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Biomedical subjects

S Karrer

Publications and source records attributed to S Karrer.

49 records · Page 3Linked to original sources

Indocyanine green: intracellular uptake and phototherapeutic effects in vitro.

Indocyanine green (ICG; absorption peak in human plasma 805 nm) was investigated for ICG-mediated phototherapy in vitro. The cellular uptake of ICG (1 microM-50 microM) into HaCaT keratinocytes after an incubation period of 24 h increased up to an intracellular ICG concentration of 12.1 +/- 1.3 nmol per 10(6) cells. To examine dose dependent phototoxic effects in vitro, keratinocytes were incubated with 0 microM-50 microM ICG for 24 h and irradiated by a diode laser (805 nm) with different energy densities (0, 12, 24, 48 J cm-2). All applied ICG concentrations except for 5 microM yielded a cell killing effect in combination with irradiation depending significantly on ICG concentration and light dose. Cell viability for dark control and cells incubated with 50 microM ICG and irradiated with 48 J cm-2 was 0.82 +/- 0.15 and 0.07 +/- 0.02, respectively. Sodium azide (100 mM), a quencher of reactive oxygen species, inhibited significantly the cell killing using 50 microM ICG and 24 J cm-2. Taken together, photoactivation of ICG by irradiation with a diode laser was shown to induce effectively cell killing of HaCaT keratinocytes. Moreover, this effect was inhibited by sodium azide, thus irradiation of ICG might induce a photodynamic reaction.

Antineoplastic Agents↗

[Hydroa vacciniforme].

HISTORY AND CLINICAL FINDINGS: For three years, each time the day after intensive exposure to the sun a 5-year-old girl developed moderately painful erythema and blisters on uncovered parts of her body which subsequently healed with scarring. There was no increased photosensitivity among members of her family. There were numerous blisters and bullae, some of them confluent, filled with serous fluid on her back, on her arms an in the face. There were varioliform scars on the extensor surfaces of her arms. INVESTIGATION: There were no porphyrins in red cells, serum or urine. The characteristic skin changes were reproduced on exposure to UV-A. These findings established the diagnosis of hydroa vacciniforme. TREATMENT AND COURSE: Prolonged sun exposure was to be avoided and protective ointment was prescribed together with administration of beta-carotene, 25 mg twice daily. CONCLUSION: In children light-induced skin changes which heal with scarring may be due to hydroa vacciniforme.

Child, Preschool↗

[Treatment of pediatric hemangiomas with the flashlamp-pumped pulsed dye laser].

We treated 166 infants and children with 177 hemangiomas with the flashlamp-pumped pulsed dye laser (FPDL, 585 nm, 450 microseconds, 5 mm phi). The hemangiomas were classified as initial, superficial, cutaneous-nodular, and compound (cutaneous-subcutaneous) lesions according to the clinical involvement. After one treatment (n = 124), good results ( > 75% clearance) were obtained in 56% of initial and in 36% of the nodular lesions. With repeated treatment sessions (n = 82), good results were achieved in 63% of the initial, in 67% of the superficial and in 70% of the nodular angiomas. Complete resolution requiring one or more treatment sessions was reached in 44% of the initial, in 42% of the superficial and in 16% of the nodular lesions. In compound lesions, only the cutaneous part responds to treatment owing to the limited penetration depth of the laser light. In our opinion, early FPDL therapy of most initial and/or rapidly growing hemangiomas should be recommended especially since this therapy is fast, has few side effects and can even be used in newborns.

Child↗

9-Acetoxy-2,7,12,17-tetrakis-(beta-methoxyethyl)-porphycene (ATMPn), a novel photosensitizer for photodynamic therapy: uptake kinetics and intracellular localization.

The optimal photosensitizer for topical or systemic photodynamic therapy (PDT) has not yet been found. A promising new second-generation sensitizer is 9-acetoxy-2,7,12,17-tetrakis-(beta-methoxyethyl)-porphycene (ATMPn) whose time- and temperature-dependent uptake and intracellular localization were investigated in two human-skin-derived cell lines (HaCaT keratinocytes and dermal fibroblasts). Flow cytometry analysis (0-800 s) revealed an immediate increase in fluorescence in the cells after start of incubation with 100 ng ml-1 ATMPn (in cell culture medium). At longer incubation periods (0-24 h) a constant increase in fluorescence up to 12 h, with a steady state up to 24 h, was observed. Keratinocyte showed a faster rate of ATMPn uptake than fibroblasts within the first 12 h. Temperature-dependent ATMPn uptake was measured at 4 and 37 degrees C. An increase in fluorescence was observed even at 4 degrees C, suggesting that cellular uptake of ATMPn is partially based on passive diffusion. Confocal laser scan miscroscopy showed spotty, granular fluorescence inside the cytoplasm after incubation with ATMPn, similar to the pattern of rhodamine 123 which stains mitochondria. These results demonstrated an unusually fast intracellular, probably intramitochondrial, uptake of ATMPn in vitro. Therefore the use of ATMPn in photodynamic therapy might allow a reduction of the time span between administration of drug and irradiation.

Cell Line↗

Topical photodynamic therapy in dermatology.

Although photodynamic therapy (PDT) was first used in the treatment of skin diseases, phase-III-clinical trials were primarily conducted for the treatment of bladder cancer, endobronchial and oesophageal carcinoma. In dermatology PDT has most extensively been used for the treatment of malignant cutaneous lesions. Up to now those patients have been treated systemically with first-generation photosensitizers. However, prolonged skin photosensitivity is a major disadvantage of this form of therapy. Topical PDT utilizing a variety of sensitizers bypass this unwanted effect. Of strong interest is 5-aminolevulinic acid (ALA), first introduced in the topical PDT of skin disorders in 1990 by Kennedy and co-workers. ALA serves as a pro-drug, i.e. the active photosensitizing compound is protoporphyrin IX which is synthesized in vivo after exogenous application of ALA. In several oncologic and non-oncologic skin conditions including non-melanoma skin cancer, premalignant conditions like actinic keratoses and in psoriasis, topical ALA-PDT showed it's effectiveness. Besides ALA, new sensitizers like benzoporphyrines and porphycenes may play a role in topical PDT. However, at the moment, there is still a need for comparative studies and standardized therapeutic protocols to define the place of topical PDT in Dermatology.

Administration, Topical↗

Photodynamic therapy with topical application of 5-aminolevulinic acid in the treatment of actinic keratoses: an initial clinical study.

BACKGROUND: The incidence of actinic keratoses (AK) is rising and there is still a need for therapeutic alternatives. OBJECTIVE: To demonstrate the efficacy and tolerability of topical photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) in the treatment of AK. METHODS: Ten patients with 36 lesions (19 at hands and arms, 17 on the head) received ALA-PDT once (occlusive application of a 10% ALA emulsion for 6 h, irradiation with red light, 580-740 nm, 150 J/cm2) and were then monitored for 3 months. Therapeutic efficacy was judged using a score evaluating infiltration and keratosis of AK. RESULTS: After 28 days, significantly lower score sums were observed (head: mean = 15%; hand: mean = 67%) compared to the initial score (100%). Complete remission was achieved in 71% of AK localized on the head. No notable side effects were observed. CONCLUSION: This study demonstrated the potential of good efficacy and tolerability in the treatment of AK using topical ALA-PDT. How efficacy for lesions on the hand can be improved and whether PDT is able to concur with established treatment modalities remains to be shown in further studies.

Administration, Topical↗

Wavelength dependency of photodynamic effects after sensitization with 5-aminolevulinic acid in vitro and in vivo.

A promising new therapeutic modality for skin cancer, administration of the heme precursor 5-aminolevulinic acid followed by light irradiation, is known as photodynamic therapy. Photofrin, the only clinically approved sensitizer, has an absorption maximum at 630 nm, the wavelength used in most experimental and clinical trials with 5-aminolevulinic acid. We investigated photodynamic efficacy of irradiation with coherent light at wavelengths ranging from 622 to 649 nm in vitro and in vivo as well as the content and distribution of intracellular porphyrin after administration of 5-aminolevulinic acid. HaCaT immortalized human keratinocytes were sensitized with 30 micrograms/ml 5-aminolevulinic acid for 24 h in vitro. By cell viability determined with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, the best cell-killing effects were observed after irradiation at 635 nm. Using an amelanotic melanoma (A-Mel-3) grown subcutaneously in Syrian Golden hamsters, we confirmed these results in vivo: tumor growth was markedly delayed in animals treated with 100 mg/kg 5-aminolevulinic acid intravenously and irradiated with coherent light at 635 nm as compared to animals irradiated at 630 nm. This photodynamic effect is probably mediated by large amounts of the photosensitizing porphyrin, protoporphyrin IX, localized in cell membranes as visualized by confocal laser scan microscopy and as determined by high pressure liquid chromatography in vitro. The results suggest that irradiation at 635 nm with a coherent light source is more effective than irradiation at 630 nm for photodynamic therapy with 5-aminolevulinic acid.

Aminolevulinic Acid↗

Unilateral localized basaliomatosis: treatment with topical photodynamic therapy after application of 5-aminolevulinic acid.

A 74-year-old woman presenting with multiple unilateral localized basal cell carcinomas present for 30 years on the left side of her body is reported. There was no history of arsenic ingestion or X-ray exposure. Typical signs of nevoid basal-cell carcinoma syndrome (Gorlin's syndrome) like jaw keratocysts, skeletal malformations, and small palmoplantar pits were missing. Although treatment with many therapeutic regimens was tried, there were still tumor recurrences. Photodynamic therapy was performed after topical application of 5-aminolevulinic acid. This treatment resulted in good tumor control with an optimal cosmetic result.

Administration, Cutaneous↗

[Eruptive melanocytic nevi after chemotherapy].

BACKGROUND: Induction of melanocytic naevi by chemotherapy in children is reported in the literature. The reason for this phenomenon is not known yet. HISTORY AND CLINICAL FINDINGS: We present a 6-year-old girl who fell ill with acute lymphoblastic leukemia at the age of 2 years. After a combined chemotherapeutic treatment for 2 years followed by complete remission of leukemia, many (> 100) small pigmented naevi appeared over the whole body. The naevi did not show features suggestive of dysplasia. CONCLUSIONS: Patients with excess numbers of melanocytic naevi constitute a risk group for malignant melanoma, therefore periodic skin examination is recommended.

Antineoplastic Combined Chemotherapy Protocols↗

Topical photodynamic therapy for localized scleroderma.

Therapy of localized scleroderma is unsatisfactory, with numerous treatments being used that have only limited success or considerable side-effects. The aim of this trial was to determine whether topical photodynamic therapy would be effective in patients with localized scleroderma. Five patients with progressive disease, in whom conventional therapies had failed, were treated by application of a gel containing 3% 5-aminolevulinic acid followed by irradiation with an incoherent lamp (40 mW/cm2, 10 J/cm2). The treatment was performed once or twice weekly for 3-6 months. In all patients the therapy was highly effective for sclerotic plaques, as measured by a quantitative durometer score and a clinical skin score. The only side-effect was a transient hyperpigmentation of the treated lesions. These cases document the beneficial effect of topical photodynamic therapy in localized scleroderma. Controlled trials are now necessary to confirm these preliminary results.

Adult↗

Primary Anetoderma in children: report of two cases and literature review.

Two boys, age 7 and 9 years, with the diagnosis of primary anetoderma are presented. In one patient a growing number of indolent lesions developed for one year on the neck. The other boy complained of single lesions appearing over four months on the arms, feet, and chest wall. Individual lesions measured up to 1 cm in diameter and showed a palpable herniation phenomenon and wrinkled surface. The lesions did not have an inflammatory onset. Histologically, in both patients the diagnosis of anetoderma was verified by loss of elastic fibers and a lympho-histiocytic infiltration in the middermis. Administration of oral penicillin for three weeks did not result in marked improvement, and atrophic macules continued to appear in the younger boy. Although no autoimmunologic abnormalities or other associated diseases have arisen in our patients, long-term follow-up is mandatory to detect autoimmune disorders that are reported to occur in the course of the disease.

Child↗