A series of alkyl ether based on Ga porphyrin bisaspartic acid are prepared. Relationship tumor tissue affinity with chemical structure of these Ga complexes have investigated by means of Rt. at HPLC, biodistribution on N₂-PLS method and HPLC analysis, and interaction with proteins (HSA, LDL, HDL, transferrin). The decyl ether (n=10) -bearing Ga complex is one of the most efficient sensitizers on tumor tissue affinity. The corresponding Mn analogue are also similar to Ga complex. Based on these results, we are synthesized porphyrin derivatives shown Scheme 1.

View full abstract

To clarify the mechanism of photodynamic therapy (PDT) using ATX-70 (Gallium porphyrin complex) and a pulsed Nd: YAG laser with a Q switch (pulsed YAG laser), 36 female nude mice transplanted human pancreatic cancer were irradiated with a lower power semiconductor laser with or without ATX-70. Nude mice were divided into 3 groups; 1) control group (n=10), 2) experimental group 1 (n=14): pulsed YAG laser irradiation in a condition of 50mW and 2 kHz. 3) experimental group 2 (n=12): a frequency doubled YAG laser (532nm laser) in a condition of 15mW and 3kHz. For nude mice of experimental groups, ATX-70 was injected intraperitoneally in a dose of 25mg/kg 24 hours before and the tumors were irradiated for 10 minutes with the end of a quartz fiber inserted in a depth of 2mm. The results were as follows; 1) the difference of the therapeutic effects between control and irradiation groups with or without ATX-70 could not be recognized in experimental group 1 (pulsed YAG laser irradiation), 2) the necrotic areas of groups irradiated by 532nm laser were significantly larger than those of control group and furthermore the necrotic areas of the group irradiated with ATX-70 were rather larger than those of anther group irradiated without ATX-70. The peak power of pulsed YAG laser on the above condition wasthought to be insufficient to cause the effect of PDT On the other hand, 532nm laser may cause the therapeutic effect with ATX-70. It is suggested that results would become a key to analyzed the mechanism of PDT with ATX-70

View full abstract

Because of absorption band and tissue distribution properties, Mono L-aspartyl chlorin e6 (NPe6) is looked to as the useful photosensitizer for PDT. It is well known that NPe6 produces free radicals that induce tumor response. We performed quantitative analysis of NPe6 in saline using a diode laser (664nm). Our experiments showed the degradation rate of NPe6 solution of 3.13, 6.25, 12.5, 25, 50 and 100μmol/l exposed to 100mW and 100J light were around 60%. Otherwise the degradation rate of NPe6 solution of 12.5μmol/l exposed to 50, 100, 150mW and 100J light were also around 60%. When absorbance at 654nm decreased, the fluorescence of NPe6 at 664nm also decreased. Cleavage of the tetra pyrole structure was suggested.
Photobleaching of NPe6 did not depend on the initial concentration of NPe6 and laser power.

View full abstract

Photodynamic therapy (PDT) is a medical treatment which use photodynamic action between photosensitizer in tumor and laser light, so it is essential for light to reach tumor. To examine about possibility of PDT for the tumor that exists in deep part, we investigated laser transmission and scattering in tissue using optical parametriic oscillator pumped by third harmonics of Nd: YAG laser (YAG-OPO laser, Ishikawajima-Harima Heavy Industries Co., Ltd.). The intensity of the light through the tissue sample was detected by a photodetector. Besides, the tissue temperature during laser exposure was measured by embedded thermocouples. When the sample was a 10mm thick slice of cattle tissue, the transmitted light of 664nm laser is about 10 times as intense as that of 630nm laser. When the tissue sample was a slice of pig tissue, the transmitted light of 664nm laser and 630nm laser were of equal intensity. These results suggest that the transmission of laser light depends on absorption by the porphyrin in tissue.

View full abstract

The purpose of this study is to evaluate the photodynamic therapy (PDT) by the intertumor movement type laser irradiation methods using the Polipuropiren type tube for the advanced cancer.
Materials and Methods: The rabbit VX2carcinoma transplanted into the rabbit dorsal side of the foot. When the developing cancer reached up to the size of 32×20×20mm. A dose of 5mg/kg of the photosensitizer, a Hematoporphyrin derivative made by QUENTRON OPTICS company was administered intravenously. Immediately 24hours after administration, the polypropylene type tube was inserted into the tumor with the fiber inside which rotates with an irradiation condition of 18mm/min,12R. P. M.. A pulse repetition frequency of 80Hz and energy per pulse of 5mJ was applied consequently, along a tube with the tumor was 15J/mm.
Results: The tumor around the tube was destroyed up to the extent of 28mm in diameter. We suggest that the PDT using the intertumor movement type laser irradiation methods is applicable for the treatment of advanced cancer.

View full abstract

To investigate effects of the combination of ultrasonic irradiation on the photodynamic therapy (PDT). PDT combined with ultrasonics was performed on the erythrocyte and the cytocidal effect was evaluated from the hemolytic quantity using the absorption wave length at 414nm. In this study, the three type of PDT were carried out and compared. One was a PDT with HpD by Ar-Laser irradiation, and others were with Pc by He-Cd or Kr Laser irradiation. Some ultrasonic power (1MHz, 0.2W/cm²) was irradiated to the all types of PDT at the same time as the laser irradiation. The results indicated that cytocidal of PDT combined with ultrasonic was better than that on an ordinary PDT in this study.

View full abstract

Novel interstitial photodynamic therapy was performed in canine transmissible sarcoma (CTS), utilizing photofrin II and excimer dye laser. First, photofrin If was injected intravenously at a dose of 5mg/kg body weight. Thirty-two hours later, a laser-proof plastic tube was implanted into CTS, followed by an insertion of optic fiber and a photoradiation from the inside of tube. The tip of optic fiber rotated and performed an alternative movement. The mean diameter of tumor necrosis rapidly increased with an increase of light energy below 240J/cm, namely it was 17mm at 120J/cm, and 20mm at 240J/cm. Beyond 240J/cm,it gradually increased to 24mm at 1200J/cm. The side effect of cutaneous tissue showed an open ulcer at 240J/cm, and a scar healing at 120J/cm. The thermal effect of laser light is minimal or negligible below 480J/cm.

View full abstract

We investigated the sensitizing efficacy (yield of active oxygen production) of pheophorbide derivative (PH-1126), phthalocyanine derivatives (Al-Pc) and hematoporphyrin oligomer (HpO) by spin trapping method of electron spin resonance in cethyltrithylammonium bromide (CTAB) solution or human malignant melanoma floating cells (HMF). In the results, (1) Type I reaction was predominant in 0.1mM-CTAB solution. (2) In 10mM-CTAB solution, Type I and Type II reactions included. (3) Type II reaction was predominant in HMF cell suspension. It was suggested that the formation of the sensitizers incorporated in HMF cells must be monomer form.

View full abstract

Photodynamic therapy (PDT) of cancer has been improved by the developments of laser technology and photosensitizers. However, we need a new sensitizer because of selective cancer therapy. PH-1126 was a derivative of pheophorbide-a and produced by Hamari Chemical Ltd.. In present study, we investigated the effect of liposome for PH-1126 distribution in C3H mice.
In the results, the concentration of PH-1126/tartarate in tumor increased 38hrs after the intravascular injection and then gradually decreased. In contrast, the concentration of PH-1126/liposome in tumor increased 24hr after injection and about thirty times larger than PH-1126/tatarate.
It is considered that PH-1126/liposome can be a useful sensitizer of PDT.

View full abstract

The authors per for med PDT, without any hyper ther mic effects, using a diode laser and NPe6 in an implanted fibrosar coma in mice and achieved tumor therapeutic effects. In the present study, PDT was per 5 hours following the administration of 5.0mg/kg NPe6. With 50, 100, 150 and 200J/cm², tumor cure rates were 20, 50, 70 and 90%, respectively. The ratio of the residual amount of NPe6 following 50, 100, 150 and 200J/cm² laser exposure to no laser exposure were 73.4, 36.2, 22.1 and 15.9% compared with control group respectively. These results suggest that a certain increase of laser light dose reaching deeper layer of tumor caused an incr ease in per cent cure. In addition, the recurrence of tumor depends at least partially on the total laser light dose reaching deeper layers of tumors.

View full abstract

Tumor therapeutic effects of PDT using NPe6 as a photosensitizer and diode laser as the light source on BALB/c mice bearing Meth-A fibrosarcoma were examined. The more dose and the shorter interval time, the better cure rates were obtained. To elucidate wether the cure rates correlate to the NPe6 concentration in plasma or in tumor, NPe6 levels were measured by HPLC analysis. In conditions with plasma or tumor NPe6 concentration of nearly 0, PDT was performed and cure rates were obtained. As the results, difference of cure rates seemed to depend on the NPe6 concentration in plasma rather than in tumor. Therefor tumor therapeutic effects using NPe6 can be anticipated by the plasma NPe6 concentration at the time of PDT treatment.

View full abstract

Twenty five patients with malignant brain tumor were treated with photodynamic therapy (PDT). 16 cases were glioblastomas, 4 cases were malignant gliomas, 5 cases were metastatic brain tumors. All patients recieved a 3mg/kg of HpD or HPE 48 hours prior to photoillumination. Photoillumunation was carried out at 630 nm wavelength of argon dye pump laser to glioma. In 15 cases, laser was irradiated interstitially to the tumor bed following tumor resection. In 5 cases, a stereotactic intratumoral photoradiation was carried out. The light energy density was 180 Joules cm². The total energy ranged from 411 to 3,840 Joules/cm². The median survival time for 16 glioblastom patients was 20.5 months with al, 2 and 3 year actuarial survival rate of 75%, 50% and 25%.

View full abstract

In the liver, hematoporphyrin derivatives (HpD), which are commonly used in photodynamic therapy (PDT), accumulate in normal tissues sa well sa in tumor tissues. Therefore,PDT has been considered to be contraindicated for hepatic tumor. This seems to be the main reason for the present lack of basic investigation on this issue. In this connection, we carried out a basic study on the possibility of PDT for the treatment of hepatoma, using PH-1126, a photosensitizer which is soon excreted from normal hepatic tissues, but accumulates in high quantities in the tumor. Using rabbit VX2 hepatic cancer model, we have been reported the suggestion of promising position of PDT in the treatment of hepatoma. Using YAG-OPO laser, usefullness of adjuvant therapy with PDT was conducted on four groups, tumorectomy one week after inplantation VX2 cells (group1), tumorectomy two weeks after (group2), PDT one week after (group3), PDT one week after and tumorectomy two weeks after (group4). The animals were sacrificed 4 weeks after the initiation of PDT to determine the therapeutic effect. A no-treatment group served sa a control. Judging from the hepatic tumor size, significant inhibition of proliferation of the tumor was suggested in PDT, in which necrotic area frequently appeared, compared with the control group. As for the rate of metastasis to the lung and liver, significant inhibition of metastasis was observed in groups 1 and 4 in comparison with the conrol group. From the above results, especially lung and liver metastatic inhibition, it is suggested that PDT may be an effective adjuvant therapy for hepatic cancer.

View full abstract

By employing an excimer dye laser (EDL) instead of an argon dye laser (ADL) as the excitation light source in photodynamic therapy (PDT) for early gastric cancer, the results of PDT were obviously improved, besides with less energy intensity of the irradiated laser light. The rates of local cure obtained by PDT with Photofrin I or II and ADL were 59% (13/22) in mucosal cancer, 53% (8/15) in submucosal cancer, and 57% (21/37) in total, while the rates of local cure obtained by PDT with Photofrin II and EDL were 100% (13/13) in mucosal cancer, 86% (6/7) in submucosal cancer, and 95% (19/20) in total. For the purpose of determining how much energy was required for a complete cure in early gastric cancer, and to compare the efficacy of ADL and EDL, the relation between the response (cure or no cure) and irradiated energy intensity (dose: J/cm²) were evaluated by the depth of cancer invasion and kind of laser used in PDT. EDL of smaller dose is more efficient than ADL in terms of photodynamic action. In these studies, the size of cancerous lesion was confined within 3cm in diameter or 7cm² in area. For the application of PDT for wider lesions of early gastric cancer, we employed a new model of an EDL, because it was necessary not only to increase the average output for the irradiation of enough energy to the wider lesion within a limited time, but also to protect the single quartz fiber from destruction. The characteristics of the new laser were 630nm of wavelength, 4mJ of pulse energy, 400kW of peak power, 10nsec of pulse width, 80Hz of frequency of repetition, and 320mW of average output. In conclusion the PDT was applicable for wider lesions of early gastric cancer by employing the new model of EDL, that could produce the average output of 320mW with repetition of 4mJ in 80 times per second.

View full abstract

The effect of Excimer Dye Laser(EDL) on photodynamic therapy(PDT) has been investigated in Ethylnitrosourea(ENU)-induced rat glioma model that is more similar to human glioma. Tumor location and size before and after PDT were determined by continuous slices of Magnetic Resonance Image(MRI). PDT was carried out with an optical fiber tip contacting with the brain surface nearer to the tumor, 48 hours after intravenous administration of hematoporphyrin derivatives(HpD) (2mg/kg). The anti-tumor effects were studied histologically about 4weeks after laser irradiation. In result, MRI after PDT implied tumor necrosis and no recurrence at the target area. Histological examination suggested that EDL has higher selection to tumor tissue rather than normal brain tissue. In the histological study in border zone between tumor and normal brain tissues after PDT, EDL was more selectively effectual to the tumor cells than Argon Dye Laser(ADL), although ADL has been investigated for glioma models established by implanting C6 cells, as reported previously in Part I and II. EDL had not adverse effects such as severe cerebral edema and hemorrhage. In coclusion, EDL in PDT was suggested to be more effectual on tumor cells and less invasive on the surrounding normal brain tissues.

View full abstract

We made a fundamental study on an appropriate injection schedule of 5-FU for the purpose of achieving higher concentration of 5-FU within tumor tissue in laser irradiation. [Method] We used 6 weeks old male BALB/c mice, and colon 26 cells were transplanted on abdominal walls of the mice by intracutaneous injection. And 10 days later, we used the mice. 5-FU 50mg/kg was administered intraperitoneally, 5/10/15/20min later tumors were treated by contact irradiation (10W 1sec: total 100J). They were extracted 30/60 min later, and we measured intratumoral 5-FU consentration. [Results] In the case of 5 min later irradiation, intratumoral 5-FU consentration was highest (30.4×103ng/g; 30min, 7.45×103ng/g; 60min) than other groups. [Conclusion] It is suggested that 5-FU be more effective when injected 5min prior to laser irradiation.

View full abstract

A new system, which we call the Real-Time Laser Flowgraphy, have been developed to visualize blood flow in retina using laser-speckle effects. In this paper, we build up a graphical user interface to ease the handling with a mouse operation. Some additional programs are developed to measure the width of the vessels, and to visualize pulsation of the blood flow in 3-D color graphics. The blood flow of human retinal arterioles and veinules are analyzed with this system. It is found that the blood flow evaluated from BR(the Blur Rate of the speckles) is influenced by the width of the vessels.

View full abstract

Experiments have been undertaken to quantify the thermal injury threshold for the plant (Cymbidium) leaf by pulsed CO₂, lasers as a function of exposure time (t) and irradiance(h). Experimental data graphically indicate the relationship of the form: h=14/√tfor the visible threshold lesion.
Meanwhile, the maximal surface temperature rise at the beam center can be theoretically related under some hypotheses as Δ=2h/√t/J√kρC√π, or by substituting physical constants ΔT=7.09h√t. This equation predicts the temperature rise of 103.6°C±11.7°C above the ambient temperature of 25.5°C for the threshold. Substitution of the mean ΔT value into the equation yields a time-irradiance relationship of the form: h=14.6/√t, which completely agrees with the graphically derived form as presented in Fig.6.
The equation is furthermore used to draw the family of isothermal curves for the leaf surface temperatures of 60°, 100°, 122°(TG onset of leaf thermal decomposition), 129.1°(ΔT=103.6) and 300°C(Fig.9). These isotherms suggest a critical surface temperature of 120-130°C for the threshold in plant leaves.

View full abstract

We have developed a Laser Flowgraphy system which calculates the relative velocity of blood flow. In this series of experiments, to bring relative velocity into relation with absolute velocity, we construct a velocimetry which calculates the cross correlation value for some particle-images detected by an image-sensor. Preliminary results of comparative experiments with a blood flow in frog's webs are shown.

View full abstract

An extremely weak light emission, usually invisible by the human eye, originating from the cells, tissues and organs of all living organisms is generally referred to as“biophoton emission”. This phenomenon is quite different from the well-known bioluminescence, that is visible light emission from firefly and luminescent bacteria for example. Our earlier studies on biophoton emission from the human body surface showed that the emission intensity is stronger in the index and middle fingers than the middle of the palm.
We are continuing a systematic study and highly sensitive measurements of biophoton emission from the human body surface. Its purpose includes to examine correlation between biophoton emission properties and other biological/physiological parameters, and their characterization.
In this paper, we report the measured results of ultraweak biophoton emission from three fingers of right and left arms, especially at the acupuncture points and abdominal region on fingers. Also these data measured for 48 hours are compared and examined for two young men.

View full abstract

Enteric nervous plexus is composed of myentericus plexus and subserous plexus. These plexuses extend in two dimensions, communicate each other, and form a pseudo three-dimensional structure. Nervous plexuses, stained with Di-4-Anepps, were observed with two methods; laser induced fluorescence and laser scanning confocal microscope. As a result, with the supra-vital staining method, the two plexuses could be observed in three dimensions without exfoliation of the plexus layers used in the traditional ways.

View full abstract

Basic studies concerning destruction of bacteria were reported by a few authors. The purpose of this study was to investigate bctericidal effect of argon laser with or without dye solution. We used MRSA, which was clinically isolated strain. Non contact laser irradiation was introduced by a quarts fiber. Three kinds of dye solutions (MB, PSP, IG) were selected in terms of safety to the body and their characteristic absorption. Their absorption maxima were measured by double-beam spectrophotomater. Bactericidal effect was determined by inhibition circle of bacterial growth. Among three lasers (argon, He-Ne, Diode), we investigated which laser was most effective on destruction of bacteria. By using electron microscopy, morphology of MRSA following argon laser irradiation was presented. Argon laser was most effective in three lasers with or without dye solution. Diode laser had bactericidal effect only in the present of PSP. He-Ne laser had no inhibitory effect of bacterial growth because of low output energy. Laser irradiation induced degeneration of cytoplasma and nucleoid of bacterial cell.

View full abstract

Although various kinds of lasers have become to beutilized as a scalpel, their effects on living tissue and its healing process have not been clarified yet.
The objective of this study is to compare the tissue reactions to Nd: YAG laser, high output diode laser (wave length: 810nm) and Er: YAG laser. Rat gluteal muscle was used for this study. Irradiated muscles were examined with light microscope and Scanning Electron Microscope (SEM) immediatly, 3days, 5days and 7days after irradiation.
Four layers of heat influences were observed in very wide and very deeprange with Nd: YAG laser cutting; from surface, char layer, necrotic layer, degeneration layer transient zone and normal layer. On the other hand, cutting surface by Er: YAG laser with high peak power and few Hz of pulserate was very sharp, and almost normal tissue was naked under the microscopic and SEM observation. However, very thin layered heat infuluence appeard on the surface of the irradiation of low peak power and several Hz of pulserates.
The wound by Er: YAG laser with high peak and few Hz showed the best healing in ones by these lasers.

View full abstract

Recently low power laser has been used widely in clinicas. The low power semiconductor laser irradiation shows wound healing and analgeic effects at the damagedsite.
However, the mechanism of these semiconductor laser effects has not yet been elucidated. To investigate the influence of semiconductor laser irradiation on cultured human keratinocytes, we studied the cell vialility using MTT assay and measured 1L-1α by ELISA. The number of viable cells was significantly increased by semiconductor laser irradiation for 15sec (115±0.5%of control) and 20sec (112±1.0%). The production of 1L-1α was also increased by laser irradiation for 20sec (increase of 33±5.0pg/ml). These results seggest that low power laser displays significant biological effects on human kerationcytes for activation.

View full abstract

The transmittance of ArF excimer lasers were improved through the Hollow Light Guide with aluminum reflector. The hollow light guide uses thin polytetra-fluoroethylene (teflon) slab and polyolefin coat as its material. The size of the guide's hollow part is 8mm width, 0.5mm height, with 100cm length. In the previous data, the transmittance and the maximum delivery laser energy of ArF laser were 50%/m and 20mJ/pulse, respectively. ArF laser damage on aluminum plate as the reflector of the hollow light guide and the transmittance have been tried in various atmosphere such as air, nitrogen, oxygen and helium. ArF laser damage of aluminum in nitrogen was the largest of atmosphere all and laser damage in helium was the smallest of them all. The transmittance of the hollow light guide in nitrogen and helium were higher than that in air and oxygen. Finally, the medium of laser delivery of the hollow light guide had better use the helium instead of the air. ArF laser transmittance was obtained 62%/m. We have tried the vacuum evaporated aluminum on phosphor bronze thin plate as the reflector. The transmittance is 85.6%at 15cm long higher than 82.4%of the aluminum plate as the previous reflector.

View full abstract

Our goal is the development of a new quantitative and non-invasive evaluation method of human embryo at in vitro fertilization-embryo transfer. We constructed a fiber-optic long-term monitoring system to evaluate mouse embryo activity. We set two fibers in orthogonal to the optical axis of a microscope to obtain the independent freedom for optical measurement. Since the change of blastomere and intercellular microstructure in embryo might induce the change in light scattering, we employed simple light scatteringmeasurement. A He-Ne laser with 632.8nin in wavelength was used as a light source. The laser light was delivered to the fixed embryo by a emission fiber (56μmΦ; core). The scattering light was collected by a detection fiber (400μmΦ; core) with high numerical aperture. The light scattering with various angle could be detected by changing the arrangement of these fibers. The micropipette and detection fiber were equipped by the individual manipulators with five freedom (X, Y, Z, α,β) to arrange the interrelation of the embryo and fibers. We used the lock-in amplifiers to reduce environmental light noise. The transmission detectivity of 0.13% was attained. The light scattering intensity was documented by a digital recorder with a 14 bit A/D converter. The maximum measurement term extended to over 8h with 1s collection interval. We think this long-term measurement is sufficient to monitor the division period of embryo. We could observe light scattering change, which may be attributed to the structural change in mouse embryo.

View full abstract

To propose Tm: YAG laser LTK (Laser Thermal Keratoplasty), we compared the porcine corneal coagulation depthes produced by Ho: YAG laser (wavelength=2.10 μm) and Tm: YAG laser (wavelength=2.01μm) in vitro. The radiant exposures of both lasers varied from 2.5to 22J/cm² and the number of laser pulses ranged from single shot to 20 shots. The corneal coagulation depthes were as thick as the human corneal thickness (0.7mm) for Ho: YAG laser and less than that for Tm: YAG laser in the case of single shot. The corneal coagulation depthes were thicker than the penetration depth of either lasers. In the case of varing the number of laser pulses, the relation between the corneal coagulation depthes and the radiant exposures was independent of the number of laser pulses for Tm: YAG laser (2 Hz), however the corneal coagulation depthes increased with the number of laser pulses for Ho: YAG laser (4 Hz). The energy efficiency of the coagulation gave the reason why the depth of corneal coagulation were thicker than the penetration depth. These results demonstrated the capability of Tm: YAG laser LTK without endothelium injury.

View full abstract

This paper describes a new method developed for the study on regeneration of enteric nerve plexus after laser photocoagulation necrosis. Under conventional techniques, in which the tissue must be fixed and the mucosa and smooth muscle are peeled off, degenerated enteric nervous systems have been observed to regenerate the structure and function.
In this study, we succeeded to observe fine images of a myenteric plexus without the complicated processes. Using the confocal laser scanning microscope with Di-4 Anepps, the process of regeneration of the nerve fibers, glial cells and basal laminae was observed. Just after laser photocoaguration, there were no glial cells in a ganglions of the plexus, however 18 hours later, the ganglion was again filled with glial cells.

View full abstract

The semiconductor laser (laser diode: LD) technologies have been expanded rapidly in the industrial world. Their high power, high efficiency and long life time were achieved practically. Applications of the high power LD are the laser source of laser printer, barcode reader, communications, optical memories, laser processing and therapeutic medicine. The pulsed laser diodes are applicable to the laser range detection system and the temperature distribution sensor. In the recent trend, the semiconductor laser array have been developed. The semiconductor laser array are useful pumping source for solid state lasers. The holosteric laser will be realized by LD array usage in the near future. The problems of the laser diode are the heat of LD tips and their beam quality. The LD systems needs the cooling system and the special collimator. The dye lasers and gas lasers will be replaced by LD and/or LD pumped solid state lasers.

View full abstract

The effect of low reactive level laser (LLL) on the wound healing have not been extensively characterized, and the cellular mechanisms of action of LLL are only partially undersgtood. In this study, we have studied the effect of helium-neon (He-Ne) laser irradiation in human keratinocytes and fibroblasts. Keratinocyte counts were dosedependently increased after irradiation of 10J/cm² and decreased after irradiation of 20J/cm². Single dose of LLL (1 to 2J/cm²) stimulated keratinocyte growth after 96 and 144 hours. Cell cycle analysis revealed that G2/M was increased with 5 to 10J/cm² of irradiation, and DNA histogramwas normal diploid pattern. The expression of EGF-receptor was not affected with single irradiation of 1 to 20J/cm², however each 3 day irradiation of 10J/cm² showed the increased expression of EGF-receptor. The expression of involucrine was not altered by laser treatment. There was a significant difference in migration of the leading edge in irradiated “wounds” compared to non-irradiated“wounded”controls. Plasminogen activator activity of keratinocyte cultured medium was increased with LLL. Type 1 collagenase activity of fibroblast was reduced, and the amount of HGF was increased. Our result revealed that He-Ne laser stimulates proliferation and migration of cultured human keratinocyte. This may contribute the efficacy of LLL irradiation in wound healing.

View full abstract

We reported that vascular ring of a rat thoracic aorta reproducibly showed either contraction or relaxation during irradiation with low power laser (wavelength=325nm, 351nm, 458nm, 514.5nm, 800nm). To study the thermal effect, the tension of vascular rings was observed isometrically with the same absorbed energy by Argon ion laser irradiation at each wavelength (351nm, 458nm, 514.5nm, 800nm). Furthermore, to investigate the mechanism of laser induced vasorelaxation, the tension changes in normal buffer were compared with those in the buffer containing the following drug: 1) guanylate cyclase inhibitor (10^-5M methyleneblue); 2) nitric oxide synthetase inhibitor (10^-4 ML-NMMA,10^-4 ML-NAME); 3) the optical isomer of L-NAME (10^-4 MD-NAME); 4) 10^-4 MNaNO₂
Laser irradiation of the wavelength ranging from the ultraviolet to the short visible induced vasorelaxation. Otherwise, vasocontraction was caused by the irradiation at the long visible to the near-infrared. At each wavelength the vascular rings tended to contract with the higher absorbed energy. The vasorelaxation caused by ultraviolet laser irradiation (325nm) was inhibited by methyleneblue, and not influenced by L-NMMA. Moreover, the photovasorelaxation was enhanced by NO₂ containing molecules ( L-NAME, D-NAME) or NaNO₂.
These results suggest that the photovaso contraction is due to the thermal effect of laser irradiation and the photovasorelaxation is due to the primary photochemical effect of the irradiation. We conclude that the primary photochemical effect may be ascribed to NO like substance generated by laser irradiation.

View full abstract

We previously observed that Argon ion laser (wavelength=351nm) induced vasorelaxation and Ti: Sapphire laser (800nm) induced vasocontraction of a rat thoracic aorta in vitro. To investigate effects of laser irradiation on vessels in vivo we observed change in a diameter of a rat femoral artery during laser irradiation. Moreover, we investigated the mechanism for photovasorelaxation in vivo using four drugs as follows: L-NMMA (10_-4M) L-NAME (10_-4M), D-NAME (10_-4M) and NaNO₂ (10_-5M).
He-Cd laser (325nm) produced vasorelaxation (150-200%) and Ho: YAG laser (2100nm) produced vasocontraction (80-90%), and the vasorelaxation was enhanced with the drugs mentioned above.
These results of the present study were consistent with those of our previous in vitro studies. From the findings that the photovasorelaxation was enhanced with L-NAME, D-NAME and NaNO₂, we consider that NO-like substance generated by laser irradiation plays an important role in laser-mediated vasorelaxation in vivo as well as in vitro.

View full abstract

As the second step of our last study which suggested the possible efficacy of LPL therapy for SD patients, we conducted a single blinded test using 10mW and lmW LPLs. Objects were 30 SD patients (middle class, 15 cerebrovascular disease type, 15 Alzheimer type). A group received sham irradiation, B group received 10mW irradiation for 3 months, while c group recieved 1mW irradiation for the same period. The irradition points, time and checking methods were same as last yesr. We found statiscally significant difference between the SD level of A group and B group and also A group and C group without regard for the cause of disease and the difference of out put of LPL confirming our last report which suggested possible efficacy of LPL therapy for SD patiients.

View full abstract

The helium-neon (He-Ne) laser with wavelength of 632.8nm has photobiological effects and clinically used for pain relief of herpes zoater and wound healing such as ulcer, decubites, and burn. He-Ne laser has also used for inhibitation of inflammation of eczema and atopic dermatitis. However the cellular mechanism and effect of He-Ne laser are poorly understood. In this paper, we reported the influence of He-Ne laser irradiation on contact dermatitis and histamine release from rat peritoneal mast cells. The irradiation of He-Ne laser (12.2jicm²) at 1 hour, 5, 0, minutes before, and 5 minutes, 6, 24 hours after occurrence of irritated or allergic contact dermatitis were made on right ear of ICR-mice. 24 and 30 hours after irradiation, the swelling of the ear was measured by using a dial thickness gage, and the anti-inflammatory ability of He-Ne laser irradiation was shown by thickness ratio. Although the laser was unable to decelerate of iritiated dermatitis, the allergic response was decelerated. According to the circumstances, the irradiation of 5 minuts after occurence of contact dermatitis accelerate the thickness ratio. The influence of He-Ne laser irradiation was studied on the histamine release from Wister-rat peritoneal mast cells. The spontaneous histamine release was inhibited by laser irradiation, while substance P and compound 48/80-induced hiatamine release was not inhibited. Our findings suggest that He-Ne laser has anti-inflammatory effect.

View full abstract

Effects of laser irradiation on hard tissue have been investigated by measuring the change of elemental composition of hydroxyapatite. ArF, KrF and CO₂ lasers were used to irradiate hard tissue; cow's thighbone and dental enamel. Electron Probe Micro Analysis (EPMA) was used to obtain the Ca/P ratio on an irradiated tissue surface.
The ratio did not show any change for the case of KrF and CO₂ laser irradiation. In the case of ArF laser irradiation, a remarkable change in the ratio was observed for both cow's thighbone and dental enamel i. e. the peak of the ratio appeared at low fluence region. At high fluence region, the ratio increased with increasing the repetition rate for cow's thighbone but it did not change for dental enamel. These results can be explained by the relation between the bond strengths of P-O and the photon energy and by the thermal ablation.

View full abstract

Effects of ultraviolet laser irradiation on biological lipid have been studied for the medical application. A suet has been adapted as a biological lipid. Drilling depths of a suet for ArF, KrF and XeCI excimer lasers have been measured. Drilling ability for KrF excimer laser was remarkably better than that for other lasers. In addition, drilling without thermal disturbance was found in the low repetitive irradiation, suggesting that the dominant process on the drilling was the photochemical effect. In ArF excimer laser irradiation, the thermal damage zone was created by the thermal effect due to the nonradiative transition. Denaturation of a suet after excimer laser irradiation is examined from the ultraviolet absorption spectra. The absorption owing to the conjugate double bond in a suet was influenced by ArF and KrF laser irradiations.

View full abstract

We studied scattering of the probe beam at ablation plume on KrF excimer laser (λ=248nm) escharectomy to monitor ablation condition. The transient change of the probe-scattering light of He-Ne laser (λ=633nm) from the ablation plume was detected. We measured the gradient of the rise slope (Gr Slope) and the e-holding decay time of the probe-scattering waveform. Gr Slope at high fluence (5J/cm²) irradiation was two times sharper than that of near threshold fluence (1J/cm²). The e-holding decay time was 1.2 times longer at 10 shots. Gr Slope and e-holding decay time showed to have relation to the ejection velocity and the diffusion time of the ablation plume respectively. We evaluated performances of this reflectometry by comparing with the time-resolved photography. The reflectometry may be the useful information from the ablated surface to maintain the optimum control of the irradiation condition without remaining hard char grains.

View full abstract

Due to their high reliability, modest electrical and cooling repuirements, and their compactness, diode laser systems are attractive for medical use. We briefly reviewed requirements made on diode lasers for three medical applications (low-energy level laser therapy, photodynamic therapy of tumors and surgery) in this paper. Then our newly developed diode laser system for photodynamic therapy (664nm, 500mW at tissue) has also been presented more specifially.

View full abstract

Recently, endoscopic laserthermia using Nd: YAG laser at lower power level has been evaluated in gastrointestinal (GI) cancer. Endoscopic laserthermia can give an effect to the cancerous tissue at the deeper layer than ordinary laser irradiation, with the more safety. Laserthermia had developed based on the advances of contact irradiation method and improved by computer control. Ordinary hyperthermia can be applied only to a patient with good general condition, due to its influences to general body. As the effect of endoscopic laserthermia is limited to a local lesion, it can be applied to a patient with worse general condition. In practice, endoscopic laserthermia is able to be applied not only to radical treatment of early gastric cancer, but also recanalization of obstruction due to the advanced cancer of GI tract, such as esophageal or cardiac cancer. Its effect is used to be increased by combination of cancer chemotherapy or PDT.

View full abstract

From 1980 to June 1994, we have been treated 122 cases of an early gastric cancer, using laser endoscopy. Laser endoscopic treatment is used to be performed to the patient with early gastric cancer in high surgical risk condition, co-existence of an active cancer of an another site or refuse of surgery. The treatment was extremely excellent, as 94% for an early gastric cancer less than 2cm and without U1. An accident (bleeding and perforation) by the treatment was few, as 0.6% in each. On the contrary, it was much higher by an endoscopic mucosal resection, using high frequency electric current. As the efficacy rate was low for a lager and sm-invasing lesion, development of new method is necessary.

View full abstract

On 40 cases of residual tumor after endoscopic mucosal resection for eraly gastric cancer we performed laser irradiation with Nd-YAG laser as an additional treatment. Residual rate after laser treatment was 10.0%(4/40), and recurrence rate during follow-up was 16.0%(4/25), exclusing short period follow-up cases. In 3 of 4 recurrent cases, cancer disappeared after the second laser irradiation. The final cancer free rate was 82.8%(24/29). Normaly additional laser treatment was indicated for inoperable patient. In 8 of 40 cases in operable patients,we performed additional laser treatment. None of 8 cases were found residual or recurrence tumor following period of 6-47 months (mean: 21months). We think that the lesion is belonged to the criteria of non lymph-node metastasis group,and when collected tissue by endoscopic mucosal resection is enough for evaluating the lesion,additional laser therapy is a non invasive good treatment for residual tumor.

View full abstract

In endoscopic laser radiation for treating malignant biliary stenosis, the endoscopist often encounters difficulty due to a lack of visual field. To solve this probrem, the YAG laser lateral radiation tip, capable of safe radiation even under gaidance of X-ray imaging, was clinically applied to treatment of cholangiocarcinoma.
The subject was a 60-year-old female who underwent chorecystectomy and side-to-side choledochoduodenostomy 20 years ago. In March, 1993, abdominal echography revealed a tumor mass about 10cm in diameter, centering in the posterior segment of the right hepatic lobe, the biopsic diagnosis being papillary adenocarcinoma. ERCP detected an anomalous arrangement of pancreatico-biliary ducts. We persuated the patient's family and patient to make the patient undergo surgery, but failed to obtain consent; the patient was followed up as an outpatient. In April, 1994, the patient developed jajundice, and was re-admitted to our hospital. PTCD was performed on the dilated left and right hepatic ducts. Afer the PTCD fistulae were dilated, both hepatic ductal stenosis were radiated with YAG laser, using a lateral radiation tip, under guidance of X-ray imaging. The radiation output was 15-20 watt; the tip was gone and returned little by little in the stenoses several times. Later, the radiation effect was confirmed by fistulography and cholangioscopy; underradiated portions were further radiated using an ordinary tip. After laser treatment, the billiary stenoses improved markedly; the patient was discharged from the hospital, with a Wall stentbeing expandable metallic stent in the left and right bile duct.
Katsu et al. developed a laser tip capable of rectangular refraction and hence lateral radiation of a laser beam, and applied it to treatment of malignant esophageal stenosis. Inthe present study, the lateral radiation tip was clinically applied it to treatment of malignant biliary stenosis, which were difficult to radiate due to lack of visual field and was found to permit easy radiation even under gaidance of X-ray imaging, a clinically useful aspect.

View full abstract

When a early gastric cancer is associated with ulcer or ulcer scar, endoscopic mucosal resection is difficult because the lesion is not held by a injection of normal saline into a submucosal layer under a lesion. Endoscopic treatment for this type of early gastric cancer is limited only by a tissue coagulation method. We performed laser irradiation on 20 cases of this type of early gastric cancer which surgical treatment was considered to be a high risk. A Nd-YAG laser was applied by the non-contact method with an output of 50-70 Watt. Final cancer free rate for over all cases was 85.0%(17/20) and 88.9% for differentiated type of adenocarcinoma, 81.8% for undifferentiated type. Comparing with early gastric cancers without ulcerative changes, those required more cycles of irradiation.

View full abstract

We developed new laser therapy to attain reliable theraml treatment at deep portion of gastric wall. Nd: YAG laser was used to generate the steam jet over 100°C, The steam jet was emitted to the canine gastric walls for 30 seconds or 60 seconds under anethtesia. After 6 hours, dogs were sacrified and pathological studies were performed. We found mild coagulation, hemorrage and marked edema at submucosal layer however no remarkable change at proper muscle.Using our new method,the coagulation deapth might be controlled so that we think this method can be applied to the treatment of early gastric cancer.

View full abstract

We developed an ultrathin 0,8mm in diameter pancreatoscope system using a sequential electric endoscope system. We have used this system for differential diagnosis between pancreatic cancer and chronic pancreatitis which showed local stricture of the main pancreatic duct. For the purpose of improving diagnostic ability and image quality, we studied angulation system of ultrathin pancreatoscope and applied image processing by means of computed analysis to pancreatoscopic images. The results were as follows; 1) ultrathin pancreatoscopy has characterised findings of the ductal mucosa at stenotic areas, 2) image processing using“Band enhancement”and“Paint out method”could improve image quality of pancreatoscope. Although the device and the technique have been improved, several problems such as limitation of the observation field and durability remain to be solved.

View full abstract

Spherical laser coagulation therapy is a novel surgical procedure in which intrahepatic tumors are coagulated with sphericaly irradiating laser energy emitted from an intrahepaticaly accessed laser probe. The tip of the laser fiber is round and tapering to sphericaly disperse laser energy. Gas generated around the fiber tip by tissue vaporization evacuated through a Teflon tube in which laser probe is inserted. Preoperative simulation of the laser fiber insertion is important to avoid damaging important vessels in this therapy. Simulation of the needle puncture for the tumors in the liver were carried out with Computer Aided Surgery (CAS) system, which reconstruct the three-dimensional diagnostic model, from the set of sliced images, e. g. a x-ray computerized tomography and/or a magnetic resonance imaging. With this reconstructed model, the safety areas of needle punctuation was indicated and the clinical. applications were performed in open, percutaneous and laparoscopic approach.

View full abstract

Laparoscopic surgery for gynecologic disease was performed with various lasers (Nd: YAG, KTP/YAG, Ho: YAG), electrocautery (monopolar, bipolar, Argon beam coagulator) and Harmonic scalpel. Our materials included 49 endmetriosis (26 with endometrioma, 23 without it), 4 dysmenorrhea, 7ovarian cyst (paraovarian cyst: 2, dermoid cyst: 1, serous cyst: 3, mucinous cyst: 1), 2 Fitz Hugh Curtis syndrome, 1 pyosalpinx, 2 adenomyosis, 3 myoma and 2 carcinoma in situ of the uterine cervix. For the treatment of ovarian tumor, dranage, ethanol fixation, ablation of lining, stripping of lining and adnexectomy were performed on them. For the treatment of adhesion, lysis and/or TUSL (Transection of UteroSacral Ligament) were underwent. For the treatment myoma, adenomyosis with and carcinoma in situ of the uterine cervix, LAVH (Laparoscopically Assisted Vaginal Hysterectomy) was carried out.
An excellent result after laparoscopic surgery was obtained and the advantage and disadvantage of each equipment were discussed.

View full abstract

We treated 82 patients by thoracoscopic surgery from May 1991 to August 1994 in Keio University Hospital. The patients were 59 males and 26 females and the age was ranged from 15 years old to 79 years old, with mean age of 37 years old. Thoracoscopic laser treatment was mainly used for spontaneous pneumothorax with multiple small bullae. Initially we used Nd: YAG laser for spontaneous pneumothorax but we experienced ruptur of the irradiated bulla. Now we used CO₂ laser because CO₂ laser coagulates only 0.2-0.5mm in the depth. The power level used in the treatment ranged from 5 to 10 watts, irradiated by continuous waves. CO₂ laser thoracoscopy is effective and safe in treating spontaneous pneumothorax with multiple small bullae.

View full abstract

The development of current thoracoscopic surgical equipment and instrumentation allowed recent advancement of the procedures¹⁾. Among that equipment, endoscopic staplers and Nd: YAG laser were the two most important components²⁾. Endoscopic staplers are used to separate the lung tissue, blood vessels, bronchus and so on. The cut end is safely sealed. Although they are easy to use, there are some limitations to employ the staplers. Thick tissue cannot be separated and the stapler cannot be applied on some part of the lung as diaphragmatic surface, mediastinal side near the vessels and around the pulmonary ligament. Enucleation of the nodules in the lung cannot be performed by the stapler. Nd: YAG laser with contact tip scalpel is also used to separate the tissue. The bleeding as well as the air leakage from lung parenchyma is controlled by this method and reinforced by the application of free beam Nd: YAG laser. Bleeding from the vessels and air leakage from the bronchioles must be closed by clips or suture. Though some advanced technique is required, there is almost no limitation of the separation with Nd: YAG laser method. Enucleation is possible, any part of the lung with any thickness can be separated. Another important application of the laser is to contract an emphysematous lung surface to reduce the residual volume and to normalize the static lung compliance. After the ablation of the emphysematous lung surface, the patient's lung function and clinical symptoms are improved. In conclusion, endoscopic staplers are playing the role of spreading the procedure while Nd: YAG laser does expanding the application of thoracoscopic surgery.

View full abstract

One hundred and thirty four lesions of peripheral arterial occlusive diseases were treated with PTLA, using 1064nm continuous wave Nd: YAG laser during the period of March, 1985 through March, 1993. In most cases a ceramic tip was used for contact lasing method. A bare laser fiber was also used in a small number of lesions. The initial success rate of PTLA is 87.3%. The cumulative patency rate dropped to 67.7% at 8 years from 89.7% at 6 years. The main cause of decreased patency rate seems to be due to inclusion of more difficult cases to treat. Our 5-year cumulative patency rate of all lesions treated by PTLA revealed 10 to 15% improvement, when compared with that of conventional PTA. Our 6-year comulative patency rate revealed a better patency rate among lesions less than 10cm in length than that of lesions longer than 10cm. PTLA has been especially useful in lesions in which a guidewire could not be passed, and also in hard lesions. Laser ablation of atheromatous plaque seemed to prevent recoiling of stenotic arterial wall and to create better compresibility. PTLA seems to be a useful adjunct to improve initial success rate and the long term patency rate of PTA.

View full abstract