Reference limits for erythema-effective UV doses.

Diagnostic phototesting, including the determination of the minimal erythema dose (MED), is a useful procedure to detect abnormal sensitivity to UV radiation. We aimed to estimate the reference limits (RLs) of the MED in a reasonably large reference sample of white individuals. Skin phototypes and MED values for broadband UVB and for UVA were determined in 461 white subjects. When appropriate, the 95% reference intervals, including the 0.025 fractile and 0.975 fractile, were computed for the MED-UVB reference values (by means of parametric methods) and the MED-UVA reference values (by means of nonparametric methods). MED data were also converted to standard erythema doses (SEDs). As described elsewhere we observed a considerable overlap of MED values for all skin phototypes and confirmed that age and sex do not substantially influence the MED. The lower RLs observed for MED-UVB were 33 mJ cm(-2) (0.5 SEDs) and for MED-UVA 12.6 mJ cm(-2) (1.2 SEDs). The MED and SED findings from this investigation may serve as reference data for white individuals and give support to the clinician in differentiating between normal and pathologically abnormal photosensitivity. Although the MED data given here are limited to the phototest device used in the present study, the SED results establish comparability between our data and phototest results obtained from laboratories using different UV sources.

UVA1 and UVB irradiated skin investigated by optical coherence tomography in vivo: a preliminary study.

In histological studies, it has frequently been demonstrated that ultraviolet (UV) exposure, in particular UVB, can induce significant thickening of the viable epidermis and/or stratum corneum. Since skin biopsy alters the original skin morphology and always requires an iatrogenic trauma, we aimed to introduce optical coherence tomography (OCT) in vivo for the investigation of changes of epidermal thickness (ET) following UVA1 and UVB irradiation. Twelve healthy subjects received daily 60 J/cm2 of UVA1 and 1.5 minimal erythema doses UVB on their upper back over 3 consecutive days. Twenty-four hours after the last irradiation, OCT assessments were performed on UV exposed and adjacent nonirradiated control sites. Data of ET as expressed by comparison of the averaged A-scans differed significantly between nonirradiated (94.2 +/- 15.7 microm), UVA1 (105.4 +/- 12.8 microm) and UVB (125.7 +/- 22.1 microm) exposed sites. In comparison to the nonirradiated sites, UVA1 exposed skin showed significant (P = 0.022) increase of ET of 11% and UVB exposed sites a significant (P < 0.001) increase of 25%. ET of UVA1 and UVB exposed skin sites differed significantly (P =0.005). Our results obtained from OCT in vivo measurements confirm data of previous histological studies indicating that not only erythemogenic doses of UVB, but also suberythemogenic doses of UVA1 may have a significant impact on ET. OCT appears to be a promising bioengineering technique for photobiological studies. However, further studies are needed to establish its measurement precision and validity, and to investigate in vivo spectral dependence on UV induced skin changes such as skin thickening.

Nephrogenic fibrosing dermopathy.

Nephrogenic fibrosing dermopathy (NFD) is an uncommon, recently described fibrotic skin disorder that has been observed in patients with end-stage renal disease. We describe a 81-year-old man with end-stage renal disease who developed NFD in the seventh year of haemodialysis. Laboratory investigations revealed considerably increased circulating immune complexes and anti double stranded DNA antibodies. Because the pathogenesis of NFD may not entirely be attributable to haemodialysis, the role of circulating factors in the development of cutaneous manifestations requires further investigation.

Effects of repeated sunbed exposures on the human skin. In vivo measurements with confocal microscopy.

BACKGROUND: Ultraviolet (UV) lamps used in commercial sunbeds are usually defined as UVA sources. Although it is well accepted that sunbed exposure significantly increases melanin pigmentation, its capacity to induce epidermal thickening is discussed controversially. OBJECTIVES: The aim of this study was to assess non-invasively the effects of repeated sunbed exposures on epidermal thickness, cell size, and pigmentation by means of confocal laser-scanning microscopy (CLSM) in vivo. METHODS: Eight volunteers had sunbed exposures six times in a 3-week period (cumulative dose: 126 J/cm(2) UVA). During irradiation, a small site (2 cm x 2 cm) on the lateral aspect of the inner forearm was covered with a UV-opaque sheet (non-exposed site). CLSM was performed with the Vivascope (Lucid, Henrietta, NY, USA) 24 h after the last UVA exposure on non-exposed sites and UVA-exposed sites that were on the medial aspect of the inner forearm at a distance of 2 cm to the non-exposed measurement site. The following parameters were assessed: thickness of the horny layer (DSC), minimal thickness of the epidermis (E(min)), minimal thickness of the viable epidermis (VE(min)), cell size of the granular layer (A(gran)), and the epidermal melanin content (MI). Additionally, colorimetric measurements have been carried out on non-exposed and UVA-exposed sites. RESULTS: DSC of the UVA-exposed skin was significantly higher than the one of non-exposed sites (mean+/-SD: 15+/-2.9 microm vs. 12.8+/-3 microm). Although E(min) was significantly higher in UVA-exposed sites (mean+/-SD: 40.4+/-3.6 microm vs. 39+/-2.9 microm), a slight but not statistically significant (P>0.05) decrease of VE(min) was observed (25.5+/-2.1 microm vs. 26.2+/-2.4 microm). The median of cell size of the granular layer (A(gran)) significantly (P=0.008) differed between non-exposed (752.1 microm(2)) and UVA-exposed sites (600 microm(2)). MI was significantly (P=0.014) higher for the UVA-exposed skin (1.12 vs. 1.34). Accordingly, colorimetry revealed significantly (P< 0.01) lower skin brightness for UVA-exposed sites (L*=60.2+/-4.3) as compared with non-exposed sites (L*=63.4+/-3.9). CONCLUSIONS: Sunbed exposures seem to induce photoadaptation not only by skin pigmentation but also by epidermal thickening that is predominantly due to an increase in thickness of the horny layer. Moreover, our data indicate that UVA radiation has an influence on the cell size of the granular layer. CLSM is a promising tool for photobiological studies in vivo.

Hepatitis B-assocciated adult-onset Still's disease presenting with neutrophilic urticaria.

Adult-onset Still's disease (AOSD) is an uncommon systemic inflammatory disorder that is characterized by quotidian fever, articular manifestations, neutrophilic leukocytosis, and maculopapular rash. The aetiology of the disease is unknown, however, an infectious cause has been suggested. Here we describe a patient in whom neutrophilic urticaria was the cutaneous manifestation of AOSD. In addition, the patient suffered from chronic hepatitis B infection that may be a potential trigger factor of AOSD. In patients with AOSD, serological investigations for detection of infection should include hepatitis serology. Further, we suggest that urticarial lesions may be a more common cutaneous manifestation of AOSD than has been recognized previously. Thus it is important to include AOSD in the differential diagnosis of urticaria.

Radata - implementation of resistance analysis and expert advice for optimized HAART switches in general practice of HIV-infected individuals via a compiling internet presence.

BACKGROUND: HIV-infected patients fail viral load suppression, because resistance against antiretroviral drugs arises or for other reasons. HIV-resistance analyses can aid to achieve effective HAART regimen. Furthermore, clinical benefits from genotyping in study settings are significantly higher for treating physicians, who can include external advice from HIV-experts into HAART switch. OBJECTIVE: To develop a compiling internet presence to provide expert advice for HAART switch in general practice of HIV-infected individuals after therapy failure. - DESIGN: A multifactorial (genotyping, drug monitoring, adherence, expert advice) interdisciplinary internet service (www.radata.de) with an associated server hosted database. PATIENTS AND METHODS: HIV-infected patients after failure to HAART are eligible for registration to the Radata project. Genotyping is performed according to protocols specific for each participating institution. Therapeutic drug monitoring (NNRTIs, PIs) follows setting for drug level detection by mass spectrometry. An adherence self-report is completed by every patient. Clinical documentation is provided by the treating Primary Care Physician. Clinical expert advice for implementation into HAART switch in daily clinical practice for treating physicians is provided by HIV-experts according to data obtained. Clinical and laboratory follow-up visits are scheduled firstly 4 weeks after HAART switch and three monthly afterwards, over a period of one year. RESULTS: Technical resources and a compiling internet presence for generation of resistance analysis based expert advice were developed. Initially, 7 HIV-treatment centres, 7 laboratories and 17 HIV advisors contribute to Radata database project. 15 patients were enrolled during test period. 30 expert advices were generated during the test phase. Expert advice was provided in 6 weeks median for implementation into HAART switch. 13 out of 15 expert advices were implemented into HAART switch by treating Primary Care Physicians. CONCLUSIONS: Radata is a novel database concept with features to generate expert advice for implementation into HAART switch of HIV-infected subjects. A test period has shown, that the concept is technically approved to fit all requirements with regard to data collection, evaluation and to generate expert advice for therapy switch in daily clinical practice.

HHV-8 DNA in blood and the development of HIV-associated Kaposi's sarcoma in the era of HAART--a prospective evaluation.

OBJECTIVE: To explore the significance of HHV-8 viremia in HIV-positive individuals for the risk of developing Kaposi's sarcoma (KS) in the era of highly active antiretroviral therapy. METHODS: 237 HIV-positive patients were included in this prospective evaluation and followed over an average duration of 34 months. HHV-8 DNA in peripheral blood mononuclear cells (PBMCs) and CD4-lymphocytes were determined. In addition AIDS-defining conditions and antiretroviral therapy were documented of all participating subjects. RESULTS: HHV-8 DNA was detectable in PBMCs of 12.6% out of all individuals. 53.3% of these patients initially complained about KS, although 9.2% of patients without HHV-8 DNA in PBMCs were found on KS as well. Furthermore, four patients in total were observed with newly developed KS during follow up visits. None of these patients were noted with detectable HHV-8 DNA at their initial evaluation. CONCLUSIONS: Prevalence of HHV-8 DNA in PBMCs of subjects in this investigation was quite similar to former investigations. However, new diagnosed KS occurred less frequently than demonstrated in previous studies. All of those observed patients with new KS manifestations were negative for HHV-8 DNA in PBMCs at study entry. This observation differs from earlier studies which have postulated the detection of HHV-8 DNA in PBMCs as a predictive value for development of KS. Due to results as presented, a single HHV-8 DNA test in blood has no predictive value in support of predictability of KS development. With respect toto costs and to a less complicated performance antibody assays should be preferred.

Remission of cutaneous Mycobacterium haemophilum infection as a result of antiretroviral therapy in a Human Immunodeficiency Virus--infected patient.

We describe the first Mycobacterium haemophilum infection that occurred in a patient with human immunodeficiency virus in Germany and report 7 newly diagnosed cases of M. haemophilum infection. In the former case, a local M. haemophilum skin infection resolved as a result of successful antiretroviral therapy only; however, that clinical outcome may not be possible for more invasive forms of the disease.

Remission of a cutaneous Mycosis fungoides after topical 5-ALA sensitisation and photodynamic therapy in a patient with advanced HIV-infection.

BACKGROUND: Treatment of Mycosis fungoides (MF) in HIV-infected patients is controversially discoursed. Photodynamic therapy (PDT) after topical sensitization with 5-aminolevulinic acid (5-ALA) is a new and effective modality for treatment of skin malignancies. OBJECTIVE: In this report we describe, what is, to our knowledge, the first case of a patient with MF through advanced HIV-infection, successfully experiencing topical 5-ALA sensitization and PDT. METHODS: 5-ALA ointment was applied to plaques and held in occlusion for 4 hours. PDT was applied using the PDT 1200 irradiation source (Waldmann Medizintechnik System) with 180 J/cm superset 2. RESULTS: Complete remission of MF was achieved, after two completed cycles of photodynamic therapy. CONCLUSION: MF lesions in the presended case showed a high response to 5-ALA sensitization and PDT. This modality appeared to be very effective in treatment of MF in a HIV-infected patient and could be a valuable treatment option for cutaneous T-cell lymphoma in HIV-infected patients.

Resistance analyses in HIV infected patients with a history of multiple antiretroviral treatment regimens.

OBJECTIVE: To assess HIV-1 isolate based resistance profiles from extensively pretreated patients and effects of a resistance guided switch of antiretroviral therapy. METHODS: In a prospective study phenotypic and genotypic resistance analyses were performed on HIV infected individuals with failure of the current therapy and history of at least three antiretroviral regimens. Antiretroviral therapy was changed according to the results. Viral load and CD4 lymphocyte counts were measured at baseline, after 10 (SD 2), and 24 (2) weeks. RESULTS: All patients (n=52) failed their actual regimen. Currently versus ever previously taking the specific drug, resistance associated mutations and phenotypic resistance to AZT and 3TC were found in over 80% of individuals; resistance to DDI and D4T was detected in less than 10% of cases. A resistance guided switch of therapy was followed by a median decrease of viral load of 0.5 log10 units after 24 weeks. Individuals resistant to two or more drugs compared with patients with resistance to less than two drugs of ongoing treatment, were switched to a regimen containing DDI, D4T, and a PI or NNRTI. After 10 (SD 2) weeks viral load decrease was pronounced in patients with resistance to at least two drugs in the previous regimen. CONCLUSIONS: Among different RTI, the profile of clinically relevant resistance indicates pronounced differences when looking at separate drugs. Regarding virological response, in the context of available drugs, resistance tested with currently used methods is of limited value in extensively pretreated patients and seems to have its value primarily in first or second switch of therapy.

Characterization of Slit protein interactions with glypican-1.

We have demonstrated previously that the Slit proteins, which are involved in axonal guidance and related developmental processes in nervous tissue, are ligands of the glycosylphosphatidylinositol-anchored heparan sulfate proteoglycan glypican-1 in brain (Liang, Y., Annan, R. S., Carr, S. A., Popp, S., Mevissen, M., Margolis, R. K., and Margolis, R. U. (1999) J. Biol. Chem. 274, 17885--17892). To characterize these interactions in more detail, recombinant human Slit-2 protein and the N- and C-terminal portions generated by in vivo proteolytic processing were used in an enzyme-linked immunosorbent assay to measure the binding of a glypican-Fc fusion protein. Saturable and reversible high affinity binding to the full-length protein and to the C-terminal portion that is released from the cell membrane was seen, with dissociation constants in the 80-110 nm range, whereas only a relatively low level of binding to the larger N-terminal segment was detected. Co-transfection of 293 cells with Slit and glypican-1 cDNAs followed by immunoprecipitation demonstrated that these interactions also occur in vivo, and immunocytochemical studies showed colocalization in the embryonic and adult central nervous system. The binding affinity of the glypican core protein to Slit is an order of magnitude lower than that of the glycanated proteoglycan. Glypican binding to Slit was also decreased 80--90% by heparin (2 microg/ml), enzymatic removal of the heparan sulfate chains, and by chlorate inhibition of glypican sulfation. The differential effects of N- or O-desulfated heparin on glypican binding also indicate that O-sulfate groups on the heparan sulfate chains play a critical role in heparin interactions with Slit. Our data suggest that glypican binding to the releasable C-terminal portion of Slit may serve as a mechanism for regulating the biological activity of Slit and/or the proteoglycan.

Measurement of airborne ultrasonic slow waves in calcaneal cancellous bone.

Measurements of an airborne ultrasonic wave were made in defatted cancellous bone from the human calcaneus using standard ultrasonic equipment. The wave propagating under these conditions was consistent with a decoupled Biot slow wave travelling in the air alone, as previously reported in gas-saturated foams. Reproducible measurements of phase velocity and attenuation coefficient were possible, and an estimate of the tortuosity of the trabecular framework was derived from the high frequency limit of the phase velocity. Thus the method offers a new approach to the acoustic characterisation of bone in vitro which, in contrast to existing techniques, has the potential to yield information directly characterising the trabecular structure.

On the ultrasonic attenuation and its frequency dependence in the os calcis assessed with a multielement receiver.

Measurements of broadband ultrasound attenuation (BUA) on a single sample using different devices have previously shown significant variations. We have used a new 3x3 array transducer to allow the evaluation of three new approaches to the BUA algorithms and the extent to which the variations might be reduced. Ten human os calces were measured using the array. The attenuation and its slope, the BUA, were calculated using three methods: 1. A phase sensitive approach, summing the individual signals from the multielement array in the time domain (TD); 2. a phase insensitive approach, summing the signals in the frequency domain (FD); 3. averaging of the individually measured attenuation and BUA values (AV). The TD and AV approaches resulted in slightly larger values for both attenuation (approximately 4%) and BUA (approximately 7%) than with the FD method. The differences between the TD and FD method may be due to phase cancellation. However, the three sets of results were not significantly different (p<0.05), which suggests that measurements on commercial equipment using large receiver apertures are not strongly affected by phase cancellation, averaging or scattering. Nevertheless, it is not clear if the differences observed are of clinical relevance, which should be investigated in the future. Our study shows that the 3 approaches are strongly related (r2> or =0.94), suggesting that translation may be possible between methods.

A model for ultrasonic scattering in cancellous bone based on velocity fluctuations in a binary mixture.

A scattering model based on velocity fluctuations in a binary mixture (marrow fat and cortical matrix) was used to estimate the ultrasonic attenuation in cancellous bone as a function of volume fraction. The calculation of velocity fluctuations alone seems to be suitable for the qualitative estimation of attenuation. The predicted values of the attenuation were of the same order of magnitude as experimentally determined values from the literature. This agreement was achieved with only a small number of variables (the velocities of the two components and the scatterer size) in the model, representing a major advantage compared with other theories. Hence the suggested approach appears to be a good starting point for further theoretical investigations using scattering theories. However, this has to be accompanied by accurate ultrasonic and microstructural measurements.