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Biomedical subjects

S Karrer

Publications and source records attributed to S Karrer.

At least 37 records · Page 2Linked to original sources

[Truss-induced macular amyloidosis].

A 80-year-old male presented with a long time history of a localized red-brown macule with superficial lichenification and slight scaling in the right groin. An earlier skin biopsy revealed the presence of amyloid deposits. The patient therefore had a complete internal checkup including a rectal biopsy for exclusion of systemic amyloidosis. However, the laboratory data did not reveal any specific abnormalities including immunoglobulins and Bence-Jones protein. The rectal biopsy was also nonspecific. After skin examination, a rebiopsy was performed at our department showing acanthosis and spongiosis of the epidermis with parakeratosis. A homogenous eosinophilic deposit was present in the upper dermis and stained positive with thioflavine. At the second visit the patient wore a truss for a right inguinal hernia, perfectly matching the area of the skin lesion. Thus, the diagnosis of a localized macular amyloidosis was confirmed very likely due to permanent local friction. The classification of localized cutaneous amyloidoses should include local trauma as a cause to avoid unnecessary and exhausting internal checkups to exclude systemic involvement.

Aged↗

[Fluorescence-assisted biopsy of basal cell carcinomas].

BACKGROUND AND OBJECTIVE: The diagnosis of precancerous and cancerous skin lessons in pretreated or scarred skin can be difficult. The determination of the right biopsy site in a suspected area depends largely on the physician's experience. PATIENTS/METHODS: The possibility of using a CCD-camera system and measuring tumor fluorescence following topical application of 5-aminolevulinic acid was employed in a single case to facilitate accurate choice of biopsy site. RESULTS: An user-independent evaluation of the induced fluorescence intensity was achieved by means of the described optical system and digital imaging. The contrast of the acquired fluorescence images can be significantly enhanced and allows the determination of a threshold. As result an initial, clinically not visible basal cell carcinoma was detected and excised by a punch biopsy in toto. CONCLUSIONS: Using the described optical system the early recognition of a superficial basal cell carcinoma and the determination of the exact biopsy site was achieved in pretreated skin. The routine employment of the system will be assessed in a prospective study.

Administration, Topical↗

Ehlers-Danlos type VIII. Review of the literature.

Ehlers-Danlos type VIII is a rare disorder characterized by soft, hyperextensible skin, abnormal scarring, easy bruising, and generalized periodontitis with early loss of teeth. To illustrate the clinical dermatological and dental features, we present the case history of a 20-year-old patient who has suffered from poor healing of wounds at the shins and knees since childhood, which have developed into hyperpigmented atrophic scars. In the course of orthodontic treatment during the last 3 years, severe apical root resorption, gingival recession, and loss of alveolar bone were observed. Family history was noncontributory for any skin or tooth disorders. The typical clinical signs confirmed the diagnosis of Ehlers-Danlos syndrome type VIII. As there is no specific treatment for the disorder, management is limited to the symptomatic treatment of the dental disease. It seems advisable to consider carefully the indications for orthodontic treatment in patients with Ehlers-Danlos type VIII syndrome.

Adult↗

Does smoking influence the efficacy of bath-PUVA therapy in chronic palmoplantar eczema?

Bath-PUVA therapy has been described as successful treatment for palmoplantar eczema. However, our own observations showed that patients with palmoplantar eczema of the dyshidrotic or hyperkeratotic type responded only partially to bath-PUVA therapy. In order to evaluate environmental influences possibly having an impact on the efficacy of this therapy, smokers and non-smokers suffering from palmoplantar eczema treated with bath-PUVA therapy were compared. A retrospective study was conducted involving 62 patients, 39 non-smokers and 23 smokers, with palmar and/or plantar eczema resistant to local corticosteroids. Bath-PUVA therapy was performed according to the European standard regimen for oral PUVA therapy. The total number of treatments and the cumulative UVA-dose were similar in smokers and non-smokers (smokers 24+/-17.7 (mean+/-SD) and 67.6+/-51.3 J/cm2 vs. non-smokers 25.7+/-16.3 and 68.5+/-49.3 J/cm2). In the group of non-smokers, 31% showed complete remission (CR; 100% clearance), 33% partial remission (PR; more than 50% clearance) and 36% no change after treatment (NC; less than 50% clearance). In contrast, the group of smokers showed only 13% CR and 22% PR, whereas 65% exhibited NC. The differences regarding complete or partial remission between the groups were statistically significant (Student t-test for paired samples; P<0.05). Regarding the different type of eczema, bath-PUVA proved to be more successful in the dyshidrotic type of eczema as compared to the hyperkeratotic type in non-smokers (P<0.05). In the group of smokers no CR was achieved in patients suffering from the dyshidrotic form of eczema. Smoking is likely to be a reason for the failure of bath-PUVA therapy in the treatment of chronic palmoplantar eczema, in particular regarding smokers with eczema of the dyshidrotic type where no complete remission was achieved.

Adult↗

No generalized skin phototoxicity after intravesical application of 5-aminolevulinic acid for fluorescence diagnosis of superficial bladder cancer.

INTRODUCTION: A prospective monocenter open study was carried out to evaluate if generalized phototoxic skin reactions occur after intravesical application of 5-aminolevulinic acid (ALA) for fluorescence diagnosis of superficial bladder carcinomas. PATIENTS AND METHODS: On 21 patients, skin phototoxicity was determined prior to as well as 4, 8 and 28 h after intravesical instillation of a 3% ALA solution by exposing small skin areas to a progressively graded series of defined UVA-light doses (n = 9; 5-80 J/cm(2)). RESULTS: Prior to ALA instillation, erythema or pigmentation as signs of cutaneous phototoxicity occurred at an UVA-light dose of 28 +/- 1.5 J/cm(2) (mean +/- SEM). A reduction of the minimal phototoxic dose (MPD) was not detected 4 (28 +/- 1.9 J/cm(2)), 8 (28 +/- 1.6 J/cm(2)) and 28 h (28 +/- 1.5 J/cm(2)) after ALA instillation. Consequently phototoxic reactions were not observed. CONCLUSIONS: A reduction of MPD for UVA was not detected. Therefore, it is not necessary to protect the skin of patients from ambient or daylight after intravesical instillation of ALA for fluorescence diagnosis.

Administration, Intravesical↗

Long-pulse dye laser for photodynamic therapy: investigations in vitro and in vivo.

BACKGROUND AND OBJECTIVE: Continuous wave lasers or incoherent lamps are used effectively for photodynamic therapy (PDT). As the mechanism of action of pulsed lasers in PDT is not known, we investigated the efficacy of PDT with 5-aminolevulinic acid (ALA) using a long-pulse (1.5 ms) tunable flashlamp-pumped pulsed dye laser (LPDL) in vitro and in vivo. STUDY DESIGN/MATERIALS AND METHODS: HaCaT human keratinocytes were incubated with ALA (3 mmol/l) and irradiated (0-50 J/cm(2)) using the LPDL at 585 nm, 595 nm, or 600 nm vs. an incoherent light source (580-740 nm). Topical ALA-PDT was performed on 24 patients with actinic keratoses (AK) on the head (n = 200) after incubation with a 20% ALA emulsion and irradiation by either an incoherent light source (160 mW/cm(2), 60-160 J/cm(2)) or the LPDL (585 nm, 18 J/cm(2)). RESULTS: Maximal cytotoxic effects in vitro were achieved using the LPDL at 585 nm or the incoherent lamp (50 J/cm(2)). Sodium azide, a quencher of singlet oxygen, significantly reduced cell killing, suggesting that the cytotoxic effects are mainly mediated by singlet oxygen. This is supported by an increase of lipid peroxides as determined by malondialdehyde after adding D(2)O. Complete remission was achieved in 79% of 100 AK treated by ALA and the LPDL and in 84% of 100 AK treated by ALA and the incoherent lamp. Pain during light treatment was significantly reduced by using the LPDL. Control lesions (LPDL without ALA) did not clear. CONCLUSION: These results show the in vitro and in vivo efficacy of ALA-PDT using a pulsed light source mediated by singlet oxygen.

Adolescent↗

Photosensitization of human skin cell lines by ATMPn (9-acetoxy-2,7,12,17-tetrakis-(beta-methoxyethyl)-porphycene) in vitro: mechanism of action.

9-Acetoxy-2,7,12,17-tetrakis-(beta-methoxyethyl)-porphycene (ATMPn) is a promising new photosensitizer characterized by high absorption around 640 nm and high singlet oxygen yield. To study the mechanism of action in vitro we have investigated uptake, intracellular localization, cell survival and ultrastructural changes following photodynamic treatment in human cell lines derived from the skin (SCL1 and SCL2, squamous cell carcinoma; HaCaT keratinocytes; N1 fibroblasts). Using flow cytometry we have determined the cellular fluorescence as a marker for the uptake of ATMPn after incubation for 60 min. Co-staining with ATMPn and fluorescent dyes specific for cell organelles reveals an intracellular localization of ATMPn in lysosomes. Following irradiation using an incoherent light source (580-740 nm) and a light fluence of 24 J cm-2, phototoxicity is determined by means of the 3-4.5 dimethylthiazol-2,5 diphenyl tetrazolium bromide (MTT) assay. For all cell lines ATMPn concentrations above 15 nM yield a significant phototoxic effect. The 50% effective concentration, EC50, for SCL1 cells is 11.2 +/- 2.9 nM ATMPn. ATMPn uptake and phototoxicity are more effective for HaCaT and SCL1 as compared to SCL2 and N1 cells. Growth curves confirmed the results of the MTT assay. Because of the high lysosomal accumulation of ATMPn, already low photosensitizer concentrations without dark toxicity yield a high photodynamic effect. Immunofluorescence and electron microscopy reveal damage to tonofilaments, plasma membrane and mitochondria, indicating a mechanism unrelated to apoptosis. A dose yielding complete cell killing, as needed for oncological indications, might lead to necrosis, whereas lower sub-lethal doses result in induction of apoptosis.

Cell Line↗

Photo-oxidative killing of human colonic cancer cells using indocyanine green and infrared light.

Despite of the approval of Photofrin in various countries, chemically defined sensitizers for photodynamic therapy (PDT) are still needed for the absorption of light in the infrared spectrum, which provides a maximal penetration of light into tissue. Therefore, both the efficacy and the mechanism of action of the clinically approved dye indocyanine green (ICG) and laser irradiation were investigated in vitro. For the investigation of phototoxic effects, HT-29 cells were incubated 24 h prior to irradiation by using different concentrations of ICG (10-500 microM). In each experiment, cells were irradiated using a continuous wave (cw)-diode laser (lambda(ex) = 805 nm, 30 J cm(-2), 40 mW cm(-2)). After laser irradiation, cell viability of dark control and of cells incubated with 500 microM ICG was 1.27+/-0.11 or 0.28+/-0.05 respectively. Using 100 microM ICG and D2O, cell viability was further decreased from 0.46+/-0.03 (H2O) to 0.11+/-0.01 (D2O). Using D2O and 100 microM ICG, the concentration of malondialdehyde, a marker of lipid peroxidation, increased from 0.89+/-0.10 nmol 10(-6) cells to 11.14+/-0.11 nmol 10(-6) cells. Using 100 microM ICG and laser irradiation sodium azide or histidine (50 mM), quenchers of singlet oxygen reduced the cell killing significantly. In contrast, when using mannitol, a quencher of superoxide anion and hydroxyl radical, cell killing was not inhibited. According to the present results, photoactivated ICG seems to kill colonic cancer cells due to the generation of singlet oxygen and the subsequent formation of lipid peroxides. Therefore, ICG might present a promising photosensitizer for PDT; first clinical results confirm these findings.

Cell Death↗

Epidermodysplasia verruciformis treated using topical 5-aminolaevulinic acid photodynamic therapy.

We describe a 65-year-old woman who had had wart-like lesions on the hands, lower arms and forehead for about 45 years. She had already had several basal cell carcinomas excised. Histological study, electron microscopy and in situ hybridization [human papilloma virus (HPV)-types 5/8/12/14/19-23/25/36] of skin biopsies confirmed a diagnosis of epidermodysplasia verruciformis (EV). Photodynamic therapy (PDT) was performed using a 20% 5-aminolaevulinic acid ointment applied for 6 h to the lesions and irradiating using an incoherent light source (lambda = 580-740 nm, 160 mW/cm2, 160 J/cm2). Following PDT, blistering and crusting of the lesions occurred, but these healed completely within 2-3 weeks without scarring, and the cosmetic result was excellent. Six months after PDT a skin biopsy was taken. In situ hybridization was positive for HPV type 8 in skin which was clinically and histologically normal. Twelve months after PDT a few lesions had recurred on the hands. Although permanent cure of EV cannot be achieved by any therapy at present and single lesions continue to appear in this patient, topical PDT might result in better control of HPV-induced lesions.

Administration, Topical↗

Treatment of digital mucous cysts with a carbon dioxide laser.

Digital mucous cysts are common tumours of the distal interphalangeal joint, causing pain, cosmetic disfigurement and nail deformities. This study describes six patients suffering from digital mucous cysts, some of which recurred after surgery. Carbon dioxide laser vaporization was performed under local anaesthesia, resulting in complete remission in four out of six patients. In two patients, the mucous cyst recurred within 3 weeks and 11 months, respectively, after laser therapy. Although complete remission cannot be achieved in all patients, carbon dioxide laser vaporization of mucous cysts is fast and easy to perform. No side-effects of therapy, such as nail deformities, pain or infection, occurred. For this reason, more aggressive treatments, such as radical excision of the cyst, could be restricted to cases in which carbon dioxide laser therapy fails.

Aged↗

[Acne comedonica following radiation therapy].

HISTORY AND CLINICAL FINDINGS: A 50-year-old female patient underwent extirpation of a moderately differentiated, partially tubular ductal carcinoma of the left mamma and dissection of the left axilla followed by postoperative radiation therapy (total dose 58/48 gy). 2 weeks after the radiation therapy was stopped, treatment with goserelin subcutaneously was started. 6 weeks later numerous open and closed comedons appeared which were sharply confined to the radiation areas of left mamma and sternum. DIAGNOSIS, TREATMENT AND COURSE: Because of the clinical diagnosis of acne comedonica following radiation therapy a local treatment with benzoyl-peroxide gel 5% and erythromycin cream 2% was performed, which led to improvement of the skin lesions within a few weeks and total restitution within 3 months. During one year no comedons have occurred although the local therapeutics are not applied constantly anymore. CONCLUSION: Acne comedonica in the radiation area is a rarely known side effect of radiation therapy. Although the skin lesions cause no pain or itching they can affect the patient due to cosmetic changes. Local treatment with comedolytic acne therapeutics is effective.

Acne Vulgaris↗

[Allopurinol in treatment of cutaneous sarcoidosis].

Several reports more than ten years ago provided evidence that allopurinol may be effective for cutaneous sarcoidosis. We therefore treated two patients with histologically confirmed scar sarcoidosis and two with nodular sarcoidosis. A daily dosage of 300 mg allopurinol was given over a period of 4-7 months as single drug therapy. In both patients with scar sarcoidosis, the skin manifestations completely regressed while in the patients with nodular sarcoidosis there was significant improvement. The concomittant pulmonary involvement in two patients was unpredictable, in one patient improved while the other was deteriorated, The mode of action is still unclear but because of the positive results and the low rate of side effects, allopurinol seems a reasonable agent for treating cutaneous sarcoidosis.

Administration, Oral↗

[Minocycline-induced hyperpigmentation].

A common adverse effect of minocycline therapy is cutaneous pigmentation. We describe two patients who presented with hyperpigmentation caused by minocycline. One patient, aged 54 years, had taken minocycline due to lung silicosis for 3 years before black pigmentation of the face occurred. The other 49 year-old patient developed grey-black hyperpigmentation on both lower legs after a 6-month therapy with minocycline for folliculitis. This patient was treated with the Q-switched ruby laser and the pigmentation resolved in the treated area. The different clinical and histological forms of minocycline-induced hyperpigmentation are discussed.

Administration, Oral↗

Indocyanine green and laser light for the treatment of AIDS-associated cutaneous Kaposi's sarcoma.

Indocyanine green (ICG) is clinically approved for the determination of liver function, cardiac output and plasma volume. In this pilot study, ICG was used as photosensitizer in combination with a diode laser to treat AIDS-associated Kaposi's sarcoma (KS) in three patients. Directly and up to 50 min after intravenous administration of ICG (2-4 mg kg(-1) body weight), KS (n=57), mainly plaque-type, were irradiated using a diode laser (lambda em=805 nm, 100 J cm[-2], 0.5-5 W cm[-2]) matching the absorption maximum. Complete remission of KS (n=16) was achieved when irradiated 1-30 min after injection of the second dose of ICG (2 x 2 mg kg(-1) b.w., 30 min apart) with 3-5 W cm(-2) and 100 J cm(-2). Biopsies (n=3) revealed necrosis of the tumour 24 h and complete remission 4 weeks after therapy. In general, systemic side-effects were not observed and cosmetic results were very good. However, hyperpigmentation occurred temporarily in lesions located on the lower extremities. These findings show that AIDS-associated KS can be effectively treated after photosensitization with ICG and subsequent irradiation with an appropriate diode laser. However, additional investigations need to elucidate the exact mechanism of action of ICG-mediated phototherapy and have to show the efficacy for the treatment of other highly vascularized solid tumours.

Acquired Immunodeficiency Syndrome↗

[Photochemotherapy with indocyanine green in cutaneous metastases of rectal carcinoma].

HISTORY AND ADMISSION FINDINGS: Six weeks before admission of a 47-year-old man with known rectal carcinoma, small nodular metastases had occurred over the front of both his thighs. Examination showed many aggregatet cuti-color or livid nodes, diameter 0.5 cm. The patient's poor general condition excluded the usual palliative measures. TREATMENT AND COURSE: Photochemotherapy of the skin metastases with indocyanine green (ICG; absorption maximum 805 nm), a non-toxic dye approved for diagnostic purposes, was undertaken on a trial basis. The dye, being bound to plasma proteins, is retained in the intravacular space. Immediately after administration of the dye (2.5 mg/kg intravenously) the skin metastases were irradiated by diode laser (lambda = 805 nm, 100 J/cm2, 3 W/cm2, radiation diameter 2 cm). This necrosed the metastases and clinically as well as histologically resulted in their complete disappearance with scarring of the treated area. CONCLUSION: This case illustrates the effectiveness of photochemotherapy with ICG against solid skin tumours of increased microvascular density.

Humans↗

[Steroid-induced scabies norvegica].

Two patients aged 50 and 84 years presented with generalized itching eczema that has been treated with external and internal steroids for months. Despite therapy, the condition worsened continuously. Examination of skin scrapings revealed numerous mites, so Norwegian scabies was diagnosed. General examinations excluded underlying diseases. Treatment with steroids over months most likely led via immunosuppression to the exacerbation of the disease.

Adrenal Cortex Hormones↗

Topical application of a first porphycene dye for photodynamic therapy--penetration studies in human perilesional skin and basal cell carcinoma.

Photodynamic therapy (PDT) in dermatology has been proven to be a successful noninvasive therapeutic modality for treating skin cancer. To facilitate its clinical introduction, the development of topical photosensitizers is necessary to avoid generalized, cutaneous photosensitivity. Therefore the penetration of synthetic chemically pure 9-acetoxy-2,7,12,17-tetrakis-(beta-methoxyethyl)-porphycene (ATMPn) into human skin was studied. Single specimens of freshly excised perilesional skin (n = 70) and basal cell carcinomas (n = 28) were evaluated after topical application of ethanolic ATMPn solutions (0.1% and 0.05%) for various times (2, 6, 16, 20 h). The penetration depth of ATMPn, recognized as red fluorescence in cryostat sections, was determined qualitatively by fluorescence imaging using a system of scoring related to the morphological structure of human skin (0 no fluorescence, 5 fluorescence deeper than basement membrane). Perilesional skin incubated for 2 or 6 h revealed fluorescence restricted to the upper parts of the epidermis, while after 16 or 20 h of incubation fluorescence was detected down to the basement membrane resulting in a significantly higher score (mean sum of scores : 2 h 2.6 +/- 0.4; 6 h 3.2 +/- 0.1; 16 h 3.8 +/- 0.1; 20 h 3.6 +/- 0.1). Quantitative evaluation by digital image analysis confirmed the qualitative results. Fluorescence was limited to the epidermis and the fluorescence intensity of the epidermis was higher after 16 h (4.9% of the fluorescence standard) than after 6 h (4.1%) incubation. Basal cell carcinomas showed fluorescence in the deep dermis as early as after 6 h incubation, but restricted to tumour cell nests. These results suggest that penetration of ATMPn into tumour tissue after topical application might be sufficient for topical PDT and that poor penetration into surrounding tissue might prevent scar formation following irradiation for PDT. The penetration characteristics of ATMPn now have to be proven in an in vivo setting.

Administration, Topical↗