as follows: Grade 0; A thick endoscope can pass through. Grade 1; A thin endoscope can pass through. Grade 2; 5mm at the narrowest part in width. Grade 3; A pinhole or complete obstruction.
The improvement by one grade or more for one month or longer was designated as “technical success”. Dietary intake was graded as follows: Grade 0; no dysphagia, Grade 1; sometimes solids, Grade 2; semisolids only, Grade 3; complete dysphagia. The improvement by one grade or more for one month or longer was designated as“functional success”. The period of the non-hospitalization for one month or longer after the first laser therapy was designated as “clinical success”. The technical success,the functional success and the clinical success were 65%, 74%, 61%, respectively.
Good adaptability to laser therapy, as to the patient's characteristics, was noted for as follows: Tumors located in the tower or mid third of the esophagus, with a length of 6cm and shorter, and a performance status of grade 2 or under. In addition, the patients with peritonitis carcinomatosa were not adapted to laser therapy.
We conclude that Nd: YAG laser therapy is a useful palliative treatment for improving the malignant stenosis in the esophagus.

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There is increasing interest in the endoscopic study of tissue laser-induced autofluorescence in the detection of malignancy. Flavins, NADH, and collagen have been regarded as a major source of fluorescence in colonic tissue. However, the basis of the different autofluorescence between normal and cancerous tissues is unknown. Human colonic tissues were obtained from resected specimens. To study the existance of fluorescence, frozen sections of normal and cancerous tissues were observed by fluorescence microscopy under 400-440 nm excitation. The strong autofluorescence was seen from the submucosal layer corresponding with the collagen. Tissue fluorescence did not decrease in a reductant or acid solution. These results indicate that flavines and NADH do not affect tissue fluorescence. In cancerous tissue, decrease of autofluorescence arose from the collagen in the submucosal layer, which was substituted by cancer cells, was recognized

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Background & Aim: Autofluorescence was reported to appear in accordance with oxygen radical induced mucosal injury ischemia-reperfusion stress. Since oxygen radicals derived from activated neutrophils injured gastric mucosa in non-steroidal anti-inflammatory drugs (NSAIDs) induced acute gastric mucosal lesions (AGML), mucosal fluorescence intensity also increase in this lesions. We have already reported relations between NSAIDs induced AGML and mucosal fluorescence to help us for early diagnosis. As a clinical apparatus, we established a simultaneous endoscopic fluorescence analyzing system: SEFAS. In this study, we examine whether SEFAS can diagnose NSAIDs induced AGML with mucosal fluorescence or not. Methods: Male Wistar rats were administrated 30 mg/kg indomethacin intraperitoneally. Sequential change of mucosal, fluorescence intensity was measured with a simultaneous endoscopic fluorescence analyzing system. Results: After the indomethacin treatments, mucosal fluorescence intensity increased time-sequentially. However, mucosal fluorescence of control rats did not increase to show a significant change after 45 min. Conclusions: A new endoscopic apparatus, SEFAS, can diagnose NSAIDs-induced lesions by mucosal fluorescence intensity measurements.

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A new catheter combined with angioscope, ultrasonic transducer and laser fiber is developed. This newly developed catheter (EU Catheter) has the outerdiameter of 3.5 mm and has two working channels in which transducer of intravascular ultrasound and laser fiber is inserted. A high-energy diode laser is used to perform valvoplasty or to bore transluminal channels in the left ventricle. In the animal experiment, EU catheter is approached transcutaneously from the femoral artery into the target lesions. By using EU-C, safe and accurate valvoplasty or angioplasty were performed. As our new challenge using EU-C, percutaneous TMR fron the ebdocardium was applied. After left thoracotomy, left coronary artery is ligated to make the ischemic area in the left ventricle. TMR was performed with the diode laser from the endocardium with the peak power of 8W. Contact ablation method with the intermittent ablation was used. Laser induced channel maintained fully patency within 2days after operation and partial patency within 25days.In conclusion, our new surgical mewthod of TMR using EU catheter is thought to provide long term channel patency in the left ventricle.

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Recently, the effects of photodynamic therapy (PDT) on atherosclerosis using Hematoporphyrine derivative (HpD), a photosensitive material, have been reported. This study was performed to evaluate the possibility of inducing regression of atherosclerotic foci by photodynamic therapyusing hematoporphyrin derivative (HpD). Atherosclerotic rabbits were given 5mg/kg of HpD intravenously. Twenty-four hours after HpD administration, the aortae was exposed to 200mw output argon dye laser beam at 630nm for 10 minutes, or 400mw for 5 minutes. In these groups, most intimal cells and endothelial cells had become necrotic and disappeared, and a loss of intima was observed. And then, 5mg of HpD was applied to the atherosclerotic lesion on the aorta of each rabbit through a Dispatch catheter. The lesions were then exposed to 200mw output YAG-OPO laser beam at 630nm for 10minutes from the intimal side of the aorta. Results were almost same as given HpD intravenously. The above data suggest that PDT caused effective regression of the atherosclerotic lesions.

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Background. Recently, access to the coronary arteries became available to laser angioplasty based upon a new concept which utilizes a pulsed laser source and multifiber, “over-the-wire” guided catheters. The aim of this study was to evaluate the early results and the side effects of coronary angioplasty using an excimer or a Holmium-YAG laser.
Methods and Results. Forty-two consecutive patients were treated with the Holmium-YAG laser (group I) and 61 consecutive patients were treated with the excimer laser (group II). The procedural success rate was 98% and 87% for group I and II, respectively. It was similar in calcified and in non-calcified lesions and in total occlusions and stenoses. Failures were due to the inability for the laser catheter tip to reach the lesion, to cross the obstruction, or to obtain a significant reduction in stenosis. There was no death, no myocardial infarction and no need for emergency CABG. Dissection occurred more frequently in group II than in group I patients (26.2% vs 7.1%, p<0.04). Conclusions. Multifiber, wire-guided catheters provide an easy access to the coronary arteries. Excimer laser angioplasty using large, densely packed catheters is effective but induces a high rate of dissections. Technical improvements are required to ablate more tissue.

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Three studies were undertaken to investigated whether argon laser welding is better than conventional suture technique in vascular anastomoses. A first study was designed to evaluate the patency and structural integrity of laser anastomosis using canine femoral arteriovenous anastomoses. Argon laser anastomosis showed excellent patency and did not developed aneurysm formation or intimal hyperplasia. A second study was designed to evaluate laser anastomosis in growing arteries. Vessels anastomosed with laser showed higher growth ratio than conventional suture anastomoses. A third study was designed to investigate whether argon lasers anastomosis is better in the repair of large veins. Vessels anastomosed with argon laser showed no luminal narrowing. Electron micrographs revealed that collagen fibrils in welded area were denatured. These data suggest the feasibility of this method for clinical use.

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Background: Transmyocardial Laser Revascularization (TMLR) by CO2 laser is expected as a new method in patients with end-stage ischemic coronary disease who are not candidate for PTCA or A-C bypass. The mechanism of TMLR is now suspected that arterial blood perfusion will be supplied directly from the left ventricle into the ischemic myocardium through new channels created by CO2 laaser. In 1985 Okada et al, performed the first clinical TMLR operation as a sole therapy all over the world. And now TMLR operations are carring out in many countries. Though the improvement of clinical symptom is evident, the mechanism of TMLR is still controversial.
Object: To assess the theory and evaluate the effectiveness of TMLR in the setting of canine acute myocardial infarction model.
Method: Mongrel dogs were anesthetized and acute myocardial ischemia of 3×3cm in size was made by the method of multiple coronary ligation on the free wall of the left ventricle.In AMI group (n=3), no further treatment was made. On the other hand, in TMLR group (n=3), new channels were made on the ischemic area by CO2 laser (CW 100W×0.2 sec) 30 minutes after coronary ligation. Myocardial blood flow (MBF) and myocardial temperature (MT) were measured at 30 minutes after ligation (MBF (30), MT (30)) and 60 minutes after ligation (MBF (60), MT (60)). In addition, the value of creatine kinase MB was followed for 48 hours in both groups (TMLR group n=11, AMI group n=4).
Results: 1) In TMLR group, MBF (30) was 13.9±8.4 ml/100g/min and MBF (60) was 22.4±14.4 ml/100g/min, and the change ratio of it was +61.1±43.1%. In AMI group, MBF (30) was 12.6±10.9 ml/100g/min and MBF (60) was 10.9±9.1ml/100g/min, and the change ratio of it was -19.9±14.3%. From these findings, there was significant changes of myocardial blood flow between both groups (p<0.05). 2) In TMLR group, MT (60) -MT (30) was +0.73 ±0.42°C. On the contrary, in AMI group, MT (60) -MT (30) was -0.07±0.12°C. From these findings, myocardial temperature significantly increased (p<0.05) in TMLR group compared with that of in AMI group. 3) The peak time of CK-MB on average was 12 hours after ligation in TMLR group, and 24 hours after ligation in AMI group. The value of CPK-MB at 24 hours after ligation was 5220 _??_ 870 IU/L in AMI group, and 2618 _??_ 2918 IU/L in TMLR group. In TMLR group the peak time was significantly short and the value of CK-MB was remarkably low at 24 hours after ligation.
Conclusion: On the basis of the changes according to myocardial blood flow, myocardial temperature andCK-MB, it was suggested that new laser channels by CO2 laser would play a great role to increase the local blood flow and salvage acute ischemic myocardium.

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The clinical application of the Er: YAG laser is now developing in periodontics and restrative dentistry. So far, there are few studies on evaluation for the periodontal usage of the Er: YAG laser. The purpose of the present study was to make assessment of the effects of the Er: YAG laser for periodontal treatment, especially soft tissue surgery, scaling and curettage and at the same time to examine if there is the contribution of bactericidal effect of the laser to the clinical improvement. The experiments were carried out by using the newly-developed Er: YAG laser apparatus accompanied with a contact tip (The Er: YAG Laser; ML 22, HOYA Co. and J. Morita Co., Japan). Thirty-one patients with soft tissue lesions(13 males and 18 females from 24 to 71 years old), and 60 patients with calculus deposits(21 males and 39 females from 19 to 72 years old) were treated with the laser. The clinical parameters evaluated were pain, redness, swelling of the gingiva, and the subjective patient comfort parameters including uneasiness with the sound and vibration associated with laser treatment. Additionally, hemorrhage and wound healing during and after the surgery, the roughness of the root surface after scaling, and the effectiveness of scaling using the laser were examined. we also performed laser irradiation into periodontal pockets of 9 periodontal patients(3 males and 6 females from 38 to 67 years old) with a newly emerging contact tip. The change of oral bacterial flora detected by PCR method setting a target for periodontopathic bacteria and clinical improvement were studied. Laser surgery caused less hemorrhage and resulted in better wound healing when compared with conventional methods. I t was noted to remove calculi easily from root surface with the laser in 95% of the cases. Although the scaled site showed some irregularity, it was not clinical significant in 98% of the cases. There were no complications or side effects during this clinical study. The disappearance of some periodontopathic bacteria and the clinical improvement was admitted in 7 out of nine cases which were treated with laser irradiation into periodontal pockets. In conclusion, this study suggests that Er: YAG laser is useful for periodontal treatment and its clinical result may be mainly due to bactericidal effect of the laser.

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Medical lasers can be divided into two general groups: High powered lasers (e.g. CO₂, argon, Nd-YAG etc.) which utilize the thermal effect for cutting or coagulation, and low-power lasers (e.g. diode, He-Ne etc.) which utilize photoactivation or photo-chemical reactions to relieve pain or promote wound healing. It is good indication of soft tissue tumours resection using high powered CO₂, or Nd-YAG lasers. Various low-power output lasers are used frequently in the oral region. We have obtained good results by treating neurological ailments such as facial palsy and pain in the maxillofacial region by irradiating the stellate ganglion with 300mW output power of Nd: YAG laser and diode lasers.

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Nd: YAG laser and acidulated phosphate fluoride (APF) weres applied on incipient caries of young permanent teeth. They were followed up for at least two years to investigate the effect of a combinate application of laser and fluoride on inhibition of demineralization of incipient caries. The results were as follows. (1) The roughnesses of the enamel surfaces treated with laser and APF were altered for smoother in 80% of the subjects and white lesions were changed to clear surfaces in 60% of the subjects. (2) Decalcification of pits and fissures having stains was inhibited by the combinate application in 54% of the subjects, however, the rest of them were shown caries induced.

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Many biomedical applications of lasers have been developed. In many cases, however, selection of a particular laser has been based largely on availability, and treatment protocols have often been developed by an empirical approach. The choice of lasers and exposure parameters must be based on an understanding of the mechanisms of treatment, the optical and thermal properties of the tissue, or rational, theoretical approach to maximize therapeutic benefits and minimize adverse reaction such as scarring. Selective photothermolysis has been proposed as a construct which may be useful in designing laser systems for biomedical applications, especially for the treatment of pigmentary dermatoses. The necessary conditions are (1) tissue structures which preferentially absorb a wavelength of light more than the surrounding tissue,(2) a pulse of light sufficiently short and energetic to produce localized high temperatures in the absorbing structures, and (3) a predominantly thermal mode of initiation of tissue damage. The concept of selective photothermolysis has been confirmed by our gross and ultrastructural observations of albino and black guinea pig skin irradiated with single laser pulses. At present, various kinds of Q-switched lasers, with a pulse of light sufficiently short and energetic enough to produce localized high temperatures in the targets, are used for the treatment of many pigmented skin lesions and demonstrated to be useful for treatment of dermal melanocytosis and black, brown, and blue tattoos which showed no significant response to previous therapies. In the patients with basal pigmentation, however, patients with postinflammatory pigmentation or chloasma show no response, although most patients with solar lentigo and all patients with mucosal pigmentation reveal a good response after only one laser treatment. Therefore, it becomes more important to differentiate several pigmented lesions responsive for laser treatment from the others.

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In the past several years, Q switched ruby lasers have been found to be effective in the treatment of deep dermal pigmented lesions of the skin, especially Ota's nevus. The recently developed Q-switched ruby laser is already to supersede the conventional therapeutic procedures such as dry ice, skin abrasion or skin grafting treatments, patients who had been treated by those procedures, which are difficult to treat, are also treatable with ruby laser. In those patients, it needs more times of irradiation and it takes about from 2 years to 3 years which requires 1 more year to diminish the lesion completely. However, we have designed a new therapeutic protocol which involves the combined use of both Q-switched and conventional normal-pulsed lasers, exploiting the specific advantages of each type.

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Selective photothermolysis with a long-pulse flashlamp dye laser with 585 nm is becoming widely accepted as a treatment for cutaneous vascular lesions because of high efficacy with a very low risk of scarring. The light of dye laser penetrated into 1,400 μAm depth of the human skin and induces selective intravascular and perivascular coagulation necrosis. However, the numbers and diameters of blood vessels were significantly decreased only in tissues down to a depth of 600 μm 3 months after the laser irradiation. Fifty two out of 550 patients (9.5%) with port-wine stains (PWS) showed an excellent clinical improvement after single treatment and up to 4 times additional irradiation further improved clinical responses in as much as 115 patients with excellent improvement. The degrees of clinical responses are dependent on histological type, age, anatomic location and color of PWS lesions. Treatments of strawberry mark are usually begun in a thin flat stage or at initial presentation with some success especially for their superficial lesions. However, they hardly affect the size of tumor and often leave atrophic and redundant skin surface with scarring. Finally practical problems in dye laser treatment of hemangioma were discussed.

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We have used the Q-switched ruby laser in the treatment of pigmented skin lesions since 1991 to treat approximately 2,000 patients out of which more than 1,000 were treated for nevus of Ota. This laser was effective in treating almost all cases of nevus of Ota, ectopic mongolian spot, blue nevus, ephelides and aquired bilateral nevus of Ota-like macules, However, a large degree of variation was observed among individuals when treating pigmented nevus, and the laser was ineffective in some cases despite repeated irradiation of the affected area. Great care should be taken with patients with nevus spilus because reccurence was observed in many cases and sometimes the area actually became darker. It was found that the laser was effective in removing black tattoos, but the treated site was aggravated in many cases where the tattoo was red or yellow.

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This study was performed to demonstrate the accumulation state of hematoporphyrin derivative (HpD) in atherosclerotic lesions and check the possibility of safety making atherosclerotic foci diagnose and regress using doxycycline (DOXY) or HpD with photodynamic reaction. Atherosclerotic rabbits were given respectively 5mg/kg HpD intravenously. Twenty-four hours after HpD administration, from the aortas of all the rabbits, fresh-frozen sections were prepared and observed using fluorescent microscope. Fluorescent microscopy revealed that HpD red fluorescence concentrated in the intima in the atherosclerotic lesions and was not found in the media. Next, after 24 hours of HpD administration, the thoracoabdominal aortae of the atherosclerotic rabbits were removed for the determination of fluorescent spectra. A positive correlation of was found between the intimal thickness and spectral wave height at 630nm. In cases of ischemic heart disease with 90% or more coronary stenosis, four hours after 200mg DOXY administration, coronary endoscopy was performed and the spectrum of DOXY was analyzed in the observation sites. A unique spectrum with its peak at 560nm was observed in the stenotic lesions and the height of this wave was reduced in the normal coronary regions. Next, new atherosclerotic rabbits were given 5mg/kg HpD intravenously. Twenty-four hours after HpD administration, the aortas of the rabbits were exposed to a 200-milliwatt output argon-pumped dye laser beam at 630nm for ten minutes from the adventitial side,in room air. Seven days after irradiation, most intimal and endothelial cells disappeared, and the intima of photoradiated regions were thinner. When a catheter with a lateral direction fiber was inserted into the blood flow of the rabbit aorta, seven days after photoradiation, most intimal and endothelial cells had become necrotic and disappeared, and a loss of intima was observed. Next, new atherosclerotic rabbits were given 15mq Photofrin through a Dispatch catheter that could deliver Photofrin to a limited area of a aorta. Ten minutes after administration, the aortic regions were exposed to 200mW output YAG-OPO laser beam at 630nm for 10 minutes. The PDT regions showed necrosis of the intimal cells and disappearance of the intima. These findings suggest that PDT using a Dispatch catheter is effective and may be used for human coronary arteries.

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In the 1980's, we had treated thirty-seven patients with early gastric cancer by photodynamic therapy (PDT) with Photofrin I or H and an argon dye laser. The energy intensity was over 90 J/cm². However, the rates of cure were only 57%. In order to improve the therapeutic effectiveness of PDT, we started employing the pulse laser, such as an excimer dye laser (EDL; Hamamatsu Photonics, Hamamatsu, Japan) in 1990 and an optical parametric oscillator system pumped by a Q-switched Nd: YAG laser (YAG-OPO laser; Ishikawajima-Harima Heavy Industries, Tokyo, Japan) in 1995, because the pulse laser with extremely high peak power was expected to be more efficient at exciting HpD than a continuous wave laser. EDL has peak power of 400 kW and YAG-OPO laser 700 kW. We treated thirty-five patients with early gastric cancer using Photofrin^R and the EDL or the YAG-OPO laser, who were at poor risk for conventional surgery. The entire lesion, plus a 5-mm wide perimeter of mucosa, was irradiated uniformly with laser beams transmitted endoscopically. The energy intensity was over 60 J/cm². By employing pulse lasers, the rates of cure were markedly improved to 95%(18 of 19) in mucosal cancer, 71%(12 of 17) in submucosal cancer, 83% in total, including two cases that required the second session of PDT. With the YAG-OPO laser, a wide mucosal carcinoma was cured, whose size was 19 cm² in area, though the energy intensity was 48 J/cm². Concerning responses to PDT, signet-ring cell carcinoma and submucosal cancer had tendencies of resistance to the treatment by PDT. We treated five patients with advanced gastric cancer using Photofrin^R and the EDL and one patient with type 2' advanced MP' cancer, whose tumor was 13cm² in area, was cured completely. There were no serious side effects caused by PDT. In conclusion, a pulse laser with extremely high peak power had markedly improved cure rates of PDT for early gastric cancer and demonstrated the possibility of treatment of advanced gastric cancer in case of no metastasis using PDT in the future.

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According to statistics from 179 gynecology clinics in Japan, there are about 3000 C. I. S. reported annually, and when severe dysplasia and micro-invasive cancer are included this number becomes about 5000 cases annually. Recently, the number of younger patients who wish to preserve fertility has been increasing, and in order to cope with these demands, PDT has been receiving special attention due to its usefulness as a break-through treatment method. It can preserve patients- fertility while leaving the cervix intact and can be performed without anesthesia since there is no bleeding.In addition, the CR ratio is very high, and it is considered that PDT has no negative affect on pregnancy and delivery.
We have performed PDT on 100 cases, and 97 became CR (97%).
Among these 100 cases, 71 were C. I. S. 26 were dysplasia, and in recent cases we have perfomed PDT on 2 micro-invasive carcinoma, and 1 was endocervical adenocarcinoma, micro-invasive. All cases became CR after the treatment. Also, even where there was stump remnant, in which a total hysterectomy is usually needed after cold knife conization, the patient became CR after PDT treatment, and had a normal pregnancy and delivery.
We expect that in the near future, PDT will be perfomed using small lasers with variable laser wave length, and without any hospitalization due to the ongoing progress and development of photosensitizer which has a shorter retention time.

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In ophthalmology, photodynamic therapy (PDT) using hematoporphyrin derivatives has been applied for the treatment of retinoblastoma and uveal melanoma. Recently, PDT is expected for a new treatment modality to ocular neovascularization. In the present study, the efficacy of PDT using a new hydrophilic sensitizer, ATX-S10NaII for the treatment of experimental choroidal neovascularization (CNV) was investigated. CNV was induced in rat fundi by intense argon laser photocoagulation. Fluorescein angiographic study revealed accumulation of ATX-S10 in the CNV from 30 minutes to 4 hours after dye injection. Laser (diode laser, λ=670nm) irradiation applied immediately after dye injection with radiant exposures of 7.4J/cm², or 2 to 4 hours after dye injection with radiant exposures of 22.0J/cm², induced occlusion of the CNV without singnificant injury to the retinal vessels. PDT using ATX-S10 using appropriate treatment parameters can occlude CNV. ATX-S10 is supposed to be a promising new generation sensitizer which has rapid elimination from the body and little skin phototoxicity, and it appears to be useful in the treatment of ocular neovascularization.

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We have applied Stereotactic Intratumoral Photodynamic Therapy using HPE and argon-dye laser for 20 malignant brain tumors of 16 cases. The 6 females and 9 males were from age of 22 to 77. The average age was 52.5 years old. There were 7 cases of glioblastoma (3 recurrence), 4 cases of astrocytoma grade III, 4 cases of metastatic brain tumors and 1 case of PNET. All tumors clearly showed a reduction in tumor volume 4 weeks after stereotactic PDT. In the case of 20.7cc or lower volume (85%,17 tumors), therapeutic effects was obtained for all of them. The largest tumor which showed complete disappearance on enhanced CT or MRI had a volume of 4.6cc.
The data indicate that it is possible to consider stereotactic intratumoral PDT showing adequate therapeutic effects as an adjuvant therapy for malignant brain tumors.

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For accurate surgical procedures of oral soft lesions, it is essential to prevent bleeding of the surgical site. High power diode laser gains attention recently as a new measurement because of being compact, portable and almost equivalent to the conventional Nd: YAG laser. We used high power diode laser device (3W) which was developed by Osada Electrics Industry Company. The cutting edge is relatively clear because of it's fine fiber tip (0.1mm spot size). The major advantages are more excellent hemostasis and minimal thermal damage to surrounding tissues. However, the weak point is unsuitable to dissect a lesion from around connective tissues. Therefore, all our laser procedures were performed in combination with using surgical scissors, mucoperiosteal membrane elevator. First, circumferential incision around each lesion is carried out by moving a laser spot and. created about 1.5mm-depth necrotized layer. Next, surgical scissors or mucoperiosteal membrane elevator is inserted into the necrotized layer and bluntly dissected away the lesion. If necessary, these procedures should be repeated. Following the extirpation, the wound is closed with interrupted sutures except ranulas. Our technique was used for 10 oral lesions consisted of 3 ranulas, 6 mucous cysts and a small carvenous hemangioma. The results may be summarized as follows: (1) By following our technique, we could completely remove 10 lesions without rupturing the cystic walls and a hemangioma. (2) This laser was useful for cosmetic procedures because of the minimal thermal damage to the surrounding tissue. (3) The laser wounds healed slower than ordinary blade. Clinically, however, they appear to heal with minimal post-operative pain and no scarring. (4) We feel that this diode laser is a suitable tool in treatment of oral soft lesions together with using surgical scissors and mucoperiosteal membrane elevator. However, care should be taken to avoid production of a char layer.

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The UltraPulse^TM carbon dioxide laser (Coherent, Inc., Palo Alto, California) was used in skin ablation to treated superficial skin tumors, fine wrinkles, and as a laser scalpel for incisions and excisions. Thermal damage using this laser was much less than with traditional continuous wave and normal pulsed modalities. An animal model was employed to measure the histological thermal damage of various laser irradiations.
The results with the UltraPulse^TMproved it to be an effective treatment device with minimum thermal damage and no complications. Furthermore, laser ablation depth was controlled by the number of laser passes. In some cases, post-operative hyperpigmentation developed, especially near the zygomatic prominence area, but pigmentation returned to normal after the application of 4% hydroquinone with 0.025% Retin-A^TM emollient cream (Shantel Irradiance, Los Angeles, California) for several weeks.
The UltraPulse^TM is a useful and effective device for plastic and aesthetic surgery.

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We experimentally evaluated diode laser welding between the vessel and artificial graft by tension/strain characteristics. We used extracted fresh porcine coronary artery strip, which the intima was removed intentionally, and collagen-coated knitted dacron. graft (Hemashield). An 830nm diode laser (power density, 57W/cm²) was employed to make welding with contact irradiation method, after topical application of indocyanine green dye (peak absorption, 805nm) and compression (3.5kg/cm²) of irradiation spot. The laser irradiation time was 30s in all. The specimens were strained axially until ultimate breakage occured in order to draw a stress-strain profile graph. We compared welded vessel-graft tissue group with welded vessel-vessel tissue group. Welded vessel-graft tissue (27.9±1.9g/mm², n=10) withstood significantly higher stress(p<0.01) than welded vessel-vessel tissue (17.1±1.9g/mm², n=10). No significant differences in strain limits of Hook's law, which was relative length until Hook's law could not be applied, were noted between welded vessel-graft tissue group and welded vessel-vessel tissue group. We obtained Young's modulus from a stress-strain profile graph. There was the significant difference in Young's modulus between the two groups (1.24±0.09×10⁶dyn/cm²vs. 2.29±0.22×10⁶dyn/cm², n=10, p<0.05). And then, histrogical study of welded vessel-graft tissue showed that the vascular collagen fibers melted and invaded into fibers of the knitted dacron graft on the irradiation spot.

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Recently, some recent cases of malignant transformation after laser therapy for oral precancerous lesions have been reported in the follow-up periods. Thus, the present study attempted to determine the cancer promoting or inhibiting effects of laser irradiation in experimentally-induced oral precancerous lesions.
Premalignant lesions were experimentally induced in F344 male rat tongues by 0 ppm 4-nitroquinoline 1-oxide (4NQO) dissolved in their drinking water for 8 weeks. Then, after a -week interval, laser vaporizations were performed with a CO₂ laser device using non-contact laser, with 6W power output irradiated for 5 seconds. The rats were divided into 3 groups (untreated, laser vaporization one and three times), and the tongues were excised at 3 days, 1,, 4 and 16 weeks after laser vaporization. The early wound healing process following laser vaporization was investigated histopathologically, and cell proliferation in normal and premalignant lesions was assessed using BrdU and GST-P immunohistochemically. The incidence of neoplasms was investigated histopathologically to observe the long-term wound healing process.
In the early tissue repair following laser vaporization, although there was no difference in the wound healing process involving loss of epithelium, inflammatory cell infiltration, granulation tissue formation and epithelialization, the wound healing in precancerous lesions tended to take longer. Also, the survival premalignant epitheliums showing GST-P positive staining and the epitheliums regenerated from those portions were observed. Moreover, the BrdUlabeling index of the regenerated epitheliums showing GST-P negative staining (i. e., normal) at first indicated temporary cell growth, and a decrease weeks later. However, the cell growth of the regenerated epitheliums in premalignant portions showing GST-P positive staining was lower than that with GST-P negative staining and tended to take longer.
In the long-term wound healing process after laser vaporization, a decrease in the incidence of neoplasms was observed in the laser vaporization groups, suggesting a decrease in the number of premalignant lesions. However, the depth of invasion and tumor area were enhanced. Repetitive laser vaporization also caused a progression.
On the basis of the above-mentioned findings, when oral precancerous lesions were not completely removed by laser vaporization, it was suggested that there was a risk of cancer promotion from the surviving epitheliums.

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Background. Malignant tumor cells are believed to be shed into the bloodstream during conventional surgical resection of a primary tumor. In head and neck neoplasms, laser resection (Nd: YAG and CO₂) is one treatment for resection of organ-confined primary tumors. To date, however, the evidence of malignant tumor cell dissemination during laser resection remains unclear. In this study, the author have examined the effect of laser reduction on the shedding of tumor cells into blood and micrometastasis formation in the lung using a marker gene-tagged mouse Lewis lung carcinoma model.
Methods. 1×10⁶ Lewis carcinoma cells transfected with hygromycin-resistant gene (Hyg) were injected subcutaneously into C57BL male mice, and tumor cells in blood and the lung were estimated after 10 minutes of laser reduction of primary tumors leaving 1/5 of them by polymerase chain reaction for Hyg as atarget gene. Macroscopic metastasis was estimated by counting visible parietal nodules in the lung after fixation in Bouin's solution.
Results and conclusion. The detection rate of circulating tumor cells in blood was higher in the Nd: YAG (54.5%) and CO₂ (60.0%) laser treatment group than in the control group (30.0%). Macroscopic metastasis in the lung were also increased in the Nd: YAG and CO₂ laser treatment group, when compared with the control group. These results suggest that laser reduction of malignant tumor enhances tumor cell shedding into the bloodstream.

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A newly developed Laparoscopic Dual Hook (DH) using STATLase-SDL as an energy source was successly dissect vessels. We measured the interluminal bursting pressure (BP) at the vessels stump of jugular vein of pigs (n=44). The BP immediately after transection at laser power of 12W was highest value above 200mmHg. These of 1 day or 8 days after transection were also highest than 200mmHg. These results do not depend on diameter of vessels. Histopathological examinations of cut end of vessels were carried out by HE and EVG stainings.
This equipment may be useful in Vein Harvesting and laparoscopic surgery safety.

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Because of its advantages as small unit size, portability, and low cost, the diode laser is expected to come into wide use in laser therapy. We evaluated the ability of the diode laser in the treatment of superficial bladder pathology. To have vaprization abilites, we attempted to use diode laser with indocyanine green (ICG) pretreatment. The medical diode laser system (DIOMED25, Diomed Company, UK) was used with 25W at 805nm. The applied output power was 5W and was delivered to the tissue through a flexible silica glass fiber. Bladder of anesthatized dog was used. The irradiation was performed in the noncontact mode with a spot diameter of 2mm. To assess the enhancement effect of indocyanine green (ICG), ICG solution (1mg/ml, 0.3ml) or normal saline was injected submucosally immediately before the irradiation. The temperature at the subadventitial layer was measured with a needle type thermocouple and the intensity of transmitted laser which passed through the whole layer was evaluated by a laser power meter. After observing the macroscopic appearance of the bladder surface, the specimen was kept in 10% formalin for histological consideration. With ICG pre-injection, vaporization and coagulation of the mucosa was obvious within 10 seconds and the whole mucosal layer was vaporized in 40 seconds. The subadventitial temperture measurement revealed that the temperture increase in the subadventitial layer is reduced by the ICG pretreatment. The transmitted of laser did not increase by the ICG pretreatment. Our results suggest that the diode laser with ICG pre-injection can be used to vaporize and coagulate the superficial pathology of urinary bladder more selective and safer.

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To establish a non-invasive and quantitative measurement method for human embryo viability, we studied fiber-optic viscoelasticity measurement system for the embryo. The morphological change of ultrastructure in the embryo which relates to the viability may induce the viscoelasticity change of the whole embryo. The viscoelasticity of a certain object can be measured by the displacement, stress and their phase difference in the case of driven vibration was externally loaded. We studied the efficacy of the fiber-optic reflectometry to measure the displacement using gelatin gel model object (1cm×1cm×1cm). Since the spot size of the reflected light from vibrational surface of the object changes in proportion to the displacement, we can detect the displacement by the reflecting light collected by a fixed fiber tip. We used a He-Ne laser with 632.8nm in wavelength as the light source. We used a single optical fiber of which core diameter was 200μm for illumination and detection. we employed a solenoid-actuator as the external vibrator, We carried out the linear relation between the reflected light intensity and displacement in the range from 230μm to 400μm. We aim to measure the viscoelasticity of gelatin with various concentrations by the fiber-optic reflectometry which we constructed. We might realize a non-contact external vibration by a pulsed laser irradiation The modified system which includes non-contact vibration driver may be available to measure the the embryo viability to use for in vitro fertilization-embryo transfer.

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A new therapeutic modality for cutaneous malignancies, ultrasonic irradiation of tumors administrated with sensitizers, is known as sonodynamic therapy (SDT). In previous references, a few photosensitizers (such as hematoporphyrin, Photofrin-II [Pf-11], and gallium-porphyrin analogue ATX-70) have been reported to have sonodynamically cytotoxic effects. In recent years, many photosensitizers have been developed, for example, ATX-70, a pheoforbide derivative (PH-1126), hematoporphyrin oligomer (HpO), 5-aminolevulinic acid (5-ALA), Photofrin-II and aluminum phthalocyanine tetrasulphonate (AlPcS4). The antitumor effects of PDT or SDT with the sensitizers were determined and compared in C3H mice bearing transplanted squamous cell carcinoma (SCC). In order to enhance the efficiency, the combination of PDT and SDT with PH-1126 or ATX-70 were compared with that of PDT or SDT alone. From the results, the combined antitumor effect of PDT and SDT was stronger than that of single PDT or SDT. In conclusion, it was suggested that combined treatment (PDT+SDT) developed the efficiencies of these single treatments.

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In bronchial, esophageal and gastric photodynamic therapy (PDT) we were dazzled by the reflection of red laser light during photoradiation, especially in the use of the pulse laser such as an excimer dye laser. Initially we placed a green filter on the eyepiece of the fiberscope to protect the naked eye from being dazzled during photoradiation. Later, we also inserted a green filter in front of the CCD-camera in an OES-TV system with a NTSC signal. The red spot of laser light could be observed clearly, but the mucosal image turned to green and the boundary between cancer and surrounding mucosa became unclear. We, therefore, developed a new device for endoscopic photoradiation that consists of a conventional fiberscope and a new OES-TV system which has a high resolution and sensitivity with automatic gain controller and the signal can be sent out by RGB. We inserted an interference filter specially made to order in front of the CCD which specifically absorbs a red light, whose transmissivity rate at 630 nm wavelength is 15% and the full width at half maximum is 26 nm, while an average transmissivity is 94%. In order to make an optimal balance between a white xenon light and the red laser beam, we also inserted a neutral density filter of ND-0.8 which transmits 16%. However, these filters were not enough to absorb the red laser beam. By this trial we could find the spectral specificity of the filter to make the optimal balance in the use of the excimer dye laser of 4mJ/pulse and 80Hz. In conclusion, the filter should be qualified the specifications as follows: an average transmittance requires more than 20%, the transmissivity rate at 630 nm should be less than 1%, and the rates between an average transmittance and the transmissivity rate at 630 nm should be more than 20 times.

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The purpose of this study is to examine anti-tumour effect of PDT with ATX-S10Na (II)-the Diode Laser. Material and Methods: colon26 carcinoma was transplanted under the skin of dorsal surface of CDF1 mouse. Seven days later, when the cancer grew up to the size of 10×10×6mm, the mice were administered ATX-SlONa (II) intravenously at a dose of 18mg/kg. Four hours later, the mice were irradiated. Anti-tumor effect was evaluated by change of tumor volume. Results: It was possible to put PDT with ATX-S10Na (II) into operation in plural times continuously, and anti-tumor effect by this method was observed remarkably.

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The purpose of this study was to determine that photodynamic therapy (PDT) using mono-L-aspartyl chlorin e6 (NPe6) and a diode laser radiation can induce a state of systemic immunosuppression. The effect of treatment on immunological responses were evaluated by examining the capacity of transcutaneous PDT with NPe6 and light to inhibit hypersensitivity to trinitrochlorobenzene (TNCB) in Balb/c mice.
The reduction in TNCB-induced ear swelling in PDT treated mice were compared to untreated mice. Pretreatment of mice with PDT resulted in 65% suppression of contact hypersensitivity to TNCB. Inhibition of the response could be produced even when sensitization with TNCB was attempted 2 weeks after PDT procedure. Prior sensitization or challenge with TNCB followed by PDT also decreased at 50% suppression of their response to TNCB. Thes decreased reactivity exhibited not only the induction but also the elicitation phase of the reaction. In adoptive transfer studies, it was shown that the immunosuppression was associated with the adherence to plastic dishes in spleen cells.

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It has been found previously that PDT with various photosensitizer can induce systemic immunosuppression. We have now found that the survival of mouse allogenic skin graft is prolonged by PDT treatment of mice with NPe6 that is newly photosensitizer and have a good activity for tumor treatment. Normal Balb/c mice transplanted with C3H/HeN skin rejected the graft within 9.2±1.1 days. Recipient mice treated 24 or 72 hr previously with NPe6-PDT rejected skin allografts at 15.6±0.5 and 12.6±2.4 days respectively. Humoral immunity to hen egg-white lysozyme was not significantly changed by NPe6-PDT. These results demonstrate that NPe6-PDT causes systemic immunosuppressin of cellular immunity but unaffected to humoral immunity.

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The light distribution in vivo during Photodynamic Therapy is dependent on a pre-administered photosensitizer in the target tissue. To discuss the light absorption of photosensitizer (ME2906), the light distribution in normal muscle at 664nm was measured with optical detector fiber. From this distribution, the absorption coefficient of ME2906 in tissue was calculated. As an optical source, a semiconductor laser is prepared. The incident laser beam diameter at the tissue surface is 10mm, and the power density was 100mW/cm². In proportion as the concentration of ME2906 increases, absorption coefficient of ME2906 increases in the range from 0.06 to 0.16mm^-1. This coefficients are related to ME2906 concentrations in the plasma and tissue. Therefore, ME2906 concentrations of plasma were examined by high-performance liquid chromatography (HPLC).

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PDT involves the treatment of tumors in the presence of ME2906 and laser light. Macrophages play an important role in natural tumor defence. It has been found previously that secretion of cytokine and PGE2 from mouse peritoneal macrophages(PEC) were affected by ME2906-PDT in vitro. We investigated the effects of ME2906-PDT on secretion of IL-12 from PEC and direct cytotoxicity (not cytolysis) of these secretas to tumor cells cultured in vitro. The progressive increase in IL-12 secretion occured with increasing ME2906 doses from o to 10 μ/ml, due to no PDT toxicity. The direct cytotoxicity of secreta from PEC treated PDT to Meth A cells was most strong at 10μ/ml of ME2906 in vitro. This dose agreed with the doses of ME2906 that were TNF a and IL-12 secretion from PEC treated ME2906-PDT. These data suggested that circulating or tumor-associated macrophages, when sensitized by ME2906 and exposure to laser light, may be stimulated to produce TNF α, IL-12 and/or other substances. These substances are not only associated with tumor regression in vivo, but may, on part, mediate this tumor regression through effects on the microvasculatere.

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The purpose of this study is to evaluate morphological changes and biochemical effect of photosensitized HeLa cells after the pulsed and continuous wave (CW) laser irradiation. The fluence of the CW and the pulsed laser held constant at 40 J/cm². The wavelength of the lasers was 514 nm. After the irradiation, the degree of cytopathy were detected by assessing viability of the cells using the 3-(4, 5-dimethylthazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and LDH-release in the medium. Although the cells irradiated the both laser lights showed 90% in survival within 15h, small number of cytotoxicity reaction were observed in the cells exposed to the pulsed laser light after 27h incubation and the rapid release of LDH from the cell, however, was promoted by additional 5 h incubation. The cells irradiated by the CW laser showed the whole membrane degradation and swollen nuclei. In contrast, for the cells irradiated by the pulsed laser showed condensation of chromatin material around the periphery of the nucleus. These results corresponded with observation of pressure-wave exposed cells. On the basis of these results, using a pulsed laser as a light source for PDT was found to allow the pressure wave in the cell, which serves the acoustic effect on disrupting the cell in addition to the well-known photochemical effect.

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In order to estimate the best concentrations of different two photosensitizers and the dose of laser each lights for the anti-tumor effect of these photochemical combined treatments.
We examined of anti-tumor effect of the photochemical treatment by optical parametric oscillator (OPO) laser lights with two photosensitizers administrations for the transplanted tumors of a cultivated murine leukemia (L5178Y) cells to Balb/c nude mouse and of squamous carcinoma cell (SCC) to C3H/He mouse because there is an advantageousness of turnable wavelengths in the OPO laser. Different two photosensitizers of a 2.5g/gbw pheophorbide-a derivative (PH-1126) and 1mM 5-aminolevulinic acid (5-ALA) as a protoporphyrin IX (Pp-IX) precursor were used when both sensitizers were administrated together. The tumor sizes, the survival fraction and tumor histological changes of the nude mice were observed after the treatments.
From these results, it was found that (1) it was observed the anti-tumor effect by PH-1126 also in the case of the single irradiation at even 630nm of the 5-ALA absorption peak, (2) the combined irradiations at 630nm and 650nm for the double administrations were obtained 86% anti-tumor effect from comparing of the growth curves, 20% expanded the life span from the survival fraction of the mice, and observed the deepened necrosis and pyknosis or disappear-changes of nuclear of the tumor cells about 1-1.5 cm at the depth 1 week after the laser treatments comparing that of the single treatment for the single each photosensitizer.

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Recent years have seen the development of several kinds of lasers for otolaryngological use. This report describes an application of KTP laser to two cases of juvenile subglottic stenosis. The KTP green beam vaporizes, coagulates and cuts with excellent hemostatic results. The flexible optical fiber can reach more secluded sites than can the CO₂ laser. The KTP laser's fiberoptics are both flexible and provide high accessebility to tissue; also, the whole system is easy to maneuver. It is necessary, however, to use a narrower gauge fiber when using KTP fiberoptics in the more confined area of a juvenile larynx.

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To evaluate the ability of the Dual Hook (DH) to dissect and coagulate larger vessels, we experimentally applied this to cutting of the carotid artery of pigs. Blood pressure of animals and bursting pressure (BP) were measured. Histological examination was done by HE staining.
The hemostatically cut through arteries up to 3 mm in diameter. The interluminal bursting pressure was 307±35.2mm Hg after transection. The transected sites of arteries revealed well-apposed tissue sealing of vessel wall. In conclusion, the DH could perform hemostatic transection of large vessels.

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