RESUMEN
BACKGROUND: Polymorphous light eruption (PLE) is a very common photodermatosis in which patient history is highly specific. Phototesting is used to confirm the diagnosis and to determine the action spectrum and the severity of this disease. In daily practice and in research studies, it would be convenient to assess disease severity by patient history only. OBJECTIVES: This study aims to assess PLE disease severity via patient history and compares this with severity assessment via phototesting. PATIENTS AND METHODS: Sixty-one patients with PLE were asked 10 standard questions and all were phototested. The answers to the standard questions were coded with linear scores ranging from 0 to 10. The score of each question was plotted as independent variable in a multiple linear regression model against the score of the phototest (minimal number of irradiations necessary to elicit a positive skin lesion, with a maximum of 6 irradiations) as dependent variable using an enter approach. Furthermore, the scores of the separate questions were added to form a total score, the PLE-severity assessment score (PLE-SAS). The medians of these PLE-SASs were compared with the result scores obtained by phototesting. Phototesting was done with ultraviolet A and ultraviolet B irradiation. RESULTS: Fifty-seven of the 61 patients had a positive test result (93%). Using the multiple linear regression model, the severity assessment by patient history (PLE-SAS) compared with the result of phototesting showed two significant contributing questions (adjusted PLE-SAS) (P < 0.05) but with a regression coefficient of 0.2. A significant difference in median scores with the severity assessment (PLE-SAS and adjusted PLE-SAS) between patients testing positive after 1-3 irradiations compared with those testing positive after 4-6 irradiations was present (P < 0.05). However, the overlap quartile range between both groups was such that the PLE-SAS and the adjusted PLE-SAS have little predictive value in individual patients. CONCLUSIONS: We showed that in PLE, disease severity as determined using the PLE-SAS or adjusted PLE-SAS did not reliably predict severity as assessed by phototesting. Two significant contributing questions were not discriminating enough to be used as predicting questions to assess severity. Accurate patient history proved to be a reliable method to diagnose PLE. Phototesting is useful to determine the responsible ultraviolet action spectrum and to exclude differential diagnoses like photosensitive eczema, lupus erythematosus or chronic actinic dermatitis. PLE-SAS cannot replace phototesting for determining the severity of PLE.
Asunto(s)
Trastornos por Fotosensibilidad/diagnóstico , Índice de Severidad de la Enfermedad , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos por Fotosensibilidad/fisiopatología , Encuestas y CuestionariosRESUMEN
BACKGROUND: Photoallergic contact dermatitis can be difficult to diagnose if not appropriately investigated. Currently, the most common U.K. photoallergens appear to be sunscreen chemicals. The investigation of choice is photopatch testing (PPT), which is probably underused. In part, this is due to differences in methodology and results interpretation. OBJECTIVES: To conduct PPT using a group of sunscreen chemicals, defined indications and a standardized methodology including interpretation and relevance of reactions in patients attending for investigation at 17 centres across the U.K., Ireland and the Netherlands. METHODS: Patients (n = 1155) who fulfilled the inclusion criteria were investigated with PPT using sunscreen chemicals in addition to suspected topical products. Readings were taken at 24, 48 and 72 h following standardized ultraviolet A irradiation (5 J cm(-2)). The clinical relevance of any reaction was recorded. RESULTS: Of the 1155, 130 had allergic reactions (11.3%). Of these, 51 had photoallergy (PA) (4.4%), 64 had contact allergy (CA) (5.5%), and 15 patients had combined PA and CA (1.3%). Multiple PA was seen in some. The most common photoallergen was benzophenone-3 (27 reactions; 21%). Most reactions (60%) were clinically relevant. The most common indication for testing in patients found to have PA was a history of reacting to a sunscreen (41%). The other 59% had an exposed-site dermatitis/skin problem or a photodermatosis. Some centres (n = 8) performed readings after the standard 48-h reading, and an extra 32 PA and 22 CA reactions were detected, which were not evident at 48 h. A new photoallergen (octyl triazone) was detected in two patients. CONCLUSIONS: Sunscreen PA and CA are probably equally uncommon. Most reactions, of both reaction types, were relevant clinically. A large proportion of patients (59%) found to have PA was unaware of reacting to a sunscreen chemical, suggesting that PA should be considered as an explanation in any exposed-site dermatitis. Although this study focused on reactions at 48 h postirradiation, readings performed up to 96 h, while inconvenient, add value by detecting additional relevant responses. A previously unknown photoallergen was found, highlighting the need for awareness of novel photoallergens in the marketplace. A standardized PPT method not only encourages more use of this investigation, but also facilitates comparison of results between centres and so will improve our understanding of PA.
Asunto(s)
Dermatitis Fotoalérgica/diagnóstico , Pruebas del Parche/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alérgenos/efectos adversos , Niño , Preescolar , Dermatitis Fotoalérgica/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas del Parche/normas , Factores Sexuales , Protectores Solares/efectos adversos , Protectores Solares/química , Rayos Ultravioleta/efectos adversosRESUMEN
BACKGROUND: There is a clear relationship between ultraviolet (UV) radiation (UVR) and the clinical manifestations of patients with lupus erythematosus (LE). Cutaneous lesions are induced or exacerbated by exposure to UVR. Of patients with LE, 24-83% are reported to be photosensitive to UVR. LE tumidus appears to be the most photosensitive subtype of LE, followed by subacute cutaneous LE (SCLE). In general, the history of patients with LE correlates poorly with the presence or absence of photosensitivity, due to a delayed time interval between UV exposure and exacerbation of skin lesions. Phototesting using artificial UVR and visible light is a reliable way of diagnosing photosensitivity. OBJECTIVES: To investigate the photoreactivity of patients with various subtypes of LE using an individualized phototest protocol. The results of phototests were correlated with the history of photosensitivity, the subtype of LE, the presence of autoantibodies and the use of anti-inflammatory medication by these patients. METHODS: Phototesting with UVA, UVB and visible light was performed in 100 patients with LE. The diagnosis of LE was established both on clinical examination and skin histology. Serological studies were also performed in all patients. The phototests were performed on large skin areas of the forearm or trunk; the first dose was twice the minimal erythema dose and the dosage was increased according to the individual reactions of the patients at the test sites. Follow-up of skin reactions at the test sites was performed for up to 2 months. Histological examination of the photoprovoked skin lesions was carried out in 57 patients. RESULTS: Of the 100 patients included (81 women and 19 men; mean age 41 years, range 17-79), 46 had chronic discoid LE, 30 SCLE and 24 systemic LE. An abnormal reaction to UVR and visible light was found in 93% of our patients with LE. No clinical or histological evidence at the phototest sites of polymorphic light eruption was found. There was no correlation between photosensitivity and LE subtype, presence of autoantibodies or medical history. Concomitant use of anti-inflammatory medication seemed to exert only minimal influence on the results of phototesting. CONCLUSIONS: When using an extended phototesting protocol, almost all patients with LE in this study showed clinical and histological evidence of aberrant photosensitivity. Therefore, patients with LE should receive thorough advice and instruction on photoprotective measures, regardless of their history, LE subtype or presence of autoantibodies.
Asunto(s)
Lupus Eritematoso Cutáneo/complicaciones , Lupus Eritematoso Sistémico/complicaciones , Trastornos por Fotosensibilidad/etiología , Adolescente , Adulto , Anciano , Antiinflamatorios/uso terapéutico , Femenino , Glucocorticoides/uso terapéutico , Humanos , Lupus Eritematoso Cutáneo/tratamiento farmacológico , Lupus Eritematoso Discoide/complicaciones , Lupus Eritematoso Discoide/tratamiento farmacológico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Trastornos por Fotosensibilidad/diagnóstico , Prednisona/uso terapéutico , Estudios Retrospectivos , Pruebas Cutáneas/métodos , Rayos UltravioletaRESUMEN
BACKGROUND: Most clinical studies using photodynamic therapy (PDT) with topical application of delta-aminolaevulinic acid (delta-ALA) use red light because it allows greater depth of penetration. However, given the porphyrin-like spectrum of delta-ALA-induced photosensitivity, violet light provides a maximal overlap with the excitation spectrum of protoporphyrin IX, meaning that PDT with violet light uses less light energy to induce the phototoxic reaction. AIM: To study the efficacy of violet light in combination with topical delta-ALA PDT in the treatment of pre-malignant and malignant skin lesions. METHODS: Eight hours after 20% delta-ALA was applied topically, photoirradiation was performed with an incoherent light source (Philips HPM-10, 400 W) emitting predominantly violet light (400-450 nm). Lesions received 10-20 J/cm2 during an exposure time of 30 min. The 38 subjects treated included three with basal cell naevus syndrome with multiple (> 30) superficial and nodular basal cell carcinomas (BCCs), one subject had multiple lesions of Bowen's disease, involving 50% of the scalp, and the remaining 34 subjects presented a total of 35 superficial BCCs, 10 nodular BCCs, four large solar keratoses and five solitary lesions of Bowen's disease. RESULTS: Complete remission both clinically and histologically was seen after a single treatment in 82% of the superficial BCCs (100% after a second treatment), 50% of the nodular BCCs, one of the four solar keratosis lesions (partial remission in the other three) and 90-100% of the solitary lesions of Bowen's disease. CONCLUSIONS: delta-ALA PDT using violet light appears to be a well tolerated and effective alternative treatment for premalignant and malignant skin lesions, especially when there are multiple lesions or large patches comprising a large area of skin.
Asunto(s)
Enfermedad de Bowen/tratamiento farmacológico , Carcinoma Basocelular/tratamiento farmacológico , Queratosis/tratamiento farmacológico , Fotoquimioterapia/métodos , Neoplasias Cutáneas/tratamiento farmacológico , Administración Tópica , Adulto , Anciano , Anciano de 80 o más Años , Ácido Aminolevulínico/administración & dosificación , Enfermedad de Bowen/diagnóstico , Carcinoma Basocelular/diagnóstico , Femenino , Estudios de Seguimiento , Humanos , Queratosis/diagnóstico , Masculino , Persona de Mediana Edad , Fármacos Fotosensibilizantes/administración & dosificación , Neoplasias Cutáneas/diagnóstico , Resultado del Tratamiento , Terapia UltravioletaRESUMEN
AIM: To assess the retinal phototoxicity hazards of and to provide safety margins for endoillumination during vitrectomy. METHODS: The absolute power and spectral distribution from various light sources and filter combinations that are commercially available for vitreous surgery were measured. The maximal exposure times based on the ICNIRP safety guidelines for photochemical and thermal injury of the aphakic eye were calculated. Additionally, the effect of various measures that reduce the risk of phototoxicity was evaluated. RESULTS: Measurements of the spectrum and energy indicated that the ICNIRP safety guidelines for photochemical retinal damage are exceeded within 1 minute for nine out of 10 combinations tested. With an additional 475 nm long pass filter, light levels below 10 mW, and a distance from light probe to retina of at least 10 mm, the allowable exposure time can be increased up to 13 minutes. Thermal damage can be anticipated when the light probe touches the retina. CONCLUSION: Commercially available light sources for endoillumination during vitrectomy are not safe with respect to photochemical retinal damage. Even with maximal precautions macular phototoxic damage remains a factual danger during vitrectomy.
Asunto(s)
Iluminación/efectos adversos , Traumatismos por Radiación/etiología , Retina/efectos de la radiación , Vitrectomía , Calor/efectos adversos , Humanos , Periodo Intraoperatorio , Iluminación/métodos , Guías de Práctica Clínica como Asunto , Dosis de Radiación , Traumatismos por Radiación/prevención & controlRESUMEN
AIMS: To evaluate the efficacy of bath psoralen-ultraviolet A (PUVA) therapy in severe cases of atopic dermatitis (AD) in adults using the extended Six Area, Six Sign Atopic Dermatitis (SASSAD) score. METHODS: Thirty-five adult subjects with severe AD underwent bath PUVA therapy for a maximum of 30 sessions ranging from one to three times a week. The only other treatment allowed during the study was topical application of hydrocortisone. RESULTS: There were a total of six drop-outs, three due to aggravation of symptoms. After the maximum 30 sessions the remaining 29 subjects showed 82.1% improvement in the severity of lesions, 75.2% reduction in extension of lesions, 74% improvement in itching and 79% improvement in night-time rest. Patient evaluations gave an overall score of 8.8 on a scale of 0-10.
Asunto(s)
Dermatitis Atópica/tratamiento farmacológico , Terapia PUVA/métodos , Adolescente , Adulto , Anciano , Baños , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pacientes Desistentes del Tratamiento , Satisfacción del Paciente , Proyectos PilotoRESUMEN
BACKGROUND: Polymorphous light eruption is a common chronic idiopathic photodermatosis. The action spectrum and therapy are under debate. OBJECTIVE: The aim of the study was to analyze the clinical aspects of this dermatosis, the photodiagnostic tests, and the results of therapy in an academic center. METHODS: To obtain a reasonable follow-up period, we examined all available data of the patients who underwent diagnostic phototests in the period 1985 through 1991. Our procedure of phototesting included determination of minimal erythema doses, photoprovocation tests, and photopatch tests. The evaluation of the effect of the therapy was based on the patients' experiences, time spent outdoors, and amount of sun exposure. RESULTS: Our collection included data on 35 men and 75 women. The age at onset differed significantly between men and women (averages 46 and 28 years, respectively; P <.01). The minimal erythema doses for UVB were lowered in 43% of the men and in 4% of the women (P <.01); the minimal erythema doses for UVA were lowered in 37% of the men and in 11% of the women (P <.01). The photoprovocation tests showed a pathologic reaction to both UVB and UVA in 88% of the men and in 52% of the women (P <.01). In the remaining patients we found pathologic reactions to UVB alone (for men 9%, for women 24%; P >.05) or UVA alone (for men 3%, for women 24%; P <.01). The abnormal reactions to visible light were almost exclusively observed in those patients who reacted pathologically to both UVB and UVA (43% of the male patients, 11% of the female patients; P <.01). The photopatch tests showed a large number of positive test results, mainly to skin care products or sunscreens (75% of all patients). The 70 most sensitive patients (64%) were treated with prophylactic UVB therapy 2 or 3 times a week at home or initially in the outpatient department. This treatment was normally done from February to June, but in severe cases throughout the whole year. CONCLUSION: Phototests revealed abnormal reactions to UVB as well as UVA and to some extent also to visible light. Prophylactic UVB therapy is a successful treatment for polymorphous light eruption.
Asunto(s)
Trastornos por Fotosensibilidad/patología , Rayos Ultravioleta , Adulto , Edad de Inicio , Anciano , Dermatitis por Contacto , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pruebas del Parche , Trastornos por Fotosensibilidad/diagnóstico , Trastornos por Fotosensibilidad/terapia , Estudios Retrospectivos , Factores Sexuales , Protectores Solares , Terapia UltravioletaRESUMEN
After ultraviolet exposure Langerhans cells (epidermal CD1a+ cells) disappear from the healthy skin, and CD11b+ macrophage-like cells, which are reported to produce interleukin-10, appear in a matter of days. These phenomena are related to the ultraviolet-induced local suppression of contact hypersensitivity reactions. A defect in this suppression might allow inadvertent immune reactions to develop after ultraviolet (over)exposure; i.e., it could cause ultraviolet-B-induced polymorphous light eruption. In order to test this we first exposed buttock skin of eight healthy volunteers to six minimal erythema doses from Philips TL12 lamps, and indeed observed a dramatic disappearance of CD1a+ cells 48 and 72 h later, at which time the number of CD11b+ cells increased in the dermis, and some occurred in the epidermis. The epidermis thickened and showed large defects, filled by CD11b+ cells, just below the stratum corneum. In 10 patients with polymorphous light eruption (five with a normal minimal erythema dose and five with a low minimal erythema dose) CD1a+ cells were present in the epidermis as well as in the dermis before exposure. Strikingly, these cells were still present in considerable number at 48 and 72 h after exposure to six minimal erythema doses. CD11b+ cells already present in the dermis before ultraviolet exposure, increased after ultraviolet exposure, and subsequently also invaded the epidermis. Despite the six minimal erythema doses, there were no apparent defects in the epidermis of the polymorphous light eruption patients. This deviant early response to ultraviolet radiation is likely to be of direct relevance to the polymorphous light eruption and is perhaps useful as a diagnostic criterion.
Asunto(s)
Antígenos CD1/análisis , Antígeno de Macrófago-1/análisis , Trastornos por Fotosensibilidad/patología , Piel/efectos de la radiación , Adulto , Anciano , Anciano de 80 o más Años , Células Epidérmicas , Epidermis/química , Epidermis/efectos de la radiación , Femenino , Humanos , Inmunohistoquímica , Células de Langerhans/química , Células de Langerhans/citología , Células de Langerhans/efectos de la radiación , Macrófagos/química , Macrófagos/citología , Macrófagos/efectos de la radiación , Masculino , Persona de Mediana Edad , Trastornos por Fotosensibilidad/metabolismo , Dosis de Radiación , Piel/química , Piel/citología , Rayos UltravioletaRESUMEN
BACKGROUND: Sun exposure has a beneficial effect on acne vulgaris, but it is not clear which wavelengths contribute to the favourable effect. OBJECTIVE: The aim of the study was to investigate the effect of visible light on acne vulgaris and define the most effective wavelengths. METHODS: Thirty patients (15 men and 15 women) with mild to moderate acne vulgaris, involving the face and/or the back and/or the chest, were treated with three different light sources. They were treated 3 times a week, for a total of 7 weeks, each field for 20 min per session. RESULTS: All the light sources using 'full spectrum', green and violet improved the acne, leading to 14% (p > 0.10), 22% (p < 0.05) and 30% (p < 0.02) improvement, respectively. No statistically significant differences between the three different light sources were found, although there was a tendency that violet light was better than the other light qualities. No side-effects were observed. CONCLUSION: Visible light is a moderately effective alternative for treatment of acne vulgaris.
Asunto(s)
Acné Vulgar/terapia , Fototerapia , Acné Vulgar/patología , Adolescente , Adulto , Dorso , Color , Dermatosis Facial/patología , Dermatosis Facial/terapia , Femenino , Humanos , Luz , Masculino , Pacientes Desistentes del Tratamiento , Satisfacción del Paciente , Fototerapia/métodos , Dosis de Radiación , Inducción de Remisión , TóraxRESUMEN
Ultraviolet B (UVB) light is known to be immunosuppressive, but, probably because of a small UVC component in the emission spectra of some of the UVB lamps used, reports vary on effective dose levels. To prevent potentially lethal graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation, alloreactive donor T-cell activity must be suppressed. In this study, a narrow wavelength UVB lamp (TL01, 312 nm peak emission) was used to determine what doses of UVB were required to abolish rat lymphocyte proliferation while simultaneously preserving rat bone marrow progenitor cell and primitive hematopoietic stem cell viability. Lymphocyte proliferation, as measured by 3H-Thymidine incorporation, in response to lectin stimulation was abolished below detection at doses greater than 3,500 J/m2. When T-cell clonogenicity was measured in a limiting dilution assay, a small fraction (0.6%) was maintained at doses up to 4,000 J/m2. Cytotoxic T-lymphocyte (CTL) activity was reduced after treatment with 4,000 J/m2, but a significant level of cytotoxicity was still maintained. Natural killer cell cytolytic activity was not affected by doses up to 4,000 J/m2. At 4,000 J+m2 there was a 10% survival of colony-forming units-granulocyte-macrophage; a 1% and 4% survival of day-8 and day-12 colony-forming units-spleen, respectively; and 11% survival of marrow repopulating ability cells. Up to 25% of late cobblestone area forming cells (4 to 5 weeks), reflecting the more immature hematopoietic stem cells, were preserved in bone marrow treated with 4,000 J/m2, indicating that early stem cells are less sensitive to UVB damage than are more committed progenitor cells. Thus, a potential therapeutic window was established at approximately 4,000 J/m2 using this light source, whereby the potentially GVHD-inducing T cells were suppressed, but a sufficient proportion of the cells responsible for engraftment was maintained.
Asunto(s)
Médula Ósea/efectos de la radiación , Activación de Linfocitos/efectos de la radiación , Linfocitos/efectos de la radiación , Animales , Supervivencia Celular/efectos de la radiación , Citotoxicidad Inmunológica/efectos de la radiación , Relación Dosis-Respuesta a Droga , Hematopoyesis/efectos de la radiación , Células Madre Hematopoyéticas/efectos de la radiación , Inmunidad Celular , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Ratas , Ratas Endogámicas BN , Rayos UltravioletaRESUMEN
We have earlier reported on determining UV-induced DNA damage in murine epidermal cell suspensions by flow cytometric analysis of the fluorescence from a fluorescein isothiocyanate-labeled antibody (H3) directed against thymine dimers (T < > T). Here we present an optimization of the technique for analysis of epidermal cell suspensions from 4 mm biopsies from human skin. Cells with different DNA contents can easily be distinguished in flow cytometry by the intensity of DNA-specific 7-amino-actinomycin D fluorescence. Genuine G2-M-phase cells can further be distinguished from cell doublets by pulse-shape discrimination. Thus, T < > T levels in individual cells with different DNA contents (i.e. G0-G1, S or G2-M phases) can be determined after in vivo exposure of human skin to environmentally relevant UVB (280-315 nm) doses. The method was applied to measure the decrease of T < > T in nonreplicating cells (G0-G1 phase) and replicating cells (S phase or G2-M phase) from seven volunteers exposed to twice their minimal erythema dose. The reduction in the average T < > T-specific fluorescence at 24 h after exposure was 46% (ranging between 16% and 66%) for the G0-G1 cells and 70% (ranging between 37% and 100%) for the S + G2-M cells. The difference was statistically highly significant. Determination of individual DNA repair capacities with this method can become a convenient diagnostic tool for patients with DNA repair disorders, or it may even be used to identify individuals with low repair proficiencies and increased risk of developing skin cancers.
Asunto(s)
Dímeros de Pirimidina/metabolismo , Dímeros de Pirimidina/efectos de la radiación , Piel/metabolismo , Piel/efectos de la radiación , Rayos Ultravioleta/efectos adversos , División Celular/fisiología , División Celular/efectos de la radiación , Daño del ADN , Citometría de Flujo , Humanos , Técnicas In Vitro , Piel/citologíaRESUMEN
UV-induced DNA damage in mononuclear leucocytes can be quantified by flow cytometry of fluorescence from a labelled monoclonal antibody that specifically binds to thymine dimers (T<-->T): specific fluorescence is already detectable after exposures of 1-2 J m-2 of 254 nm radiation and shows a linear relationship with dose. The distribution of UV fluences over an irradiated volume can thus be ascertained by measuring the UV-induced T<-->T loads of the individual cells from that volume. After irradiation of mononuclear cells in a phosphate buffer solution in a Petri dish, most cells showed a similar intensity of specific T<-->T fluorescence, forming a single sharp peak in the fluorescence histogram. This signifies an even distribution of fluences over the cells. It was noticed, however, that a variable minor fraction of mononuclear cells (usually less than 10%) could be resistant to immunostaining; this fraction was rejected from the calculation of the specific fluorescence. The flow cytometric technique was also applied to blood cells exposed in an ISOLDA device, which is in use in Russian clinics for UV irradiation of whole blood for therapeutical purposes. Only a small fraction of mononuclear cells in a sample of whole blood treated in ISOLDA acquired a detectable T<-->T load after exposure to lamps which emit predominantly either UVC or UVB light ((3.6 +/- 1.0)% and (1.8 +/- 0.4)% of all analysed cells respectively). This small fraction had received a large variation in fluences, resulting in differences in nuclear T<-->T loads by a factor of 200.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Daño del ADN , Leucocitos Mononucleares/efectos de la radiación , Dímeros de Pirimidina/análisis , Rayos Ultravioleta , Sangre/efectos de la radiación , Citometría de Flujo/métodos , Humanos , Técnicas In Vitro , Leucocitos Mononucleares/metabolismo , Microscopía Fluorescente/métodosRESUMEN
Exposure of platelet concentrates (PCs) to ultraviolet B radiation (UVB) has been advocated as an alternative method for prevention of the onset of HLA sensitization in recipients. In this study, pooled PCs were irradiated in a Haemonetics UV irradiator (Haemonetics Corp, Braintree, MA) at a dose that did not induce platelet activation. The effect of UVB irradiation on prevention of primary HLA sensitization was evaluated in a prospective controlled clinical study performed in cardiac patients undergoing cardiopulmonary bypass. Patients were treated with filtered red blood cells and a single transfusion of either standard (control group) or UVB-irradiated (UVB group) pooled platelets prepared from 12 donors. Five of 39 patients in the control group and 6 of 62 patients in the UVB group developed allo-antibodies against HLA antigens, which is not significantly different (P = .62). This unexpected finding prompted us to check the efficacy of UVB irradiation. We determined UVB-specific DNA damage in cells by measuring the fluorescence from a labeled specific monoclonal antibody against thymine dimers. With this novel flow cytometer technique, we estimated in UVB-irradiated leukocytes in saline that a mean fluorescence intensity (MFI) of 47 +/- 2 arbitrary units (n = 6) correlated with abolition of alloreactivity in mixed lymphocyte cultures and delayed cell death (within 72 hours). MFI in leukocytes suspended in plasma and exposed to the clinical dose of UVB was sixfold higher (310 +/- 41 arbitrary units) and resulted in early cell death (within 24 hours). We hypothesize that this high level of UVB radiation induces fragmentation of the leukocytes. As a consequence, the poor results of UVB irradiation may be explained by the onset of HLA-alloimmunization induced by soluble donor HLA class I antigens processed and presented by host antigen-presenting cells.
Asunto(s)
Plaquetas/inmunología , Plaquetas/efectos de la radiación , Antígenos HLA/inmunología , Isoanticuerpos/sangre , Transfusión de Plaquetas , Rayos Ultravioleta , Supervivencia Celular , Puente de Arteria Coronaria , Daño del ADN , Prótesis Valvulares Cardíacas , Humanos , Leucocitos/inmunología , Leucocitos/efectos de la radiación , Prueba de Cultivo Mixto de Linfocitos , Masculino , Activación Plaquetaria , Transfusión de Plaquetas/efectos adversosRESUMEN
Ultraviolet B (UVB) irradiation of platelet concentrates (PCs) has been proposed as a novel technology to prevent HLA sensitization. We have recently reported that 2 J/cm2 of UVB radiation abolishes alloreactive lymphocyte responses in vitro. In order to increase the efficacy of UV irradiation for the prevention of HLA sensitization, we exposed PCs to 4 or 8 J/cm2 of UVB and evaluated the effect of UV radiation on platelet integrity during storage. We report here that UV exposed platelets show a progressive increase in the expression of activation markers P-selectin (GMP-140; CD62) and LIMP-CD63 (GP-53; CD63) on the platelet membrane over time in a dose-dependent manner compared to age-matched controls. Platelet metabolism was also enhanced as evidenced by significant changes in lactate and pH during post-irradiation storage. Based on these findings we transfused PCs within 4 h after UV irradiation. PCs exposed to 4 J/cm2 showed normal post-transfusion recoveries and haemostatic functions, while poor platelet recoveries were found after administration of PCs exposed to 8 J/cm2. We hypothesize that the rapid expression of P-selectin on platelets exposed to the higher dose of UVB leads to an increased binding of these platelets to leucocytes in the circulation resulting in poor platelet recoveries.
Asunto(s)
Plaquetas/efectos de la radiación , Conservación de la Sangre , Activación Plaquetaria/efectos de la radiación , Rayos Ultravioleta , Antígenos CD/análisis , Transfusión de Componentes Sanguíneos , Plaquetas/inmunología , Relación Dosis-Respuesta en la Radiación , Humanos , Selectina-P , Glicoproteínas de Membrana Plaquetaria/análisis , Transfusión de Plaquetas , Tetraspanina 30 , Trombocitopenia/sangre , Trombocitopenia/terapiaRESUMEN
Information on the variation in carcinogenicity with wavelength is crucial in risk assessments for skin cancers induced by UV radiation. Until recently the wavelength (lambda) dependencies of other detrimental UV effects, such as sunburn, have been used as substitutes. Direct information on the lambda dependency can only be obtained from animal experiments. To this end we accumulated a large data set on skin tumors induced by chronic UV exposure of albino SKH:HR1 mice (14 different broadband UV sources and about 1100 mice); the data come from the Photobiology Unit of the former Skin and Cancer Hospital in Philadelphia and from the Department of Dermatology of the University of Utrecht. The lambda dependency was extracted from this data set (a statistically satisfactory description with chi 2 = 13.4, df = 7) and represented by the Skin Cancer Utrecht-Philadelphia action spectrum, i.e., a set of factors to weight the exposures at different wavelengths according to their respective effectiveness (inversely proportional to the daily exposure required for a median tumor induction time of 300 days). The fits obtained with other already available action spectra proved to be poor (chi 2 > 60, df = 11). The maximum effectiveness was found at 293 nm, and above 340 nm the effectiveness showed a shoulder at about 10(-4) of the maximum. A sensitivity analysis of the final solution for the lambda dependency showed a large margin of uncertainty above 340 nm and an information gap below 280 nm. The large variation in tumor responses in the present data set can be transformed to a coherent, common dose-response relationship by proper spectral weighting with this single action spectrum.
Asunto(s)
Neoplasias Inducidas por Radiación/etiología , Neoplasias Cutáneas/etiología , Rayos Ultravioleta/efectos adversos , Animales , Relación Dosis-Respuesta en la Radiación , Femenino , Masculino , Cómputos Matemáticos , Ratones , Ratones Pelados , Modelos Biológicos , Espectrofotometría Ultravioleta/métodosRESUMEN
The photodermatosis in erythropoietic protoporphyria (EPP) is caused by the accumulation of photosensitizing protoporphyrin (PP) in the skin, due to a defect in ferrochelatase, the enzyme that inserts ferrous iron into PP to form heme. Hydroxyl radical (.OH) and singlet oxygen generation with subsequent lipid peroxidation are thought to play a major role in the pathogenesis of the photodermatosis in EPP. Hydrogen peroxide (H2O2) can generate .OH in the Haber-Weiss as well as the Fenton reaction, and is thus a potentially harmful intermediate in the photoreduction of O2. The use of oxyradical scavengers, such as beta-carotene, has been reported to be beneficial in the treatment of EPP photodermatosis. In this study, N-acetylcysteine (NAC) 1800 mg/day was used for 3 reasons: (i) its -SH groups directly scavenge H2O2; (ii) ferrochelatase can be activated by sulfhydryl groups; (iii) NAC was reported to upregulate the glutathione redox system, which is a major endogenous anti-oxidant system. However, in a double-blind crossover placebo controlled study on 6 EPP patients, we could neither demonstrate an effect through photosensitivity tests, nor on light hypersensitivity as reported by the patients. This dosage of NAC could not increase reduced glutathione and did not affect the red blood cell PP content nor the excretion of PP in the feces. Neither were adverse effects observed. We conclude that the oral administration of NAC, in the relatively low dose used here, is not effective in the treatment of photodermatosis in EPP.