RESUMO
We analyzed the epidemiological changes of rheumatoid arthritis (RA) over three decades using patients from a single center in Singapore. All patients who fulfill the 1987 American College of Rheumatology criteria for RA were invited to enroll in a prospective disease registry. We analyzed the patient demographics, disease manifestation, management and patient-reported outcomes, including quality of life (QoL), in the three categories according to the year of disease onset: before 1989 (group I), 1990-1999 (group II) and after 2000 (group III). There were 1,153 patients with 231, 532 and 390 in groups I, II and III, respectively. The mean disease durations were 25, 12 and 4.8 years, respectively. The majority was female (84.1 %) and Chinese (76.6 %) with no socio-demographic differences across the three periods. The age of onset rises and the prevalence of rheumatoid factor falls with the proximity of disease onset. Patients with most recent disease onset had the earliest access to the rheumatologist. They also had the highest tender and swollen joint counts, lowest deformed joint count and highest remission rate. Patients in group I report better mental and emotional QoL though many developed marked disability. We have documented changes of the manifestations of RA that are dependent and independent of improved treatment. Significant differences in accessibility to the rheumatologist, RA activity, functional capacity, quality of life and comorbidities were seen in subsequent cohorts due to treatment evolution and more efficient healthcare delivery.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/etnologia , Atenção à Saúde/tendências , Reumatologia/tendências , Idoso , Análise de Variância , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/fisiopatologia , Artrite Reumatoide/psicologia , Distribuição de Qui-Quadrado , Avaliação da Deficiência , Emoções , Feminino , Humanos , Masculino , Saúde Mental , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Qualidade de Vida , Sistema de Registros , Indução de Remissão , Singapura/epidemiologia , Inquéritos e Questionários , Fatores de Tempo , Resultado do TratamentoRESUMO
We describe a 35-year-old Chinese woman with Behçet disease complicated by recurrent gastrointestinal flares. During admission for acute lower abdominal pain, a computed tomographic scan of the abdomen showed thrombosis of the left ovarian vein. She was treated with increased immunosuppressant and oral anticoagulant. Although she was not compliant to oral anticoagulant with her international normalized ratio frequently subtherapeutic, her symptoms abated and the thrombosis resolved. There has been only 1 reported case of a patient with Behçet disease presenting with postpartum ovarian vein thrombosis and pulmonary embolism and no reported case of Behçet disease with ovarian vein thrombosis occurring outside pregnancy and the puerperium. Ovarian vein thrombosis is a rare cause of abdominal pain that should be considered in patients with Behçet disease.
Assuntos
Dor Abdominal , Síndrome de Behçet , Ovário/irrigação sanguínea , Trombose Venosa , Dor Abdominal/complicações , Dor Abdominal/fisiopatologia , Adulto , Anticoagulantes/administração & dosagem , Síndrome de Behçet/complicações , Síndrome de Behçet/fisiopatologia , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Imunossupressores/administração & dosagem , Coeficiente Internacional Normatizado , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Veias/fisiopatologia , Trombose Venosa/diagnóstico , Trombose Venosa/tratamento farmacológico , Trombose Venosa/etiologia , Trombose Venosa/fisiopatologiaAssuntos
Doenças do Pé/complicações , Debilidade Muscular/etiologia , Neoplasias de Tecido Conjuntivo/complicações , Neoplasias Cutâneas/complicações , Adulto , Doenças do Pé/diagnóstico , Humanos , Imageamento por Ressonância Magnética , Masculino , Dor Musculoesquelética/etiologia , Neoplasias de Tecido Conjuntivo/diagnóstico , Osteomalacia , Síndromes Paraneoplásicas , Tomografia por Emissão de Pósitrons , Neoplasias Cutâneas/diagnósticoRESUMO
BACKGROUND: Blomia tropicalis is an important domestic dust mite in the tropics and subtropics. This study describes cDNA cloning of the group 4 allergen of B. tropicalis, and the evaluation of the sensitization of this allergen in atopic populations from 2 geographic regions. METHODS: cDNA cloning was carried out using the Smart RACE cDNA amplification kit. The full-length Blo t 4 cDNA was isolated by cDNA library screening, 5' and 3' rapid amplification of cDNA ends and long-distance PCR. Sequence analysis was performed with a combination of the Clustal W, CGC and Blast program packages. The cDNA was expressed in Pichia pastoris yeast. The skin prick test was used to evaluate the sensitization profile of recombinant Blo t 4, crude dust mite allergen extracts and major B. tropicalis recombinant allergen Blo t 5. RESULTS: The cloned Blo t 4 had a molecular weight of 56 kDa and had 68% amino acid homology with group 4 allergens of Dermatophagoides pteronyssinus and 65% with those of Euroglyphus maynei. A sensitization profile to the expressed recombinant Blo t 4 allergen (28%) showed an unusually higher frequency than to the major allergen Blo t 5 (22%) in allergic subjects from Chengdu, PR China. In comparison, the subjects from Singapore showed very low sensitization to Blo t 4 (4%) compared with Blo t 5 (84%). CONCLUSIONS: Group 4 allergens of B. tropicalis may be an important dust mite allergen in certain distinct populations.
Assuntos
Alérgenos/imunologia , Hipersensibilidade/imunologia , Ácaros/imunologia , alfa-Amilases/imunologia , Adolescente , Adulto , Alérgenos/metabolismo , Sequência de Aminoácidos , Animais , Antígenos de Plantas , Sequência de Bases , Criança , Pré-Escolar , China/epidemiologia , Clonagem Molecular , Humanos , Hipersensibilidade/epidemiologia , Pessoa de Meia-Idade , Ácaros/enzimologia , Dados de Sequência Molecular , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Alinhamento de Sequência , Singapura/epidemiologia , Testes Cutâneos , Adulto Jovem , alfa-Amilases/genéticaAssuntos
Angioedema/diagnóstico , Angioedema/tratamento farmacológico , Angioedemas Hereditários/diagnóstico , Angioedemas Hereditários/tratamento farmacológico , Angioedema/epidemiologia , Angioedemas Hereditários/epidemiologia , Consenso , Comportamento Cooperativo , Humanos , Cooperação InternacionalRESUMO
INTRODUCTION: The aim of this study was to ascertain the outcomes of chronic hepatitis B (CHB) infection following immunosuppressive therapy in 38 consecutive oriental patients with systemic rheumatic diseases. MATERIALS AND METHODS: This is a retrospective consecutive, non-comparative study. RESULTS: The majority of patients were female (26, 68.4%), predominantly Chinese (92.1%), with a mean age 54 +/- 14 years (range, 16 to 87). The mean duration of rheumatic disease was 9 +/- 11 years (range, 0.1 to 48), with rheumatoid arthritis (52.6%) and systemic lupus erythematosus (23.7%) being the most common. The mean duration of CHB infection was 6 +/- 5 years (range, 0.1 to 17), with the majority diagnosed during pre-methotrexate screening (50.0%) and asymptomatic transaminitis following initiation of immunosuppressive therapy (23.7%). Upon diagnosis of rheumatic disease, all patients had normal alanine aminotransferase (ALT). Of these, 18.2% were positive for hepatitis B e antigen (HBeAg) and 78.1% were positive for anti- HBe antibody. Twenty (52.6%) developed ALT elevation, which was more than twice the upper limit of normal in 12 patients. ALT normalised spontaneously in 12 patients without hepatic decompensation or change in therapy. Seven (18.4%) patients received lamivudine for 18 +/- 22 months (range, 2 to 61). Two patients developed YMDD mutation subsequently treated with adefovir (1) and adefovir/lamivudine (1). There were 3 (7.9%) hepatitis B virus (HBV)-unrelated deaths [infection (2), genitourinary malignancy (1)], and 1 from HBV-reactivation complicated by septicaemia. None have developed hepatocellular carcinoma. CONCLUSION: Elevated ALT occurred in 52.6% of patients, with only 18.4% requiring anti-viral therapy for HBV reactivation. HBV-related mortality was low. With the appropriate precautionary measures, prednisolone and immunosuppressants (except methotrexate and leflunomide) may be used safely in patients where clinically indicated.
Assuntos
Hepatite B Crônica/epidemiologia , Doenças Reumáticas/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , Antivirais/uso terapêutico , Povo Asiático , Comorbidade , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Lamivudina/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prednisolona/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento , Ativação ViralRESUMO
[This corrects the article DOI: 10.1186/s40413-016-0122-3.].
RESUMO
One of the major concerns in the practice of allergy is related to the safety of procedures for the diagnosis and treatment of allergic disease. Management (diagnosis and treatment) of hypersensitivity disorders involves often intentional exposure to potentially allergenic substances (during skin testing), deliberate induction in the office of allergic symptoms to offending compounds (provocation tests) or intentional application of potentially dangerous substances (allergy vaccine) to sensitized patients. These situations may be associated with a significant risk of unwanted, excessive or even dangerous reactions, which in many instances cannot be completely avoided. However, adverse reactions can be minimized or even avoided if a physician is fully aware of potential risk and is prepared to appropriately handle the situation. Information on the risk of diagnostic and therapeutic procedures in allergic diseases has been accumulated in the medical literature for decades; however, except for allergen specific immunotherapy, it has never been presented in a systematic fashion. Up to now no single document addressed the risk of the most commonly used medical procedures in the allergy office nor attempted to present general requirements necessary to assure the safety of these procedures. Following review of available literature a group of allergy experts within the World Allergy Organization (WAO), representing various continents and areas of allergy expertise, presents this report on risk associated with diagnostic and therapeutic procedures in allergology and proposes a consensus on safety requirements for performing procedures in allergy offices. Optimal safety measures including appropriate location, type and required time of supervision, availability of safety equipment, access to specialized emergency services, etc. for various procedures have been recommended. This document should be useful for allergists with already established practices and experience as well as to other specialists taking care of patients with allergies.
RESUMO
BACKGROUND: Severe acute respiratory syndrome (SARS) emerged in later February 2003, as a new epidemic form of life-threatening infection caused by a novel coronavirus. However, the immune-pathogenesis of SARS is poorly understood. To understand the host response to this pathogen, we investigated the gene expression profiles of peripheral blood mononuclear cells (PBMCs) derived from SARS patients, and compared with healthy controls. RESULTS: The number of differentially expressed genes was found to be 186 under stringent filtering criteria of microarray data analysis. Several genes were highly up-regulated in patients with SARS, such as, the genes coding for Lactoferrin, S100A9 and Lipocalin 2. The real-time PCR method verified the results of the gene array analysis and showed that those genes that were up-regulated as determined by microarray analysis were also found to be comparatively up-regulated by real-time PCR analysis. CONCLUSIONS: This differential gene expression profiling of PBMCs from patients with SARS strongly suggests that the response of SARS affected patients seems to be mainly an innate inflammatory response, rather than a specific immune response against a viral infection, as we observed a complete lack of cytokine genes usually triggered during a viral infection. Our study shows for the first time how the immune system responds to the SARS infection, and opens new possibilities for designing new diagnostics and treatments for this new life-threatening disease.
Assuntos
Regulação da Expressão Gênica , Genes MHC da Classe II/fisiologia , Síndrome Respiratória Aguda Grave/genética , Antígenos Virais/sangue , Antígenos Virais/imunologia , Regulação da Expressão Gênica/genética , Genes MHC da Classe II/imunologia , Humanos , Lactoferrina/sangue , Lactoferrina/genética , Leucócitos Mononucleares/química , Análise em Microsséries , Reação em Cadeia da Polimerase/métodos , Síndrome Respiratória Aguda Grave/sangueRESUMO
Toxic epidermal necrolysis (TEN) is a severe, immune-mediated, mucocutaneous reaction resulting in extensive keratinocyte apoptosis. High-dose human intravenous immunoglobulins (IVIG) have been proposed as an effective treatment for TEN. Retrospective data from 8 patients with TEN and 4 patients with Stevens-Johnson syndrome-toxic epidermal necrolysis (SJS-TEN) overlap treated with high-dose IVIG were analysed. The total dose of IVIG administered was 2 g/kg body weight, with the exception of 2 patients who received a total dose of 1.5 g/kg body weight. Their mean age was 49.9+/-18.8 years (range, 19 to 70 years). The mean time from the first sign of skin lesion or mucosal or epidermal detachment to commencement of IVIG was 8.7+/-5.5 days (range, 3 to 22 days). Of the 11 patients who survived, the mean time to objective response was 3.6+/-1.9 days (range, 2 to 8 days). The length of stay (LOS) in hospital was 20.4+/-8.0 days (range, 10 to 37 days). The survival rate was 91.6%. One patient developed permanent mucocutaneous sequelae following TEN. There were no adverse reactions to IVIG. We conclude that high-dose IVIG may be a safe and effective therapy for Asian patients with TEN.
Assuntos
Imunoglobulinas Intravenosas/uso terapêutico , Síndrome de Stevens-Johnson/tratamento farmacológico , Adulto , Idoso , Feminino , Humanos , Tempo de Internação , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Estudos Retrospectivos , Singapura/epidemiologia , Síndrome de Stevens-Johnson/mortalidade , Síndrome de Stevens-Johnson/patologia , Análise de SobrevidaRESUMO
OBJECTIVE: To determine the clinical features of our systemic lupus erythematosus (SLE) patients presenting with pulmonary hemorrhage (PH). METHODS: We reviewed the records of all SLE patients who had PH between 1994 and 2001, a total of 22. RESULTS: All patients had radiographic infiltrates. The mean drop in hemoglobin was 3.2 +/-1.1 g/dL, hemoptysis occurred in 50%, the Dlco was increased in 10 of 11 patients (91%), and 11 of 14 patients who underwent bronchoscopy had positive findings. All received high-dose prednisolone and most also were given pulse methylprednisolone (MEP) and cyclophosphamide. All patients required care in the intensive/monitored care unit, 14 were intubated, 11 had plasmapheresis, and 8 died as a result of PH (mortality rate, 36%). SLEDAI and SLAM were able to indicate active disease in SLE patients with PH (median SLEDAI, 19 [interquartile range, 10 to 24] and mean SLAM, 16.1 +/- 5.8). There was a statistically significant increase in the SLEDAI from 1 month prior to PH to the time of PH (P =.014), indicating that the patients were having a significant disease flare. The median SLEDAI and SLAM scores of patients who died were slightly higher than that of survivors. CONCLUSION: PH in SLE patients occurred in those with severe, multiorgan involvement, with high SLEDAI scores. A high degree of suspicion should be maintained in lupus patients with active disease and unexplained infiltrates on chest radiographs and dropping red cell indices, even in the absence of hemoptysis. Early aggressive management with high-dose steroids and intravenous pulses of cyclophosphamide is advocated and may explain recent trends of improved survival. Plasmapheresis may be useful for the acutely ill patient who does not respond to the above measures but does not clearly lead to improved survival.
Assuntos
Hemorragia/etiologia , Pneumopatias/etiologia , Lúpus Eritematoso Sistêmico/complicações , Adulto , Ciclofosfamida/uso terapêutico , Feminino , Glucocorticoides/uso terapêutico , Indicadores Básicos de Saúde , Hemorragia/mortalidade , Hemorragia/terapia , Humanos , Imunossupressores/uso terapêutico , Pneumopatias/mortalidade , Pneumopatias/terapia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Masculino , Plasmaferese , Prednisolona/uso terapêutico , Índice de Gravidade de Doença , Análise de SobrevidaRESUMO
BACKGROUND: Antituberculosis (anti-TB) drug allergy often involves multiple concurrently administered drugs which subsequently need to be reinitiated as no better alternatives exist. OBJECTIVE: To describe the results of tailored sequential desensitization-rechallenge (D-R) for anti-TB drug allergy. METHODS: Consecutive patients who had undergone D-R to anti-TB drugs between 1 September 1997 and 31 January 2012 were recruited. Following resolution of the acute reaction, anti-TB drug was restarted at 1:6,000 to 1:3 of the final daily dose (FDD), with gradual single or multiple step daily dose escalation to the FDD. Subsequent drugs were sequentially added ≥3 days later when the preceding drug was tolerated. Full blood count and liver function tests were monitored prior to addition of each new drug. RESULTS: There were 11 patients of whom 10 were male, predominantly Chinese (8 patients). Regimens comprised at least 3 drugs: isoniazid (INH), rifampicin (RIF), ethambutol (EMB), pyrazinamide (PZA), or streptomycin. All patients had nonimmediate reactions, with cutaneous eruptions, where maculopapular exanthema (MPE) was the most common (8 patients). Drug-induced hypersensitivity syndrome (DIHS) occurred in 6 patients, and Stevens Johnson syndrome (SJS) in 2 patients. D-R to INH was successful in 7/9 patients (77.8%) and to RIF/EMB/PZA/streptomycin in all. Of the 2 patients who failed INH D-R, 1 developed fever and MPE on day 3, the other MPE on day 8. D-R with INH and RIF respectively was successful in 2 patients with SJS. Among DIHS patients, 1 failed D-R with INH (fever and MPE on day 3). There were 23/25 (92%) successful D-R among the 11 patients. All patients completed TB treatment of ≥5 months' duration with no cases of drug-resistant TB. CONCLUSION: Tailored sequential TB drug D-R is successful where no better alternative therapies are available, with careful dose escalation and close monitoring, and after a careful risk-benefit assessment.
RESUMO
AIM: We sought to evaluate the relationship of urine levels of soluble cellular adhesion molecules sVCAM-1 (vascular) and sICAM-1 (intercellular) in systemic lupus erythematosus (SLE) patients with or without lupus nephritis, and to explore their correlation with renal disease activity. METHODS: Paired serum and urine samples of 121 Asian SLE patients, and urine samples of 19 normal healthy controls were collected. Demographic data, disease activity and damage scores, and selected laboratory parameters, including levels of anti-double stranded DNA antibody, complements C3, C4, and creatinine were captured. Renal disease activity was scored with renal SLE Activity Measure revised (rSLAM-R). Serum and urine sVCAM-1 and sICAM-1 levels were assayed by enzyme-linked immunosorbent assay. RESULTS: Urinary sVCAM-1 and sICAM-1 were elevated in SLE patients compared to controls. Significantly higher levels of urine sVCAM-1 found in patients with active lupus nephritis correlated with rSLAM-R. In addtion, significantly more patients with active lupus nephritis had detectable levels of urine sICAM-1, but no correlation with renal activity was observed. CONCLUSION: Urinary sVCAM-1 may serve as a potential biomarker for early diagnosis of lupus nephritis as levels correlated with even mild abnormalities of urine sediment. In addition, both urine sVCAM-1 and sICAM-1 levels may be useful in identifying patients at risk of lupus nephritis.
Assuntos
Molécula 1 de Adesão Intercelular/urina , Nefrite Lúpica/diagnóstico , Molécula 1 de Adesão de Célula Vascular/urina , Adulto , Biomarcadores/sangue , Biomarcadores/urina , Estudos de Casos e Controles , Diagnóstico Precoce , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Molécula 1 de Adesão Intercelular/sangue , Modelos Logísticos , Nefrite Lúpica/sangue , Nefrite Lúpica/imunologia , Nefrite Lúpica/urina , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Singapura , Regulação para Cima , Molécula 1 de Adesão de Célula Vascular/sangueRESUMO
This study surveyed the prescription patterns of adrenaline auto-injectors (AAs) in Singapore to examine the frequency, triggers, and demographic pattern of anaphylaxis requiring such prescriptions. A 6-year retrospective review of 417 consecutive patients prescribed AAs in Singapore from January 1999 to December 2004, as identified from hospital pharmacy records. There were 417 patients identified, consisting of 295 (70.7%) Singaporeans with the remaining being non-Singaporean residents. Based on population census, the frequency of AA prescriptions was estimated at 1 per 10,000 Singaporeans. Demographic factors associated with AA prescriptions were male gender (OR = 1.361; p = 0.002); minority ethnic groups, which included Eurasians, Caucasians, Koreans, and Japanese (OR = 15.873; p < 0.001); and children <15 years of age (OR = 2.593; p < 0.001). The most common food allergens resulting in AA prescriptions were peanut (41.9%) and shellfish allergy (28.5%). Multiple logistic regression analysis showed that peanut allergy was independently associated with Eurasian ethnicity (OR = 5.045; p = 0.021); and shellfish allergy with Indian ethnicity (OR = 2.757; p = 0.034). The estimated frequency of AA prescriptions in Singapore is relatively low at 0.01%. The incidence of peanut and shellfish allergy in the Asian population appears to differ from that seen in Western populations.
Assuntos
Anafilaxia/epidemiologia , Prescrições de Medicamentos/estatística & dados numéricos , Epinefrina/uso terapêutico , Adolescente , Adulto , Idoso , Anafilaxia/etnologia , Anafilaxia/imunologia , Criança , Pré-Escolar , Epinefrina/administração & dosagem , Feminino , Hipersensibilidade Alimentar/epidemiologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Singapura/epidemiologiaRESUMO
OBJECTIVE: We have previously validated the English version of the Systemic Lupus Erythematosus Quality of Life Questionnaire (SLEQOL) in our patients with lupus. Many of our Chinese patients are not fluent in English and therefore a Chinese version (SLEQOL-C) has been adapted for their use. METHODS: Two independent translators translated the SLEQOL into Chinese. A consensus version was derived from both sets of translations. Back translation of this version was performed by another 2 independent translators who had neither been involved in the forward translation nor encountered the SLEQOL. The final version, SLEQOL-C, was finalized after rectifying the discrepancies revealed by the back translation. Linguistic validity was tested in open interviews with bilingual patients with lupus. The SLEQOL-C and SLEQOL were administered to patients to determine whether they displayed differential item functioning (DIF). RESULTS: In general, most of the items in English could be expressed in Chinese precisely, although a few instructions had to be altered slightly to make them more idiomatic. The forward and back translations of the SLEQOL were accomplished without major difficulties. A total of 638 patients were interviewed (62.8% with the SLEQOL and 37.2% with the SLEQOL-C). Using DIF analysis, there was no detectable test bias due to language use after controlling for repeated observations, age, sex, and ethnicity. CONCLUSION: The SLEQOL-C has semantic, idiomatic, and conceptual equivalence to the SLEQOL. The rigorous process of cross-cultural translation provides some measure of quality in the content validity.
Assuntos
Comparação Transcultural , Idioma , Lúpus Eritematoso Sistêmico/fisiopatologia , Qualidade de Vida , Inquéritos e Questionários , Adulto , China , Feminino , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/psicologia , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos TestesRESUMO
CD38 is a type II transmembrane glycoprotein found in myriad mammalian tissues and cell types. It is known for its involvement in the metabolism of cyclic ADP-ribose and nicotinic acid adenine dinucleotide phosphate, two nucleotides with calcium mobilizing activity independent of inositol trisphosphate. CD38 itself has been shown to have clinical significance in certain diseases with possible utilization in diagnostic and prognostic applications. Previous studies on several autoimmune diseases have shown the usefulness of recombinant CD38 protein expressed from Escherichia coli and Pichia pastoris in the detection of autoantibodies to CD38 via Western blot and ELISA. In this study, we produced a 6 x His-tagged GST-CD38 fusion protein using a recombinant baculovirus/insect cell expression technique that was purified as a soluble protein. The fusion protein was purified to homogeneity by affinity and gel filtration chromatography steps. It has an apparent molecular mass of 56 kDa on SDS-PAGE gel stained with Coomassie blue and was recognized on Western blots by antibodies against human CD38 as well as the polyhistidine tag. Peptide mass fingerprinting analysis confirmed the identity of human CD38 in the fusion protein.
Assuntos
ADP-Ribosil Ciclase/genética , Antígenos CD/genética , Clonagem Molecular/métodos , Glutationa Transferase/genética , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/isolamento & purificação , ADP-Ribosil Ciclase/imunologia , ADP-Ribosil Ciclase 1 , Animais , Afinidade de Anticorpos , Antígenos CD/imunologia , Baculoviridae , Linhagem Celular , DNA Complementar/genética , Histidina , Humanos , Insetos/citologia , Glicoproteínas de Membrana , Sondas Moleculares , Mapeamento de Peptídeos , Proteínas Recombinantes de Fusão/imunologiaRESUMO
Severe acute respiratory syndrome (SARS) is caused by a novel and highly infectious virus named SARS coronavirus (SARS-CoV). Among the serological tests currently available for the detection of SARS-CoV, a whole-virus-based immunofluorescence assay (IFA) was considered one of the most sensitive assays and served as a "gold standard" during the SARS epidemic in Singapore in 2003. However, the need to manipulate live SARS-CoV in the traditional IFA limits its wide application due to the requirement for a biosafety level 3 laboratory and the risk of laboratory infection. Previously, we have identified two immunodominant epitopes, named N195 and Sc, in the two major structural proteins, the N and S proteins, of SARS-CoV (Q. He, K. H. Chong, H. H. Chng, B. Leung, A. E. Ling, T. Wei, S. W. Chan, E. E. Ooi, and J. Kwang, Clin. Diagn. Lab. Immunol., 11:417-422, 2004; L. Lu, I. Manopo, B. P. Leung, H. H. Chng, A. E. Ling, L. L. Chee, E. E. Ooi, S. W. Chan, and J. Kwang, J. Clin. Microbiol. 42:1570-1576, 2004). In the present study, the N195-Sc fusion protein was highly expressed in insect (Sf9) cells infected with a recombinant baculovirus bearing the hybrid gene under the control of a polyhedrin promoter. An IFA based on Sf9 cells producing the fusion protein was standardized with 23 serum samples from patients with SARS, 20 serum samples from patients with autoimmune diseases, and 43 serum samples from healthy blood donors. The detection rates were comparable to those obtained with a commercial SARS-CoV IFA kit (EUROIMMUN, Gross Groenau, Germany) and a conventional IFA performed at the Singapore General Hospital. Our data showed that the newly developed IFA could detect SARS-CoV in 22 of the 23 SARS-CoV-positive serum samples and gave no false-positive results when the sera from patients with autoimmune diseases and healthy individuals were tested. The detection rate was identical to those of the two whole-virus-based IFAs. Thus, the novel N-S fusion antigen-based IFA could be an attractive alternative to present whole-virus-based IFAs for the diagnosis of SARS-CoV infection.
Assuntos
Anticorpos Antivirais/sangue , Fluorimunoensaio/métodos , Glicoproteínas de Membrana/imunologia , Proteínas do Nucleocapsídeo/imunologia , Síndrome Respiratória Aguda Grave/diagnóstico , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/isolamento & purificação , Proteínas do Envelope Viral/imunologia , Animais , Anticorpos Antivirais/imunologia , Sequência de Bases , Humanos , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Dados de Sequência Molecular , Proteínas do Nucleocapsídeo/genética , Proteínas do Nucleocapsídeo/metabolismo , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/imunologia , Proteínas Recombinantes de Fusão/metabolismo , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/imunologia , Glicoproteína da Espícula de Coronavírus , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/metabolismoRESUMO
BACKGROUND: Dapsone 100 mg/pyrimethamine 12.5 mg (Maloprim; Beacons Chemicals Pte Ltd, Singapore) is routinely prescribed for antimalarial chemoprophylaxis in military servicemen in Singapore who are not glucose-6-phosphate dehydrogenase-deficient. METHODS: We report a series of three male National Servicemen with hypersensitivity syndrome from Maloprim. RESULTS: The three patients were diagnosed with hypersensitivity syndrome based on the presence of features of a drug hypersensitivity syndrome including fever, lymphadenopathy, maculopapular exanthema, hepatitis, and definite exposure to weekly Maloprim alone. A mild Coombs positive hemolytic anemia was also observed in one patient. All the clinical, hematologic, and biochemical derangements normalized within 3 months of tapering regimens of moderate-dose prednisolone. CONCLUSIONS: Drug hypersensitivity syndromes can occur even on low-dose, weekly drug regimens. Hypersensitivity syndrome from weekly Maloprim is potentially reversible when recognized and treated early.
Assuntos
Antimaláricos/efeitos adversos , Dapsona/efeitos adversos , Hipersensibilidade a Drogas/etiologia , Malária/prevenção & controle , Pirimetamina/efeitos adversos , Adulto , Combinação de Medicamentos , Hipersensibilidade a Drogas/tratamento farmacológico , Glucocorticoides/uso terapêutico , Humanos , Masculino , Militares , Prednisolona/uso terapêuticoRESUMO
BACKGROUND: Drug allergies are unpredictable immunologic adverse effects, usually immunoglobulin E-mediated immediate hypersensitivity or T-cell-mediated delayed hypersensitivity. There is a paucity of accurate prospective data on drug allergy in hospitalized patients. OBJECTIVE: To describe the incidence, manifestations, and outcome of drug allergy in hospitalized patients. METHODS: All newly developed cases, confirmed or suspected, of drug allergy in inpatients using a network-based electronic notification system. Each notification was evaluated by an allergist-immunologist during the same admission. RESULTS: From December 1, 1997 to December 31, 1999, 366 cases were reported from a total of 90,910 admissions. After review, only 210 cases were verified to have drug allergy. Antimicrobials and anti-epileptic drugs comprised 75% of the drug allergies reported. Cutaneous eruptions were the most common clinical presentation (95.7%), with maculopapular rash being the most common morphology. Systemic manifestations occurred in 30%, of which hepatitis was the most common. Serious adverse reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, and generalized exfoliative dermatitis occurred in 11 (5.2%) patients. There was no case of anaphylaxis attributable to drug allergy. After adjusting for underreporting, the incidence of drug allergy in our hospitalized patients was 4.20 per 1,000 (95% confidence interval [CI] 2.93 to 5.46), drug allergy developing during the course of inpatient treatment 2.07 per 1,000 (95% CI 1.45 to 2.69), and mortality attributable to drug allergy 0.09 per 1,000 (95% CI 0.06 to 0.12) hospitalizations. CONCLUSIONS: A network-based, allergist-immunologist-verified, surveillance system enables more accurate labeling of drug allergy. The incidence of drug allergy and mortality in hospitalized patients is low.
Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/epidemiologia , Adolescente , Adulto , Idoso , Feminino , Hospitais Gerais , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
To identify a major antigenic determinant for use in the development of a rapid serological diagnostic test for severe acute respiratory syndrome (SARS) coronavirus infection and to study the immune response during SARS coronavirus infection in humans, we cloned the full length and six truncated fragments of the nucleocapsid gene, expressed them, and purified them as glutathione S-transferase-tagged recombinant proteins. The reactivities of the recombinant proteins to a panel of antibodies containing 33 SARS coronavirus-positive sera and 66 negative sera and to antibodies against other animal coronaviruses were screened. A truncated 195-amino-acid fragment from the C terminus of the nucleocapsid protein (N195) was identified that had a strong ability to detect antibodies against SARS coronavirus. No cross-reaction was found between the N195 protein and antibodies against chicken, pig, and canine coronaviruses. The N195 protein was used to develop a Western blot assay to detect antibodies against SARS coronavirus in 274 clinically blinded samples. The specificity and sensitivity of this test were 98.3 and 90.9%, respectively. The correlation between our Western blotting assay and an immunofluorescence assay (IFA) was also analyzed. The results of our Western blot assay and IFA for the detection of SARS coronavirus-positive sera were the same. Thus, the N195 protein was identified as a suitable protein to be used as an antigen in Western blot and other possible assays for the detection of SARS coronavirus infection.