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  • Articles  (57)
  • Photodynamic therapy  (57)
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  • 1
    ISSN: 1435-604X
    Keywords: Argon dye laser ; Photodynamic therapy ; Gastric cancer ; Adenocarcinomas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract Twenty-eight patients with gastric cancer were treated by photodynamic therapy. Haematoporphyrin derivative was used as a photosensitizer and an argon dye laser as a light source. Histologically, all tumours were adenocarcinomas. On the basis of endoscopy, 17 cases were categorized as early-stage cancer and were classified as type IIc (10 lesions), Ha (three lesions), combined type IIc and type III (three lesions) and type I (two lesions). In 11 patients with advanced-stage cancer, endoscopy showed one case of Borrmann I, three of Borrmann II, six of Borrmann III and a single case of Borrmann IV. In the 17 patients with early-stage cancers (18 lesions), complete remission was obtained in 10 patients (11 lesions). Of 13 resected cancers complete remission was confirmed in six lesions on the basis of detailed histological examination of resected specimens. In the advanced stage tumours all 11 patients showed incomplete remissions. It is considered that an incomplete response in the early-stage cancers is due to insufficient light dosage because of the wide area of tumour, because the site of the lesion is anatomically difficult to photoradiate and because the invasion extends to the muscular layer and serosa.
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  • 2
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    Lasers in medical science 10 (1995), S. 13-18 
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; Larynx ; Oval cavity ; Light dose rates
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract Photodynamic therapy (PDT) has the potential to treat early carcinomas of the oral cavity and larynx while preserving normal tissue. However, normal tissues retain the photosensitizing agents and may be activated by high light fluence and dose rates resulting in normal tissue necrosis. The effects of varying dose rates of light delivery on various tissues in the upper aerodigestive tract have not been evaluated to date and are necessary to determine a ‘therapeutic light dose range’ that will result in selective tumour necrosis. Thirty adult mongrel dogs received intravenous Photofrin, 2 mg kg−1, 48 h prior to PDT treatment. Photodynamic therapy was administered to the tongue, buccal mucosa and larynx with a microlens fibre and implantable cylindrical diffuser at various dose rates from 20 to 125 J cm−2 at 150 mW cm−2. At the same dose rate of light delivery, the tongue was the most sensitive organ, followed by the buccal mucosa, and last by the larynx. The differential tissue effect of identical dose rates of therapy must be taken into account when administering PDT so that selective tumour necrosis with normal tissue preservation may be achieved. This study indicates the need to perform evaluations of the effect of PDT on other tissue types in an animal model with each new photosensitizer prior to administering PDT to those areas in humans.
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  • 3
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    Lasers in medical science 11 (1996), S. 3-10 
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; Non-tumour ; Arteries ; Fibrocellular intimal hyperplasia ; Aminolaevulinic acid ; Phthalocyanine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract Photodynamic therapy is being investigated as a cancer therapy. As a cytotoxic treatment, it may also have therapeutic benefits in certain non-tumour conditions. The mechanism of photodynamic therapy is discussed in relation to its cancer therapy. The literature on non-tumour applications of photodynamic therapy is subsequently reviewed, highlighting its vascular applications in particular. Arterial angioplasty restenosis has proved resistant to all treatments tried thus far. Because fibrocellular intimal hyperplasia arising from the proliferation of vascular medial smooth muscle cells forms the pathological basis of restenosis, photodynamic therapy has been considered in its prevention. The literature on two second-generation photosensitizers (5-aminolaevulinic acid and phthalocyanine) which are likely to achieve clinical application are reviewed with regard to their photodynamic effects on fibrocellular intimal hyperplasia. This review concludes that photodynamic therapy shows enough promise for the inhibition of fibrocellular intimal hyperplasia for large animal studies to be pursued.
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  • 4
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; 5-Aminolaevulinic acid ; Pancreas ; Bile duct ; Duodenum ; Fluorescence microscopy ; Light dosimetry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract Photodynamic therapy (PDT) using 5-aminolaevulinic-acid-(ALA)-induced protoporphyrin IX (PPIX) increases survival in hamsters with pancreatic cancer. However, experiments with other photosensitizers on this model show a high risk of duodenal perforation. In this paper, the pharmacokinetics and PDT effects of ALA on normal tissues in the pancreatobiliary region are presented. Using quantitative fluorescence microscopy, maximum PPIX fluorescence was seen in the bile ducts, less in the duodenal mucosa and least in the muscularis propria and pancreas. For PDT, light was delivered either using a bare fibre touching the tissue (single-point illumination), or irradiating a 1.5 cm diameter circular area. Single-point PDT (50 J) produced only localized reversible damage without perforation. Surface irradiation of the whole periampullary region (50 J cm−2) caused extensive damage, sometimes with perforation. Before PDT can be used safely to treat tumours of the pancreas and bile duct, further studies are necessary to understand its effect on larger areas of normal tissue.
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  • 5
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; PDT ; mTHPC ; Early cancer ; Squamous cell carcinoma ; Oesophagus ; Bronchi ; Photosensitizer ; Light dosimetry ; Clinical
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract There have been few studies to date of clinical photodynamic therapy (PDT) with tetra(m-hydroxyphenyl)chlorin (mTHPC). This paper describes the results of the authors' experience with this second-generation photosensitizer, used in the treatment of 40 early cancers of the oesophagus and the bronchi. Surface illumination of the tumour was performed, in most cases, 4 days after intravenous injection of 0.15 mg kg−1 of mTHPC, using 652 nm or 514 nm continuous wave laser light. Endoscopic follow-up with biopsies and brushings was possible for 35 tumours: 27 (77%) showed no recurrence after disease-free follow-ups that ranged from 3 to 38 months. Major complications, all of which were after red light illumination, included one bronchial stenosis, one oesophagotracheal fistula and two probable occult perforations of the oesophagus. Photodynamic therapy with green light renders such perforations of the oesophageal wall essentially impossible at the applied conditions, and appears not to reduce the efficacy of the treatment. Skin photosensitization, which was never observed later than the first week after injection, occurred in 12 patients. Hence, PDT with mTHPC is a safe and effective treatment for early carcinomas of the oesophagus and the tracheobronchial tree.
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  • 6
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; Early stage lung cancer ; Superficial oesophageal cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract In 1994, the Ministry of Health and Welfare of Japan approved photodynamic therapy (PDT) for the treatment of early stage lung cancer (T0 and T1), superficial oesophageal cancer, superficial early stage gastric cancer and carcinoma in situ and/or dysplasia of the cervix. The decision to do so was based on studies carried out by the PDT Research Group of the Ministry, including PDT treatment of 168 early stage central lung cancers (123 superficial lesions and 45 nodular lesions) and 32 superficial oesophageal cancers. The results presented in this article were analysed according to the extent of the lesion. Of the 123 superficial lung cancers, complete remission (CR) was obtained in 93% of 89 lesions less than 1.0 cm in diameter. Larger lesions responded less well. Complete remission was obtained in 97% of the 33 superficial oesophageal cancers, although three of six patients with lesions over 3.0 cm in diameter later died of metastatic disease. The authors believe PDT to be a suitable and effective treatment for early stage lung and oesophageal cancers.
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  • 7
    ISSN: 1435-604X
    Keywords: Photosensitizer ; Photodynamic therapy ; mTHPC ; Temoporfin ; Pharmacokinetics ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract A Phase I photodynamic therapy (PDT) clinical trial was carried out with Temoporfin (Foscan®, mTHPC) at the Departments of Otolaryngology at Orebro Medical Center (OMC) and Long Island Jewish Medical Center (LIJMC). A range of drug doses, consisting of 0.3, 0.15, 0.075 and 0.0375 mg kg−1, were utilized. Light treatment was performed on the sixth day after injection of the photosensitizer mTHPC. Photodynamic therapy was done on prostate cancer (six cases), bronchial cancer (one case), nasopharyngeal cancer (three cases), laryngeal cancer (eight cases), mesothelioma (one case), laryngeal papilloma (five cases) and basal cell nevus syndrome (one case). A number of patients were treated more than once. Plasma was collected and analysed at 1, 24, 48, 72, 96, 120 and 144 h and at 2 weeks post-injection, to follow the loading and clearance rate of the photosensitizer. Normal and malignant tissues were collected immediately prior to PDT, chemically extracted, and analysed for drug content spectrofluorometrically. Plasma drug levels were proportional to the dose. The half-life of the drug was 45.4 h across the entire dose range. The ratio of the drug in the tumour compared to normal adjacent mucosa was in the range of 2–3. There were no significant adverse effects. These data establish the basis for full clinical trials.
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  • 8
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    Lasers in medical science 11 (1996), S. 237-246 
    ISSN: 1435-604X
    Keywords: Fluorescence ; Time-resolved confocal microscopy ; Porphyrins ; Fluorescence polarization ; Photodynamic therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract The application of a novel time-resolved confocal fluorescence microspectrometer to studies of the distribution and speciation of porphyrin photosensitizers in rat C6 cerebral glioma cells is described. The instrument combines a mode-locked argon ion laser excitation source with time-correlated single photon counting fluorescence detection and has sub-micron spatial and sub-nanosecond temporal resolution. The porphyrins studied were haematoporphyrin derivative (HpD), haematoporphyrin IX (HP), porphyrinc (Pc) and the tetrakiscarborane carboxylate ester of 2,4-(α,β-dihydroxyethyl) deuteroporphyrin IX (BOPP). From the heterogeneous emission observed in vitro, assignments and spatial location of various porphyrin species are proposed.
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  • 9
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    Lasers in medical science 4 (1989), S. 183-186 
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; Gastrointestinal tumour ; Advanced lesions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract In the study, 120 patients with advanced gastrointestinal tumours were treated by PDT; 5 mg/kg of HpD was intravenously given 48–72 h prior to PDT. The light source was an argon dye laser with an output beam of 630 nm. The irradiation time varied from 15–25 min with a power of 100–350 mW cm−2. The entire tumour was irradiated with a light dose of 100–250 J cm−2. Of the 120 patients, 20 had cancer of esophagus, 72 had cancer of the gastric cardia, 18 had cancer of the stomach and 10 had cancer of the rectum. Eighty-eight patients (73.3%) had a response to PDT. Twelve patients with CR were followed up for one to five years, two patients died during the two years after PDT.
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  • 10
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; Haematoporphyrin ; Argon dye laser ; Early stage esophageal cancer ; Head and neck cancer ; Squamous cell carcinoma ; Adenocarcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract This is the report of a pilot study in which the technique of photodynamic therapy (PDT)—in which malignant tissues are destroyed by light after being previously photosensitized by haematoporphyrin or its derivative—was performed using a high power argon-dye laser system which operated at 630±5 nm and optical fibres with either a microlens or a diffusing tip. A total of thirty-seven patients were utilized for this study, including twenty-five patients affected by esophageal carcinoma, five by recurrences of head and neck cancer, four by gastric cancer and three by lung cancer. Among the sixteen cases with superficial or localized cancer of the esophagus, complete and partial responses were observed in seven and six patients, respectively. In advanced and recurring cancers less satisfactory results were obtained. Thus, PDT seems to be useful in cases of small superficial cancers, either primary or recurrent after previous treatments.
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  • 11
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; Superficial bladder tumours ; Dosimetry ; Isotropic light sensors ; Photosensitizers ; Wavelength of irradiation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract The use of photodynamic therapy (PDT) for the treatment of superficial tumours on the bladder wall is described. Details are given on the laser, methods of delivering light into the bladder, suitable commercial dosimetry systems and instrumentation suitable for making light measurements on the bladder wall during therapy. New alternative photosensitizers are discussed in some detail. Some early clinical results are presented and the current problems with this type of therapy are highlighted.
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  • 12
    ISSN: 1435-604X
    Keywords: Bladder tumour ; Diagnosis ; Fluorescence ; Photodynamic therapy ; Photosensitization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract Most methods of modern laser tumour therapy are physically based on the conversion of light to heat. Recently tumours have also been treated using ionizing processes for tissue ablation. Photodynamic laser therapy (PDT), however, involves light-induced non-thermal biochemical processes and the use of a photosensitizer. Several drugs are known to be stored selectively in tumours after systemic application. This transient marking can be used for diagnostic and therapeutic procedures. The marker most commonly used is dihaematoporphyrin ether/ester (DHE) intravenously injected at doses of 0.2–3.0 mg/kg bodyweight for diagnosis and therapy, respectively. The corresponding clearance intervals after injection of DHE range from 3–48 h to 25–75 h. Detection of photosensitized tumours might offer great advantages. The highly sensitive two-wavelength laser excitation method with computerized fluorescence imaging recently has been transferred to the hospital for clinical tests. Photoinduced production of singlet oxygen is claimed to be the initial process which leads to later tumour destruction and therapy. PDT has been applied to 20 patients suffering from superficial tumours (TIS GII–III) recurred after application of other treatments. The results after PDT were evaluated by three-monthly check-ups (endoscopy, cytology, bladder mapping, renal ultrasonography) as well as by computed tomography (CT) examination at 8–13 month intervals. In six patients treated by PDT no tumour recurrence has been found over the whole observation period of up to 5 years. Four patients have remained free of tumour (12 and 14 months) after repeated transurethral resection (TUR) and Nd-YAG laser therapy following PDT. Due to an initial application of insufficient irradiation four patients required a second PDT. In one patient a circumscribed dysplasia appeared at the left ostium 26 months following PDT and was treated successfully by means of thermal Nd-YAG laser irradiation following TUR. In six patients slight mucosal atypia persisted for a period of at least 2.5 years. One cystectomy had to be performed because of bladder shrinkage. The dissected bladder, however, was free of tumour. These preliminary results suggest that PDT is justified in patients who are in a worst-case situation with cystectomy recommended in case of recurrent superficial TIS bladder carcinoma and indicate the future potential of photodynamic therapy of tumours. Homogeneous irradiation of the area to be treated and a reliable light dosimetry are prerequisites for an effective tumour therapy. Standard instruments for a routine application do not exist, but are under development.
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  • 13
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    Lasers in medical science 5 (1990), S. 289-292 
    ISSN: 1435-604X
    Keywords: Cancer ; Laser ; Chromophores ; Photodynamic therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract Chromophores in tissue are of considerable interest for the tissue interactions with lasers in the visible light range. The natural chromophores in man are essentially melanin and red cell haemoglobin. With the development of Photodynamic Therapy (PDT) in the treatment of human cancer, the new technology of exogenous chromophores was developed and continues to expand both in laser medicine and laser surgery. This technology relates specific chromophores to specific wavelengths for the destruction of tumours and has been very effective for PDT in those instances where there is accessibility to the tumour mass by the laser beam. The problems today are concerned with how to mark these malignant foci deep in the tissue, how to detect them, and how to direct selected laser beams to the marked carcinomatous tissue. In laser medicine, the field is expanding especially for tissue and laboratory diagnostics.
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  • 14
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; PDT ; Fluorescence ; Haematoporphyrin derivative ; HPD ; Diagnosis ; Murine tumour ; Laser ; Pharmacodynamic ; Pharmacokinetic ; Regrowth delay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract Eight commercially available HPD-photosensitizers intended for photodynamic therapy were tested in a murine tumour model with regard to their therapeutic efficacy. The regrowth delay of the fibrosarcoma SSK-2 on the mouse C3H, Neuherberg-line, was determined 3, 24, 48 and 72 h after injection of the drugs (dose: 9 mg kg−1 body weight). The corresponding pharmacodynamics, as measured by regrowth delay, were approximated by an exponential function and the characterizing coefficients derived. These coefficients served to quantify the photodynamic properties of the drugs. The pharmacodynamics of five substances were compared with those obtained fluorometrically. The latter showed shorter decay constants than the therapy-correlated substances which indicates different metabolic behaviour of the therapeutic and diagnostically useful fluorescent components of haematoporphyrin-derived photosensitizers.
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  • 15
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; Skin photosensitivity ; Antihistamines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract We have investigated the incidence of cutaneous phototoxicity in 47 patients who received photodynamic therapy between April 1988 and March 1990. Of these, 15 patients received antihistamines as part of a pilot study to evluate their photoprotective role. Patients were followed-up for a minimum of 8 weeks. One out of the fifteen who received antihistamines and 15 out of the 32 patients who did not (p〈0.005), developed cutaneous phototoxicity. On the basis of these results we have initiated a randomized double-blind trial to evaluate the role of antihistamines in haematoporphyrin derivative-induced cutaneous phototoxicity.
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  • 16
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; Tumour ; Haematopor-phyrin derivative ; Photoproduct ; Laser illumination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract Illumination of haematoporphyrin derivative in phosphate-buffered solutions causes the formation of a stable photoproduct with new absorption and fluorescence bands. We report data showing photodynamic activity of the photoproduct. Praestomic tumour OJ-5, carcinosarcoma W-256 (mice) and adenocarcinoma Akatol of colon (rats) have been used. Dynamics of tumour growth, life span of animals and morphological changes of tumour tissues have been the main criteria used to show the photoproduct activity.
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  • 17
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    Lasers in medical science 1 (1986), S. 117-120 
    ISSN: 1435-604X
    Keywords: Gold-vapour laser ; Argon-pumped dye laser ; Photodynamic therapy ; Cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract This paper compares the relative merits of the continuous wave argon-pumped dye laser and the pulsed gold-vapour laser as used clinically for photodynamic therapy. At comparable power and energy outputs, the biological effect of the two appears to be the same. However, for 1 W output (a suitable level for clinical use), the gold laser is simpler and easier to install and run, although it requires a larger diameter fibre for light delivery (0.6 mm v. 0.2 mm). The wavelength of the dye laser is tunable, whereas that of the gold is not, although the gold laser can be easily converted to a copper-vapour laser which can pump a tunable dye laser.
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  • 18
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    Lasers in medical science 1 (1986), S. 163-174 
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; Malignant glioma ; Laser ; Haematoporphyrin derivative ; Photosensitizer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract Interest in photodynamic therapy in the treatment of malignant gliomas began in the 1950s. Following the publication of papers showing that haematoporphyrin was excluded from the intact blood-brain barrier and that glioma cells grown in culture and subcutaneously could be killed by a combination of light and haematoporphyrin, a number of clinical trials was started, none of which has shown any measurable improvement in patient survival. The reason for this may relate to a lack of understanding of the mechanisms of photodynamic therapy and a lack of the scientific data needed to optimize photodynamic selectivity. This review discusses the potential role of photodynamic therapy in glioma treatment, and reviews the current clinical and experimental work in the field.
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  • 19
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    Lasers in medical science 1 (1986), S. 193-195 
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; γ-Irradiation ; Hypoxia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract The presence of adequate oxygen appears to be essential for photodynamic therapy (PDT) of tumours (1, 2). We used the mouse sarcoma 180 tumour model to investigate how the reoxygenation of the tumour cell population after a single exposure to γ-irradiation influenced the effect of photodynamic therapy. The combination of γ-irradiation with PDT leads to a significant enhancement of the therapeutic effect. The best effect is observed when the γ-irradiation precedes the PDT by 24 h, at which time reoxygenation of the tumour is greatest. Also, there is some enhancement of the effect when PDT is given before γ-irradiation, although the mechanism of this is not yet clear.
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  • 20
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    Lasers in medical science 10 (1995), S. 19-24 
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; Light dosimetry ; Fibre optic probes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract We describe the calibration of fibre optic probes used to perform in vivo light dosimetry studies during the treatment of skin lesions by photodynamic therapy. Results from six individual detectors show that the linearity of the calibration and the calculated radiant energy fluence rate within a liquid phantom are independent of the type and sensitivity of the probe. The method of calibration is also shown to yield the optical interaction coefficients of the phantom.
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  • 21
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; Haematoporphyrin derivative ; In vivo ; Laser ; Light source ; Murine tumour
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract The performance of a low cost, table-top/portable light source was tested against an argon ion pumped dye laser for in vivo photodynamic therapy (PDT). The prototype delivers up to 1 W via a 4 mm flexible lightguide within a 30 nm bandwidth centred at any wavelength from 300 nm to 1200 nm at fluence rates of up to 8 W cm−2. An in situ bioassay using regrowth delay of tumour T50/80 was used to quantify the relative efficacy of the prototype with a laser. The tumours were sensitized with haematoporphyrin derivative (HpD) and externally irradiated. There was no significant difference in the response of the tumour to treatment between the two light sources (p = 0.69). Mean growth delays ranged from 2 days (light dose 10 J cm−2) to 20 days (light dose 100 J cm−2). The estimate for the difference in means (laser minus prototype growth delay) was only 0.66 days and was not statistically significant. This in vivo study demonstrates that the prototype is equivalent to a laser in PDT effect. The device has low capital/running cost, is simple to use and is one of the most powerful, spectrally efficient non-laser PDT sources available.
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  • 22
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; Isotropic fibre optic light diffusers ; Construction of diffusers ; Quality assurance of diffusers ; Calibration of diffusers ; Goniometer ; Integrating sphere
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract Spherical isotropic fibre optic light diffusers are used in photodynamic therapy either as a light source or as a light detector. The construction of light diffusers using different materials is described, viz. an optical method involving local polymerization of a dental fissure sealant, which is referred to as the Henderson method, and a second method using plastic or ceramic pre-fabricated spheres. Quality tests necessary for reliable clinical use are presented for the mechanical strength, output power and isotropy. The maximum pull-off force and blow-off output power for the different kinds of diffusers were determined. The calibration procedures are given for measurement of the output power and wavelength of the light emitted by a diffuser and for measurement of the fluence rate by a light-detecting diffuser, using a compact integrating sphere device. With all types of diffusers described, an isotropy can be obtained of better than ± 20% measured over a 320° angle for spheres as small as ≈ 1 mm. Larger ceramic diffusers are particularly suitable for delivering high output powers. A 3-mm-diameter ceramic diffuser mounted on a 600-μm-core fibre can emit up to ≈ 5 W of continuous wave (CW) visible light in air. Diffusers used for light detection can measure the light fluence rate in tissue with ≈15% accuracy or better if calibration factors are determined for each individual probe.
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  • 23
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    Lasers in medical science 11 (1996), S. 139-143 
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; Fluence ; Irradiance ; Light source
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract Photodynamic therapy is generally carried out using a laser, usually a dye laser with the wavelength tuned to suit the particular sensitizer. The availability of broad-band sources for use in photodynamic therapy is challenging the role of the laser, since the non-laser sources are more portable and less expensive. Also, the wavelengths utilized may easily be changed by optical filtering. However, the use of a broad-band source introduces serious problems with dosimetry. The concept of the ‘total effective fluence’ takes account of the incident spectral irradiance from the light source, optical transmission through tissue (preferably including backscatter), and absorption by the sensitizer. Application of the concept to various light sources demonstrates the potential value of this simple concept.
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  • 24
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; Diode laser ; mTHPC ; Depth of necrosis ; Normal rat liver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract Initial pre-clinical evaluation of a new 652 nm diode laser system for photodynamic therapy was performed to establish its efficacy in photo-activating the second-generation photosensitizer meta-tetrahydroxyphenychlorin (mTHPC). The diode laser was compared directly to a copper vapour laser pumped dye laser using depth of necrosis in normal rat liver as a measure of the photodynamic effect. No significant difference between the two lasers was observed.
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  • 25
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; Photofrin ; Oral mucosa ; Normal tissue damage ; Light dosimetry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract Photodynamic therapy (PDT) is a treatment modality with potential application for premalignant lesions and squamous cell carcinoma of the oral mucosa. PDT in principle has dual selectivity. This may result from a ‘preferential’ retention of the photosensitizer in target tissue. In addition, the photodynamic activity will be limited to the irradiated area because PDT will not affect tissues in the absence of excitation light. The specificity of PDT is limited by the fact that normal tissues also retain the photosensitizer to some degree, which makes these tissues susceptible to PDT damage. To optimize PDT for oral malignancies, a study was undertaken on normal tissue to investigate the responses in rat palatal mucosa and surrounding anatomical structures. Eighty male Wistar rats were used in the study. Photofrin was administered i.v. at four doses (0, 2.5, 5 or 10 mg kg−1 body weight). Irradiation for PDT was performed 24 h later. An argon pumped dye laser system was used to produce light of two different treatment wavelengths (514.5 and 625 nm), and various energy density levels (0, 25, 50, 100 or 200 J cm−2). Early effects of PDT were studied at 2 days and late effects at 2 months after treatment. Twenty-four hours after i.v. administration of Photofrin, it was found that PDT affects normal tissues of the oral cavity both macroscopically and microscopically. Combinations of photosensitizer doses ≥5 mg kg−1 and light doses≥100 J cm−2 caused severe and permanent damage to the palatal mucosa and adjacent normal structures such as palatal bone and dentition. Light scattering and internal reflection usually raise the fluence rate in tissue above the irradiance of the incident beam. In an additional study using six male Wistar rats, the energy fluence rate at two treatment wavelengths (514.5 and 625 nm) was measured ex vivo in the palatal mucosa and adjacent anatomical structures. As expected, the energy fluence rates were wavelength, tissue and depth dependent. At the air-mucosa boundary, light of 625 nm was found to have a three-times higher fluence rate than the primary incident beam. Under similar conditions, the fluence rate of 514.5 nm was found to be less, but still twice as high as the primary incident beam. At deeper levels of the rat maxilla, fluence rates were still elevated compared with the incident beam. For 625 nm light, this phenomenon was observed up to the level of the nasal cavity. These increased fluence rates could largely explain the pattern of damage to normal mucosa and surrounding anatomical structures.
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    Lasers in medical science 5 (1990), S. 115-120 
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; Photosensitization ; Pharmacokinetics ; Photofrin II ; Phthalocyanines ; Liposomes ; Lipoproteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract The scope and potential of the photodynamic therapy of tumors can be enhanced through an adequate control of the factors which improve the selectivity of tumour targeting by the systemically injected photosensitizer and increase the efficiency of photosensitized tumour damage. Promising results are obtained by using hydrophobic photosensitizers which can be specifically transported and released to the tumour by serum lipoproteins, especially low-density lipoproteins. The photosensitizer molecule should possess those structural features which induce a high probability of photoactivation by 700–800 nm light, as well as a high yield of long-lived triplet state. The use of liposome-delivered Zn-phthalocyanine as a second generation phototherapeutic agent for tumours is proposed.
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  • 27
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    Lasers in medical science 5 (1990), S. 107-113 
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; Light delivery ; Light dosimetry ; Tissue optics ; Scattering ; Absorption ; Diffusor ; Dosimetry probe
    Source: Springer Online Journal Archives 1860-2000
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    Notes: Abstract Photodynamic therapy (PDT) has attracted attention because it was considered to be a selective form of cancer treatment causing minimal damage to normal tissues. This is not exactly true, because the ratio between the photosensitizer concentrations in tumour and surrounding normal tissues is not always much more than one. Nevertheless, tumour destruction by PDT with relatively little damage to normal tissue is possible in many cases. This requires sophisticated light delivery and/or light dosimetry techniques. In this respect the limited penetration of light into biological tissues can sometimes be useful. In this paper a qualitative and sometimes quantitative discussion is given of the physical phenomena determining the energy fluence in a biological tissue. Most important is light scattering, the contribution of which depends on the geometrical conditions. Finite beam surface irradiation, irradiation of hollow organs (bladder) and interstitial irradiation are discussed separately. The emphasis is on light ‘dose’ and light dose distribution. It is emphasized that PDT dosimetry in general is complicated by photosensitizer distribution (which is usually not known), by photobleaching of the sensitizer, by possible effects of hyperthermia, and by changes in optical properties during and as a result of PDT.
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  • 28
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    Lasers in medical science 5 (1990), S. 181-183 
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; Haematoporphyrin derivative ; Lung cancer
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    Topics: Medicine , Physics , Technology
    Notes: Abstract The main purpose of cancer therapy is to treat malignant tissue with the least damage to normal surrounding structures. Photodynamic therapy (PDT) seems to be able to fulfil this simple but fundamental premise. The mechanism of action of the photosensitizer—light system can be summarized in two main points. Chiefly, it seems to be a photodynamic process, with energy transfer from the light to the photosensitizer and from it to the oxygen molecules. Oxygen is excited and becomes singlet oxygen, which is extremely reactive and very noxious for tissues in which it develops. Secondly, a thermal mechanism related to light absorption and consequent temperature rise also seems to be involved in malignant necrosis by PDT. Thirteen males were submitted to endoscopic PDT. A total of 15 treatments were given: 2 patients were submitted to 2 sessions of PDT. Forty-eight hours after HPD administration (72 h in a few cases), the lesions were exposed to a 630 nm light from an argon-dye laser system. The total estimated energy dose delivered to the tumour surface was 90–150 J/cm2 in 11 cases. All cases treated responded well and total disappearance was obtained. Median follow-up was 9.5 months (1–20 months) and the estimated energy delivered from 90–600 J/cm2. No major complications were reported.
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  • 29
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    Keywords: Haematoporphyrin derivative ; Photodetection ; Photodynamic therapy ; ‘Early’ squamous cell carcinoma ; Pharynx ; Oesophagus ; Bronchi ; Fluoro-endoscope ; Cationic dyes ; Monoclonal antibodies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract The efficacy of photodynamic therapy (PDT) alone was evaluated on 41 ‘early’ squamous cell carcinomas of the pharynx (10), oesophagus (15) and tracheo-bronchial tree (16). All lesions but two were synchronous second primaries in ENT-patients suffering from a more extensive cancer, governing the overall oncological prognosis. Photofrin I (3 mg/kg) or Photofrin II (2 mg/kg) were injected 72 h prior to the red light irradiation, supplied by an argon pumped dye laser. A diffusing cylinder was used to obtain a homogeneous light distribution at the tumour site (60 J to 150 J/cm2). In the oesophagus and bronchi, the results are good for cancers staged in situ or microinvasive at endoscopy (two recurrencies for 23 lesions treated). For more advanced cancers (submucosal in the oesophagus or invading the bronchial cartilage), the results are less satisfactory (three recurrencies for eight lesions treated). In the pharynx where light dosimetry is more difficult, the rate of recurrencies is higher (3/10 lesions treated). In the bronchi (one case) and oesophagus (one case), the longest disease-free survival is now 5 years. The irradiation of a non-cancerous zone of normal buccal mucosa on 25 patients having received HPD showed necrosis in all cases with light doses as low as 50mW/cm2 for 20 min (60 J cm−2), even with Photofrin II. We encountered six complications (three cicatricial stenosis, two fistulae, one severe sunburn), most of them resulting from the lack of selectivity of HPD. According to these experiments, PDT is efficient at destroying early squamous cell carcinomas in the pharynx, oesophagus and bronchi, but the tumour selectivity of HPD is poor in the digestive tract lined with squamous cell epithelium. The only hope for the future lies in the synthesis of a more selective and more stable photosensitizer. This discussion reviews possible directions of research for the development of new dyes (cationic dyes, dyes attached to monoclonal antibodies, etc), for PDT and hyperthermia, for photodetection of early cancers using a fluoro-endoscope, and finally, for tumour depth profiling in hollow organs using lasers of different wavelengths.
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  • 30
    ISSN: 1435-604X
    Keywords: Haematoporphyrin derivative ; Singlet oxygen ; Photodynamic therapy ; Dosimetry
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    Description / Table of Contents: Résumé La photochimiothérapie est un nouveau traitement des cancers débutants. Alors que des essais cliniques de phase 1–2 sont entrepris, les indications pour ce type de traitement demeurent rares, principalement du fait d'une dosimétrie approximative de la captation de l'hématoporphyrine dérivée par les tissus cancéreux humains. La fluorescence émise par l'HPD peut Être utilisée in-vivo pour un diagnostique ‘topographique’ de la répartition de l'HPD, mais aussi le dosage quantitatif des espèces fluorescentes présentes dans le mélange HPD. Le dosage de l'oxygène singulet, généré lors de la réaction photochimique, est nettement plus difficile à réaliser mais a été proposé pour le dosage in-vivo des formes porphyriniques ‘actives’ présentes dans le milieu. Les applications cliniques de telles mesures représentent une condition essentielle pour le developpement de la photochimiothérapie car à côté des possibilités de diagnotiques offertes par l'analyse de la répartition intratumorale de l'HPD, un dosage précis permettrait d'optimiser le moment du traitement, arbitrairement fixé aujourd'hui à 72 heures.
    Notes: Abstract Photodynamic therapy is a new treatment for early carcinomas. Although undergoing phase 1/2 clinical assays, clinical indications for this therapy remain rare mainly because of the approximate dosimetry of HPD uptake by tumour tissues in human beings. In this review we present the potential interest and limits of both direct fluorescence detection or dosimetry of HPD and in vivo measurements of singlet oxygen, produced during photodynamic therapy. Clinical applications of such measurements should represent one of the main conditions for the future development of photodynamic therapy.
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  • 31
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; Tetrapropylporphycene ; Liposomes, Electron microscopy ; Tumour necrosis
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    Notes: Abstract Red light irradiation of a transplanted MS-2 fibrosarcoma in mice at 24 h after injection of liposome-zbound tetra-n-propyl-porphycene (TPP, 2mg kg−1 b.w.) caused an efficient tumour necrosis. Electron microscopy analysis of tumour specimens taken at different times after the phototherapeutic treatment showed the development of direct damage of malignant cells between 3 and 6 h; the earliest detectable alterations occurred at the level of mitochondria. The endocellular damage gradually progressed with extensive vacuolization of the cytoplasm and, at later stages, formation of pyknotic nuclei. On the other hand, the vascular system of the tumour appeared to be well preserved up to about 9 h, when several endothelial alterations were detected. The damage of the tumour tissue was essentially complete 24 h after the phototreatment. The pattern of tumour modification is consistent with a preferential transport and tumour release of the liposome-bound TPP by low-density lipoproteins.
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  • 32
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    Lasers in medical science 1 (1986), S. 217-220 
    ISSN: 1435-604X
    Keywords: Upper respiratory tract cancer ; Oronasopharyngeal cancer ; Photodynamic therapy ; Argon pumped dye laser ; Gold-vapour laser
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    Topics: Medicine , Physics , Technology
    Notes: Abstract Photodynamic therapy has been effective in the management of cancers arising in multiple sites, particularly skin, bronchi and bladder. In head and neck cancer, however, its use has been confined to the palliation of advanced lesions that have proved refractory to conventional therapy. While this use is unquestionably valid, the true therapeutic value of photodynamic therapy appears to be in managing early mucosal cancers of the upper aerodigestive tract. These include early superficial cancers and ‘condemned mucosa’. At the University of Cincinnati, photodynamic therapy has been used on a variety of such early cancers where, for a variety of reasons, conventional therapy was not possible, and with most encouraging results. The first 20 cases are reported here, to highlight the technical aspects encountered in management, together with the pitfalls and problems. This experience has led to the development of a multi-institutional study to compare the safety and efficacy of photodynamic therapy with those of carbon dioxide laser excision of superficial carcinoma of the oral cavity and oropharynx.
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    Lasers in medical science 1 (1986), S. 235-244 
    ISSN: 1435-604X
    Keywords: Dihaematoporphyrin ether ; Aluminium chlorosulphonated phthalocyanine ; Penetration depth ; Diffusion theory ; Photodynamic therapy
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    Notes: Abstract The additional optical absorption in tissue resulting from the uptake of exogenous photosensitizers increases the effective attenuation of photoactivating light. This may be significant for the irradiation of solid tumours in photodynamic therapy, since it reduces the depth or volume of tissue treated. The effect has been studied in vitro by using dihaematoporphyrin ether (DHE) and 630 nm light in tissues representing a wide range of absorption and scattering conditions. While the attenuation may be markedly changed by small concentrations of DHE in pure scattering media, tissues with significant inherent light absorption are little affected by the additional absorption of DHE at concentrations relevant to clinical photodynamic therapy. However, it is shown that for other potential photosensitizers such as the phthalocyanines, which have substantially greater absorption at the treatment wavelength than DHE, the penetration of light in tissues may be significantly reduced.
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  • 34
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    Lasers in medical science 1 (1986), S. 181-186 
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; Hypoxia ; Misonidazole ; Hyperthermia ; Tumour models ; Xenon lamp ; Argon-dye laser system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract Three animal tumour models, colon carcinomaK 173 in rats, sarcoma 180 in mice and pigmented melanoma IC-Sofia in hamsters, were subjected to photodynamic therapy (PDT) in combination with the administration of misonidazole or with hyperthermia (43°C±0.1°C). The results showed that combined application of PDT with these modalities increases the therapeutic effect, which depends particularly on the sequence of their application. Misonidazole reduced the inhibition of PDT caused by acute hypoxia.
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  • 35
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    Lasers in medical science 10 (1995), S. 67-71 
    ISSN: 1435-604X
    Keywords: Oesophageal cancer ; Photodynamic therapy
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    Notes: Abstract Twenty-three patients, 12 males and 11 females aged 42–86 years (mean age 69.6), with inoperable oesophageal cancer were treated by endoscopic photodynamic therapy. Inoperability in 20 patients was due to extent of tumour and existence of metastases, in two because of poor general condition and in one patient due to recurrence at the site of previous anastomosis. Prior to treatment, patients' degree of dysphagia and their functional status were recorded. Using barium contrast studies and endoscopy, the extent and location of the tumour within the lumen of the oesophagus were mapped out. Treatment protocol consisted of intravenous administration of the photosensitizer, Polyhaematoporphyrin, followed 24–48 h later by illumination of the tumour with 630 nm light produced by a copper vapour pumped-dye laser and delivered via a 400μm internal diameter optical fibre with a cylindrical diffusing end. All treatments were undertaken under general anaesthesia as day case procedures. There was no treatment-related mortality nor was there any complication apart from a mild skin photosensitivity reaction in one case. Every patient's swallowing and functional status was improved at 6 weeks post-treatment. Ten patients needed more than one treatment: five required oesophageal dilatation. Thirteen patients survived a mean period of 6.2 months. Two needed oesophageal intubation 3–4 weeks before their death. Ten patients are alive at 6–14 months. This study suggests photodynamic therapy in inoperable oesophageal cancer to be a useful treatment method and in suitable cases an alternative to other forms of palliation. Its value lies in the fact that it can be used to treat cancer at any level of the oesophagus irrespective of histology.
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  • 36
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    Keywords: 5-Aminolaevulinic acid ; Protoporphyrin IX ; Photodynamic therapy ; Skin neoplasms ; Basal cell carcinoma ; Actinic keratosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract Photodynamic therapy (PDT) with topical application of 5-aminolaevulinic acid (ALA, 20% w/w) was used to treat superficial basal cell carcinoma (BCC, 16 patients), Morbus Bowen (one patient), basal cell naevus syndrome (BCNS, three patients), actinic keratosis (AK, two patients), chronic inflammation (CI, one patient), and metastasized BCC (one patient). The interval between ALA application and illumination was 3–6 h. The incident light dose was 50–100 J cm−2, mostly 75 J cm−2, at 633 nm wavelength. This was based on the fluorescence excitation spectrum, measured on the skin of human volunteers. In a few cases, 514.5 nm light was used. A complete response (CR) rate of 79% (median follow-up 13 months) was obtained with 42 BCC lesions. The treatment of five areas with AK, two areas with CI and one area with M. Bowen yielded three CR for AK and five partial remissions (PR). Photodynamic therapy of metastasized BCC, after either topical or oral ALA, was not successful. Treatment of BCNS was satisfactory with 100% CR in one patient (22 lesions), PR in a second patient (20 lesions), and good palliation in a third patient (〉250 lesions). The treatment was well tolerated, although the illumination had to be interrupted occasionally due to pain. Healing usually occurred in 2 weeks. Cosmetic results were good to excellent. 5-Aminolaevulinic acid application over 16–19 h and repeated treatments made it possible to obtain CR of non-superficial lesions. The selective tumour fluorescence was then lost, however, due to fluorescence of normal skin, but the cosmetic outcome did not deteriorate. 5-Aminolaevulinic acid PDT may be a good alternative outpatient treatment, especially in elderly patients and for large treatment areas. The excellent cosmetic outcome warrants further study in younger patients. More work is necessary to establish optimal ALA-treatment schemes.
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  • 37
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; Diffusing fibre tips ; Interstitial light delivery ; Light dosimetry
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    Topics: Medicine , Physics , Technology
    Notes: Abstract Optimal delivery of light to the tumour is of considerable importance in photodynamic therapy. The most effective way of delivering laser light to the tumour tissue is through an implanted optical fibre. In order to investigate the possible effects taking place at the tips of fibres implanted in tissue, fibres were used to deliver light to human blood and the transmission of light by the blood was measured at different power levels. The maximum power level which could be delivered without charring or coagulation at the fibre tip was measured for five different fibres. Three plane cut fibres and two with 1.5 cm long diffusing tips were studied. Charring and coagulation, which resulted in practically no light being delivered more than 0.5 mm from the fibre tip, were observed at relatively low-output powers (70-130 mW) for all the plane-cut fibres. This is less than the level required to deliver a clinically useful dose in a reasonable time. In contrast, neither charring nor coagulation was observed at the diffusing tips for output powers up to 1.1 W and consequently these should be the fibres of choice for interstitial photodynamic therapy. Observed changes in light transmission through the blood with increasing output power indicate that, for accurate light dosimetry, a means of monitoring delivered light in vivo during photodynamic therapy is essential.
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  • 38
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    Lasers in medical science 4 (1989), S. 205-210 
    ISSN: 1435-604X
    Keywords: Tumour imaging ; Tc-99m-HpD ; Kinetics ; Photodynamic therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract The in vivo uptake of Tc-99m-labelled HpD in a murine tumour has been investigated using nuclear imaging techniques. Eighty-four per cent of the palpable tumours were visualized with good contrast resolution. The peak tumour-to-surrounding-normal-tissue ratio of 5:1 was at 4 h post-injection indicating the optimum time of imaging. The high level of HpD in the blood-pool component of the tumour could indicate that photodynamic therapy administered within 2 h after intravenous injection (‘early PDT’) could lead to damage of tumour vasculature and tumour necrosis. The therapeutic response achieved by this early method needs to be investigated.
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  • 39
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; Cylindrical diffuser ; Interstitial treatment
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    Notes: Abstract A simple method for the manufacture of disposable, cylindrical, diffusing fibre tips is described. The method is suitable for plastic clad silica fibres with core diameters in the range 200–600μm. Light diffusing tips up to 40 mm in length have been constructed. The method is highly reproducible, construction is typically less than five minutes and the financial cost is negligible. The diffusers are highly efficient, delivering an amount of light at least equal to that transmitted by a plane cut fibre of the same core diameter. The uniformity of light emission along the diffuser can be modified to meet the requirements of any given treatment. The diffusers have been successfully used in interstitial photodynamic therapy.
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  • 40
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    Lasers in medical science 4 (1989), S. 79-84 
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; Haematoporphyrin derivative ; Misonidazole ; Radiosensitizers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract Fifty-six Fischer 344 rats bearing subcutaneous 9L-gliosarcoma tumours were studied to determine if Misonidazole (MISO), combined with photodynamic therapy (PDT), would be more effective than PDT alone. PDT, like conventional radiation, is potentiated by oxygen, and if there are areas of hypoxic cells within the tumour it is possible that the addition of the radiosensitizing drug should make the treatment more effective. Thirty-nine rats were divided into eight groups as controls. Seventeen rats were divided into three groups and received MISO combined with PDT, five rats were exposed to a laser dose of (nm = 630) 300 J at 300 mW, seven rats to a laser dose of 600 J at 600 mW and five rats to a laser dose of 2160 J at 600 mW. The tumours were approximately 1 cm3 when treated. Animals treated with either PDT at 300 J or 600 J failed to show any effect on growth of the tumour. At 2160 J a definite delay in growth was observed but addition of MISO did not potentiate this effect. The results indicate this combined therapy did not slow the growth rate of the tumours in this model. The implication of these results are discussed.
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  • 41
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    Lasers in medical science 5 (1990), S. 199-201 
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; Basal cell carcinoma ; Squamous cell carcinoma ; Carcinoma in situ lesions
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  • 42
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    Lasers in medical science 5 (1990), S. 245-252 
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; Supratentorial tumours ; Cerebral gliomas ; Cerebral metastasis
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    Topics: Medicine , Physics , Technology
    Notes: Abstract Experience with intraoperative PDT in 50 patients with malignant supratentorial tumours is reported; in 33 cases the tumour was recurrent. In 45 patients the tumour was a cerebral glioma and in five cases a solitary cerebral metastasis. There were 29 males and 17 females with an age range of 17–73 (mean 48) years. All patients received either haematoporphyrin derivative (HPD) or dihaematoporphyrin ether (DHE) 18–24 h preoperatively. A photoilluminating device, of the authors' design, was coupled to an argon dye pump laser in order to deliver light at 630 nm to a tumour cavity created by radical tumour resection and/or tumour cyst drainage. The total light energy delivered ranged from 440 to 3888 J and the light energy density ranged from 8 to 175 J/cm2. In eight patients a line fibre(s) was used to administer interstitial light as a supplement to the cavitary photoillumination. The additional light dose ranged from 60 to 945 J/cm. There were two postoperative deaths as the consequence of haematoma accumulation in the tumour resection cavity. In three patients neurological function was worse postoperatively and did not recover. Postoperative cerebral oedema was pronounced in some cases and required second craniotomy in two patients (the histology from both showed haemorrhagic necrosis of residual tumour). Four patients developed wound infections; two of these required surgical treatment. Four patients, two of whom were hemiparetic, developed deep vein thrombosis and required anticoagulant therapy. There were no adverse systemic reactions to the administration of either photosensitizer and only three skin photosensitivity reactions. Follow up ranged from 1 to 30 months. In the group of 45 patients with gliomas the death rate per observation year was 0.92 for the interval between PDT and death. For the interval between first diagnosis and death the rate was 0.41 deaths per observation year. The median survival was 8.6 months with a 1 and 2 year actuarial survival rate of 32% and 18%, repectively. In 12 patients a complete or near complete CT scan response was identified post PDT. These patients tended to have a tumour geometry (e.g. cystic) that allowed complete or near complete light distribution to the tumour. The median survival for this group was 17.1 months with a 1 and 2 year actuarial survival of 62% and 38%, respectively. In the 33 cases without a complete response the median survival was 6.5 months with a 1 and 2 year actuarial survival of 22% and 11%, respectively. Photodynamic therapy of malignant brain tumours can be carried out with acceptable risk. Good responses appear to be related to adequate light delivery to the tumour.
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  • 43
    ISSN: 1435-604X
    Keywords: Phthalocyanines ; Photodynamic therapy ; Pharmacokinetics ; MS-2 fibrosarcoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract The pharmacokinetic behaviour of Zn-phthalocyanine (Zn-Pc) has been studied in mice bearing a transplanted MS-2 fibrosarcoma using liposomes of dipalmitoyl-phosphatidylcholine containing 15% moles of cholesterol as drug delivery systems. The presence of cholesterol optimizes the Zn-Pc localization in the tumour inducing a significantly larger uptake as well as a better selectivity. Experimental photodynamic therapy of the MS-2 fibrosarcoma has been performed using two different protocols. The data obtained show that an efficient tumour necrosis can be photosensitized by very low Zn-Pc doses (0.035–0.3 mg kg−1) at both short and long time intervals after injection of the dye.
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  • 44
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    Lasers in medical science 5 (1990), S. 395-398 
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; Lasers ; Light dosimetry ; Skeletal muscle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract For precise light dosimetry in photodynamic therapy (PDT), the light penetration characteristics of the tissue concerned need to be assessed. Several attenuation coefficients have so far been measured using 633 nm wavelength red light and human tissue obtained from autopsy or surgery. However, the validity of such ex vivo derived values remains uncertain, and hence is evaluated further in this study. Using a rat thigh muscle model, the tissue transmittance of 633 nm red light was compared between in vivo and ex vivo. Transmittance (in vivo) following preliminary injection of 40 mg kg−1 haematoporphyrin derivative (HPD) was also measured in muscle and liver. The effective attenuation coefficient (⌆eff) ex vivo in muscle was 0.98±0.06 mm−1 and in vivo 0.97 ± 0.05 mm−1. Values agreed within experimental error indicating that in this tissue, changes from in vivo to post-mortem produced no alteration in optical penetration at 633 nm. Preliminary injection of HPD did not influence the penetration depth in muscle although significant changes were observed in an organ of high porphyrin avidity, the liver (0.68±0.08 mm vs 0.40±0.08 mm with HPD). Until techniques for in vivo measurements of light attenuation coefficient become available, the use of ex vivo derived values with 633 nm wavelength light would seem appropriate.
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  • 45
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; Tumour ; Oral and maxillofacial regions
    Source: Springer Online Journal Archives 1860-2000
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    Notes: Abstract Seventy-two complete remission cases with tumours of the oral and maxillofacial regions treated by photodynamic therapy, which were followed-up long-term, are presented. The results were satisfactory. All of the 34 cases that have been followed-up for more than 5 years are alive, healthy and free of tumour.
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  • 46
    ISSN: 1435-604X
    Keywords: Lewis lung carcinoma ; Liposomes ; Photodynamic therapy ; Pulsed laser irradiation ; Zn(II)-phthalocyanine
    Source: Springer Online Journal Archives 1860-2000
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    Notes: Abstract The effectiveness of a pulsed dye laser (673 nm) for photodynamic therapy (PDT) of tumours in the presence of Zn(II)-phthalocyanine (ZnPc) was evaluated using Lewis lung carcinoma-bearing mice. The tumours were irradiated with different pulse energies (from 0.4 to 10 mJ) at a constant fluence of 0.6 J cm−2 at 24 h after administration of 0.25 mg kg−1 body weight liposome-incorporated ZnPc. Maximal PDT effect, as evaluated by changes in mean tumour diameter, animal survival time and histological evaluation of tumour necrosis, was observed after 3.0 mJ pulse energy irradiation which appears to yield a deeper light penetration and a more efficient sensitizer excitation when compared with lower or higher pulse energies. Electron microscopic analysis of photo-treated tumour indicates preferential damage to malignant tissue as compared to endothelial cells.
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  • 47
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; Non-laser light source ; 5-Aminolaevulinic acid ; Non-melanoma skin cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract The efficacy of a prototype non-laser light source for photodynamic therapy was assessed in clinical practice in the treatment of Bowen's disease and actinic keratoses. The light source, incorporating a 300 W short arc plasma discharge, was adjusted by appropriate filters to produce a bandwidth of 630±15 nm. Topical 5-aminolaevulinic acid was applied 4 h before irradiation to permit production within the lesion of the active photosensitizer, protoporphyrin IX. Individual lesions received 94–156 J cm−2. Twenty lesions of Bowen's disease and four actinic keratoses were treated in 12 patients. Patients were reviewed at monthly intervals and treatment repeated if residual disease was present. Clearance was achieved with a single treatment in 15 lesions and in all of the remaining nine lesions after a second treatment. The treatment was well tolerated, with pain absent or mild during treatment in 22 lesions, with only one lesion requiring local anaesthesia. Over the 10 days following treatment, no pain was associated with 21 treated lesions. During a 12 month follow-up period, two Bowen's disease lesions recurred. The overall complete response rate was 92%. Scarring was evident following PDT in only three lesions. Photodynamic therapy using this portable non-laser light source appears to be an effective and well-tolerated treatment for Bowen's disease and actinic keratoses.
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  • 48
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    Lasers in medical science 11 (1996), S. 23-29 
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; Head and neck cancer ; Chlorin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract Over the past 30 months, the authors have treated a wide variety of head and neck cancer patients with meta-tetrahydroxyphenylchlorin (mTHPC)-mediated photodynamic therapy (PDT). This drug is a powerful, second-generation photosensitizer with significant advantages over earlier drugs. Treatment ranged from palliation and adjunctive to curative procedures. Results to date are very encouraging, with marked advantages over standard methods of treatment with respect to morbidity, both functional and aesthetic. Potential cure rates remain essentially unchanged, very much dependent on the stage of the tumour. These promising early results justify a multicentre study for treatment of early head and neck cancer using this drug and light combination. This is now underway.
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  • 49
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    Lasers in medical science 11 (1996), S. 155-161 
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; Interstitial ; Dunning R3327 prostate tumour ; Threshold light dose ; Cylindrical diffuser ; Diffusion theory
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract Interstitial photodynamic therapy (PDT) could be an alternative radical treatment for prostate cancer. The ability to predict the depth of necrosis is necessary for light treatment planning using multiple optical fibres. The extent of PDT necrosis was studied in subcutaneously implanted R3327-AT6 Dunning prostate tumours which had similar optical characteristics to human prostate. Tumour-bearing subjects were given 20 mg kg−1 Haematoporphyrin esters (HPE) and irradiated 24 h later with 630 nm laser light. Five subjects per group were treated with increasing light doses (50–450 J cm−1) delivered interstitially via a single 2 cm long cylindrical diffuser. After 450 J cm−1 of irradiation, 4.3±0.8 cm3 [standard error of the mean (s.e.m.)] of tumour tissue was necrosed to a depth of 10.5±0.8 mm around the diffuser. There was an approximately linear correlation between the volume of PDT necrosis around the fibre and prescribed light dose. The mean threshold light dose for PDT effect was 18±2 J cm−2. In this tumour with a mean photosensitizer concentration of 16±1.5μg g−1, low light doses produced tumour necrosis. PDT using multiple diffusers could destroy a relatively large tumour volume and the ‘diffusion theory’ model reliably predicted the depth of necrosis.
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  • 50
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; Early stage carcinoma ; Bronchi ; mTHPC ; Light dosimetry ; Fluorescence ; Spectroscopy ; Photosensitizer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract Under identical conditions (drug and light dose, timing), the results of photodynamic therapy (PDT) of carcinomas of the bronchi with tetra(meta-hydroxyphenyl)chlorin (mTHPC) show large variations between patients. Before patients underwent PDT treatment, the mTHPC level was measured in the lesion, the normal surrounding tissue and the oral cavity, with an apparatus based on fluorescence spectroscopy. The fluctuations in degree of tissue reaction and tumour destruction between patients could be explained by individual variations in the mTHPC level in the mucosa of the bronchi. The patients who showed the highest mTHPC fluorescence signal also had the strongest response to PDT. In addition, a correlation between the mTHPC level in the oral cavity and bronchial mucosa was found. It is concluded that PDT can be improved by measuring the mTHPC level in the bronchi or the oral cavity before treatment by fluorescence spectroscopy, and then by adjusting the light dose to be applied to the observed mTHPC level.
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  • 51
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; Dosimetry ; 5-Aminolaevulinic acid ; Protoporphyrin IX ; Photobleaching ; Topical application
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract Photodynamic therapy (PDT) based on topical application of photosensitizers is currently in clinical use for the treatment of basal cell carcinoma of the skin, and it has been evaluated in animal models for photo-ablation of the endometrium. This paper presents a dosimetry model which indicates that a limiting factor in treating thick tumours will be the transport of the drug into the tumour rather than depletion of the optical distribution. The model predicts that an optical irradiation of 100 mW cm−2 at 635 nm for 20 min, ie well below the threshold for hyperthermic reaction, will give an adequate light dose to a depth of 3 mm. The time required for photosensitizers to diffuse to this depth is in the range of 3–15 h, dependent on the diffusion properties of the tissue.
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  • 52
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    Lasers in medical science 4 (1989), S. 155-158 
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; Gynaecological oncology ; Lasertherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract Tumour recurrences in the gynaecological field after conventional therapy are a big problem because there is little choice for other therapies without inflicting further damage. Photodynamic therapy (PDT) is indicated because it is selective and without side-effects in flat or small recurrences. We treated 15 patients with vaginal and vault recurrences of cervix carcinoma, adenocarcinoma in the corpus uteri and rectum. The PDT was performed after 24–48 h with Hp, 5 mg/kg body weight, injection, and an argon-dye laser for 13 cases, tungsten and xenon lamps in 2 cases. All patients were previously treated with conventional therapy (i.e. surgery, radiotherapy, chemotherapy). Doses ranged from 60 to 500 J cm−2. The results were: 8 complete local responses, 6 partial responses, 1 no change. Four patients died because of distant metastases or progression. One partial response was treated with brachytherapy and is now disease free. All the other patients are still living. In all cases we have seen no side-effects from PDT. The patients were sheltered from the sunlight for 20–30 days after therapy.
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  • 53
    ISSN: 1435-604X
    Keywords: Phthalocyanines ; Photodynamic therapy ; Biodistribution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract Phthalocyanines may be an alternative group of macrocycles applicable for use in photodynamic therapy (PDT) of cancer. Although as a class, phthalocyanines localize in tumours, efficacy of cytotoxicity appears to depend to some degree on the specific compound. Biodistribution patterns of the phthalocyanines are similar to those for dihaematoporphyrin ether (DHE); the major sites of deposition being liver, kidney and spleen while the remaining organs show varying degrees of accumulation. The optimal time for PDT when using phthalocyanine appears to be between 24 and 48 h.
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  • 54
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    Lasers in medical science 5 (1990), S. 233-239 
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; Tumours ; Gastroenterology ; Laser ; Endoscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract Photodynamic therapy (PDT) is the local destruction of tissue by the interaction of light with a previously administered photosensitizer producing a photochemical effect. This technique has been demonstrated to permit the eradication of small tumours in experimental and clinical practice, with clear biological advantages. This paper reviews PDT experience in gastroenterology, together with concepts currently under experimental investigation.
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  • 55
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    Lasers in medical science 4 (1989), S. 221-227 
    ISSN: 1435-604X
    Keywords: Optical properties ; Photodynamic therapy ; Glioma ; Brain tumour
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract The in vitro optical properties of slices of human brain tissue were measured. The experiments were performed with an integrating sphere and covered the wavelength range from 400 to 1100 nm. Both normal brain tissue (white and grey matter) and tumour tissue (a malignant glioma and a melanotic melanoma) were investigated. From the experimental data the Kubelka-Munk absorption and scattering coefficients were determined. From these data we calculated the transport absorption and scattering coefficients by using the diffusion approximation. Blood and water appeared to be the dominant chromophores. In the wavelength range mentioned, the absorption coefficients varied over more than two orders of magnitude. The scattering coefficients increased slowly towards the shorter wavelengths.
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  • 56
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; Light transmission in tissue
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract The maximum rate at which the light dose may be delivered during interstitial photodynamic therapy (PDT) has been measured for several types of delivery fibre. Measurements of light irradiance at the skin surface overlying subcutaneous experimental tumours were made during interstitial irradiation by 200Μm core diameter fibres whose output ends were either plane-cut or 5 mm long cylindrical diffusers. For plane-cut fibres, a rapid fall in light transmission, due to blood coagulation at the fibre tip, was observed at output powers greater than 229 mW and 104 mW in tumours with and without photosensitizer, respectively. Such a rapid fall was not observed with cylindrical diffusing fibres at output powers up to 1 W. In the clinical use of PDT the fibre output power is held constant at a level below which thermal effects may occur. In a second study, therefore, the irradiance at the skin surface was monitored for this treatment regime. A decrease in light transmission during treatment was observed. Plane-cut fibres showed a greater decrease than cylindrical diffusing fibres and for a given fibre type, non-photosensitized tumours showed a greater decrease than photosensitized tumours. For cylindrical diffusing fibres at output powers of 150 mW or less there was a 9% decrease in irradiance measured at the skin surface during the first 1000 s of treatment. The decrease was larger (30–40%) for fibre output powers in the range 200–300 mW.
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  • 57
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    Lasers in medical science 6 (1991), S. 147-154 
    ISSN: 1435-604X
    Keywords: Urology ; Photodynamic therapy ; Dosimetry ; Irradiance ; Space irradiance ; Light energy fluence rate ; Glass bladder model ; Bladder model ; Blood ; Intralipid ; Methylene blue ; Erythrosin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract The shape of the bladder and the optical characteristics of the tissue within the wall can be shown to play an important role in the amount of light actually received at the wall. The use of estimated doses even assuming spherical geometry, cannot therefore be relied upon. This paper describes some experimental work carried out on a glass model that was used to simulate the bladder. A specially constructed dual detector was used which consisted of an isotropic probe and semiconductor detector. This enabled measurements of irradiance and space irradiance (light energy fluence rate) to be made simultaneously. By changing the optical characteristics of the wall a four-fold increase in space irradiance was measured. Contamination of the water contained within the model by blood was also investigated and has shown that with concentrations as low as 0.5% the delivered light dose reaching the wall can be reduced by up to 50% at a wavelength of 510 nm. Some in vivo measurements are also presented together with some comments on the difficulties that have been encountered when transferring measurements from the ‘model’ to the patient.
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