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  • Articles  (131)
  • Photodynamic therapy  (57)
  • dispersion  (38)
  • biocompatibility  (35)
  • Electronic structure and strongly correlated systems
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  • Technology  (131)
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  • Articles  (131)
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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
    Electronic Resource
    Electronic Resource
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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
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    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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    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
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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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    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
    ISSN: 1435-604X
    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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    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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    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
    ISSN: 1572-8781
    Keywords: MPC ; BMA ; AMPS ; biocompatibility ; cellulose triacetate ; diffusion-limiting effect ; glucose sensor ; needle type ; glucose oxidase ; serum ; whole blood
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    Topics: Medicine , Technology
    Notes: Abstract A multifunctional membrane with biocompatibility, diffusion-limiting effect, and the ability to curtail the responses of an H2O2 electrode to ascorbate and urate was prepared. It was composed of MB, AB, and CTA, where MB is the copolymer of 2-methacryloyloxyethyl phosphorylcholine (MPC) and n-butylmethacrylate (BMA), AB is the copolymer of acrylamide-2-methylpropane sulfonic acid (AMPS) and BMA, CTA is cellulose triacetate. Investigation of the biocompatibility of this membrane showed that, compared with CTA, relatively few platelets bound to it. The membrane was coated onto the working electrode of a needle-type glucose sensor on which immobilized glucose oxidase membrane has been coated. The sensor did not respond to ascorbate and urate at their concentration normally encountered in blood. Its response was not inhibited by metal ions in blood at usual concentration. The sensor exhibited superior thermostability in addition to a rapid response (〈90 seconds in batch operation), good reproducibility (RE〈5%), good stability (more than 36 hours continuously in heparinized whole blood), and a wide dynamic range (5–650 mg/dl glucose). The sensor was used to determine glucose in serum. The data obtained from the sensor showed good agreement with that from a clinical autoanalyzer (R=0.973).
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    Transport in porous media 7 (1992), S. 127-145 
    ISSN: 1573-1634
    Keywords: Miscible displacement ; dispersion ; in-situ concentration measurement ; computerized data acquisition
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    Notes: Abstract A technique for measurement of thein-situ concentration in an unconsolidated porous medium has been developed. The method involves measurement of electrical conductivityin-situ, under dynamic conditions, for flow involving brine of differing concentrations, at selected locations along the porous medium and relating it to the brine strength. Data acquisition and analysis is carried out using a Hewlett — Packard micro-computer and its interface. A user-friendly software was designed and developed for the system. The measurement technique was evaluated by studying the effect of brine concentration, brine flow rate, and by conducting miscible displacements experiment. The experimentally measured dispersion coefficients for the porous medium agreed closely with the value predicted by the correlation available in the literature.
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    Transport in porous media 28 (1997), S. 109-124 
    ISSN: 1573-1634
    Keywords: seepage ; conductivity ; double-periodic structure ; advection ; dispersion
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    Notes: Abstract A study is made of steady two-dimensional seepage in a porous massif composed by a double-periodic system of ‘white’ and ‘black’ chequers of arbitrary conductivity. Rigorous matching of Darcy's flows in zones of different conductivity is accomplished. Using the methods of complex analysis, explicit formulae for specific discharge are derived. Stream lines, travel times, and effective conductivity are evaluated. Deflection of marked particles from the ‘natural’ direction of imposed gradient and stretching of prescribed composition of these particles enables the elucidation of the phenomena of transversal and longitudinal dispersion. A model of pure advection is related with the classical one-dimensional vective dispersion equation by selection of dispersivity which minimizes the difference between the breakthrough curves calculated from the two models.
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    Transport in porous media 9 (1992), S. 25-37 
    ISSN: 1573-1634
    Keywords: Waves ; dispersion ; shock tube ; gas bubbles
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    Notes: Abstract The propagation of compressional waves in a porous medium is investigated in case the pore liquid contains a small volume fraction of gas. The effect of oscillating gas bubbles is taken into account by introducing a frequency-dependent fluid bulk modulus, which is incorporated in the Biot theory. Using a shock tube technique, new experimental data are obtained for a porous column subjected to a pressure step wave. An oscillatory behaviour is observed, consisting of two distinct frequency bands, which is predicted by the theoretical analysis.
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    Transport in porous media 23 (1996), S. 107-124 
    ISSN: 1573-1634
    Keywords: solute transport ; Fick's law ; dispersion ; dispersivity ; equation of motion ; non-Fickian dispersion equation ; scale effects
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    Notes: Abstract The Fickian dispersion equation is the basic relationship used to describe the nonconvective mass flux of a solute in a porous medium. This equation prescribes a linear relationship between the dispersive mass flux and the concentration gradient. An important characteristic of the Fickian relationship is that it is independent of the history of dispersion (e.g. the time rate of change of the dispersion flux). Also, the dispersivities are supposed to be medium constants and invariant with temporal and spatial scales of observation. It is believed that in general these restrictions do not hold. A number of authors have proposed various alternative relationships. For example, differential equations have been employed that prescribe a relationship between the dispersion flux and its time and space derivatives. Also, stochastic theories result in integro-differential equations in which dispersion tensor grow asymptotically with time or distance. In this work, three different approaches, which lead to three different non-Fickian equations with a transient character, are discussed and their primary features and differences are highlighted. It is shown that an effective dispersion tensor defined in the framework of the transient non-Fickian theory, grows asymptotically with time and distance; a result which also follows from stochastic theories. Next, principles of continuum mechanics are employed to provide a solid theoretical basis for the non-Fickian transient dispersion theory. The equation of motion of a solute in a porous medium is used to provide a rigorous derivation of various dispersion relationships valid under different conditions. Under various simplifying assumptions, the generalized theory is found to agree with the conventional Fickian theory as well as several other non-Fickian relationships found in the literature. Moreover, it is shown that for nonconservative solutes, the traditional dispersion tensor is affected by the rate of mass exchange of the solute.
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    Transport in porous media 3 (1988), S. 473-489 
    ISSN: 1573-1634
    Keywords: Advection ; dispersion ; particles ; characteristics ; finite-element ; continuous fluid velocity
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    Notes: Abstract A Eulerian-Lagrangian scheme is used to solve the two-dimensional advection-dispersion equation. Concentration and its partial differential operator are decomposed into advection and dispersion terms. Thus, advection is formally decoupled from dispersion and solved by continuous forward particle tracking. Dispersion is handled by implicit finite elements on a fixed Eulerian grid. Translation of steep gradients of concentration in advection-dominated flow regimes, is done without numerical distortion. Continuous spatial distribution of velocities are evaluated by using Galerkin's approach in conjunction with Darcy's law based on hydraulic input data from each element. The method was implemented on coarse FE grid with linear shape functions, demonstrating no over/under shooting and practically no numerical dispersion. Simulations, covering a wide range of Peclet numbers, yield high agreement with analytic and practical results.
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    Transport in porous media 4 (1989), S. 85-96 
    ISSN: 1573-1634
    Keywords: Stability ; linear stability analysis ; miscible displacement ; aspect ratio ; mobility control ; dispersion
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    Notes: Abstract Chang and Slattery (1986, 1988b) introduced a simplified model of dispersion that contains only two empirical parameters. The traditional model of dispersion (Nikolaevskii, 1959; Bear, 1961; Scheidegger, 1961; de Josselin de Jong and Bossen, 1961; Peaceman, 1966; Bear, 1972) has three empirical parameters, two of which can be measured in one-dimensional experiments while the third, the transverse dispersivity, must be measured in experiments in which a two-dimensional concentration profile develops. It is found that nearly the same linear stability behavior results from using either model.
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    Transport in porous media 23 (1996), S. 275-301 
    ISSN: 1573-1634
    Keywords: free convection ; through flow ; vadoze zone ; salinization ; dispersion ; multigrid
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    Notes: Abstract Evaporation of groundwater in a region with a shallow water table and small natural replenishment causes accumulation of salts near the ground surface. Water in the upper soil layer becomes denser than in the depth. This is a potentially unstable situation which may result in convective currents. When free convection takes place, estimates of the salinity profile, salt precipitation rate, etc., obtained within the framework of a 1-D (vertical) model fail. Very simplified model of the process is proposed, in which the unsaturated zone is represented by a horizontal soil layer at a constant water saturation, and temperature changes are neglected. The purpose of the model is to obtain a rough estimate of the role of natural convection in the salinization process. A linear stability analysis of a uniform vertical flow is given, and the stability limit is determined numerically as a function of evaporation rate, salt concentration in groundwater, and porous medium dispersivity. The loss of stability corresponds to quite realistic Rayleigh numbers. The stability limit depends in nonmonotonic way on the evaporation rate. The developed convective regime was simulated numerically for a 2-D vertical domain, using finite volume element discretization and FAS multigrid solver. The dependence of the average salt concentration in the upper layer on the Rayleigh number was obtained.
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    Transport in porous media 24 (1996), S. 275-296 
    ISSN: 1573-1634
    Keywords: chemical flooding ; ternary ; immiscible ; surfactant ; numerical simulation ; interfacial tension ; phase behavior ; miscibility ; capillarity ; numerical grid ; adsorption ; dispersion
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    Notes: Abstract This is the second of two joint papers which study the influence of several physical properties on the transport phenomena in chemical flooding. To that aim, we use a previously reported ternary two-phase model into which representative physical properties have been incorporated as concentration-dependent functions. Physical properties such as phase behavior, interfacial tensions, residual saturations, relative permeabilities, phase viscosities and wettability have been analyzed in the first paper. In this paper, we discuss the influence of capillary pressure, adsorption of the chemical component onto the rock and dispersion. Although arising from different phenomenological sources, these transport mechanisms show some similar effects on concentration profiles and on oil recovery. They are studied for systems with different phase behavior. A numerical analysis is also presented in order to determine the relevance of the number of grid blocks taken in the discretization of the differential equations. This numerical analysis provides useful guidelines for the selection of the appropriate numerical grid in each type of displacement.
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    Transport in porous media 3 (1988), S. 217-256 
    ISSN: 1573-1634
    Keywords: Salinity ; advection ; dispersion ; aquifers ; flow model ; transport model ; simulation ; sea water ; connate water ; leakage
    Source: Springer Online Journal Archives 1860-2000
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    Notes: Abstract Historical information of the hydraulic and salinity aspect, detailed geological information, and information on the physical characteristics of the different layers comprising the formation, are needed for simulating the saltwater transport process in aquifers. In most simulation studies of field situations, there is an inadequacy of data and the modeller has to make justifiable assumptions to analyze a particular situation in order to provide an insight into the problem. A quasi-three-dimensional solute transport model is used to analyze the saltwater encroachment phenomena in aquifers underlying the City of Bangkok; first by calibrating the model's performance with available historical data and then by assessing the extent of future saltwater encroachment with the implementation of the regulatory pumpage to be followed in order to restrict the alarming rate of land subsidence. Model simulation indicates a substantial reduction in the rate of encroachment of the saltwater front with a reduction of pumpage after 1987.
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    Transport in porous media 3 (1988), S. 549-562 
    ISSN: 1573-1634
    Keywords: Adaptive mesh ; finite element method ; dispersion
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    Notes: Abstract A Galerkin finite element method is used along with a self-adaptive strategy of domain discretisation to model dispersion in an axisymmetric cylindrical porous medium. A solution strategy is proposed based on the use of a Gear scheme for the time stepping and partial vectorisation of the code. The domain is highly discretised in the area of the sharp transient front, while the remainder is coarsely discretised. The area covered by the fine mesh is determined by the value of the local concentration gradients. Numerical results are presented for the one and two dimensional cases.
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    Transport in porous media 30 (1998), S. 57-73 
    ISSN: 1573-1634
    Keywords: groundwater ; nonergodic transport ; dispersion ; heterogeneous formations ; hydrogeology
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    Notes: Abstract Flow of an inert solute in an heterogeneous aquifer is usually considered as dominated by large-scale advection. As a consequence, the pore-scale dispersion, i.e. the pore scale mechanism acting at scales lower than that characteristic of the heterogeneous field, is usually neglected in the computation of global quantities like the solute plume spatial moments. Here the effect of pore-scale dispersion is taken into account in order to find its influence on the longitudinal asymptotic dispersivity D11we examine both the two-dimensional and the three-dimensional flow cases. In the calculations, we consider the finite size of the solute initial plume, i.e. we analyze both the ergodic and the nonergodic cases. With Pe the Péclat number, defined as Pe=Uλ/D, where U, λ, D are the mean fluid velocity, the heterogeneity characteristic length and the pore-scale dispersion coefficient respectively, we show that the infinite Péclat approximation is in most cases quite adequate, at least in the range of Péclat number usually encountered in practice (Pe 〉 102). A noteworthy exception is when the formation log-conductivity field is highly anisotropic. In this case, pore-scale may have a significant impact on D11, especially when the solute plume initial dimensions are not much larger than the heterogeneities' lengthscale. In all cases, D11 appears to be more sensitive to the pore-scale dispersive mechanisms under nonergodic conditions, i.e. for plume initial size less than about 10 log-conductivity integral scales.
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    Transport in porous media 31 (1998), S. 133-143 
    ISSN: 1573-1634
    Keywords: transport ; solute ; flux-averaged concentration ; stratification ; conductivity ; distribution ; arrival time ; dispersion
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    Notes: Abstract Two-dimensional and steady solute transport in a stratified porous formation is analysed under assumption that the effect of pore-scale dispersion is negligible. The longitudinal dispersion produced as a result of the vertical variation of hydraulic conductivity is analysed by averaging the variability of a solute flux concentration and conductivity. The evolution of the solute flux concentration is expressed with respect to the correlated variable, that is the travel (arrival) time τ at a fixed location and the averaging procedure is constructed to satisfy the boundary condition where the inlet concentration is a known function of time. In such a statement, a velocity-averaged solute flux concentration is described by a conventional dispersion model (CDM) with a dispersion coefficient which is a function of the arrival time. It is demonstrated that such CDM satisfies the assumption that hydraulic conductivity of the layers is gamma distributed with the parameter of distribution which is chosen to represent a reasonable value of the field scale solute dispersion. The overall behaviour of the model is illustrated by several examples of two-dimensional mass transport.
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    Transport in porous media 21 (1995), S. 175-188 
    ISSN: 1573-1634
    Keywords: diffusion ; dispersion ; percolation ; fractals ; scaling
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    Notes: Abstract Two fundamental questions regarding the application of percolation theory to transport in porous media are addressed. First, when ‘critical path’ arguments (based on a sufficiently wide spread of microscopic transition rates) are invoked (in analogy to the case of transport in disordered semiconductors) to justify the application of percolation theory to the determination of relevant transport properties, then for long time scales (compared to the inverse of the ‘critical’ percolation rate), the fractal structure of the ‘critical’ path is relevant to transport, but not at short time scales. These results have been demonstrated concretely in the case of disordered semiconductors, and are in direct contradiction to the claims of the review. Second, the relevance of deterministic or stochastic methods to transport has been treated heretofore by most authors as a question of practicality. But, at least under some conditions, concrete criteria distinguish between the two types of transport. Percolative (deterministic) transport is temporally reproducible and spatially inhomogeneous while diffusive (stochastic) transport is temporally irreproducible, but homogeneous, and a cross-over from stochastic to percolative transport occurs when the spread of microscopic transition rates exceeds 4–5 orders of magnitude. It is likely that such conditions are frequently encountered in soil transport. Moreover, clear evidence for deterministic transport (although not necessarily percolative) exists in such phenomena as preferential flow. On the other hand, the physical limitation of transport to (fractally connected) pore spaces within soils (analogously to transport in metal-insulator composites) can make transport diffusive on a fractal structure, rather than percolative.
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    Transport in porous media 24 (1996), S. 1-33 
    ISSN: 1573-1634
    Keywords: unsaturated flow ; large-scale averaging ; dispersion ; high-resolution numerical simulations ; NAPL spills
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    Notes: Abstract Infiltration of water and non-aqueous phase liquids (NAPLs) in the vadose zone gives rise to complex two- and three-phase immiscible displacement processes. Physical and numerical experiments have shown that ever-present small-scale heterogeneities will cause a lateral broadening of the descending liquid plumes. This behavior of liquid plumes infiltrating in the vadose zone may be similar to the familiar transversal dispersion of solute plumes in single-phase flow. Noting this analogy we introduce a mathematical model for ‘phase dispersion’ in multiphase flow as a Fickian diffusion process. It is shown that the driving force for phase dispersion is the gradient of relative permeability, and that addition of a phase-dispersive term to the governing equations for multiphase flow is equivalent to an effective capillary pressure which is proportional to the logarithm of the relative permeability of the infiltrating liquid phase. The relationship between heterogeneity-induced phase dispersion and capillary and numerical dispersion effects is established. High-resolution numerical simulation experiments in heterogeneous media show that plume spreading tends to be diffusive, supporting the proposed convection-dispersion model. Finite difference discretization of the phase-dispersive flux is discussed, and an illustrative application to NAPL infiltration from a localized source is presented. It is found that a small amount of phase dispersion can completely alter the behavior of an infiltrating NAPL plume, and that neglect of phase-dispersive processes may lead to unrealistic predictions of NAPL behavior in the vadose zone.
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    Transport in porous media 1 (1986), S. 179-199 
    ISSN: 1573-1634
    Keywords: Stability ; linear stability analysis ; miscible displacement ; dispersion ; mobility control
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    Notes: Abstract A linear stability analysis has been performed for a miscible displacement in a semi-infinite system of finite thickness and unbounded width. A more general description of dispersion has been adopted than those used by previous workers. It is shown that, when there is a step change in concentration and the mobility ratio is unfavorable, the displacement can be unstable at the injection boundary. But, if the concentration is changed sufficiently slowly with time at the entrance to the system, the displacement is stable to infinitesimal perturbations, no matter how unfavorable the mobility ratio. When the mobility ratio is favorable, the displacement is unconditionally stable.
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    Transport in porous media 1 (1986), S. 319-338 
    ISSN: 1573-1634
    Keywords: heterogeneity ; dispersion ; saturated flow ; unsaturated flow
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    Notes: Abstract This invited lecture enumerates various categories of flow and transport in heterogeneous media with particular reference to this Symposium. Specific attention is given to five topics within these categories. (1) We explore the compounding of spatially variable local permeability K to produce an apparent permeability K * on a scale large compared with that of variation of K. An inverse method generates and analyzes flow systems with K spatially periodic in two and three dimensions. (2) Physical arguments indicate that apparent hydraulic properties of an unsaturated composite medium may not represent any conceivable mean of the properties of the component media. (3) Conventionally, buried holes are thought to stay empty during generally unsaturated soil-water flow. The hole, however, acts as an obstacle to flow so that water may seep through it. The larger the hole the more likely this will happen. (4) Dispersion in heterogeneous porous systems with no maximum scale of variation is explored using a Lagrangian mode of analysis. (5) Comments are offered on ‘geostatistics’ and its application to heterogeneous soils and aquifers.
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    Transport in porous media 18 (1995), S. 231-243 
    ISSN: 1573-1634
    Keywords: Stratified formations ; kinematic mixing ; dispersion ; random fields
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    Notes: Abstract The mixing process in fluid flow is presented as the bending and stretching of material lines or filaments. A mixing exponent, which quantifies their specific rate of stretching, is defined and analyzed for the case of groundwater flow though stratified formations characterized by a Gaussian autocovariance function. The analysis is performed for purely advective mixing as well as for advective-dispersive mixing. The mixing exponent was found to be proportional to the variance of hydraulic conductivity and inversely proportional to the correlation scale of hydraulic conductivity and to the pore-level dispersion coefficient.
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    Transport in porous media 6 (1991), S. 607-626 
    ISSN: 1573-1634
    Keywords: dispersion ; dispersivity ; heterogenity ; miscible ; porous media ; scaling
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    Notes: Abstract This paper discusses scaling of mixing during miscible flow in heterogeneous porous media. In large field systems dispersivity appears to depend on system length due to heterogeneities. Three types of scaling are discussed to investigate the heterogeneous effects. Dimensional analysis of mixing during flow through geometerically scaled heterogeneous models is illustrated using measured dispersion. Fractal analysis of mixing in statistically scaled heterogeneous porous media is discussed. Analog scaling of pressure transients in heterogeneous porous media is suggested as an in-situ method of estimating dispersion.
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    Transport in porous media 12 (1993), S. 143-159 
    ISSN: 1573-1634
    Keywords: Heterogeneity ; layers ; displacement ; numerical simulation ; flow in porous media ; dispersion
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    Notes: Abstract Beadpack experiments and numerical simulations have been carried out to study flow displacements, effluent profiles and streamline patterns for layered systems with flow not parallel to the layers. The effects of layer thickness, permeability contrast, angle of layer to flow direction, mobility ratio and flood rate have been examined. Each of these parameters influence the displacement profiles, and disperse the flood front. Such real effects must be considered when subsuming reservoir heterogeneities in average reservoir parameters in simulation studies, or interpreting core tests.
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    Transport in porous media 13 (1993), S. 3-40 
    ISSN: 1573-1634
    Keywords: Diffusion ; dispersion ; percolation ; fractals ; scaling
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    Notes: Abstract We review and discuss diffusion and hydrodynamic dispersion in a heterogeneous porous medium. Two types of heterogeneities are considered. One is percolation disorder in which a fraction of the pores do not allow transport to take place at all. In the other type, the permeabilities of various regions of the pore space are fractally distributed with long-range correlations. Both systems give rise to unusual transport in which the mean square displacement 〈r 2(t)〉 of a particle grows nonlinearly with time. Depending on the heterogeneities and the mechanism of diffusion and disperison, we may havefractal transport in which 〈r 2〉 growsslower than linearly with time, orsuperdiffusive transport in which 〈r 2〉 growsfaster than linearly with time. We show that percolation models can give rise to both types of transport with scale-dependent transport coefficients such as diffusivity and dispersion coefficients, which are consistent with many experimental observations.
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    Transport in porous media 13 (1993), S. 97-122 
    ISSN: 1573-1634
    Keywords: Scale up ; dispersion ; porous media ; random field
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    Notes: Abstract Dispersion is the result, observable on large length scales, of events which are random on small length scales. When the length scale on which the randomness operates is not small, relative to the observations, then classical dispersion theory fails. The scale up problem refers to situations in which randomness occurs on all length scales, and for which classical dispersion theory necessarily fails. The purpose of this article is to present non-Fickian, theories of dispersion, which do not assume a scale separation between the randomness and the observed consequences, and which do not assume a single length scale. Porous media flow properties are heterogeneous on all length scales. The geological variation on length scales below the observational length scale can be regarded as unknown and unknowable, and thus as a random variable. We develop a systematic theory relating scaling behavior of the geological heterogeneity to the scaling behavior of the fluid dispersivity. Three qualitatively distinct regimes (Fickian, non-Fickian and nonrenormalizable) are found. The theory gives consistent answers within several distinct analytic approximations, and with numerical simulation of the equations of porous media flow. Comparison to field data is made. The use of Kriging to generate constrained ensembles for conditional simulation is discussed.
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    Transport in porous media 15 (1994), S. 15-30 
    ISSN: 1573-1634
    Keywords: Experiment ; dispersion ; layered heterogeneity ; permeability ; averaging ; permutation
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    Notes: Abstract Experiments were run in three linear, homogeneous, nonuniform porous media constructed in lucite columns using spherical glass beads. The columns were also joined end to end to create an in series layered heterogeneous porous media. Each column, all combinations of columns and several permutations were studied with a factorial experimental design to determine the effects of porosity, permeability, velocity, length, and column order upon dispersion. Attempts to predict the heterogeneous results from the homogeneous results were made, and a statistical regression based on the factorial design was calculated. Results showed that no simple averaging procedure accurately predicted the heterogeneous results. The statistical regression showed permeability, velocity, viscosity, length and column order to be significant.
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    Transport in porous media 17 (1994), S. 19-32 
    ISSN: 1573-1634
    Keywords: LGA model ; heterogeneous porous media ; miscible displacement ; dispersion ; tracer
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    Notes: Abstract The lattice gas automaton (LGA) model proposed in the previous paper is applied to the problem of simulating dispersion and mixing in heterogeneous porous media. We demonstrate here that tracer breakthrough profiles and longitudinal dispersion coefficients can be computed for heterogeneous porous media.
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    Transport in porous media 18 (1995), S. 245-261 
    ISSN: 1573-1634
    Keywords: Porous media ; miscible flow ; tracer ; dispersion ; convective flow ; stochastic ; stream tube ; continuous time random walk
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    Notes: Abstract A simple theoretical model is described for deriving a 1-dimensional equation for the spreading of a tracer in a steady flow at the field scale. The originality of the model is to use a stochastic appoach not in the 3-dimensional space but in the 1-D space of the stream tubes. The simplicity of calculation comes from the local relationship between permeability and velocity in a 1-D flow. The spreading of a tracer front is due to local variations in the cross-sectional area of the stream tubes, which induces randomness in travel time. The derived transport equation is averaged in the main flow direction. It differs from the standard dispersion equation. The roles of time and space variables are exchanged. This result can be explained by using the statistical theory of Continuous Time Random Walk instead of a standard Random Walk. However, the two equations are very close, since their solutions have the same first and second moments. Dispersivity is found to be equal to the product of the correlation length by the variance of the logarithm of permeability, a result similar to Gelhar's macrodispersion.
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    Transport in porous media 18 (1995), S. 263-282 
    ISSN: 1573-1634
    Keywords: Porous media ; dispersion ; miscible flow ; heterogeneities ; stochastic ; stream tube ; layered ; fractal
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    Notes: Abstract Large-scale dispersion in heterogeneous porous media is studied by using a simple model based on stochastic calculation of convective flow in a bundle of stream tubes. The advantage of this approach is that there is a local relationship between velocity and permeability in the 1-dimensional space of the stream tubes. Dispersion is due to the variation in stream tube cross-section, related to the permeability field. First, the arrival times of the tracer in the stream tubes are related to the stochastic properties of the permeability field (variance and covariance). Then, transport equations are derived from the moments of the arrival times. The results agree with more complicated studies. For a permeability field with long-range correlation, the transport equation is not unique. It depends on the assumptions involving moments higher than two. Assuming a Gaussian shape for the tracer flux leads to equations similar to the ones obtained in previous studies of time-dependent dispersivity. Without this approximation, the equation is non-local (integrodifferential) and leads to a memory effect. In the last part of this paper, the general results are illustrated with several correlation functions for the permeability field: purely random, exponential and power law covariance, and perfectly layered media.
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    Transport in porous media 18 (1995), S. 283-302 
    ISSN: 1573-1634
    Keywords: Solute transport experiments ; heterogeneous media ; dispersion ; scale-dependency
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    Notes: Abstract Laboratory tracer experiments were conducted to investigate solute transport in 12.5-m long, horizontally placed soil columns during steady saturated water flow. Two columns having cross-sectional areas of 10×10cm2 were used: a uniformly packed homogeneous sandy column and a heterogeneous column containing layered, mixed, and lenticular formations of various shapes and sizes. The heterogeneous soil column gradually changed, on average, from coarse-textured at one end to fine-textured at the other end. NaCl breakthrough curves (BTC's) in the columns were measured with electrical conductivity probes inserted at 50- or 100-cm intervals. Observed BTC's in the homogeneous sandy column were relatively smooth and sigmoidal (S-shaped), while those in the heterogeneous column were very irregular, nonsigmoidal, and exhibited extensive tailing. Effective average pore-water velocities (v eff) and dispersion coefficients (D eff) were estimated simultaneously by fitting an analytical solution of the convection-dispersion equation to the observed BTC's. Velocity variations in the heterogeneous medium were found to be much larger than those in the homogeneous sand. Values of the dispersivity,α=D eff/v eff, for the homogeneous sandy column ranged from 0.1 to 5.0 cm, while those for the heterogeneous column were as high as 200cm. The dispersivity for transport in both columns increased with travel distance or travel time, thus exhibiting scale-dependency. The heterogeneous soil column also showed the effects of preferential flow, i.e., some locations in the column showed earlier solute breakthrough than several locations closer to the inlet boundary. Spatial fluctuations in the dispersivity could be explained qualitatively by the particular makeup of the heterogeneities in the column.
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    Transport in porous media 19 (1995), S. 37-66 
    ISSN: 1573-1634
    Keywords: dispersion ; sandstone ; radial flow
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    Notes: Abstract This paper presents some experimental and theoretical results for dispersion processes occurring in consolidated Berea sandstone with radial flow geometry. A comprehensive review of the derivation and application of several analytical solutions is also presented. The Galerkin finite element method is applied to solve the advection-dispersion equation for unidimensional radial flow. Individual and combined effects of mechanical dispersion and molecular diffusion are examined using velocity-dependent dispersion models. Comparison of simulated results with experimental data is made. The effect of flow rates is examined. The results suggest that a linear dispersion model,D=αu, whereD is the dispersion coefficient,u the velocity andα a constant, is not a good approximation despite its wide acceptance in the literature. The most suitable mathematical formulation is given by an empirical form of $$D = D_0 + \mathop \alpha \limits^` u^m$$ , whereD ois the molecular diffusion coefficient. For the range of Péclet number (Pe=vd/D m,wherev is the characteristic velocity,d the characteristic length andD mthe molecular diffusion coefficient in porous media) examined (Pe=0.5 to 285), a power constant ofm=1.2 is obtained which agrees with the value reported by some other workers for the same regime. From the results of experiments and numerical modelling, the effect of mobility ratios (defined as the ration of viscosities of displaced and displacing fluids) on dispersion is found to be negligible, provided that the ratio is favourable.
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    Transport in porous media 29 (1997), S. 207-223 
    ISSN: 1573-1634
    Keywords: dispersion ; attenuation ; surface waves ; Rayleigh wave ; Love wave
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    Notes: Abstract An investigation is conducted of propagation of surface waves in a porous medium consisting of a microscopically incompressible solid skeleton in which a microscopically incompressible liquid flows within the interconnected pores, and particularly the case where the solid skeleton deforms linear elastically. The frequency equations of Rayleigh- and Love-type waves are derived relating the dependence of wave numbers, being complex quantities, on frequency, as a result those waves are dispersive as well as inhomogeneous. Nevertheless, the amplitudes of both surface waves attenuate along the surface of the porous medium, whereas they decay exponentially receding from the surface of the medium.
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    Keywords: solute transport ; nonequilibrium ; heterogeneous porous media ; dispersion ; diffusion ; experiments ; modelling
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    Notes: Abstract Two region models for solute transport in porous media assume that hydrodynamic dispersion in mobile water and solute diffusion within immobile water regions are independent. Experimental and theoretical results for transport through a macropore indicate that hydrodynamic dispersion and solute exchange are interdependent. Experiments were carried out to investigate this problem for a column packed with spherical porous aggregates. The effective diffusion coefficient of a tracer within the agreggates was determined from specific experiments. The dispersivity of the bed was determined from experiments carried out with a column filled with nonporous beads. We took advantage of the dependence of hydrodynamic dispersion on density ratios between the invading and displaced solutions to obtain a set of breakthrough curves corresponding to situations where the diffusion coefficient remains constant, whereas the dispersivity varies. Simulations reproduce correctly the experiments. Small discrepancies are noted that can be corrected either by increasing the dispersion coefficient or by fitting the external mass transfer coefficient. Increased dispersion coefficients probably reveal a modification of Taylor dispersion due to solute exchange. The fitted external mass transfer coefficients are close to the values obtained with classical correlations of the chemical engineering literature.
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    Transport in porous media 3 (1988), S. 277-297 
    ISSN: 1573-1634
    Keywords: Stability ; linear stability analysis ; miscible displacement ; aspect ratio ; mobility control ; dispersion
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    Notes: Abstract Viscous fingering and gravity tonguing are the consequences of an unstable miscible displacement. Chang and Slattery (1986) performed a linear stability analysis for a miscible displacement considering only the effect of viscosity. Here the effect of gravity is included as well for either a step change or a graduated change in concentration at the injection face during a downward, vertical displacement. If both the mobility ratio and the density ratio are favorable (the viscosity of the displacing fluid is greater than the viscosity of the displaced fluid and, for a downward vertical displacement, the density of the displacing fluid is less than the density of the displaced fluid), the displacement will be stable. If either the mobility ratio or the density ratio is unfavorable, instabilities can form at the injection boundary as the result of infinitesimal perturbations. But if the concentration is changed sufficiently slowly with time at the entrance to the system, the displacement can be stabilized, even if both the mobility ratio and the density ratio are unfavorable. A displacement is more likely to be stable as the aspect ratio (ratio of thickness to width, which is assumed to be less than one) is increased. Commonly the laboratory tests supporting a field trial use nearly the same fluids, porous media, and displacement rates as the field trial they are intended to support. For the laboratory test, the aspect ratio may be the order of one; for the field trial, it may be two orders of magnitude smaller. This means that a laboratory test could indicate that a displacement was stable, while an unstable displacement may be observed in the field.
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    Transport in porous media 3 (1988), S. 591-618 
    ISSN: 1573-1634
    Keywords: Polymer flooding ; viscous fingering ; multiphase flow ; dispersion
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    Notes: Abstract The concept of improving oil recovery through polymer flooding is analysed. It is shown that while the injection of a polymer solution improves reservoir conformance, this beneficial effect ceases as soon as one attempts to push the polymer solution with water. Once water injection begins, the water quickly passes through the polymer creating a path along which all future injected water flows. Thus, the volume of the polymer slug is important to the process and an efficient recovery would require that the vast majority of the reservoir be flooded by polymer. It is also shown that the concept of grading a polymer slug to match the mobilities of the fluids at the leading and trailing edges of a polymer slug does not work in a petroleum reservoir. While this process can supply some additional stability to the slug, it is shown that for the purposes of enhanced oil recovery this additional stability is not great enough to be of any practical use. It is found that in this case the instability has simply been hidden in the interior of the slug and causes the same sort of instability to occur as was the case for the uniform slug.
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    Transport in porous media 32 (1998), S. 97-116 
    ISSN: 1573-1634
    Keywords: dispersion ; anomalous diffusion ; Taylor dispersion ; roughness ; self-affine
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    Notes: Abstract Tracer dispersion is studied in an open crack where the two rough crack faces have been translated with respect to each other. The different dispersion regimes encountered in rough-wall Hele-Shaw cell are first introduced, and the geometric dispersion regime in the case of self-affine crack surfaces is treated in detail through perturbation analysis. It is shown that a line of tracer is progressively wrinkled into a self-affine curve with an exponent equal to that of the crack surface. This leads to a global dispersion coefficient which depends on the distance from the tracer inlet, but which is still proportional to the mean advection velocity. Besides, the tracer front is subjected to a local dispersion (as could be revealed by point measurements or echo experiments) very different from the global one. The expression of this anomalous local dispersion coefficient is also obtained.
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    Transport in porous media 32 (1998), S. 187-198 
    ISSN: 1573-1634
    Keywords: diffusion ; dispersion ; miscible ; automaton
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    Notes: Abstract A thermodynamic lattice gas (automaton) model is used to simulate dispersion in porous media. Simulations are constructed at two distinctly different scales, the pore scale at which capillary models are constructed and large scale or Darcy scale at which probabilistic collision rules are introduced. Both models allow for macroscopic (pore scale) phase separation. The pore scale models clearly show the effect of pore structure on dispersion. The large scale (mega scale) simulations indicate that when the pressure difference between the displacing phase and displaced phase is properly chosen (representing the average pressure gradient between the phases). The simulation results are consistent with both theoretical predictions and experimental observations.
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    Keywords: dispersion ; reaction ; perturbation theory ; stochastic modeling
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    Notes: Abstract We carry out a stochastic-perturbation analysis of a one-dimensional convection–dispersion-reaction equation for reversible first-order reactions. The Damköhler number, Da, is distributed randomly from a distribution that has an exponentially decaying correlation function, controlled by a correlation length, ξ. Zeroth- and first-order approximations of the dispersion coefficient, D are computed from moments of the residence-time distribution obtained by solving a one-dimensional network model, in which each unit of the network represents a Darcy-level transport unit, and the solution of the transfer function in zeroth- and first-order approximations of the transport equation. In the zeroth-order approximation, the dispersion coefficient is calculated using the convection–dispersion-reaction equation with constant parameters, that is, perturbation corrections to the local equation are ignored. This zeroth-order dispersion coefficient is a linear function of the variance of the Damköhler number, 〈(ΔDa)2〉. A similar result was reported in a two-dimensional network simulation. The zeroth-order approximation does not give accurate predictions of mixing or spreading of a plume when Damköhler numbers, Da ≪ 1 and its variance, 〈(ΔDa)2〉 〉 0.25 〈Da2〉. On the other hand, the first-order theory leads to a dispersion coefficient that is independent of the reaction parameters and to equations that do accurately predict mixing and spreading for Damköhler numbers and variances in the range √〈(ΔDa)2〉/〈Da〉≤0.3
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    Transport in porous media 36 (1999), S. 307-339 
    ISSN: 1573-1634
    Keywords: dispersion ; chromatography ; porous media ; adsorption ; homogenization ; multiple scales expansions.
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    Notes: Abstract This paper is devoted to the computation of effective equations for the transport of a solute in a chromatograph. We focus our attention on models that retain dispersion effects. A chromatograph is a biporous periodic heterogeneous medium, made up of macropores, and of small porous adsorbing crystals that have a retention effect on the solute. We use the method of multiple scales expansions. Various macroscopic behaviours appear, according to the respective orders of magnitude of the dimensionless characteristic parameters: Peclet number in the macropores, ratio of the characteristic time of diffusion in the macropores to the characteristic time of diffusion in the crystals, adsorption coefficient. Dispersion occurs for a Peclet number of order ε−1. We then discuss the effective behaviour of the solute, with respect to the orders of magnitude of the other characteristic parameters. To our knowledge, most of the models are new. Our modelling is not restricted to chromatographs. It applies to various situations of physic and chemical engineering: fixed bed reactors, catalytic cracking, ground water for instance.
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    Keywords: experiment ; aperiodic heterogeneity ; dispersion ; stochastic modeling.
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    Notes: Abstract An electrochemical technique was used to measure concentration distributions in an aperiodic heterogeneous model for comparison with a stochastic transport theory. Four identical columns, each filled with a homogeneous distribution of glass beads, were threaded together to create a single model with aperiodic heterogeneity. The layers in the model were arranged in different ways providing 24 realizations of the permeability distribution. Comparisons between experimental moment data and moments of simulated mean concentration distributions showed that the model was not able to accurately predict experimentally observed mixing behavior.
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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
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    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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    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
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    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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    Lasers in medical science 10 (1995), S. 67-71 
    ISSN: 1435-604X
    Keywords: Oesophageal cancer ; Photodynamic therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    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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  • 73
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    Keywords: 5-Aminolaevulinic acid ; Protoporphyrin IX ; Photodynamic therapy ; Skin neoplasms ; Basal cell carcinoma ; Actinic keratosis
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    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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  • 74
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; Diffusing fibre tips ; Interstitial light delivery ; Light dosimetry
    Source: Springer Online Journal Archives 1860-2000
    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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  • 75
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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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  • 76
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; Cylindrical diffuser ; Interstitial treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    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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  • 77
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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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  • 78
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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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  • 79
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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
    Source: Springer Online Journal Archives 1860-2000
    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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  • 80
    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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  • 81
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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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  • 82
    ISSN: 1435-604X
    Keywords: Photodynamic therapy ; Tumour ; Oral and maxillofacial regions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    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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  • 83
    ISSN: 1435-604X
    Keywords: Lewis lung carcinoma ; Liposomes ; Photodynamic therapy ; Pulsed laser irradiation ; Zn(II)-phthalocyanine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    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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  • 84
    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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  • 85
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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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  • 86
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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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  • 87
    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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  • 88
    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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  • 89
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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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  • 90
    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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  • 91
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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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  • 92
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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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  • 93
    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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  • 94
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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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    Annals of biomedical engineering 21 (1993), S. 489-499 
    ISSN: 1573-9686
    Keywords: Work of breathing ; Inspiratory pressure-time integral ; Respiratory modeling ; Dogs ; Humans
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract We hypothesized that the viscoelastic properties of the respiratory system should have significant implications for the energetically optimal frequency of breathing, in view of the fact that these properties cause marked dependencies of overall system resistance and elastance on frequency. To test our hypothesis we simulated two models of canine and human respiratory system mechanics during sinusoidal breathing and calculated the inspiratory work ( $$\dot W$$ ) and pressure-time integral (PTI) per minute under both resting and exercise conditions. The two models were a two-compartment viscoelastic model and a single-compartment model. Requiring minute alveolar ventilation to be fixed, we found that both models predicted almost identical optimum breathing frequencies. The calculated PTI was very insensitive to increases in breathing frequency above the optimal frequencies, while $$\dot W$$ was found to increase slowly with frequency above its optimum. In contrast, both $$\dot W$$ and PTI increased sharply as frequency decreased below their respective optima. A sensitivity analysis showed that the model predictions were very insensitive to the elastance and resistance values chosen to characterize tissue viscoelasticity. We conclude that the $$\dot W$$ criterion for choosing the frequency of breathing is compatible with observations in nature, whereas the optimal frequency predictions of the PTI are rather too high. Both criteria allow for a fairly wide margin of choice in frequency above the optimum values without incurring excessive additional energy expenditure. Furthermore, contrary to our expectations, the viscoelastic properties of the respiratory system tissues do not pose a noticeable problem to the respiratory controller in terms of energy expenditure.
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    Journal of engineering mathematics 36 (1999), S. 163-184 
    ISSN: 1573-2703
    Keywords: fiber optics ; nonlinear Schrödinger equation ; multiple scales ; dispersion ; solitons.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics , Technology
    Notes: Abstract Multiple-scale averaging is applied to the nonlinear Schrödinger equation with rapidly varying coefficients, and use the results to analyze pulse propagation in an optical fiber when a periodic dispersion map is employed. The effects of fiber loss and repeated amplification are taken into account by use of a coordinate transformation to relate the pulse dynamics in lossy fibers to that in equivalent lossless fibers. Second-order averaging leads to a general evolution equation that is applicable to both return-to-zero (soliton) and non-return-to-zero encoding schemes. The resulting equation is then applied to the specific case of solitons, and an asymptotic theory for the pulse dynamics is developed. Based upon the theory, a simple and effective design of two-step dispersion maps that are advantageous for wavelength-division-multiplexed soliton transmission is proposed. Theuse of these specifically designed dispersion maps allows simultaneous minimization of dispersive radiation in several different channels.
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  • 97
    Electronic Resource
    Electronic Resource
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 38 (1995), S. 3855-3887 
    ISSN: 0029-5981
    Keywords: Adaptive two-step methods ; periodicity ; dispersion ; dissipation ; P-stability ; Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: Adaptive two-step direct integration methods are constructed for the integration of second-order semidiscrete evolution equations possessing oscillatory solutions. The methods are based on a class of adaptive multistep methods for a semilinear test model whose frequency is known. They are constructed following the notion of diagonally implicit RK-methods by using efficient rational approximations to cos v, v ≥ 0. Our interest is centered on the dispersion (or phase errors) of the dominant components in the numerical oscillations when these methods are applied to a linear homogeneous test model. Two-step methods which have high order of dispersion (up to 12), whereas the algebraic order is relatively low (2 or 4), are derived. Applications of these methods to linear as well as non-linear test models and to semidiscretized hyperbolic equations reveal a good behaviour with regard to error propagation when they are compared with other conventional methods.
    Additional Material: 14 Ill.
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  • 98
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 36 (1997), S. 560-563 
    ISSN: 0021-9304
    Keywords: bone ; implant ; hydroxylapatite ; biocompatibility ; histomorphometric implant saturation ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Bone implant materials are often used to fill in bone gaps that frequently result from orthognathic and craniofacial reconstruction. The substrate hydroxylapatite (HA) is commonly implanted into the bone voids, resulting from these conditions due to its established biocompatibility and osteoconductive properties. The porous structure of HA provides a three-dimensional guideline for fibrovascular ingrowth, facilitating the process that ultimately results in the deposition of new bone. Porous HA (Interpore, 200) implants were implanted in the mandible or maxilla of nine humans and removed after 14-30 months (19.1-month mean). There was no evidence of an inflammatory response. The sample composition and apposition against the implant were determined using point counting and a digitizing tablet and software. Percent ingrowth in available space (%IAS) was defined as %Bone/(%Bone + %Void). A new measure of implant saturation (%IAS - %Apposition of bone) was established to help determine the fundamental manner in which long-term HA implants incorporate bone. In the mean, the samples were composed of 27% bone, 21% void, and 53% implant. The apposition percentages averaged 60% bone, 16% void, and 24% soft tissue. The %IAS averaged 58%, and implant saturation averaged -3%, indicating that a near-balance between the implant and surrounding bone has been established. © 1997 John Wiley & Sons, Inc. J Biomed Mater Res, 36, 560-563, 1997.
    Additional Material: 1 Ill.
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  • 99
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 37 (1997), S. 100-107 
    ISSN: 0021-9304
    Keywords: Diopside ; biocompatibility ; osteogenic cell (MC3T3-E1) ; biomechanical strength ; apatite wollastonite-containing glass-ceramic (AWGC) ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Diopside was prepared by sintering a powder compact composed of CaMgSi2O6 at 1573K for 2 h. In order to clarify the biocompatibility of Diopside, the cytotoxicity of Diopside against the osteogenic cell line MC3T3-E1 and the bone-Diopside interface strength were examined. On both the 14th and 21st days of incubation of MC3T3-E1 cells with Diopside, ALP activities were not significantly lower than those of the CTRL. TEM photographs of MC3T3-E1 on Diopside after 14 days of incubation showed active secretion of crystals from osteoblast-like cells. Scanning electron microscopic analysis showed that the cells on Diopside formed multiple cell layers similar to those on the CTRL both 14 and 21 days after incubation. These results showed that Diopside had no cytotoxic effect on MC3T3-E1. The pulling test showed that failure loads of Diopside were significantly lower than those of AWGC. Histologically, there was no fibrous tissue or foreign body reaction at the bone interface. SEM-EPMA showed that Diopside had attached to the bone via a calcium-phosphorus layer. SEM back-scattered electron imaging showed that the Diopside plate had degraded to a porous state 12 weeks after implantation. These findings indicate that Diopside is a biodegradable ceramic. © 1997 John Wiley & Sons, Inc. J Biomed Mater Res, 37, 100-107, 1997.
    Additional Material: 8 Ill.
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  • 100
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 38 (1997), S. 229-234 
    ISSN: 0021-9304
    Keywords: cobalt alloy ; implant ; biocompatibility ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The behavior of the ASTM F1058 wrought cobalt-chromium-nickel-molybdenum-iron alloy (commonly referred to as Elgiloy® or Phynox) is evaluated in terms of mechanical properties, magnetic resonance imaging, corrosion resistance, and biocompatibility. The data found in the literature, the experimental corrosion and biocompatibility results presented in this article, and its long track record as an implant material demonstrate that the cobalt superalloy is an appropriate material for permanent surgical implants that require high yield strength and fatigue resistance combined with high elastic modulus, and that it can be safely imaged with magnetic resonance. © 1997 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 38: 229-234, 1997
    Additional Material: 1 Ill.
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