Fredrik Gudmundson

Photodynamic therapy of actinic keratosis at varying fluence rates: assessment of photobleaching, pain and primary clinical outcome

Background  Although photodynamic therapy (PDT) is becoming an important treatment method for skin lesions such as actinic keratosis (AK) and superficial basal cell carcinoma, there are still discussions about which fluence rate and light dose are preferable. Recent studies in rodents have shown that a low fluence rate is preferable due to depletion of oxygen at high fluence rates. However, these results have not yet been verified in humans.

Important factors for pain during photodynamic therapy for actinic keratosis

Photodynamic therapy (PDT) is an efficient treatment for actinic keratosis. A common problem, however, is pain. The aim of this study was to investigate pain during PDT for actinic keratosis. The possibility of using capsaicin cream for pain relief was also assessed. Pain was investigated during aminolaevulinic acid PDT in 91 patients. Size, redness, scaling and induration of the lesions were recorded. Maximum pain during treatment was registered, using a visual analogue scale (0-10). The pain-reducing efficacy of capsaicin was tested in a pilot study in six patients (10 lesions). These patients were pre-treated with capsaicin cream for one week before commencing PDT. Pain was found to be normally distributed around a mean value of visual analogue scale 4.6. Larger lesions gave more pain (p=0.001). The redness of the actinic lesions was found to be related to PDT-induced pain (p=0.01), the reduction of actinic area (p=0.007), and the cure rate (p=0.01). The redder the actinic area, the better the treatment outcome and the more pain experienced. Patients with the largest reduction in the actinic area experienced more pain (p=0.053). The most important factors for presence of pain seem to be the size and the redness of the lesion. No significant pain relief was experienced after pre-treatment with capsaicin.

In vivo Detection of Basal Cell Carcinoma using Imaging Spectroscopy

Photodynamic therapy has become an interesting alternative to conventional therapy for basal cell carcinomas. Delta-aminolevulinic acid is a precursor in the biosynthesis of protoporphyrin IX that accumulates to a large extent in tumour tissue. We have compared in vivo protoporphyrin IX fluorescence with the extent of basal cell carcinomas on the face, trunk and thigh determined by histological mapping in 30 lesions in 22 patients. A new non-laser based set-up was used to record the fluorescence images. Delta-aminolevulinic acid was applied for 4 h inducing high concentrations of protoporphyrin IX. Routine vertical histological sections and Mohs micrographic surgery were used to map the extent of the tumours. In 50% of lesions we found a good correlation between the fluorescence imaging and histological mapping. In 23% the correlation was partial. In the other lesions we found no correlation at all. This method may be used to delineate basal cell carcinomas more accurately than current methods.

A spectroscopic study of the photobleaching of protoporphyrin IX in solution

Abstract Photodynamic therapy (PDT) has developed into an important new clinical treatment for cancer during the past 30 years. The method is non-invasive and based on the photochemical activity of a photosensitising agent present in cells and tissues. In so-called ALA-PDT, protoporphyrin IX (Pp IX) is induced from aminolaevulinic acid (ALA) applied topically or systemically. It has been shown that Pp IX is photodegraded by a photo-oxidation process and that its photoproducts have a characteristic absorption band around 670 nm, as observed both in solution and in cells incubated with ALA. In this study, the involvement of oxygen in the photobleaching process was verified by studying the effect of oxygen depletion using the freeze–pump–thaw (FPT) method. A solution of Pp IX in dimethylformamide (DMF) was exposed to light in the wavelength region 600–700 nm (peak centred at 620 (±25) nm) both in the presence and in the absence of oxygen. The bleaching process was observed by absorbance and fluorescence measurements. Photobleaching was observed in the presence of oxygen, as verified by the build-up of a photoproduct absorbing at 670 nm. When the sample was deoxygenated with the FPT method, the photoproduct absorption peak at 670 nm was missing. These results confirm that the formation of photoprotopor-phyrin is a photo-oxidation process and that no photobleaching takes place in the absence of oxygen. When comparing our results to the studies carried out by N2 bubbling, the N2 bubbling seems to be insufficient to remove the oxygen completely from the solution.

Fluorescence contrast and threshold limit: implications for photodynamic diagnosis of basal cell carcinoma

This study was designed to evaluate what application time of delta-5-aminolaevulinic acid (ALA) results in highest contrast between tumour and normal skin, in the interval 1-4 h, when using photodynamic diagnosis (PDD) of basal cell carcinomas (BCC) located on the face. Moreover, a value of the demarcation limit has been derived based on the fluorescence variation in normal skin adjacent to the tumour. Forty patients were included in the study, randomly allocated to four different groups with varying ALA application time in the range 1-4 h. The contrast, defined as the ratio between the fluorescence intensity in ALA-treated tumour tissue and normal skin, was calculated for each patient, and the mean values in each group were evaluated as a function of ALA application time. In addition, the fluorescence intensity variation in ALA-treated normal skin adjacent to the tumour was assessed. The results from this study show a peak of the mean contrast values after 3 h ALA application, but due to large interpatient variation, the mean contrast did not differ significantly in the interval 2-4 h. After 2 h ALA application, the fluorescence intensity variation in the normal ALA-treated skin was found to be at a maximum, which suggests that 2 h ALA application is not preferable when using PDD. Based on data of the fluorescence variation in ALA-treated normal skin after 3 and 4 h ALA application, a tolerance interval was calculated implying that values above 1.4 times the mean normal fluorescence indicate an abnormal condition. This tolerance limit agrees well with results obtained in a former study.

The influence of a catalytic surface on the gas-phase combustion of H2 + O2

Abstract The OH concentration outside a Pt catalyst at 1300 K, in a stagnation flow of 90% O 2 and 10% H 2 , has been studied by planar laser-induced fluorescence (PLIF), and compared to measurements outside a heated glass surface. The total pressure in the system was varied from 0.2 to 120 torr. At low pressure, surface reactions were observed for the Pt surface, but not for the glass. At higher pressure, gas-phase ignition occurred for both systems, but not at the same pressure: ignition occurred at a lower pressure outside the inert glass surface. Computer modeling using CHEMKIN confirmed these results. The difference in gas-phase ignition is also seen in the modeling results, and it is due to the removal of atomic O and H from the gas by adsorption and reaction on the catalytic surface. The catalytic reaction mechanism on the surface plays an important role as it enhances the removal of radicals, compared to a surface where only radical recombination back to reactants is allowed.

Analysis of the kinetics for the H2 + \( - \frac{1}{2}\)O2 ⇌ H2O reaction on a hot Pt surface in the pressure range 0.10–10 Torr

AbstractThe H2 +

Evaluation of hydroxyl desorption rates from platinum using spatially resolved imaging of laser-induced fluorescence

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