RESUMO
Models describing dengue epidemics are parametrized on disease incidence data and therefore high-quality data are essential. For Thailand, two different sources of long-term dengue data are available, the hard copy data from 1980 to 2005, where hospital admission cases were notified, and the electronic files, from 2003 to the present, where clinically classified forms of disease, i.e. dengue fever, dengue haemorrhagic fever, and dengue shock syndrome, are notified using separate files. The official dengue notification data, provided by the Bureau of Epidemiology, Ministry of Public Health in Thailand, were cross-checked with dengue data used in recent publications, where an inexact continuous time-series was observed to be consistently used since 2003, affecting considerably the model dynamics and its correct application. In this paper, numerical analysis and simulation techniques giving insights on predictability are performed to show the effects of model parametrization by using different datasets.
Assuntos
Bases de Dados Factuais , Dengue/epidemiologia , Modelos Estatísticos , Dengue/diagnóstico , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Prevalência , Sensibilidade e Especificidade , Dengue Grave/diagnóstico , Dengue Grave/epidemiologia , Tailândia/epidemiologiaRESUMO
Darier disease (DD) is an autosomal-dominant skin disorder characterized by loss of adhesion between epidermal cells (acantholysis) and abnormal keratinization. Recently we constructed a 2.4-Mb, P1-derived artificial chromosome contig spanning the DD candidate region on chromosome 12q23-24.1. After screening several genes that mapped to this region, we identified mutations in the ATP2A2 gene, which encodes the sarco/endoplasmic reticulum Ca2(+)-ATPase type 2 isoform (SERCA2) and is highly expressed in keratinocytes. Thirteen mutations were identified, including frameshift deletions, in-frame deletions or insertions, splice-site mutations and non-conservative missense mutations in functional domains. Our results demonstrate that mutations in ATP2A2 cause DD and disclose a role for this pump in a Ca(2+)-signalling pathway regulating cell-to-cell adhesion and differentiation of the epidermis.
Assuntos
ATPases Transportadoras de Cálcio/genética , Doença de Darier/genética , Mutação , ATPases Transportadoras de Cálcio/metabolismo , Feminino , Regulação da Expressão Gênica , Humanos , Isoenzimas/genética , Isoenzimas/metabolismo , Queratinócitos/fisiologia , Masculino , Dados de Sequência MolecularRESUMO
Previously, we have shown that pyruvate kinase, liver and red cell isoform (PKLR) deficiency protects mice in vivo against blood-stage malaria, and observed that reduced PKLR function protects human erythrocytes against Plasmodium falciparum replication ex vivo. Here, we have sequenced the human PKLR gene in 387 individuals from malaria-endemic and other regions in order to assess genetic variability in different geographical regions and ethnic groups. Rich genetic diversity was detected in PKLR, including 59 single-nucleotide polymorphisms and several loss-of-function variants (frequency 1.5%). Haplotype distribution and allele frequency varied considerably with geography. Neutrality testing suggested positive selection of the genein the sub-Saharan African and Pakistan populations. It is possible that such positive selection involves the malarial parasite.
Assuntos
Eritrócitos/enzimologia , Polimorfismo de Nucleotídeo Único , Piruvato Quinase/genética , Sequência de Aminoácidos , Ordem dos Genes , Haplótipos , Humanos , Desequilíbrio de Ligação , Malária/enzimologia , Malária/genética , Modelos Moleculares , Dados de Sequência Molecular , Conformação Proteica , Piruvato Quinase/química , Alinhamento de SequênciaRESUMO
Retinoic acid early transcripts-1 (RAET1) or unique long 16 (UL-16) binding proteins (ULBPs) is a gene cluster encoding for molecules acting as ligands to natural killer group 2 D (NKG2D), a receptor expressed on immune cells. Binding of these ligands to the receptor activates immune cells leading to killing of tumor cells and also viral-infected cells. The information on polymorphism of RAET1 is limited. In this report, we analyze the linkages between four polymorphic RAET1 genes: RAET1E, RAET1G, RAET1H and RAET1L, in 318 unrelated Thais. The strongest linkage disequilibrium was found between RAET1E and RAET1G, with P-value, D' and r(2) of <5.0 x 10(-5), 0.707 and 0.840, respectively. RAET1E(*)001 was found to be in linkage disequilibrium with RAET1G(*)002, and RAET1E(*)002 with RAET1G(*)001. Evidently, there were possible RAET1 haplotypes with haplotype frequencies of more than 10% consisting of RAET1E(*)001; RAET1G(*)002; RAET1H(*)001; RAET1L(*)001 and RAET1E(*)002; RAET1G(*)001; RAET1H(*)002; RAET1L(*)003. This study provides basic information on polymorphisms of RAET1 and possible RAET1 haplotypes in Thais.
Assuntos
Proteínas de Transporte/genética , Antígenos de Histocompatibilidade Classe I/genética , Desequilíbrio de Ligação , Proteínas de Membrana/genética , Polimorfismo Genético/genética , Humanos , TailândiaRESUMO
Using a metagenomics approach, we have determined the first full-length genome sequence of a human parechovirus type 15 (HPeV15) strain, isolated from a child with acute flaccid paralysis and co-infected with EV-A71. HPeV15 is a rarely reported type. To date, no full-length genome sequence of HPeV15 is available in the GenBank database, where only limited VP1 sequences of this virus are available. Pairwise comparisons of the complete VP1 nucleotide and deduced amino acid sequences revealed that the study strain belongs to type 15 as it displayed 79.6% nucleotide and 93.4% amino acid identity with the HPeV15 prototype strain. Comparative analysis of available genomic regions and phylogenetic analysis using the P2 and P3 coding regions revealed low nucleotide identity to HPeV reference genomes. Phylogenetic and similarity plot analyses showed that genomic recombination events might have occurred in the UTRs and nonstructural region during HPeV15 evolution. The study strain has high similarity features with different variants of HPeV3 suggesting intertypic recombination. Our data contributes to the scarce data available on HPeVs in Africa and provides valuable information for future studies that aim to understand the evolutionary history, molecular epidemiology or biological and pathogenic properties of HPeV15.
Assuntos
Genoma Viral/genética , Paralisia/genética , Parechovirus/genética , Sequenciamento Completo do Genoma , Genômica , Humanos , Metagenômica/métodos , Anotação de Sequência Molecular , Fases de Leitura Aberta/genética , Paralisia/virologia , Parechovirus/isolamento & purificação , Parechovirus/patogenicidade , Análise de Sequência de DNARESUMO
OBJECTIVES: The long-term non-progressors (LTNPs) are a heterogeneous group of HIV-positive individuals characterized by their ability to maintain high CD4+ T-cell counts and partially control viral replication for years in the absence of antiretroviral therapy. The present study aims to identify host single nucleotide polymorphisms (SNPs) associated with non-progression in a cohort of 352 individuals. METHODS: DNA microarrays and exome sequencing were used for genotyping about 240 000 functional polymorphisms throughout more than 20 000 human genes. The allele frequencies of 85 LTNPs were compared with a control population. SNPs associated with LTNPs were confirmed in a population of typical progressors. Functional analyses in the affected gene were carried out through knockdown experiments in HeLa-P4, macrophages and dendritic cells. RESULTS: Several SNPs located within the major histocompatibility complex region previously related to LTNPs were confirmed in this new cohort. The SNP rs1127888 (UBXN6) surpassed the statistical significance of these markers after Bonferroni correction (q = 2.11 × 10-6). An uncommon allelic frequency of rs1127888 among LTNPs was confirmed by comparison with typical progressors and other publicly available populations. UBXN6 knockdown experiments caused an increase in CAV1 expression and its accumulation in the plasma membrane. In vitro infection of different cell types with HIV-1 replication-competent recombinant viruses caused a reduction of the viral replication capacity compared with their corresponding wild-type cells expressing UBXN6. CONCLUSIONS: A higher prevalence of Ala31Thr in UBXN6 was found among LTNPs within its N-terminal region, which is crucial for UBXN6/VCP protein complex formation. UBXN6 knockdown affected CAV1 turnover and HIV-1 replication capacity.
Assuntos
Proteínas Adaptadoras de Transporte Vesicular/genética , Proteínas Relacionadas à Autofagia/genética , Progressão da Doença , Estudos de Associação Genética , Infecções por HIV/genética , Polimorfismo de Nucleotídeo Único , Caveolina 1/genética , Estudos de Coortes , Células Dendríticas/virologia , Frequência do Gene , Técnicas de Silenciamento de Genes , Infecções por HIV/virologia , Sobreviventes de Longo Prazo ao HIV , HIV-1 , Células HeLa , Humanos , Macrófagos/virologia , Análise de Sequência com Séries de Oligonucleotídeos , Fenótipo , Sequenciamento do ExomaRESUMO
The expression of telomerase, a ribonucleoprotein complex, is necessary to overcome cellular senescence, and it is associated with immortal cells and cancer. However, its role in precancerous lesions such as oral leukoplakias is less known. The purpose of this study is to investigate the presence of telomerase activity in oral leukoplakia and the relationship between the enzyme and multistep tumorigenesis. Telomerase activity was detectable in 14 of 16 human head and neck squamous cell carcinomas and 10 of 26 oral leukoplakia tissues. We also showed that the expression of telomerase in the premalignant lesions was associated with phenotypic progression, the degree of dysplasia. These results indicate that telomerase is activated frequently during the late stage of oral premalignancy and may play a crucial role in head and neck squamous cell carcinogenesis.
Assuntos
Carcinoma de Células Escamosas/enzimologia , Neoplasias de Cabeça e Pescoço/enzimologia , Leucoplasia Oral/enzimologia , Telomerase/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases , Carcinoma de Células Escamosas/patologia , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Leucoplasia Oral/patologia , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Lesões Pré-Cancerosas/enzimologia , Lesões Pré-Cancerosas/patologiaRESUMO
Epidermal naevi are localized malformations of the epidermis consisting of verrucoid scaly papules and plaques following Blaschko's lines. Genetic mosaicism has been proposed to underlie the development of linear epidermal naevi. Rarely, epidermal naevi show acantholytic histology similar to Darier's disease, a dominantly inherited skin condition characterized by widespread warty papules. As patients with acantholytic dyskeratotic naevi often give a history of worsening after sun exposure and the lesions are typical of Darier's disease, numerous authors have proposed that these patients have segmental Darier's disease. The postulated relationship has not been proven, however. Recently, we identified ATP2A2, which encodes the sarco/endoplasmic reticulum Ca(2+) ATPase isoform 2 as the defective gene in Darier's disease. In this report, we investigated the involvement of ATP2A2 in acantholytic dyskeratotic naevi following Blaschko's lines in two patients. We identified a nonsense mutation (Y894X) in the first patient and a nonconservative glycine to arginine mutation at codon 769 (G769R) in the other patient. These mutations were present in affected skin, and were not detected in unaffected skin or in leukocytes. We conclude that acantholytic dyskeratotic naevi can arise from a somatic mutation in ATP2A2. These individuals are mosaics for the mutation, but the risk of transmission of generalized Darier's disease will depend on whether the germline is affected. Our findings provide further evidence that Blaschko's lines do reflect genetic mosaicism and that the term acantholytic dyskeratotic naevus might be replaced in the future by segmental Darier's disease induced by postzygotic mosaicism. J Invest Dermatol 115:1144-1147 2000
Assuntos
ATPases Transportadoras de Cálcio/genética , Doença de Darier/genética , Adulto , Códon sem Sentido , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mosaicismo/genéticaRESUMO
BACKGROUND: The facial disfigurement produced by orofacial granulomatosis causes enormous embarrassment. None of the many therapies recommended is reliably successful. Oral corticosteroids cause significant side effects and repeated injections of small quantities of triamcinolone are painful. We have injected large volumes of triamcinolone after numbing the lips using nerve block anesthesia. OBSERVATIONS: Nine patients (six males and three females, aged 10 to 47 years) with orofacial granulomatosis were investigated. No evidence of an allergic cause was found using patch or contact urticaria tests. Eating chocolate produced lip swelling in one man, and his lip shrank in size after avoiding this for 12 months. Five patients, aged 10 to 24 years, were treated with high-volume intralesional triamcinolone injections (3 to 10 mL of 10 mg/mL) after first numbing the lips using infraorbital nerve branch and mental nerve block. After 6 weeks, the lip size returned to normal in four patients and was reduced in a fifth. One patient was injected on four occasions over a 2-year period; in four other patients treated once, lip size remained reduced for over 10 months. CONCLUSION: Intralesional triamcinolone reduces lip swelling in patients with orofacial granulomatosis. Numbing the lips by nerve block anesthesia before triamcinolone injection enables adequate volumes and repeated injections to be given painlessly.
Assuntos
Síndrome de Melkersson-Rosenthal/tratamento farmacológico , Bloqueio Nervoso , Dor/prevenção & controle , Triancinolona/administração & dosagem , Adolescente , Adulto , Criança , Feminino , Humanos , Injeções Intralesionais/efeitos adversos , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Triancinolona/uso terapêuticoRESUMO
We report a 39-year-old female patient who developed pruritic erythematous telangiectatic patches with scaly follicular papules on the neck and upper chest for 4 years. Ten per cent potassium hydroxide preparation of skin scrapings revealed Demodex folliculorum. Histology showed three Demodex mites in one of the hair follicles. She was treated with a topical steroid without improvement. The skin lesions and Demodex mite disappeared after a single application of 1 per cent gamma benzene hexachloride but twice daily application of 1 per cent gamma benzene hexachloride for 2 weeks was needed to prevent recurrence.
Assuntos
Infestações por Ácaros/induzido quimicamente , Triancinolona Acetonida/efeitos adversos , Administração Tópica , Adulto , Feminino , Hexaclorocicloexano/administração & dosagem , Hexaclorocicloexano/uso terapêutico , Humanos , Infestações por Ácaros/tratamento farmacológico , Infestações por Ácaros/patologiaRESUMO
Fifty-four patients with secondary syphilis were studied in regard to the clinical manifestations, response to treatment and histopathology of the skin lesions. The correlation between the skin lesions and histopathology, between the duration of skin lesions and VDRL titer, between type of skin lesions and VDRL titer were also determined. The clinical manifestations varied from macular, maculopapular, papular, papulosquamous and urticarial lesions. The hair loss usually occurred on the scalp, but the eyebrows or even total body hair loss could occur. The response to treatment was good, only one patient relapsed. The histopathology was related to the clinical manifestations, there was sparse inflammatory cell infiltration in the dermis in macular lesions, but more dense infiltration as well as more epidermal change in papular and papulosquamous lesions. There were significant correlation between the duration of skin lesions and VDRL titer, but no correlation between types of skin lesions and VDRL titer.
Assuntos
Países em Desenvolvimento , Sífilis Cutânea/diagnóstico , Adolescente , Adulto , Biópsia , Cardiolipinas/análise , Colesterol/análise , Feminino , Humanos , Injeções Intramusculares , Masculino , Pessoa de Meia-Idade , Penicilina G Benzatina/administração & dosagem , Fosfatidilcolinas/análise , Pele/patologia , Sífilis Cutânea/tratamento farmacológico , Sífilis Cutânea/patologia , TailândiaRESUMO
One hundred patients with biopsy-proven erythema nodosum were studied at Ramathibodi Hospital from 1982 to 1992 to find out the etiology of this disease. Eighty-eight were females while twelve were males, with an age range from 6 to 72 years old (mean, 31 years old). Abnormal laboratory findings in these patients included elevation of erythrocyte sedimentation rate (76.9%), increase anti-streptolysin-O titer (10.7%), abnormal chest roentgenogram (16.7%), positive tuberculin test (50%). The cause of erythema nodosum is still unknown in a large group of patients, and it was found only in twenty-eight patients (28%). Twelve patients had tuberculosis, seven had history of antibiotic administration, six probably had streptococcal infection and the other three had Behcet's disease.
Assuntos
Eritema Nodoso/etiologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Many genes have been implicated in the risk of severe malaria, generally based on candidate gene studies in case/control populations. Among these genes, there has been conflicting reports for the implication of a variant of the intercellular adhesion molecule 1 (ICAM1), ICAM1(Kilifi), in the risk of severe malaria, while in vitro studies provided independent support for a functional role of this variant. In order to explore the possible implication of ICAM1 in the susceptibility/resistance to malaria and to try to understand its clinical relevance in the disease process, we have conducted linkage and association studies of ICAM1 in two Senegalese villages located in regions of endemic malaria. We explored the full genetic variability of ICAM1, and tested it on several clinical malarial traits which are under genetic control, focusing principally on variables related to the parasite density and the number of malarial attacks. Our study provides no evidence for a role of ICAM1 variability on the malarial phenotypes studied.
Assuntos
Molécula 1 de Adesão Intercelular/genética , Malária Falciparum/genética , Animais , Cromossomos Humanos Par 19/genética , Estudos de Coortes , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Haplótipos/genética , Humanos , Escore Lod , Malária Falciparum/epidemiologia , Repetições de Microssatélites , Polimorfismo de Nucleotídeo Único , Senegal/epidemiologiaRESUMO
BACKGROUND: Aspirin and nonsteroidal antiinflammatory drugs (NSAIDs) inhibit platelet cyclooxygenase activity, resulting in altered platelet function and thus potentially enhanced bleeding. OBJECTIVE: We examined the frequency of operative bleeding complications in dermatologic surgical patients taking these drugs and the value of template bleeding time estimates in predicting this complication. METHODS: Bleeding time was measured with and without therapy in 23 patients and was correlated to bleeding complications after skin tumor or benign lesion excision in 40 patients taking aspirin, 21 taking NSAIDs, and 20 taking neither drug. RESULTS: Bleeding time dropped significantly (p < 0.01) when patients stopped therapy for at least 5 days (median, 7 days), although bleeding time was prolonged in only 6 of 16 patients taking aspirin and 2 of 7 taking NSAID. In patients who continued antiplatelet drugs during surgery, bleeding time was prolonged in 8 of 40 patients taking aspirin and in 1 of 21 treated with NSAIDs. Excessive intraoperative bleeding occurred in three aspirin-treated patients, all of whom had a prolonged bleeding time, compared with none of those with normal bleeding times (p < 0.001, Fisher's exact probability test) and with none of those taking NSAIDs. Postoperative ooze requiring a dressing replacement occurred in one NSAID-treated patient and in three patients taking neither drug. CONCLUSION: Bleeding time is increased by aspirin and NSAID therapy but is prolonged beyond the normal range in only approximately 25% of aspirin-treated and 10% of NSAID-treated patients. Intraoperative bleeding complications occurred only in patients receiving aspirin who had a prolonged bleeding time. Postoperative oozing occurred only in NSAID-treated and in untreated patients and thus is probably unrelated to antiplatelet therapy. Patients with a normal bleeding time can continue aspirin or NSAID therapy before dermatologic surgery.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Hemorragia/fisiopatologia , Dermatopatias/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bandagens , Testes de Coagulação Sanguínea , Perda Sanguínea Cirúrgica , Feminino , Humanos , Complicações Intraoperatórias , Masculino , Pessoa de Meia-Idade , Ativação Plaquetária/efeitos dos fármacos , Complicações Pós-Operatórias , Estudos Prospectivos , Retalhos Cirúrgicos , Técnicas de SuturaRESUMO
In an attempt to improve the prediction of PUVA erythemal sensitivity, we have examined, in 251 patients, the relationship between the minimal phototoxic dose (MPD) and a number of variables, including skin type, ingested dose of 8-methoxypsoralen (8-MOP) and history of previous PUVA treatment. The MPD was determined by phototesting 2 h after ingestion of crystalline 8-MOP, given at a standard dose of 0.6 mg/kg (calculated to the nearest 10 mg). No reaction to the highest dose of UVA used for phototesting occurred in 16% of cases; the dose of 8-MOP was significantly associated with non-response. In the patients in whom an erythemal response was obtained, a significant association was found between the MPD and the variables of skin type, ingested dose of 8-MOP, and history of previous PUVA treatment. Thus, by taking these factors into account, a more accurate prediction can be made of an individual patient's erythemal sensitivity to PUVA than relying on skin type alone. That erythemal sensitivity is affected by the ingested dose of 8-MOP (even when all patients received 0.6 mg/kg) suggests that conventional psoralen dosing according to body weight is not ideal.
Assuntos
Dermatite Fototóxica/etiologia , Terapia PUVA/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Dermatite Fototóxica/patologia , Esquema de Medicação , Cor de Olho , Feminino , Cor de Cabelo , Humanos , Masculino , Metoxaleno/administração & dosagem , Pessoa de Meia-Idade , Pele/patologia , Pele/efeitos da radiaçãoRESUMO
In 41 patients about to start PUVA, the dose of 8-methoxypsoralen (8-MOP) was calculated conventionally according to body weight (0.6 mg/kg), or according to body surface area (25 mg/m2) predicted from height and weight measurements. The two different methods of dosing were used on consecutive treatment days and the plasma 8-MOP concentration was measured on each occasion 2 h after ingestion of the crystalline form of 8-MOP, given to the nearest 10 mg. Body weight calculated doses ranged from 30 to 60 mg with a significant difference in the plasma 8-MOP concentration between the dose groups, indicating a systematic variation according to the weight of the patient. When calculated according to body surface area, only two doses were used (40 or 50 mg), and there was no significant difference in plasma 8-MOP concentration between the groups. Calculation of the dose of 8-MOP using body surface area may be performed quickly and simply provided the height and weight of individual patients is known. We provide evidence that this method of dosing will improve the therapeutic effect of PUVA in psoriasis.
Assuntos
Superfície Corporal , Metoxaleno/administração & dosagem , Terapia PUVA , Fármacos Fotossensibilizantes/administração & dosagem , Psoríase/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estatura , Peso Corporal , Esquema de Medicação , Feminino , Humanos , Masculino , Metoxaleno/sangue , Pessoa de Meia-Idade , Fármacos Fotossensibilizantes/sangue , Psoríase/sangueRESUMO
Darier's disease (DD) is an autosomal dominantly inherited skin disorder characterized by loss of adhesion between epidermal cells (acantholysis) and abnormal keratinization. Recently, we identified ATP2A2 encoding the sarco/endoplasmic reticulum Ca(2+)ATPase isoform 2 as the defective gene in DD. Now we report a spectrum of ATP2A2 mutations in 19 families and six sporadic cases with DD and investigate genotype-phenotype correlations. All 21 exons and flanking intron boundaries were amplified and screened for mutations by conformation-sensitive gel electrophoresis and direct sequencing. We identified 24 novel mutations that are scattered throughout the ATP2A2 gene. Two families shared an identical mutation on a common disease-associated haplotype, suggesting inheritance from a common ancestor. The majority of the mutations (54%; 13/24) led to a premature termination codon which further supports the proposal that haploin-sufficiency is a common molecular mechanism for DD. Thirty-eight per cent of mutations (9/24) result in non-conservative amino acid substitutions at highly conserved positions. Two mutations predict mutated polypeptides lacking or carrying additional amino acids. Marked inter- and intrafamilial phenotypic variability of the disease was observed. These results illustrate the considerable diversity of ATP2A2 mutations causing DD and suggest that additional factors are important contributors to the clinical phenotype.
Assuntos
ATPases Transportadoras de Cálcio/genética , Doença de Darier/genética , Mutação , Análise Mutacional de DNA , Doença de Darier/enzimologia , Doença de Darier/patologia , Europa (Continente) , Genótipo , Haplótipos , Humanos , Isoenzimas/genética , Fenótipo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Pele/patologiaRESUMO
The variation in erythemal sensitivity of the skin during PUVA therapy with oral 8-methoxypsoralen (8-MOP) was examined by measuring both UVA and PUVA erythemal responses, together with plasma 8-MOP concentration, in 27 patients about to start PUVA therapy for psoriasis. The erythema responses were judged visually, and also measured using a reflectance instrument in order to construct dose-response curves. No significant association was found between the UVA and PUVA minimal erythema responses. The plasma psoralen concentration showed significant association with the slope of the PUVA erythema dose-response curve. The slopes of the UVA and PUVA erythema dose-response curves were significantly associated, and this association became much stronger when allowance was made for plasma psoralen concentration. These results show that erythemal sensitivity during PUVA therapy is related to both plasma psoralen concentration and inherent UVA sensitivity, but that this relationship is not apparent when sensitivity is judged visually as the minimal erythema response. The association between PUVA and UVA erythemal sensitivity suggests a common pathway in the vascular response induced by UVA radiation, with or without psoralen.
Assuntos
Eritema/etiologia , Metoxaleno/metabolismo , Terapia PUVA/métodos , Psoríase/tratamento farmacológico , Raios Ultravioleta/efeitos adversos , Adulto , Idoso , Relação Dose-Resposta à Radiação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/sangue , Pele/efeitos da radiaçãoRESUMO
The effect of psoralen in combination with 311 nm (UVB) radiation was studied in five subjects with normal skin and 10 patients with psoriasis involving both forearms. Treatment with oral 8-methoxypsoralen augmented the UVB erythemal response at 6 h after irradiation, but had no effect at 24-72 h. In eight of the nine patients who completed the trial, lesions of psoriasis on the arms treated with psoralen-UVB cleared before lesions on the arms treated with UVB alone. This study has shown that psoralen in combination with UVB has an erythemal effect on normal skin, and a therapeutic effect in psoriasis which is greater than the response to UVB alone.
Assuntos
Metoxaleno/uso terapêutico , Fotoquimioterapia/métodos , Psoríase/tratamento farmacológico , Adulto , Idoso , Feminino , Humanos , Masculino , Metoxaleno/farmacologia , Pessoa de Meia-Idade , Pele/efeitos dos fármacos , Pele/efeitos da radiação , Fatores de TempoRESUMO
In the U.K., PUVA treatment for psoriasis is usually given three times weekly, with the starting dose of UVA chosen according to the skin type of the patient. Observations on the time-course and dose-response characteristics of PUVA erythema suggest that larger doses of UVA could be used safely, provided that the frequency of PUVA treatment is reduced. We have examined this by treating 100 patients with chronic plaque-type psoriasis with a PUVA protocol in which treatment using oral 8-methoxypsoralen was given twice weekly, with the starting dose of UVA based on each patient's minimal phototoxic dose, and with weekly UVA dose increments calculated as a percentage of the dose used in the previous treatment. Clearance of psoriasis was achieved in 92% of patients. The median number of treatments required for clearance was 12, and the median cumulative UVA dose for clearance was 52J/cm2. Although erythema occurred at some stage during the course of PUVA in 48% of patients, in only 16% of cases was the erythema of sufficient intensity to result in more than one treatment being missed. These results compare favourably with previous studies in which treatment was given three or four times weekly. Thus, twice weekly PUVA treatment for psoriasis is at least as effective as treatment given more frequently, and may be safer, as lower cumulative UVA doses are required for clearance. It also allows for more efficient operation of a PUVA unit and is more convenient for patients.