To optimize conditions of photodynamic therapy (PDT) with ALA induced protoporphyrin IX (PPIX), topography of accumulation and metabolism of PPIX were analyzed in vitro. Adenocarcinoma cell lines, urothelial carcinoma cell lines, and a normal fibroblast cell line were cultured in plateau phase. ALA-induced PPIX accumulation, porphobilinogendeaminase-, ferrochelatase- activity, intracellular iron content, transferrin receptor expression and PPIX localization were determined using standard techniques. PBG activity as well as PPIX content were found higher in adenocarcinoma cells than in urothelial cells. Urothelial cell lines showed significant alterations in FC values in contrast to similar levels of FC in adenocarcinoma cell lines overall. Well differentiated cells showed higher iron content than lower differentiated cells. Transferrin receptor expression was found independent of PPIX content and intracellular iron content. In HT29, PPIX localizes mostly in the cell membrane, in SW480 and CaCo2 in mitochondria, and in urothelial cells mainly in cytosol. Data presented encourage the systematic and organ- related analysis of PPIX metabolism, since significant differences have been found between urothelial tumor cells and adenocarcinoma cells which may demand different strategies of therapy optimization and combination therapy regimens.

Background: To optimize differential effectiveness of aminulevulinic acid (ALA)-induced protoporphyrin IX (PPIX)- mediated photodynamic therapy (PDT) on normal and tumor urothelial cells, aspects of PPIX formation and parameters responsible for treatment efficiency were examined in vitro. Material and Methods: Plateau phase cells of a bladder cancer and a normal urothelial cell line were incubated using various incubation conditions and analyzed with respect to their PPIX content and cellular sensitizer distribution. PDT was performed using incoherent light from a Xenon coldlight projector. Photo toxicity was investigated using flow cytometric analysis of propidium iodide exclusion and analysis of cell size and number. Results: Following 3h incubation intervals, both cell lines showed similar PPIX localization with an amount of sensitizer three times higher in RT4 tumor cells. 1h incubation times resulted in the same ratio of PPIX amount but lead to different cellular PPIX distribution. After 3h incubation, PDT resulted in complete tumor cell kill accomplished by a marked fraction of damaged normal urothelial cells. TR4 cell kill with significantly reduced damage of UROtsa cells could be achieved using 1h incubation times. Discussion: Besides sensitizer amount, cellular localization is crucial for PDT effectiveness. Differential effectiveness of tumor and normal cells can be enhanced utilizing the finding of different PPIX distribution after short incubation times.

The investigation of tumor damage in vivo due to photodynamic therapy (PDT) using aluminium sulphophthalocyanine were performed. Obtained results showed that antitumor action of PDT is connected with different mechanisms of tumor damage; necrosis, apoptosis, and exochromatolis of tumor cells as well as vascular damages.

PDT is being used to treat small localized cancer or as an adjuvant to debulking surgery for more advanced disease. Clinical protocols for PDT are based on the assumption that optimum intervals between photosensitizer administration and illumination are at times of maximum differential between drug retention in tumor and surrounding normal tissue. Tumor destructing can, however, occur either by direct cell killing or by vascular mediated damage. The aim of this study was to investigate the relationship between plasma and tumor photosensitizer levels and PDT effect for the RIF1 murine tumor and the H-MESO1 xenograft tumor. mTHPC plasma levels decreased rapidly according to a biexponential fit. The tumor drug levels, however increased from 5 minutes to 6 hours after injection and remained high for at least 48 hours. Maximum tumor PDT response was seen at 1 to 3 hour drug-light intervals with very little effect for drug-light intervals > 24 hours. No correlation was found between tumor mthpc levels and tumor response, whereas plasma mTHPC levels and PDT correlated significantly. These studies support the hypothesis that vascular mediated damage is more important than direct tumor cell toxicity and that it is drug exposure of endothelial cells in vessels feeding the tumor which determines PDT response.

Site-specific delivery of drugs and contrast agents to tumors protects normal tissues from the cytotoxic effect of drugs, and enhances the contrast between normal and diseased tissues. In optical medicine, biocompatible dyes can be used as photo therapeutics or as contrast agents. Previous studies have shown that the use of covalent or non-covalent dye conjugates of carries such as antibodies, liposomes, and polysaccharides improves the delivery of such molecules to tumors. However, large biomolecules can elicit adverse immunogenic reactions and also result in prolonged blood circulation times, delaying visualization of target tissues. A viable alternative to this strategy is to use small bioactive molecule-dye conjugates. These molecules have several advantages over large biomolecules, including ease of synthesis of a variety of high purity compounds for combinatorial screening of new targets, enhanced diffusivity to solid tumors, and the ability to affect the pharmocokinetics of the conjugates by minor structural changes. Thus, we conjugated a near IR light absorbing dye to bioactive peptides that specifically target over expressed tumor receptors in established rat tumor lines. High tumor uptake of the conjugates was obtained without loss of either the peptide receptor affinity or the dye fluorescence. These findings demonstrate the efficacy of a small peptide-dye conjugate strategy for in vivo tumor imaging. Site-specific delivery of photodynamic therapy agents may also benefit form this approach.

Neutrophils are indispensable for successful PDT. Recently it has been observed that the administration of anti-thrombocyte antiserum prevents the occlusion of the microvasculature that normally occurs upon Photofrin-based PDT. We hypothesized that this antiserium treatment would increase the therapeutic efficacy by facilitating the accumulation of neutrophils at the lesion. To study this we implanted the isologous rhabdomyosarcoma R-1 subcutaneously into the thigh of WAG/Raj rats, and treated the tumor by interstitial Photofrin-based PDT. We found that the increasing tumor doubling time after PDT under anti-thrombocyte antiserum-induced thrombocytopenia was significantly higher that in normal rats. Strikingly, the increase in tumor doubling time did not differ if thrombocytopenia was induced before or immediately after illumination. At least 1.5 times more neutrophils than normal accumulated into the PDT-treated tumors under thrombocytopenia. If the rats were rendered granulocytopenic by the administration of anti-granulocyte antiserum first followed by anti-thrombocyte antiserum post PDT, this lead to a considerable loss of the thrombocytopenia- dependent gain in the efficacy of PDT. These findings suggest that the increased accumulation of neutrophils into the tumor underlie the enhanced efficacy of PDT and may implicate that under normal clinical conditions the full granulocyte-dependent kill potential is not utilized due to the presence of activated thrombocytes that cause blood flow stasis.

Five novel photosensitizers for photodynamic tumor therapy have been offered as potential drug substances for the prospective clinical usage. A complex of pre-clinic biological studies has been performed, unambiguously demonstrating low systemic toxicity and high photodynamic potential of the substances proposed. The one named 'Photodithazine/Photochlorin I' has already successfully passed a number of clinical test on patients having immergent vital indications.

Oxygen is the limited component in PDT, especially in the hypoxic tissues. Proteins and amino acids are the main oxidation substrates in tissues in the case of singlet oxygen while, for example, hydroxy radicals well oxidize also DNA and membrane lipids which are considered as the critical targets in PDT. We compared the quantum yields of the oxygen consumption by Type I and by Type II mechanisms in the aqueous solutions in the comparable with PDT conditions. The preparation Photosens was used as photosensitizer, human albumin serum-as oxidation substrate, and sodium ascorbate-as reductant. We conclude that the oxygen consumption proceeds mainly by Type II mechanism while PDT efficiency by Type I mechanism can be even higher.

The investigations of photodynamic activity of the dibiotinylated aluminium sulphophthalocyanine in vitro and in vivo were performed. The results obtained showed that in vitro dibiotinylated aluminium sulphophthalocyanine provides an effective damage of small cell lung carcinoma OAT-75. In vivo dibiotinylated aluminium sulphophthalocyanine induces a total damage of Erlich carcinoma with expressed vascular damage even in a concentration 0.5 mg/kg of body weight.

Ovarian cancer is the most frequent cause of gynecologic cancer-related death in the United States. In patients with advanced disease, the initial steps of the treatment, surgical debulking and chemotherapy are efficacious as evidenced by negative second look laparotomies or laparoscopies. However 1 5% to 50% of the patients with negative second look will subsequently experience recurring disease whithin 5 years and will inevitably die from the disease.(1) Therefore any approach which would improve the sensitivity and decrease the invasiveness of this procedure would be very attractive to improve the management and the quality of life of these patients.

The findings from studies on structural and functional parameters of the adrenal, thyroid, and pineal glands in conditions of ovarian hypofunction and after its correction by laser puncture are presented. An experimentally induced hypofunction of the ovaries was shown to be accompanied by a decreased hormonal synthesis in the cortical fascicular zone. The epiphysis showed ultra structural signs of increased functional activity. Application of a helium-neon laser to biologically active points of the ovarian reflexogenic zone induced normalization of the ovarian cycle, potentiating of the adrenal functional state, and a decreased thyroid hormone production and abolished the activatory effect of the dark regime on the functional state of the pineal gland.

The method of autofluorescence diagnostic has been applied to study the diseases of uterus and ovaries including tumor of uterus, ovaries and endometriosis. The fluorescence emission spectra of native samples were measured using fiber optics spectrometer. The very high fluorescence in cystic ovaries and tumor ovaries has been observed allowing one to hope that endogenous fluorochromes may play a role of photosensitizes light irradiation.

Pp IX accumulation induced by ALA was tested in a cell line of cervix carcinoma implanted in nu/nu mice, and irradiated by argon laser. It was found that the mice developed the tumor 17 days form its exposition to HeLa cells. The optimal concentration of ALA that induced maximum level of accumulation of PpIX in the tumors was 150 mg/kg by IT route. In ALA doses it was observed a decrease in the tumoral area in the first three radiations at 234.36 J/cm². It was found that nu/nu Swiss mice with implanted HeLa cells are a good model to study the epidermoide carcinoma because tumor development time is short although is valid only during first 3 months. The histology study shows that there is no cellular damage immediates at the concentrations used. IT route does not allow a high PpIX accumulation in different organs, therefore this route is more safety. It was observed a decreasing size in the irradiated tumor by using an argon laser, this preliminaries results are indicating that would be possible to propose the use of this laser in PDT applied in EC.

30 malignant brain tumors of 25 cases, that were seated deeply in the brain or in an eloquent area, were treated with stererotactic intratumoral PDT using HPE and argon-dye laser. 3mg/kg HPE was administered iv 2 days after, a stereotactic apparatus was installed and target points were determined by enhanced CT or MRI. Optical fiber was inserted into predetermined target points of tumor by stereotactic methods, and photo illumination with power output 200 mW was applied for 15 minutes. The photo illumination was repeated several times depending on tumor volume. All tumors clearly showed a reduction in tumor volume 4 weeks after stererotactic PDT. A complete response was obtained in 19 tumors, PR was in 8 tumors, NC was in 3 tumors. In the case of 22.9 ml or lower volume, therapeutic effects were obtained for all of them. The largest tumor which showed complete disappearance on enhanced CT or MRI had a volume of 4.6 ml. This study indicates that it is possible to consider stereotactic intratumoral PDT showing adequate therapeutic effects as an adjuvant therapy for malignant brain tumors.

Stereotactic guided laser-induced interstitial thermotherapy (SLITT) is a minimal invasive method to produce thermo necrosis in cerebral tumor tissue. Clinical data about dose/response relationship and patients outcome is poor. Twenty-four patients with brain tumors were treated with SLITT, totally 30 laser procedures were performed. Under local anesthesia 600 micrometers laser-fiber were inserted by the stererotactic-guided technique. IN open MR the denaturation of the tumor by a Neodym-YAG-laser was monitored using T1-weighted 3D tumor FLASH sequences. Laser energy was applied in steps of 400 to 1200 Joules. Development of necrosis at a mean total energy-dose of 2979 Joules could be monitored in all procedures. Initial signal changes were seen after a mean of 1250 Joules. Mean max total lesion size was 21.2 mm. The higher the total energy, the larger the thermo lesion, but no linear relationship could be seen. Tumor tissue response showed no dependency form tumor grading. Although lesion-size basically is energy dependent, it should be applied individually, since thermo response in brain tumors varies due to different optical properties. Energy application in steps of 500 Joules monitored in near on-line modus in an open MR-system is safe and feasible. Conclusions about the clinical value of SLITT are not definite.

The use of 980 nm diode laser irradiation within cortical tissue was investigated by the author's previous work. In the present study the lesions created in cortical and subcortical tissues and lesioning effects of diode laser applied in continuous and pulsed regimes were compared. In vivo stereotaxic neurosurgical procedure was performed on female Wistar rats' cortical and subcortical tissues. 980 nm diode laser was applied in two different regimes, cw and pulsed wave respectively. Lesion dimensions were measured and compared. The lasing parameters were found suitable for both brain regions. No significant difference was found between tissues. Lesions diameters varied in the range of 1.0-9.0 mm. Histological examination revealed data for a limited thermal damage in the surrounding tissue for all lesions. Cortical and subcortical tissues did not show significant differences due to same amount of energy delivered. The lasing regime did not influence the dimensions of lesions. Applied energy was found the key element determining the amount of lesion. Results were consistent with the findings found in the previous dosimetry studies.

In September 2000 an English and updated edition is published of the report 'Laser Safety in Health Care'. The Dutch Committee on Laser Safety in Health Care published in 1993 the original Dutch version. Important objectives of this report are to provide concise, practical recommendations on laser safety in health care and to provide sufficient information to a variety of disciplines that will motivate practitioners and assisting staff to accept the various recommendations, but also help them to implement these recommendations properly.

This paper describes a risk assessment methodology for laser applications in medicine that takes account of the different stages of the life cycle of the laser application, the individual components of the laser application and the different people at risk. In this way, the specific hazards can be identified and addressed to ensure that the risks associated with the use of lasers in medicine are adequately managed.

We investigated complications and morbidity of laser therapy and we attempted to identify factors which contribute to complications and discuss their prevention. Complications of laser therapy in 1029 patients receiving 1933 treatment episodes either by Yttrium Aluminum Garnet (YAG) laser or Photodynamic Therapy (PDT) during a 15 year period by our team were reviewed. The relevant literature was also surveyed. Two types of laser were used: YAG laser was employed endoscopically in 713 patients, al but 4 endoscopically, for esophageal/tracheo-bronchial tumors. There was no laser procedure related mortality in the entire series. There were 44 complications. There were 3 serious non- fatal incidents and 44 minor complications. There were 3 serious non-fatal incidents and 44 minor complications. Conclusions were that in this series there were no fatal/serious complications. The laser unit should have a defined protocol for prevention and therapy of complication which should include 'emergency incidence'.

Risk management of lasers can be broadly define das a process of identification of the risk, assessment of the risk and steps taken to avert the risk. The risk management may be divided into: Risk inherent to the technology and risk in clinical use. Within the National Health Service in the UK, a useful document, which provides hospital laser users with advice on safety, is the 'Guidance on the Safe Use of Lasers in Medical and Dental Practice' issued by the Medical Devices Agency for the Department of Health in the UK. It recommends the appointment of a Laser Protection Adviser (LPA) who is knowledgeable in the evaluation of laser hazards. One of the duties LPA is to ensure that Local Rules are drawn up for each specific application of a laser. A Laser Protection Supervisor (LPS) should also be appointed with responsibility to ensure that the Local Rules are observed. It is a sensible precaution that laser users should be those approved by the Laser Protection Supervisor in consultation with the Laser Protection Advisor. All laser users should sign a statement that they have read and understood the Local Rules.

We have examined a number of laser pointers that have been removed form the possession of accused persons by police in Scotland. An analysis of the first 30 consecutive items has shown that 28 were Class 3B, with radiated power up to 9.3 mW. These are potentially hazardous if viewed directly. Transient exposure is unlikely to cause long-term damage but prolonged exposure may cause permanent retinal injury.

2D fantom of tissue-seeded with bacterial cells agar plate, has been constructed to investigate light propagation during laser ablation and ability of survivors to divide and establish viruses and DNA sequences. Potential health hazard of gene transformation of survived cells by pilot and scattered radiation of surgical lasers with viral and non-viral vectors contained in laser ablation products is discussed.

At the European scale, a new strategy practice was developed, in relation to the New Approach. The EC Directives require manufactures and users to carry out risk assessment of the product and/or the working place, respectively. Until now, in Romania there were no conditions referring to a qualified protection concerning laser hazards, neither from legal, nor from technical point of view. The paper refers to the efforts devoted in the last years to overcome these drawbacks, in connection with: the preparation of national standards, the participation to international activities related to the development of written standards, the organization of courses/seminars on laser safety, and the structuring of a national facility for laser metrology. The talk describes how these activities were supported by some European programs, or bilateral cooperation with partners from Western European countries.

Laser safety training at present is based primarily on conventional lectures. We present a multimedia concept which allows for adjusting of the training to laser users' specific applications and needs. Applying a blend of written and spoken text, drawings, photographs, animations and videos, computer based multimedia training is capable of conveying information very efficiently. Preferences regarding medical fields and modes of presentations are taken into account. This concept meets the recommendations of international standards and guidelines concerning contents and is capable of presenting information in variable quantity, depth and speed thus increasing the training efficiency for the individual.

For reduction of a zone of a thermal damage limphoid tissue and certain influence on the changed wall of a lacuna cryolaser segment lacunotomy with use Nd:YAG laser is offered at chronic tonsillitis. The tip of the lighttube of a type side-focus was entered into a gleam of a lacuna. The tip was cooled by a line method of pairs nitrogen. Parameters of radiation length of a wave 1.32 microns, capacity -25 Wt, exposition -3 sec. The comparative analysis 90 histologic tissue specimens of palatal tonsils with pathological change of lacunas is carried out. The influence ona segment of lacuna up to 90 degrees, allows to expand a gleam of lacuna, by keeping thus lymphoepithelial barrier of an opposite wall. The zone of the necrobiotical changes and infiltration of a lymphoid tissue on preparations undergone to laser influence with cooling average in 2 times is less, than at application of laser influence. The operation was spent to 50 patients chronic tonsillitis.

In recent years significant improvement of power and spectral characteristics of semiconductor lasers has taken place. The power of serial single near-IR semiconductor lasers has achieved units of watts, the spectral range has been extended from 0.63 to 1.7...1.8 micrometers . The available level of semiconductor lasers, their small dimensions and weight, together with the characteristics of the modern fiberoptic systems, electronic and microprocessor components as well as small dimensions and weight of modern power supplies allow development of a compact portable self-contained blood coagulator, which is of great importance for use in various emergencies, natural calamities, and in many other areas. The report discusses the problems of designing the coagulator, its technical and user characteristics as well as the possibilities to use such a coagulator in other fields of laser medicine.

It is well known that during the curing of dental cements, polymerization shrinkage induces unacceptable stresses, which can result into cracks and an over-sensitivity of the teeth. We demonstrate that polarimetric optical fiber sensors can be used to characterize this shrinkage quantitatively. To determine the time evolution and the amount of shrinkage we embed a highly birefringent optical fiber in the dental cement and analyze the change in optical polarization at its output. This change is a measure for the dynamic stress-build up. We also demonstrate the repeatability of our characterization method for these cements. Moreover we given indications that this technique allows for in- vivo monitoring of the stress build-up dynamics between dentine and porcelain facings. This may bring durable all-ceramic restorations closer to reality. In this paper we present the principle of this original optical fiber sensor, its practical implementation and the experimental results we obtained for this application.

The physiology and pathology of the ocular microcirculation is of interest in several prevalent eye diseases. Quantification of blood flow in ocular tissues at high temporal and spatial resolution, essential for the early detection of alterations during the disease process, requires highly sensitive measurement techniques such as laser Doppler flowmetry (LDF). Spatial resolution is important when attempting to measure blood flow in tissue layers at different depths and can be increased by reducing the probing laser's spot size and using detectors with very small apertures, however, at the expense of lower Doppler signal-to-noise ratio and greater variability of the measurements. To improve LDF signal-to-noise, while retaining the increased spatial resolution of small measuring volumes, a multi- channel approach was undertaken. A new LDF analysis card was designed using a TMS320C31 digital signal processor providing independent LDF analysis of up to 4 analog input channels. Two cards are used in parallel to analyze the output signals of a compound 7-channel detector. Analysis results of all channels are continuously uploaded to a PC which averages the channels and provides the user interface.

Special features of speckle-modulated laser fields arising at in vitro measurements of different types of human cataractous lenses have been investigated experimentally. Computer analysis of digital images has allowed for estimation of destruction of the spatial coherence of a laser beam scattered by a turbid lens. Applied speckle-technologies have permitted the range of retinal angular resolution to be estimated with the help of laser retinometer at the stage of preoperative cataract diagnosis. An extent of laser retinometry at measuring visual acu9ity in patients with any type of cataract, and an incorrectness of its estimation by means of opto types charts have been set up.

The influence of random errors in measurement of eye transverse aberrations on the accuracy of reconstructing wave aberration as well as ametropia and astigmatism parameters is investigated. The dependence of mentioned errors on a ratio between the number of measurement points and the number of polynomial coefficients is found for different pupil location of measurement points. Recommendations are proposed for setting these ratios.

The influence eye micromotions on the accuracy of estimation of Zernike coefficients form eye transverse aberration measurements was investigated. By computer modeling, the following found eye aberrations have been examined: defocusing, primary astigmatism, spherical aberration of the 3rd and the 5th orders, as well as their combinations. It was determined that the standard deviation of estimated Zernike coefficients is proportional to the standard deviation of angular eye movements. Eye micromotions cause the estimation errors of Zernike coefficients of present aberrations and produce the appearance of Zernike coefficients of aberrations, absent in the eye. When solely defocusing is present, the biggest errors, cased by eye micromotions, are obtained for aberrations like coma and astigmatism. In comparison with other aberrations, spherical aberration of the 3rd and the 5th orders evokes the greatest increase of the standard deviation of other Zernike coefficients.

The main method of cataract treatment is micro surgical removing of the opaque lens from the eye with implantation of an intra ocular lens. We performed the comparative study of using various IOL models differing in its materials, index of refraction, spectral properties, configuration, shape, size and other features. Before and after the IOL implantation we performed the following test: visual acuity measuring, refractometry, keratometry, laser interferometric retinometry, color perception assessment, digital photo- and videorecording of the eye with image processing and some others. We found a number of correlations between the IOL properties and some characteristics of the patient's vision. The decentration of the IOL optical part more than 1,5 mm conduced to the non-corneal astigmatism and the prismatic effect. A small diameter of the IOL optical part and high index of refraction promotes to the appearance of the optical aberrations. Leucosapphire IOLs revealed the high degree of light reflection and the minimal adhesive ability of the IOL surface. Leucosapphire IOL revealed the high degree of light reflection and the minimal adhesive ability of the IOL surface. PMMA IOL revealed the low reflective power and the high adhesive ability. The best color vision was revealed in patients with PMMA IOL with an additional compound absorbing not only UV light but also short-wave blue light.

Background: Vascular restenosis due to intimal hyperplasia (IH) and negative vascular remodeling attenuates long-term patency of vascular interventions like PT(C)As. A new adjuvant approach to PT(C)A is endovascular PDT, which is based on local cytotoxicity by intracellular activation of aminolevulinic acid included protoporfyrin IX with laser. Aim: To prevent restenosis by inhibiting IH with endovascular photodynamic therapy. Methods: Male Wistar rats were subdivided into four groups, the sham group, the IH reference-group with PTA induced denudation of the right iliac artery, and both the PTA+light only group and PTA +PDT group illuminated at 0,12.5, 25 and 50 Joule per cm diffuser length applied at 100 mW per cm diffuser length. Results: IH increased from 0 02 at 1 week to 0.13 mm² at 4 weeks. After 4 weeks, IH was 0.14mm² in the PTA +LO group compared to 0.002 mm² in the PTA+PDT group at 50 Joule per cm diffuser length, whereas the media remained. Conclusion: A single endovascular PDT treatment adjuvant to PTA inhibits IH after 4 weeks at an optimal light dosimetry of 50 Joules per cm diffuser length and 3 hours after ALA application in this IH model. Therefore, endovascular PDT is a promising therapy to prevent restenosis after vascular interventions.

Transmyocardial laser revascularization was fount to be a new emerging technique for the treatment of end-stage coronary artery diseases. In our study, a comparison has been made of mid-IR solid-state laser radiation interaction with a myocardium tissue. For this purpose, the Tm:YAG, CTH:YAG and Er:YAG laser systems were designed, constructed and used for the interaction experiments. The ablation coefficients were measured to be 3 mm/J for Tm:YAG; 0.03 mm/J for CTH:YAG, and 10.5 mm/J for Er:YAG interacting laser radiation. From the histological examination follows that the channels ablated by Er:YAG laser radiation are without any thermal damage of the surrounding tissue and with the minimal mechanical injury, therefore Er:YAG laser could be considered as a good candidate for the TMLR.

For photodynamic therapy of solid tumors, such as prostatic carcinoma, to be achieved, an accurate model to predict tissue parameters and light dose must be found. Presently, most analytical light dosimetry models are fluence based and are not clinically viable for tissue characterization. Other methods of predicting optical properties, such as Monet Carlo, are accurate but far too time consuming for clinical application. However, radiance predicted by the P3-Approximation, an anaylitical solution to the transport equation, may be a viable and accurate alternative. The P3-Approximation accurately predicts optical parameters in intralipid/methylene blue based phantoms in a spherical geometry. The optical parameters furnished by the radiance, when introduced into fluence predicted by both P3- Approximation and Grosjean Theory, correlate well with experimental data. The P3-Approximation also predicts the optical properties of prostate tissue, agreeing with documented optical parameters. The P3-Approximation could be the clinical tool necessary to facilitate PDT of solid tumors because of the limited number of invasive measurements required and the speed in which accurate calculations can be performed.

The conventional chemotherapy is not sufficient at present, and up to 84 percent of cavernous nephrotuberculosis patients have to be underdone a nephrectomy. 62 patients received only chemotherapy. Besides 88 other patients were subjected to the radiation of the low-level laser in the pathological point in different regimes. The application of the laser therapy allowed to raise the efficiency of complex treatment up 36,1 percent, resulted in quick negativation of urine in 100 percent, permitted to avoid surgical intervention for 35,2 percent.

Present work deals with diagnostics of bladder tumors with the use of 5-amino-levulinic acid (ALA) by means of fluorescence image analysis in blue light followed by spectral fluorescence analysis of biopsy samples taken from suspicious bladder sites. It was found that fluorescence intensity of benign formations is lower than that of tumors suggesting the possible increasing of specificity of diagnostics with the use of spectral analysis.

The efficiency of autofluorescence diagnosis within urinary bladder was analyzed in the study. We examined two groups of patients: the first one consisting of 22 patients suspected to have bladder cancer and the second one consisting of 45 patients who have undergone transurethral electro resection due to urinary bladder neoplasms. Our goal was to detect cancerous tissue invisible in white-light examination. In the first group sensitivity was 100 percent and specificity was 69.23 percent. In the second group sensitivity was 96 percent and specificity was 80 percent. We also report in the study treatment efficiency of PDT in 12 patients with superficial bladder cancer. In our procedure two hours after the instillation of bladder with ALA solution, the lesion was irradiated by laser light. In 9 out of 12 treated patients regression of bladder tumor was obtained, while in 3 cases a progression of neoplasmatic process was observed.

Carcinoma in situ (CIS) of the bladder has long been known as an aggressive killer. Because of the high degree of progression to muscle invasion and the high rate of occult early metastasis, early radical cystectomy had been the preferred treatment, a highly morbid procedure. Even now, with routine use of continent diversions or oithotopic bladder replacements, most patients would agree that there is still a great deal of morbidity associated with this treatment.

Bladder cancer remains a serious public health problem in many parts of the world with an estimated 300,000 new cases a year. A majority (75%.90%) of these cancers are diagnosed pathologically as transitional cell carcinoma (TCC), except in the regions of bilharzial disease which is often associated with squamous cell carcinoma of the urinary bladder. However, in this presentation we will discuss primarily superficial TCC which constitutes 85°/o of newly diagnosed bladder cancer cases. Superficial bladder cancer includes papillary tumors involving only the mucosa (Ta) or submucosa (Ti) and flat carcinoma in suit (CIS).

In the West Siberia every tenth tuberculous patient has an extra pulmonary lesion. Urogenital tuberculosis cases are in the first place in occurrence among extra pulmonary forms. Complicated and widespread lesions of kidney are prevailing. The high concentration of anti-tuberculous drugs in the lesion locus is one of the most important component in the success treatment of tuberculosis, including nephrotyberculosis. We put the aim to increase the isoniazid concentration in tuberculous kidney by low-level laser therapy. It was proved that the laser therapy at the expense of improving of the blood microcirculation ensures to increase drug concentration in the lesion locus in 9 times.

Accurate staging can be a major problem in therapeutic planning of advanced abdominal malignancies. We experimentally combined conventional staging laparoscopy with aminolevulinic acid (ALA) induced fluorescence diagnosis (FD) to improve the detection of disseminated peritoneal tumors. Using different photosensitization times and ALA concentrations we evaluated the optimal fluorescence parameters for laparoscopic fluorescence diagnosis of intra abdominal tumor spread. In a rat tumor model we performed conventional and fluorescence laparoscopy to determine the increase of sensitivity gained by FD in terms of additionally detected lesions. After laparoscopic examination, the fluorescence emission from the tumors was spectrometically analyzed. Serum levels of ALA and PpIX were measured by HPLC to determine their systemic metabolism. Fluorescence staging laparoscopy was able to visualize even macroscopically occult neoplasms. Using 1.5 percent ALA solution and a photosensitization time of 4 hours as favorable parameters the diagnostic value of conventional staging laparoscopy was significantly improved: 35 percent of all malignant lesions were detected only by FD. Therefore, fluorescence laparoscopy suggest to be a highly promising preoperative staging tool requiring minimal technical and clinical expenditure. It provides the laparoscopist with a rapid and accurate technique to assess more thoroughly the full extent of malignant tumor growth in the abdominal cavity.

Fluorescence images were recorded simultaneously with white light images to detect dyspasia or early malignancies during regular endoscopy of the upper gastrointestinal tract, after topical administration of 5-aminolaevulinic acid. Biopsies were taken at locations where fluorescence intensity were high compared with the mean fluorescence intensity of the image. Prompt and delayed fluorescence spectra of biopsies were subsequently recorded ex vivo, and normalized fluorescence intensities of Protoporphyrin IX derived from these spectra were compared with routine histology. In contrast to routine endoscopy, one early carcinoma and one signet-ring carcinoma were found in the stomach, and malignancies in a duodenal polyp. In addition, intestinal metaplasia could be visualized in the stomach of two patients, which had not been detected in biopsies taken prior to fluorescence endoscopy.

Barrett's oesophagus is a pre-malignant condition in which stratified squamous type mucosa of the normal oesophagus is replaced by specialized intestinal type columnar mucosa. Oesophageal resection as previously considered to be the treatment of choice for high-grade dysplasia or superficial carcinoma in this columnar lined mucosa. Method and Results: We treated 4 patients with Barrett's oesophagus and high-grade dysplasia, and one patient with superficial oesophageal carcinoma with photodynamic therapy (PDT) using an argon-pumped dye laser light. PDT was also delivered using a xenon arc lamp in two patients with Barrett's oesophagus and high-grade dysplasia. mTHPC 0.15 mg/Kg was used as a photosensitizer in all of the patients. We have been able to demonstrate the elimination of columnar lined oesophageal mucosa, reduction in the length of the Barrett's segment or downgrading of the dysplasia in all but one patient, who had been treated with the dye laser. There is no evidence of recurrence in the patient who had early oesophageal carcinoma at 27 months follow-up. Conclusion: We conclude that mTHPC is useful as a photosensitizer for PDT in the management of Barrett's oesophagus with high-grade dysplasia or superficial carcinoma and the Paterson lamp is a potential alternative light source for PDT.

59 patients with stomach diseases including gastric cancer or polyp, gastritis, esofagus disease were investigated. Before gastroscopy all patients were given 5-ALA in doses 5mg, 10mg and 20mg per 1kg of body weight orally. Fluorescence diagnostics which estimates concentration of ALA-induced PPIX in regular and alternated tissues of gastric mucosa were carried out in 2-4 hours. Using of 5-ALA has shown high diagnostic effectiveness for differential diagnostics of stomach diseases. This technique has proved 10 diagnosis of cancer and revealed 15 malignant stomach diseases including 4 cancer in situ for patients with preliminary diagnosis of gastric ulcer. It also revealed 5 patients with enhanced fluorescence for which aimed biopsy has shown high degree of inflammation process. The latter were assigned as a risk group.

110 patients were subjected to colonscopy under white light and autofluorescence. An adapted Xillix LIFE system and xenon light source with interference filter were used in the autofluorescence diagnostics. Both techniques revealed 67 small lesions, including 45 neoplastic ones and 22 others in the examined patients. The autofluorescence examination revealed 43 neoplastic changes, while conventional white-light colonscopy allowed for localization of 39 neoplastic lesions. Autofluorescent imaging of large intestine mucosa is more sensitive in the detection of small neoplastic changes than traditional colonscopy.

A clinical problem in the treatment of colorectal cancer is the high rate of local tumor recurrence. Adjuvant therapy methods are necessary to receive a better clinical outcome in minimizing local tumor relapse. Adjuvant intraoperative photodynamic therapy (AIOPDT) seems to be a promising alternative therapy in the treatment of malignant colorectal diseases. IN experimental settings the success of AIOPDT depends on the accumulation of the photosensitizer (PS) in tumor tissue and may be jeopardized by high mortality rates, due to inadequate energy doses. Our study evaluated mortality rates of nude mice after AIOPDT with ALA, Photofrin II and mTHPC using the following various light doses: ALA/Photofrin II: 100J, 50J, 25J; mTHPC: 30J, 15J, 5J generated by an Argon-Dye-laser system. There was a close correlation between laser energy applied for AIOPDT and postoperative mortality rate. Initial high mortality rates were lowered by stepwise reduction of the energy dose. Mortality rates reached a maximum 24 hours after AIOPDT in all groups.

The effectiveness of PDT as an adjuvant alternative therapy method for diverse malignant tumors has been investigated in numerous studies. The therapeutic benefit and extent of side effects is mainly determined by the applied photoactive substance. The second generation photosensitizer (PS) mTHPC is capable of causing selective tumor cell death in colon carcinoma when combined with laser irradiation of a PS specific wavelength. Our study revealed PDT with mTHPC as an efficient adjuvant intraoperative modality after R1/R2 resection of a subcutaneously implanted colon tumor. There was a significant increase of postoperative recurrence-free survival time using PDT compared to a control group in a colon cancer model in nude mice. The accumulation of the PS determined by point spectrometry showed a high tumor-selectivity in the tumor, tumor bed, and overlying skin compared to muscle tissue as reference parameter.