Some fundamental studies of the Bipolar Laser Forceps (BLF) presented on the 11th annual meeting of Japan society for laser medicine were performed using the animal model of Wistar rat. The renal vessels were irradiated with BLF to evaluate the thermal effects in cutting and coagulation at the aimed tissue. Under interruption of the blood flow with the forceps, the laser was yielded to cut the vessels (M+SD: 1.5±0.1mm in diameter) completely in low power energy (M±SD: 14.9±1.4J) comparatively without thermal damage to the surrounding tissue. The findings at the lased area in 2nd, 7th and 60th days after the operation were evaluated morphorogicaly. The carbonized tissue at the limited area of lased tissue and the congestion in the proximal vessels were observed for 7 days, and after 60 days any thermal damage could not be found at the tissue. Furthermore BLF was applied in 7 cases of urological operations held in our institution. BLF showed the benefits on the hemostasis at the oozing points. The coagulation could be performed successfully with low power energy. From these results we could conclude that (1) Effective coagulation and cutting of tissues could be yielded by BLF.(2) BLF could be used for clinical application in safety.

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To develop easy and safety therapy of ureteral stricture, we studied the laser therapy of ureteral stricture using ultraviolet argon (UV Ar) laser and a novel multi-fiber catheter for laser delivery. We made an experiment in vitro to study the characteristics of the UV Ar laser ablation to ureteral tissue. The ureter was ablated sharply without excess coagulation layer, The proper laser power for the tissue ablation would be about 0.5W. We employed a new multi-fiber catheter (1.6mm in outer diameter) which consisted of 10 pixels of SiO₂ glass fibers (0.2mm in core diameter) for laser delivery and a guide wire lumen (0.9mm in diameter). The canine ureter was ablated in vivo using the UV Ar laser via the catheter. The ureter were ablated till the submucosa without the perforation. This method may be suitable for the therapy of the ureteral stricture.

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Contact pressure laser irradiation technique (PLT) is the most practical method to deliver the stronger laser beam to the target tissue by irradiating laser beam with pressing on the tissue This experiment was designed to approach the physical feature of PET using the authors original experimental system for assessing the incident laser beam intensity in tissue. This method is to estimate a CCD TV camera image of the sectional plane of a removed an liver as the experimental model of living tissue irradiated with the GaAlAs diode laser beam of wavelength 0.83 μm with the parallel or focused laser beam at the top of the sectional plane along the beam axis. In this image, it is clearly observed that the laser beam scatters spherically in the tissue. As a result of this experiment almost the same intensity of the incident laser beam was showed at the same thickness in the tissue, unrelated to pressure or non-pressure irradiation technique, and unrelated to parallel or focused laser beam. And so PET delivers more stronger laser power in tissue than non-pressure technique, and thus the more stronger laser beam can he get in tissue with increase of the pressure.

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To evaluate the diode laser application to microangio surgery, the effects of the laser irradiation on the growth promotion activities in cultured mucosal endothelial cells. Human mucosal microvascular endothelial cells (HMMECs) from the inferior turbinate on a patient with hypertrophic rhinitis or nasal allergy. The cells were plated at a density of 5×10³ cells into multiwell culture chambers ( 2cm²/well ) coated with collagen and incubated at 37°C in a humidified atmosphere of 5% CO₂ and 95% air. Laser irradiation were performed on the every second day. Cell growth assay were performed on the 2nd, 4th and 6th day after harvest.Cells numbers were counted in a Coulter counter. On the other hand the activities of growth promotion were monitored by ³H-thymidine incorporation after laser irradiation at energy densities varying from 0.5J/cm² to 50J/cm². After once diode laser irradiation, both the numbers of HMMECs and ³H incorporation were inhibited. Morphological study was done by a phase-contrast microscope, no change of cell configuration was observed following diode laserirradiation.

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Wister rats at the age of 1, 3, 6 days were irradiated with GaAlAs diode lasers (805 nm) at several power levels ranging from 13 to 200 mW for 15 min at the point located above the cerebellar culmen. They were sacrificed 6 hours after irradiation, and their cerebella were removed and processed for microscopic observation. In the mid-sagittal sections through the vermis, incidences of pyknotic cells and mitotic cells among matrix cells in the external granular layer along the primordial culmen were estimated. Cerebellar temperaturesunder irradiated spots in rats at the age of 3 days were also measured by a needle-shaped thermocouple. Cerebellar temperatures in rats irradiated at power levels more than 100 mW were significantly higher than those of sham-irradiated group. No significant difference from sham-irradiated groups was observed in the incidences of pyknotic and mitotic cells in all rats irradiated with diode lasers. In rats at the age of 3 days irradiated with diode laser of a clinical instrument (NIR monitor) of Shimadzu Corp., no significant change in temperatures and the incidences of pyknotic and mitotic cells was found in their cerebella. These facts suggest that diode laser irradiation at power less than 200 mW does no cause cell death in the neonatal rat brain.

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The effect of a Er: YAG laser on living tissues was studies through the observation of tissue evaporations using Wister rat skins.
Pulse irradiation number and repetition frequency dependences of the evaporation cross section of the tissues were observed.
Very thin coagulation layer similar to that of excimer laser was observed.
Spot size of 3mm φ was used considering or clinical applications.
A bleeding was not observed during the experiments. The evaporation crass sections were found to be proportional to the total irradiation laser energies, but independent to the repetition frequencies of the laser pulses.

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A study of permeability of pulsed laser light through rabbit was carried out in vivo and in vitro. Ne have experimentally recognized 532am and 717nm pulsed YAG-Dye laser light permeated through rabbit in vivo and in vitro. The permeability of 717nm laser light was higher than that of 532nm laser light notosensitizer (NPe 6, λ=664nm) injected into rabbit's tissue (leg muscles and liver) had an effect on absorption of 664nm laser light.
Imaging of mouse's cancer in vivo was obtained with 664nm laser light and CCD camera, after NPe6 was injected into cancerous Moose. Also imaging of blood vessel in atherosclerosis rabbit was obtained in vitro.

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Cutaneous blood flow was monitored using L-MAP 10 (M & M Co.) in fourteen patients with soft tissue expansions, nine with skin flaps, seven with fresh burns, seven with replanted fingers, two with full thickness skin grafts, two with composite grafts and eight with port-wine stains.
The expanded skins showed significant decrease of blood flow immediately after inflation following quick recovery. In the flaps, low blood flow area were keeping with their subsequent necrosis. Comparing to the deep dermal burns and deep burns, superficial dermal burns showed relatively high blood flow. Decreasing the blood flow in the replanted fingers indicated the failure of their survival. In the skin grafts and the composite grafts, low blood flow area and the necrotic area were positively relational. But in port-wine stains, the levels of blood flow had no relation with the histological depth of abnormal vessels.
The results in this study indicate that L-MAP 10 is useful for predicting the clinical survival of various skin lesions in plastic surgery.

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We successfully demonstrated quantitative judgement of the boundary between eschar and normal tissue in burned skin using laser induced fluorescence spectroscopy (LIFS). Fresh sliced rabbit skin and rabbit dermal burn skin were used as samples. In vitro and in vivo measurement were performed. Ultraviolet light (λ=325nm) was employed for excitation laser source. The extracted skin samples were examined histologically after LIES. Three peaks from the spectrum have been used to judge the boundary. We have defined eschar Index (EI) as follows.
EI=I₃₈₀×I₄₈₀/(I₅₀₇)²
I₃₈₀, I₄₅₀ and I₅₀₇ were the intensities on their wavelengths as indicated subscripts in nm. The fluorescence peaks at 363nm and 460nm might be induced by collagen containing complex, elastin and/or reductant NAM,respectively. To normalize absolute intensity level of the LIE spectrum the intensity of the fluorescence at 507nm was utilized. Lower EI value was expected for eschar. Thermal damage of tissue was consistent with EI. We could obtain following in vivo El value. 86.9±24.5 (mean±S.D., and so forth) at surface layer of eschar, 83.2±8.47 at mideschar, 126±39.4 at deep layer where slight hemorrhage was noted. Further study is necessary to apply our method to actual debridement.

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The authors evaluated the pathological feature of atheromatous plaques of rabbit model in relation to spectral properties of laser-excited fluorescence of doxycycline (Dc: tetracycline derivatives) that has selectively accumulated to the plaques.
We administrated Dc intravenously to the rabbit models and detected the spectra of their resected aorta. Excitation source used id third-harmonic beam (355 nm) of Nd:YAG laser, whose immediated power and beam diameter are approximately 10μW and 100μm respectively. We employed Hematoxylin-Eosin and Elastica-Masson stains for each 5μm section along the spotts after spectral detection.
The result shows that the intensity ratio of atheromatous plaques, that calculated as a ratio of the photon count at proper fluorescence of Dc to that at auto-fluorescence of arterial wall, have pathologically a good relation to the extent of their atherosclerotic change. The intensity ratio mainly reflected the lipid deposits that found superficially in the plaques, and approximately fibrous changes contributed to reducing the ratio. On the other side, it is thought that the lipid deposits found deeply in the plaques were related with the high value persistence of intensity ratio, especially in the plaques with severe atherosclerotic changes.
We thought Dc is one of hopeful drugs that may give us a new diagnostic parameter of atherosclerosis.

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Since 1975, 41 cases and 48 lesions were treated by endoscopic polypectomy, laser and/or strip biopsy. These were 36 cases of mucosal cancer (m) and 12 cases of submucosal cancers (sm).
Each of residual rate after treated cases detected by endoscopic biopsy was 14.2% in m cases, 52.5% in sm cases and 20.8% in total cases.
We carried out combined endoscopic therapy with chemotherapy using 5-FU and endoscopic Laserthermia to one case of early gastric cancer (IIc type, sm invasion).
We performed 5 times Laserthermia and Laser irradiation combined with chemotherapy (5-FU, 800 mg/day), and no cancerous cell in the treated area was seen after 1 year by endoscopic biopsy.

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The results of comparative study on Nd: YAG laser therapy (YAG) and photodynamic therapy using hematoporphyrin and argon dye laser (PDT) were reported.
The lesions were 60 endoscopically diagnosed early gastric cancers which were treated by either YAG (30 lesions) or PDT (30 lesions) more than 5 years ago Complete response (CR), disappearance of all tumor with negative biopsy for cancer which persisted for at least 4 weeks, were obtained in 16 of 30 (53%) lesions treated by YAG and 22 of 30 (73%) lesions treated by PDT. Recurrence of tumor was observed in 19% of the cases of YAG and 41% of the cases of PDT. For the lesions less than 1 cm, CR rates of YAG and PDT were 92%, 100%, and recurrence rates were 9%, 0%, respectively. For the lesions less than 2 cm,CR rates of YAG and PDT were 56%, 82% and recurrence rates were 7%, 44%, respectively. The efficacy (negative biopsy for cancer after the initial therapy) of YAG and PDT for the lesions less than 2 cm were 52% and 15%.
For the lesions exceeded 2 cm,CR was obtained in 2 of 5 (40%) of the lesions treated by YAG, but all the 2 lesions recurred after the initial therapy. CR rate of PDT was 50%(4 of 6 lesions) with recurrence rate of 25%.
Therefore, there were no significant differences in the efficacy of the initial therapy of YAG and PDT, if the size of lesion was less than 2 cm. However, PDT was superior to YAG if the lesion exceeded 2 cm.

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After the development of EST, various kinds of Lithotripsy has been used for fragmentation of large bile duct stones that can't be extracted by Basket catheter. Several centers have reported success in bile stone fragmentation and removal via percutaneously or via transpapillary by using various techniques. (mechanical stone extraction, ultrasonic lithotripsy, electrohydraulic lithotripsy, Nd: YAG laser) Some reports suggested that there was possibility of bile duct damage by using EHL or Nd:YAG laser.
In our hospital, almost of CBD stone was extracted by using Basket catheter or MHL. But 3% of cases has been adapted to EHL.(guided by PTCS or PCPS) In this report, five cases with large bile duct stones were treated successfully with pulsed-dye laser.(Two cases were guided by PCPS, three cases were guided by PTCS.) Lithotripsy was performed under direct vision with choledochoscopes, and there were no significant complications.
Pulsed-dye laser is thought to effect fragmentation by laser light absorption onto the stone surface. The light may initiate a plasma on the stone surface that can rapidly expand and collapse, initiating a mechanical shock wave that has less bile duct injury. Pulsed-dye laser seems to be safe and effective in endoscopically directed lithotripsy of large bile duct stones.

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This is the first report that linear polarized light was irradiated around the area of stellate ganglion percutaneously to patients of shoulder hand syndrome after stroke. Super lizer HA-30 (Tokyo Iken) was used. Non-polarized light from a tungsten lamp led to the hand probe and converted to linear polarized light through linear polarizer. Light was irradiated with the condition of 147 W/cm², 4.9 W/cm²/sec through a probe of 3.5 mm diameter. Twenty shoulder hand syndrome patients after stroke were treated. After irradiation, range of joint movements (ROM) increased, spontaneous pain relief was obtained, orpain on joint movement decreased in eighteen of twenty patients (90%). The effects continued for average 31.8 hours. There was no side effect.

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Eight RA patients with pain in one side or both knees over definite by the ARA criteria participated in a study. Low power laser irradiation treatment has an excellent clinical and pathological anti-inflammatory effect.
The laser used in this study was a Ga-Al-As diode laser with a 830nm wave length, a 10mW continuous wave of energy output and with a power density of 31.4 Watt/cm². Synovial scintigraphy is useful for evaluating the inflammatory activity of RA. A higher radionuclide arthritis index (RA index: knee joint counts/Bone counts of the center point of normal tibia) shows a non clinical effect, where as the low index definitely indicates the group of clinically effective improvement through irradiation.
RA index of 6 knees of the 8 patients decreased after one time treatment a week for 7 months. All knees of the decreased-RA index group were effective cases of low power laser treatment. This study shows a good relationship between the change of the RA index after laser irradiation and the clinical effect.

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Sixty-two patients with chronic musculoskeletal pain took part in a blinded, controlled study to assess the effectiveness of 12±2mW continuous wave Ga-Al-Arsenide (830±20nm) laser treatment. Of 62 patients 10 were cervical spondylosis, 7 periarthritis of the shoulder, 11 shoulder-hand syndrome after stroke, 20 lumbago, 8 osteoarthritis of the knee and 6 others in etiology. The subjects were assigned with a random numbers table into a control group or a treatment group. In the treatment group of 32 subjects, each was irradiated for ten minutes per day for five days over the painful area with four channel suction type probes via a fiberoptic delivery system. Treatment in the control group of 30 subjects was identical except for no emmision of laser beam in the same device.
The differences between the groups were significant in improvement of range of motion (ROM), pain and satisfaction with chi-square tests (p<0.05, 0.01, and 0.01, respectively), as well as in the ordinal variables with Wilcoxon rank-sum test(p<0.01). Adverse effects were rare and minimal with mild erythema in the treated area, which was secondary to suction of the probes.

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This study was designed to investigate the effect of He-Ne laser (λ=632.8nm, 8.5mW; Senkou Med. Mgf. Co., Tokyo) irradiation on human red cell deformability.
Blood samples were obtained from hematologically normal adult donors by venipuncture. Red cells were washed and adjusted to 30% Ht with 0.9% NaCl solution (pH 7.00). Blood sample was divided into three groups. Each group sample was separated into seven 3 ml-working aliquots. The aliquots in Group 1 were irradiated for 0 (control), 1, 3, 5, 10, 15 and 30 minutes within 2 hours after sampling. The aliquots in Group 2 and Group 3 were storaged 5°C for 24 and 36 hours, respectively, and received the irradiations after 12 hours (in both Groups), 24 hours (in Group 2) and 36 hours (in Group 3) from the sampling. Red cell deformability was measured by the Nuclepore_® filter filtration and presented as the filtration rate.
The deformability was unchanged in Group 1 (fresh cell group) from the control value, but improved significantly in Group 2 and Group 3 (damaged cell groups) after the irradiation.
These results suggest that the irradiations of the laser improve the function of cytoskeletal proteins in damaged human red cells.

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We studied the effects of low-energy semiconductor laser irradiation on capillary blood flow in the skin.
Method: Twelve healthy adult volunteers were studied. The 1st cervical vertebra, brachial artery at the elbow, and median nerve at the wrist joint were each irradiated for 5 minutes with low-energy semiconductor laser (Ga-Al-As, 10mW, 780nm). Peripheral blood flow of the skin was measured at the center of the palmar aspect of the right index fingertip before, during and 20 minutes after stimulation using a laser Doppler blood flow velocimeter. Final measurement was carried out after 20 minutes of rest. Room temperature was maintained at 25±0.5°C.
Result: Upon laser irradiation of the 1st vertebra, blood flow rose to 39.2±6.7 ml/min/100g tissue (original value 21.9±3.6 ml/min) and this increase retained throughout the meassurement period.
Upon irradiaion, blood flow at the brachial artery and median nerve rose to 32.1±5.7 and 29.5±9.8 ml/min, respectively, but blood flow decreased there after, and was below its original value after 30 minutes.

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Since July, 1988, we have conducted laser irradiation for intractable decubitus in addition to various conservative therapies. The equipment used was a gold vapor generator and Nd-YAG laser 6000 (American Laser Sonic Co.).
Summary: Underlining diseases included cerebrovascular diseases in 7 cases, palsy of the trunk or the extremities due to injury of the spine in 6 cases, post major operations in 4 cases, and diabetes mellitus, chronic renal failure, and alcoholic hepatitis in-one case each.
The size of the decubitus ranged from the size of a small egg to a human fist.
As for the effects, 15 of the 25 ulcers were completely cured (cure rate, 60%) and 10 ulcers were alleviated with remarkable reduction. No cases with exacerbation or non-effectiveness were not seen.
Conclusion: Laser therapy in addition to systemic therapy and local therapy appear to have superior effects for cases with intractable decubitus.

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We applied low power laser irradiation on cultured dorsal root ganglion (DRG) which was excised from mouse, Continuous wave Ga-Al-As diode laser of 830nm wave length and 20mW power output was irradiated for 5-15 minutes. Neurite elongation from DRG was inhibited significantly by laser irradiation. It also inhibited neurite elongation of single neuron isolated from DRG. Especially that of small diameter neuron was significantly inhibited.
By immunostaining, neurites including substance P and/or CGRP were shown to he affected severely. These results suggest that inhibitory effect of laser irradiation on neurite elongation may relate to the mechanism of pain attenuation.

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Low-power laser have been widely used in clinics, and successful application has been reported for pain control. However, due to complication of the precise mechanism and to paucity of the basic research, the clinical effectiveness of the low-power laser is yet to be evaluated. We have formed that the low-power laser has significant therapeutic effects for the patients with neurological diseases. The therapeutic effect is considered to be due to our efforts to improve the laser handpiece and the method of irradiation.
The low-power laser is defined as not to cause irreversible damage to the irradiated fields and their surrounding tissues. We used an intensity between 300 and 500mW, which is 10 times higher than the output-power of conventional equipments. The reason is that we have expected thermal effect in addition to the electromagnetic effect. This is a preliminary report on the use of Ga-Al- As diode laser (wave length: 810nm, peak power: 1000mW) for the treatment of neurological diseases; such as, facial palsy and lower lip paralysis.
The low-power laser was irradiated to the stellate ganglion with the direct contact method. Irradiation to the TSUBO (acupuncture points) is also performed according to the patients' symptoms. The irradiation time was 10-20 minutes for one time and it was repeated 1 time-2 times a week.
Here we report on the effect of low power diode laser to a case of lower lip paralysis. The effect was objectively evaluated by examining the cold vasodilatation.

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Recently, the desensitizing effect of low power laser have been studied, and many papers were reported. The details of the biological mechanism, however, not been well documented. In order to make this mechanism clear, we attempt to irradiate the laser to carrageenin induced edema which was made on rat's paw.
We have reported the result what the laser irradiation inhibited the development of edema on the rat's paw. However, these inhibitive effects were observed not only on the irradiated paw (the right side) but also on the unirradiated paw (the left side).
It has been reported that chemical mediators such as histamine, serotonin, bradykinin, were involved in the occurrence of carrageenin-induced edema on rat's paw. Therefore, it was thought that the laser irradiation affected those chemical mediators, was attempt to study whether will directly effect or not to those. So, we subcutaneously administered the mediators to a dorsal area, and then irradiated the area with the laser, The animals were divided into two namely the irradiated and control groups. Radiation was administered only to the left for 3 minutes, and repeated twice, namely at 5 minutes prior to phlogogenesis by each mediator, and just after inflammation. Immediately, after irradiation, 1% Evans blue was intravenously administered. After 30 minutes, the animals were sacrificed. The portion of the dorsal skin where transudation of the dye was found was excised to extract the dye. Quantitative analysis was then performed spectrophotometrically. Statistically, no significant difference in the quantity of the dye found on either side of the skin specimen was found between the two groups.
On the basis of these findings, it was suggested that the laser had no direct action on the chemical mediators.

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Partial labyrinthectomy with argon laser was performed on 62-year-old female for relieving from continual positional vertigo.
Laser labyrinthectomy consisted of singular neurectomy and destruction of the macula utriculi. For singular neurectomy, the posterior half of the round window niche inferior to the attachment of the round window membrane, was drilled and argon laser beam (1.0w×0.5sec, 40 times) was irradiated. The macula utriculi was also irradiated using argon laser (1.0w×0.5sec,15 times) after stapedectomy. The oval window was sealed using tragal perichondrium. A teflon piston (0.6mm×4mm) connected the long process of the incus with the perichondrium.
The patient's positional nystagmus disappeared and her hearing was maintained after laser labyrinthectomy.

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This is a case report of Low Power Laser (LPL) irradiation near Stellate Ganglion (SG)and on JOKAN (Acupuncture Point: G3) for abnormal sensation at Eyelid that is supposed to have no relation with ocular disease.
Three kinds of irradiation were tried: Near SG, on JOKAN (Individual Irradiation) and near SG and JOKAN together (Two points Irradiation).
The immediate effect (after 20 minutes) and the continuous effect (after ca. 12 hours) were observed and the following results were obtained.
1) The immediate effect was not observed by individual irradiation, but moderately by two points irradiation. The continuous effect was moderately shown by individual irradiation, but two Points irradiation was more effective.
2) The next morning after irradiation, the effect was not found by individual irradiation, but there was effect by two points irradiation.
3) In some cases, it is more effective to irradiate near SG in addition to acupuncture points and pressure points.
4) No adverse reaction was observed in any case.

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The effects of corneal refractive surgery using an excimer laser were investigated in rabbits. Incisions parallel to the corneal limbus at 12 o'clock were made at a distance of 3 mm and 5 mm from the limbus.
Corneal refraction was measured 1 to 12 weeks postoperatively.
Irradiation was carried out using an argon-fluoride laser (wavelength: 193 nm).
The laser was operated with an output energy of 320 mJ/cm²/pulse and a repetition rate of 100 Hz for 15 seconds. The depth of the incisions was 2/3 of the corneal thickness. 1) Both methods produced flattening of the perpendicular meridian against the incision after surgery. One week later, however, a larger refractive correction of 0.88 diopter (D) was obtained with the incisions 5 mm from the limbus than 3 mm from limbus.
2) Changes in horizontal refractive power 3 mm from the limbus were not the same, but all of the incisions 5mm from the limbus were due to myopic change.
3) The largest refractive correction in vertical section was obtained 2 weeks after surgery, and the refractive correction decreased gradually.
However, 12 weeks later, refractive corrections of 0.81D as result of the incisions 3 mm from the limbus and of 1.07D 5 mm from limbus were obtained.

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We treated 6 eyes of 6 patients by using transscleral cyclocoagulation with a diode laser (wavelength; 810nm). Contact transscleral cyclocoagulation was performed on 4-eyes with a Nidek diode laser D. C. 1000 with a endo coagulation probe. While noncontact cyclocoagulation was done on 2 eyes using an improved diode laser (Nidek D. C. 3000 with a new experimental probe). This treatment was performed on patients with absolute glaucoma who had previously undergone intraocular operation. Postoperative observation on each case was carried out for a period of 1 to 4 months, after cyclocoagulation had been performed.
Variables for treatment included the following: we coagulated the area 2 mm to 4 mm from the surgical corneoscleral limbus with 14 to 37 shots for a period of 0.5 to 1.0 second each with an energy of 720 to 1200 mW.
In two cases, additional coagulation was needed, but at the final observation it was found that intraocular pressure had decreased by 8 to 26 mmHg. Therefore, it appears that the diode laser can be safely and effectively used for transscleral cyclocoagulation, although long-term observation is still necessary.

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The biochemical properties of Zinc-sulfo-phthalocyanine mixture (ZnSPc: groupII) and Zinc-tetra-sulfo-phthalocyanine (ZnTSPc: groupI) were investigated against HeLa cells by spectrophotometric analysis. Cellular uptake was observed only by groupII. The affinity of groupII with protein is stronger than that of groupI. The result of photohemolysis experiment indicates that the cell membrane is the main target of cells by PDT with groupII.

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In order to clarify whether photosensitizers are incorporated to the chronic inflammatory lesion, we examined the distribution pattern of PH1126 (HAMARI PHARM. Co.) in the adjuvant arthritis of rats.
By measuring the intensity of the spectrum of PH1126 exited by excimer dye laser, a large amount of PH1126 was shown to accumulate into the synovial tissues and thymus and remain there over 96 hours. It was an aggregation of macrophages that showed the luminescence in the synovial tissue, and T cells in the thymus. It can be said that photosensitizers are incorporated well to the macrophages in the synovial tissues and young T cells in the thymus.

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Although numerous studies to isolate and characterize the components which play central role of hematoporphyrin derivative (HpD) in view of tumor-selective accumulativeness has been carried out, the conclusion remains unclear.
To investigate whether the components, which were highly accumulated in cultured tumor cells in spite of low contents in HpD, contribute to tumor-selectiveness of HDD or not, intracellular level change of the components after HpD treatment were examined by reversed-phase HPLC analysis on normal (human diploid fibroblast strain, WI-38 and rat gastric mucosa derived epithelial cell-line, RGM-1) and tumor (human gastric cancer derived epithelial cell-line, MKN-28).
Time-course experiment on decrease of intracellular level of the components (main four peaks on HPLC chromatogram) after HpD treatment revealed that one of the four components is retained longer in cells than others, but significant difference was not observed in decrease rate among the cell-lines.
However, WI-38 cells were extremely damaged than MKN-28 and RGM-1 cells by co-treatment with HpD and irradiation with light.

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For a rational therapeutic use of photodynamic therapy (PDT) in the oral region, histologic changes were quantified and the influence to cell proliferation was assessed in normal C3H tongues subjected to the following protocols: a) 2.5 mg/kg hematoporphyrin oligomers-24hr interval-180 J/cm² or 15 mJ/pulse/cm², 20 min (630nm light emitted from pulsed Nd: YAG dye laser, 10Hz); b) 10-24-180; c) 20-24-180; d) 20-24-90; and e) 20-3-180.
One day post-PDT, distortion of lingual papillae, loss of keratohyalin granules, blistering, edema formation, neutrophilic infiltration and congestion of blood vessels were observed, the severity being a function of increased photo-sensitizer and light dose and decreased time interval between them. Computer assisted image analysis revealed increase in the absolute cross-sectional areas, the connective tissues occupying the major portion. Counting delineated a decrease in the number of blood vessels. Bromodeoxyuridine immunohistochemistry indicated a stimulative effect on cell proliferation with a rise in the number of S phase cells especially in the 20-24-90 and 20-24-180 groups.
Restoration of quantitative data to the untreated control levels was attained 5 days post-PDT except for the 20-3-180 group whose further evaluation was deferred due to deaths possibly from traumatic shock. Residual edema and chronic inflammatory reaction were persistent in some mice.
Under the commonly employed doses, as a-d, above, PDT may be rendered safely in the mouse tongue model.

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Since 1980, 184 patients with central lung cancers, including 48 cases of endoscopically evaluated early-stage lesions have been treated with PDT at Tokyo Medical College, and CR rate of 77% was achieved for early-stage lesion. However, wider clinical application of Photofrin II as a photosensitizer for various cancer is hampered by the potentially serious and prolonged skin photosensitivity that can last for three weeks or more. In those patients who did not heed recommendations to avoid sunlight and use sunscreens. 90% of patients had skin photosensitivity with currently recommended doses of Photofrin II (2mg/kg) in our experience.
To prevent those side effects and reduce the impatient period, we recently tried to give reduce doses of Photofrin II by BAI. Five patients with endoscopically evaluated early-stage carcinoma and two with advanced carcinoma of the lung were given 0.7mg/kg of Photofrin II by BAI 48 hours before PDT.
Complete response was obtained in all early-stage cases and those was no evidence of skin photosensitivity when exposed to outside light under surveillance at one week after PDT.

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In photodynamic therapy, the development of effective photosensitizers, which absorb the light with long penetration depth for tissue, has been required. In this study, methylen blue, which has the relatively long absorption wavelength at 665nm, was applied for photodynamic therapy. Methylen blue was easily incorporated into HeLa cells. BY the laser irradiation of HeLa cells containing methylen blue, the cells were strongly damaged. From the electron microscopic observations methylen blue, seems to be suitable in photodynamic therapy in clinic.

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At present, we report the study on basic features of tetracycline series antibiotics, available at preset, for photosensitive substances. NPRMTC, PRMTC, MINO, DOXY and OTC were potent in order of absorption spectrum and absorbance at 355nm in each TC series antibiotics. DOXY, PRMTC, OTC, NPRMTC and MINO_were potent in order of fluorescent intensity in third harmonic beam of Nd: YAG laser (355nm) and MINO hardly radiated fluorescence. The feature of each drug for absorption and wash out on domestic rabbit arteriol sclerosis site was studied with TC series antibiotics for intravenous injection. When arteriol sclerosis site vessel was observer with time, with wash out with PBS on 4 types of antibiotics, the fluorescent intensity ratio to normal site vessel was significantly high. Doxy>NPRMTC≅PRMTC≅OTC>MINO was shown in order of fluorescent intensity ratio, in change with time among each type or drugs.

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We succeeded in diagnosing the atherosclerotic lesions with photosensitizer using Mixed Bundle Fiber (MBF). MBF can irradiating laser and detecting fluorescence contact. Another type of catheter with square arrangement of 4 MBFs was also prepared.
Fluorescence spectrum analysis was performed in aortae of atherosclerotic rabbits, in vivo and in vitro.
Fluorescence probe (DHE, Doxycycline) made clear definition between both atherosclerotic lesions and normal walls.
MBF may be suitable to evaluate the atherosclerotic lesions and could realize auto-controlling laser angioplasty system.

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For more safe and efficacious laser angioplasty, it is important to ablate the atherosclerotic lesion by as lower energy as possible. This study examined the enhancement of laser ablation in blood by using a photosensitizer.
The laser source is Argon ion laser and Hematoporphyrin Derivatives (HpD) is used as a photosensitizer. Atherosclerotic rabbits, whose atherosclerotic lesion in the aorta were induced by balloon damage and by 2% cholesterol diet, were divided into two groups, that is, HpD (5mg/kg) administration, and non-administration as controls. The laser energy was 100mW-2000mW and the exposure time was 1sec.-180sec. Laser ablation was performed in saline and in blood.
Atherosclerosis lesions using HpD were vaporized by lower energy and shorter time level than controls. It was also recognized that each ablation was enhanced in blood. Using HpD, the laser ablating threshold of atherosclerosis intima was lowered and the ablating volume was increased. Laser ablation without the perforation or the injury of normal wall will be accomplished by this method.

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An applicability of pulsed Ho:YAG laser and continuous-wave uv Ar laser for the laser angioplasty was studied by investigating an ablation characteristics of these laser irradiations in saline in vitro. We selected Ho:YAG laser in it region, and Ar laser in uv region for therapy laser, since these laser lights have large absorption for vascular tissues (30-70cm^-1), and can be used SiO₂ glass fiber for laser angioplasty. We employed a SiO₂ fiber of 200μm in core-diameter, with 0.33 to 3.82kW/cm² in intensity at the end of the fiber. The specimens were human abdominal aorta, including fibrous fatty plaque and calcified plaque. The ablation for Ar laser had a sufficient ablation energy efficiency with a good selectivity for yellow plaque. The ablation for calcified plaque using Ho:YAG laser had three times as efficient as soft region. Both laser irradiations could create sharp ablation hole. Ho:YAG occurred with the dissection at high fluence irradiation. Therefore, we determined applicable ablation ranges, 0.2-0.4kJ/cm²/Shot for Ho:YAG laser, and 1.0-2.5kW/cm² for Ar laser. Comparing these characteristics between Ho:YAG and uv Ar laser performance, we conclude that Ho:YAG laser may be one of proper choice for all kind of vascular tissues, and Ar laser may offer the best performance for ablation without calcified plaque.

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The percutaneous transluminal coronary angioplasty (PTCA) is currently a widely accepted procedure in the treatment of patients with ischemic heart disease. However, an occasional occurrence of abrupt closure and relatively high incidence of restenosis following PICA still remains problematic. Although the mechanism of restenosis is unclear, increased plaque disruption may be a contributory mechanism. So smoothing the luminal surfaces and reducing the elastic properties with the use of tissue-welding effects of thermal balloon angioplasty could be beneficial.We therefore studied the immediate effects of controlled heat application to the vessels using a newly developed argon laser-heated 3.0mm×20mm hot balloon catheter (HBA). Acute effects of HBA on normal arterial lumen in comparison with those of balloon angioplasty (BA), 5 rabbits were subjected to HBA of an external iliac artery with 15 sec laser irradiation and BA of the contralateral artery with 2 minutes. Angiography was performed before and immediately after HBA/BA. HBA-treated arteries showed an increase in diameter over that of BA-treated arteries. Scanning electron microscopic examination of the endothelium showed less platelets adhered on HBA-treated arteries compared with BA-treated arteries. No evidence of spasm or thrombosis was observed.[Conclusion] HBA decreases vessel elasticity at the dilation site and increase luminal diameter acutely and might induce less mural thrombus than BA chronically.

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Percutaneous transluminal laser angioplasty (PTLA) was performed in 55 patients with the occlusive diseases of the peripheral arteries. Argon laser and an optical fiber delivery system with metal tip probe were used for PTLA. Primary clinical success was achieved in 55 of all 70 (79%) lesions. In 44 of 55 (80%) lesions with clinical success, additional dilatation was carried out with a balloon catheter. The length of the lesions was significantly longer in a group of the 52 lesions with clinical failure, and also, the number of the calcified lesions increased remarkably in patients with clinical failure. The clinical success rates were 92% in the lesions shorter than 3 cm, 100% in 3-10 cm lesions, and 71% in the lesions longer than 10 cm in 35 femoropopliteal lesions, whereas the clinical success rate was significantly lower (p<0.05) in long lesion(≥5cm) than in short lesion (<5cm) in 35 iliac lesions. Reocclusion tended to occur more often in patients with poor distal runoff in comparison with patients with good distal runoff. At 44 months of follow up, the cumulative patency rate (CPA) was 87% in 48 cases with clinical success. In the 30 stenoses and 18 occlusions, the CPR were 91% and 82%, respectively. In the lesions shorter than 3 cm, 3-10 cm, and longer than 10 cm, the CPR were 95%, 86%, and 70%, respectively. These results suggested that PTLA might be a useful treatment for patients with chronic peripheral arterial occlusion and improve the long-term patency rate by diminishing restenosis more than conventional balloon angioplasty.

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To evaluate the mechanical factors that determine ablation depth rate in vivo, we studied samples of canine aortas in a model system. The segments of atherosclerotic arteries were irradiated using a 308nm XeCl excimer laser energy delivered through a fiberoptic that was held in constant contact with the tissue.
The effect of the mechanical factors, such as the applied pressure and laser pulse repetition rate, on the ablation depth rate was studied. The ablation depth rate was found to depend on applied pressure and laser pulse repetition rate. That is, the ablation depth rate increased as applied pressure and laser pulse repetition rate increased. No effect of the laser pulse repetition rate on ablation depth rate was observed when the tissue was irradiated by a focused bare beam (applied pressure=0). Histological finding suggested that a mechanical tearing of tissue occurs.
Conclusion: Our study suggested that in a clinical setting, not only a laser energy but also the mechanical factors such as the applied pressure and laser pulse repetition rate affected the ablation depth rate.

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Experimental results of fiberoptical delivery and a reaction on atherosclerotic tissue using a long pulse excimer laser are described. In order to improve the maximum energy delivered through optical fiber, a long pulse excimer laser which had the pulse duration of 100nsec was examined. The quartz fibers with both 300 and 400μm core diameter were used for the laser energy delivery. As a result, the maximum energies transmitted through optical fiber were 30mJ/pulse with 400μm core fiber and 16mJ/pulse with 300μm core fiber. And the average energies transmitted constantly were 20mJ/pulse and 10mJ/pulse with 400μm core fiber and 300μm core fiber, respectively. The energies were about 3 times lager than these using a conventional short pulse excimer laser. The laser energy delivered through the fiber was irradiated on the sample of atherosclerotic aorta of a rabbit in saline to investigate the tissue reaction on atheroma. The result shows that the fiberoptically delivered energy of long pulse excimer laser was enough for the destruction of atherosclerotic tissue.

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Since October 1990, laser valvoplasty have been performed using the energy from a pulsed Nd:YAG laser. The laser probes are being used as a device for commissurotomy of the stenotic mitral orifice. Commissures of the human stenotic mitral valve were obtained intraoperatively at the mitral valve replacement. By the ablation with the laser irradiation through the laser prone. successful commissurotomy was obtained. At the same time, good visual field near the commissure by the endoscope could be obtained in this study. And good aiming ability of the endoscope to the commissure could be obtained by developing the special guiding system. Laser mitralplasty may reduce the number of patients requiring the open mitral commissurotomy and this method may increase the number of patients treated without thoracotomy.

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Recently, a surgical intervention has been employed for protecting of ventricular tachycardia, that paroxysmal supraventricular tachycardia due to atrioventricular (A-V) nodal reentry is refractory to medical therapy. However, implantation of a permanent pacemaker by this method is necessary. We have studied for inducing the complete A-V Block with application of Argon-laser and Nd; YAG-laser without extracorporeal circulation. Sixteen mongrel dogs were used in this study. The Laser-probe was inserted and located under general anesthesia from their right auricle to the A-V node. And then, the probe was guided to the A-V node by manipulation, and monitoring electrogram of His bundle. Thereafter, the Laser-ablation was initiated on the A-V node. Laser power was set up at the tip of the fiber from 6W to 10W, the time of ablation between 3 and 5secs. Consequently, the complete A-V Block was produced in all dogs. After induction of complete A-V block, its hemodynamics were observed and recorded. Total energy for inducing of the complete A-V block by Nd; YAG-laser was in average of 68.2J. And, in case of Argon-laser it was 224J in average. It could be recognized in this study that, Nd; YAG-laser reached more deeper region than that of Argon-laser. All dogs deteriorated after the complete A-V Block. However, their hemodynamics were improved, whenever the rhythm was controlled by pacemaking. <Conclusions> 1) The complete A-V Block could be easily achieved by laser ablation without extracorporeal circulation. 2) Nd; YAG-laser was more effective to induce the complete A-V block than Argon-laser.

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We performed basic study of laser irradiation for the beating atrium, to evaluate its applicability for the atrial electrical isolation. The atria of 9 mongrel dogs were irradiated with Nd-YAG laser using the contact method. The target of electrical isolation was the right atrial auricule. Irradiation was stopped when right atrial auricular electrical potential disappeared. The success of isolation was determined using postoperative electrophysiological study. Isolation was successful in 7 (820±77.5J), and unsuccessful in 2 (790±30J). Transmural coagulation necrosis of the atrial muscle was noted. In conclusion, it is possible to obtain safe atrial isolation using contact laser irradiation.

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Coronary spasm or acute coronary occlusion can be serious complications of transluminal coronary laser angioplasty. It was postulated that alterations in arachidonic acid metabolism might contribute to these complications. Six mongrel dogs were anesthetized and mechanically ventilated. The hearts were exposed and an angiocatheter, 14 gauge in size, was inserted into the left anterior descending arteries. Then bare ended probe (BEP) and metal tip probe (MTP) of 1.5 mm in diameter were inserted into the coronary arteries through the angiocatheter, and Argon laser ablations were carried out with the heart beating. Coronary arterial plasma thromboxane and prostacyclin(by standard radioimmunoassay of the metabolites TXB₂ and 6-keto PGF_1α ) were monitored before and after laser ablations. Plasma 6-keto PGF_1α levels were unchanged or slightly increased in all cases. Plasma TXB₂ levels were not remarkably increased in case of uncomplicated laser ablations. However, these were markedly increased in case with laser complications, such as perforation and thermal vascular injury. These results suggest that uncomplicated laser ablations in the coronary arteries may not contribute to coronary spasm and coronary occlusion from the aspect of arachidonate metabolism.

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A new model device to simulate human artery network was developed to evaluate performance of newly developed CO laser coronary angioplasty system. The effectiveness of tip manipulatability of our laser angioscope catheter for large volume ablation of atheromatous plaque was studied using the new model device. Since the model device was simulate pathway of human femoral approach catheterization, we precisely evaluate manipulatability of the catheter tip. A 90% model stenosis which was consisted of human atheromatous artery wall was installed in segment #7 on left coronary artery of the model. The repetitive CO laser irradiations were irradiated to model stenosis. The model stenosis was clearly improved from 90% to 70% in stenosis rate. The effectiveness of tip manipulatability for large volume ablation was successfully demonstrated.

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The endoscopic coronary laser angioplasty system using excimer laser thin diameter endoscope has been developing.
In order to improve the transmitted energy through the laser fiber, long pulse excimer laser was used for the experiment. This laser could oscillate 308nm wavelength (XeCl) with maximum I 50m.1 per pulse energy and 100ns pulse duration.
In order to improve the bending function at the tip of the endoscope. the endoscope, which had 4 directional bending function at the tip and had one channel for the laser fiber, was developed and evaluated using organized thrombus inside the goat's carotid artery which was made beforehand by the interposition of artificial graft with I cm length.
Using this long pulse excimer laser, the transmitted laser energy was improved to be maximum 30mJ/pulse and average 15mJ/pulse using the optical fiber for ultra violet laser transmission with 400μm core diameter. The energy was enough to destruct the atheroma with non-contact irradiation.
The developed endoscope had 1.5mm diameter, 1.7mm diameter at the tip and 150cm inserting length. Th endoscope had 4 directional bending function with 10-20° for each direction. The laser could be scanned to organized thrombus to destructed through this endoscope. This endoscope improved the scanning ability of laser irradiation. As the endoscope had small diameter enough to attach the coronary artery, it is possible to perform the experiment with coronary artery for the next step.

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