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Biomedical subjects

Peter Altmeyer

Publications and source records attributed to Peter Altmeyer.

At least 91 records · Page 5Linked to original sources

Modulation of cathepsin G expression in severe atopic dermatitis following medium-dose UVA1 phototherapy.

BACKGROUND: During the last decade, medium-dose UVA1 phototherapy (50 J/cm2) has achieved great value within the treatment of severe atopic dermatitis (AD). The purpose of our study was to investigate to what extent UVA1 irradiation is able to modulate the status of protease activity by the use of a monoclonal antibody labeling cathepsin G. METHODS: In order to further elucidate the mechanisms by which medium-dose UVA1 irradiation leads to an improvement of skin status in patients with AD, biopsy specimens from 15 patients before and after treatment were analyzed immunohistochemically for proteolytic activation. RESULTS: Compared to lesional skin of patients with AD before UVA1 irradiation, the number of cells positive for cathepsin G within the dermal infiltrate decreased significantly after treatment. The decrease of cathepsin G+ cells was closely linked to a substantial clinical improvement in skin condition. CONCLUSIONS: In summary, our findings demonstrated that medium-dose UVA1 irradiation leads to a modulation of the expression of cathepsin G in the dermal inflammatory infiltrate in patients with severe AD. Cathepsin G may attack laminin, proteoglycans, collagen I and insoluble fibronectin, to provoke proinflammatory events, to degrade the basement membrane, to destroy the tissue inhibitor of metalloproteinases and to increase the endothelial permeability. Therefore, its down-regulation by UVA1 phototherapy may induce the reduction of skin inflammation as well as improvement of the skin condition.

Biopsy↗

Histometric data obtained by in vivo confocal laser scanning microscopy in patients with systemic sclerosis.

BACKGROUND: It would be a benefit if time-saving, non-invasive methods could give hints for diagnosing systemic sclerosis. To investigate the skin of patients with systemic sclerosis using confocal laser scanning microscopy in vivo and to develop histometric parameters to describe characteristic cutaneous changes of systemic sclerosis observed by this new technique, we conducted an exploratory study. MATERIALS AND METHODS: Fifteen patients with systemic sclerosis treated with extracorporal photopheresis were compared with 15 healthy volunteers and 10 patients with other disorders also treated with extracorporal photopheresis. All subjects were investigated using confocal laser scanning microscopy in vivo. RESULTS: Micromorphologic characteristics of skin of patients with systemic sclerosis and measuring parameters for melanisation, epidermal hypotrophy, and fibrosis for dislocation of capillaries by collagen deposits in the papillary dermis were evaluated. An interesting finding was an increased thickness of the tissue in the dermal papillae superior to the first dermal papilla vessel. It was also possible to reproduce characteristic histologic features by confocal laser scanning microscopy in vivo. Histometric parameters for fibrosis and vascular features developed in this study showed significant differences in patients with systemic sclerosis compared to controls. CONCLUSIONS: Although the predominant histopathological features in systemic sclerosis are findings of the reticular dermis and the subcutis, and in histopathological investigation the epidermis seems to remain unaffected by the disease, we have demonstrate some characteristic differences in the epidermis and papillary dermis by confocal laser scanning microscopy in vivo. Some of them have not been described so far. However, to use this technique as a tool for diagnosis and/or staging of systemic sclerosis, further studies are needed investigating the sensitivity and specificity of the histometric parameters developed in this study.

Adult↗

Apoptosis of human dermal endothelial cells as a potential side effect following therapeutic administration of UVA1 irradiation: preliminary results.

Apoptosis is a highly selective form of cell suicide with characteristic morphological and biochemical features. UVA1 phototherapy has been introduced into the treatment of many T cell-derived skin diseases. The aim of our pilot study was to assess apoptosis of endothelial cells in relation to time after irradiation with medium-dose UVA1 using four different staining techniques. With in situ nick end labelling (ISEL) and Hoechst 33342 staining we investigated DNA degradation during apoptosis and used M30 CytoDEATH to selectively stain the cytoplasm of apoptotic cells. Additionally, the expression of the tumour suppressor gene p53 was determined. ISEL and Hoechst 33342 revealed only a few positive endothelial cells 3 h after UVA1 irradiation. After 6 h almost all vessels were positively stained. By 12 h after irradiation this peak concentration had lowered again. The first p53-positive endothelial cells were seen 6 h after UVA1 irradiation and reached a maximum at 12 h after irradiation. Fibroblasts of the lower dermis were positively stained after 6 and 12 h. M30-positive endothelial cells were found from 3 to 12 hours after irradiation. ISEL and Hoechst 33342 staining clearly revealed UVA1-induced apoptotic cell elimination predominantly restricted to endothelial cells as a possible side effect of UVA1 irradiation. The induction of apoptosis was specifically verified by M30 immunostaining of early caspase cleavage. Whereas the p53-positive endothelial cells underwent programmed cell death as demonstrated by M30, ISEL and Hoechst 33342, some fibroblasts seemed to accumulate the p53 antibody, but this did not induce apoptotic cascades.

Antibodies, Monoclonal↗

Impact of UVA exposure on psychological parameters and circulating serotonin and melatonin.

BACKGROUND: People tend to feel better after exposure to ultraviolet (UV) radiation. This study was performed to investigate the impact of UVA exposure on psychological and neuroendocrine parameters. METHODS: Fifty-three volunteers were separated into 42 individuals who had UVA exposure and 11 individuals who had no UVA exposure. The UVA-exposed volunteers had irradiation sessions six times in a three-week period. All volunteers completed two questionnaires at baseline (T1) and at the end of the study (T3). For the determination of serotonin and melatonin serum levels of all volunteers blood samples were collected at baseline (T1), after the first UVA exposure (T2), and at the end of the study after the sixth exposure (T3). RESULTS: UVA-exposed volunteers felt significantly more balanced, less nervous, more strengthened, and more satisfied with their appearance at T3. By contrast, the controls did not show significant changes of psychological parameters. In comparison to T1 and T3, serum serotonin was significantly higher and the serum melatonin was significantly lower for the volunteers exposed to UVA at T2. Both, for exposed and non-exposed volunteers serotonin and melatonin levels did not significantly differ at T1 and T3. CONCLUSIONS: It remains obscure, whether the exposure to UVA or other components of the treatment were responsible for the psychological benefits observed. The changes of circulating neuroendocrine mediators found after UVA exposure at T2 may be due to an UVA-induced effect via a cutaneous pathway. Nevertheless, the positive psychological effects observed in our study cannot be attributed to circulating serotonin or melatonin.

Humans↗

Treatment of disseminated granuloma annulare with fumaric acid esters.

BACKGROUND: Granuloma annulare is a granulomatous disease of unknown etiology. Various therapies have been tried in disseminated granuloma annulare (DGA), including corticosteroids, several variants of psoralen plus ultraviolet-A radiation, ultraviolet- A1 radiation, systemic retinoids, and dapsone, with variable success. We report a patient with recalcitrant DGA who was treated with fumaric acid esters (FAE). CASE PRESENTATION: A 40-year old Caucasian woman presented with a 25-year history of recalcitrant DGA. On both legs and the abdomen there were erythematous annular plaques. She was treated with FAE in tablet form using two formulations differing in strength (low strength tablets: 30 mg dimethylfumarate, 67 mg monoethylfumarate Ca salt, 5 mg monoethylfumarate Mg salt, 3 mg monoethylfumarate Zn salt; high strength tablets: 120 mg dimethylfumarate, 87 mg monoethylfumarate Ca salt, 5 mg monoethylfumarate Mg salt, 3 mg monoethylfumarate Zn salt). After three-month therapy, an almost complete clearance of skin lesions was achieved. With the exception of temporary lymphopenia, no adverse effects were observed. The patient remained in remission during a six-month follow up period. CONCLUSIONS: Our observation has demonstrated that FAE is a potentially beneficial therapeutic option for patients with recalcitrant DGA. However controlled trials are necessary to fully explore the efficacy, optimal dosage, and safety of FAE in the management of DGA.

Adult↗

Role of clothes in sun protection.

Ultraviolet (UV) radiation is the carcinogenic factor in sunlight. Damage to skin cells from repeated UV exposure can lead to the development of skin cancer. Apart from avoidance of the sun, the most frequently used form of UV protection has been the application of sunscreens. The use of textiles as a means of sun protection has been underrated in previous educational campaigns, even though suitable clothing offers usually simple and effective broadband protection against the sun. Apart from skin cancer formation, exacerbation of photosensitive disorders and premature skin aging could be prevented by suitable UV-protective clothing. Nevertheless, several studies have recently shown that, contrary to popular opinion, some textiles provide only limited UV protection. It has been found that one-third of commercial summer clothing items provide a UV protection factor (UPF) less than 15. Given the increasing interest in sun protection, recreationally and occupationally, test methods and a rating scheme for clothing were needed that would ensure sufficient UV protection. Various textile parameters have an influence on the UPF of a finished garment. Important parameters are the fabric porosity, type, color, weight and thickness. The application of UV absorbers into the yarns significantly improves the UPF of a garment. Under the conditions of wear and use several factors can alter the UV-protective properties of a textile, e.g., stretch, wetness and laundering. The use of UV-blocking cloths can provide excellent protection against the hazards of sunlight; this is especially true for garments manufactured as UV-protective clothing. However, further educational efforts are necessary to change people's sun behavior and raise awareness for the use of adequate sun-protective clothing.

Humans↗

Comparison of methods: determination of UV protection of clothing.

Based on spectrophotometric measurements and mathematical calculations, the ultraviolet (UV) protection factor of a textile is determined in vitro. This technique is the most established test method for the determination of UV protection of a garment. However, the validity and practicality of the in vitro UV protection factor (UPF) determined in the laboratory has been a controversial issue with regard to its significance in the field. Several studies have verified the in vitro UPF by comparing it with various in vivo test protocols using solar-simulated radiation for the determination of the minimal erythema dose. The data inconsistency between these studies is certainly due to different methodology. Furthermore, UV dosimetry is a suitable method for quantifying UV transmission through a garment. Chemical dosimeters (e.g. polysulfone films) and biological UV detector films have been used in in vivo-simulated studies in the form of small portable badges monitoring solar UV transmittance through garments on manikins and mobile subjects. As sunlight consists to a considerable extent of diffuse radiation, which is more scattered and absorbed by the fabric than direct radiation, UPF values obtained by measurements in real exposure situations are usually higher than those obtained by conventional in vitro and in vivo testing with collimated radiation beams. Thus the discrepancy between laboratory-based testing and field-based measurements may be due to different radiation geometry of UV sources. Taken together, the in vitro method is the most practicable and inexpensive method for routine measurements of UPF, but dosimetry seems to be a highly useful method for determining the UPF in real exposure situations.

Materials Testing↗

Prevention of postherpetic neuralgia with varicella-zoster hyperimmune globulin.

Recovery after an acute attack of herpes zoster is followed by postherpetic neuralgia (PHN) in 9-14% of all patients. Depending on the patient's age, the severity of the acute attack of herpes zoster and the dermatome involved, the incidence of PHN may be as high as 65%. The purpose of our study was to ascertain the incidence of PHN after a prophylactic intravenous injection of varicella-zoster hyperimmune globulin (VZV-IG) (Varitect Biotest Pharma). For this double-blind placebo-controlled randomised investigation we defined PHN as pain confined to the dermatome previously affected by herpes zoster, and we required a pain intensity of at least 15% points on a visual analogue scale (VAS) for this dermatome. The inclusion criteria were the dermatological diagnosis of herpes zoster together with age over 50 years. On Day 1, 20 patients received a single intravenous infusion of VZV-IG in a dose of 2mL/kg body weight, 20 patients (control group) received a single infusion of human albumin 5% in a dose of 2mL/kg body weight. All patients received acyclovir intravenously in a dose of 15mg/kg body weight per 24h for 5 days. The patients were followed up for a total of 42 days. The incidence of PHN at Day 42 was selected as the main outcome criterion for assessing the efficacy of prophylaxis. On reaching a significant difference between the groups (t test; alpha<0.05) in favour of the active treatment group, prophylaxis of PHN by VZV-IG was assessed as effective. Pain was assessed on a VAS and a NAS. As auxiliary outcome criteria, we used the McGill Pain-Rating Questionnaire in its German version, the revised multidimensional pain scale (RMSS) and the Freiburg symptom list (FBL). All results were assessed by the t test (alpha<0.05). The frequency of PHN in the placebo group was 70% (14/20), in the active treatment group it was 35% (7/20) at Day 42. The results of the McGill test showed the variability of the perception of pain in the placebo group significantly greater. No significant group differences were found in the FBL. Being tested with the RMSS, the patients of the placebo group assessed their pains as significantly "more obstinate" (p=0.047). The results can be summed up by saying that VZV-IG not only reduces the incidence of PHN, but also that in certain respects the patients' assessments of their pain experience were different. In our study we found a 50% reduction in PHN incidence However, the outcome time point of our trial was so close to the acute phase of the zoster illness that spontaneous remissions of PHN still have to be taken into account. Despite the widely varied approaches to the problem, reliably effective therapy, let alone 100% prevention of PHN, is still not feasible.

Aged↗

Influence of wetness on the ultraviolet protection factor (UPF) of textiles: in vitro and in vivo measurements.

BACKGROUND/PURPOSE: Clothing is an important product for sunburn protection and skin cancer prevention. The moisture content of a fabric, which can increase during its wearing, may decrease the fabric's capability of protecting the skin from solar UV radiation, that is, lower its UPF (ultraviolet protection factor). Due to limited data about the effect of fabric wetness on UPF, this study was undertaken to investigate the following: (a) the effect of saturating a variety of fabrics with tap water and with salt water on fabric UPF and (b) whether wetted-fabric UPF values reflect only the fact that the fabric is wet during testing or the fact that the skin is hydrated and the fabric is wet. METHODS: For objective a, 69 summer fabrics were spectrophotometrically (in vitro) assessed when "dry" and when saturated with tap and salt water. In vitro UPFs, percent UVA transmission and percent UVB transmission values were calculated from the transmission data. For objective b, 100% cotton and 100% polyester fabrics were tested in vivo to determine in vivo UPF values. The minimal erythema dose (MED) was determined for each of the 12 subjects on unprotected "dry" skin and on "hydrated" unprotected skin. MEDprotected was determined when the subject's skin was covered with "dry" and with saturated fabric. In vivo UPFs were calculated using this data. Student's paired t-tests were used to determine the effect of wetting. RESULTS: With one exception, in vitro UPF values were the same when the fabrics were saturated with tap water and when they were saturated with salt water. However, saturating the fabrics with water had different effects on the UPF, UVA transmission, and UVB transmission values. For linen, viscose and polyester fabrics, UPF significantly increased. For the cotton fabrics and the polyester + TiO2 fabrics, UPF significantly decreased. For the modal + TiO2 fabrics and the polyester crepe + TiO2 fabrics, UPF significantly increased. From the in vivo testing, the MED of the "hydrated unprotected" skin was not different than the MED of "dry unprotected skin." Values obtained from subtracting dry-fabric in vivo UPF values from dry-fabric in vitro values and subtracting wet-fabric in vivo UPF values from wet-fabric in vitro values are not different. CONCLUSION: Fabrics do not need to be tested when saturated with tap and with salt water. Testing fabrics wet and dry should be done, as the effect of saturating fabric on UPF value varies. Fortunately, UPF values for wetted fabrics reveal only the effect of increased moisture content in the fabric and have nothing to do with wetting of the skin by the fabric.

Adult↗

Age related changes of human skin investigated with histometric measurements by confocal laser scanning microscopy in vivo.

BACKGROUND/AIMS: The confocal laser scanning microscope Vivascope (Lucid, Henrietta) allows skin to be studied in real-time with a resolution of 0.5 microm horizontal and 1.3 microm vertical in vivo. In this study, we present the results of a comparison between the skin of an older and a younger group of volunteers by in vivo histometric measurements. METHODS: To investigate changes caused by age, 13 young (18-25years) and 13 older (>65years) volunteers were examined. The following parameters were measured using the Vivascope at the volar forearm: minimal thickness of the epidermis (E(min)), size of cells in the granular layer (A(gran)), thickness of the horny layer (DSC), thickness of the basal layer (DSB) and number of dermal papillae per area (Papl). The image analysis program image tool was used to measure the size of the cells and the thickness of the basal layer. RESULTS: The older group of volunteers showed a significant increase in E(min), no significant change in DSC, a significant decrease in dermal papillae and in the thickness of the basal layer, and an increase in A(gran) compared to the younger group. CONCLUSIONS: Histometric measurements by in vivo confocal laser scanning microscopy are a sensitive and non-invasive tool for characterizing and quantifying histological changes of the epidermis and papillary dermis due to ageing.

Adolescent↗

Low-dose ultraviolet A1 phototherapy for extragenital lichen sclerosus: results of a preliminary study.

BACKGROUND: Lichen sclerosus (LS) is a chronic inflammatory skin disease in which numerous therapies have been used, with only limited success. Because low-dose UVA1 phototherapy has been shown to be an effective treatment option for localized scleroderma, which shares several similar clinical and histologic features with LS, we initiated a clinical trial with this phototherapeutic modality in patients with LS. METHODS: Ten patients suffering from extragenital LS were treated with low-dose UVA1 phototherapy 4 times weekly with single UVA1 doses of 20 J/cm(2). Forty treatment sessions were performed within 10 weeks, resulting in a cumulative UVA1 dose of 800 J/cm(2). RESULTS: Low-dose UVA1 phototherapy resulted in a marked reduction of the clinical score and a significant (P <.05) decrease of ultrasonographically measured skin thickness as well as a highly significant (P <.001) increase of dermal density. The patients reported a remarkable softening and repigmentation of the affected skin. CONCLUSION: Analogous to the treatment results in localized scleroderma, low-dose UVA1 phototherapy seems to be an effective and well-tolerated treatment option for extragenital LS.

Adult↗

High-resolution laser Doppler perfusion imaging aids in differentiating between benign and malignant melanocytic skin tumours.

Malignant melanomas are characterized by heterogeneity and asymmetry as well as by a higher density of blood vessels than benign pigmented tumours. The aim of this study was to evaluate the benefit of high-resolution laser Doppler perfusion imaging (LDPI) in the differential diagnosis of pigmented skin tumours. One-hundred-and-eighty-nine patients were examined with the LDPI, 22 with malignant melanomas, 39 with clinically suspicious dysplastic melanocytic naevi and 27 with basal cell carcinomas. Following examination, the tumours were excised and examined histologically. A control group of 101 melanocytic naevi showed clinically and, with epiluminescence microscopy, definitely benign criteria. These naevi were not excised. In malignant melanomas there was a 3.6+/-1.5 times higher perfusion than in healthy skin. The corresponding figures for clinically suspicious melanocytic naevi and basal cell carcinomas were 2.2+/-1.1 and 2.0+/-0.7, respectively. The increase in flow in malignant melanomas was significantly higher than in clinically suspicious melanocytic naevi and basal cell carcinomas (p < 0.001). All malignant melanomas showed at least 1.8 times higher flow values than healthy skin. When this value is taken as the basis for the diagnosis "benign or malignant", the LDPI proved a sensitivity of 100% and a specificity of 85%. If only the distinction between malignant melanomas and clinically suspicious naevi is considered, the specificity is reduced to 48%. There was no correlation between tumour thickness and increase in the mean perfusion of malignant melanomas (r = 0.14; p = 0.5). High-resolution LDPI can be used as an additional automatic screening method.

Adult↗

Skin changes and tumours after renal transplantation.

Skin involvement in chronic renal failure is characterised by a multitude of different aspects. Apart from the typical yellow-brown discolouration of the skin, most often patients complain of pruritus and xerosis cutis. A marked actinic elastosis is noticed. Dialysis treatment alters and partly aggravates these pre-existing skin conditions. When chronic renal failure leads to a kidney transplantation, some of the reversible skin pathology, e.g. pruritus, xeroderma, tends to ameliorate, but a high tendency to develop malignancies becomes prominent.

Humans↗