Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 17 de 17
Filtrar
1.
J Clin Immunol ; 33(1): 162-71, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22926405

RESUMO

PURPOSE: Acute Hemorrhagic Leukoencephalitis (AHLE) is a rare demyelinating disorder of acute onset, rapid deterioration and significant morbidity and mortality. Most often described as a post-infectious complication of an upper respiratory illness, its precise pathophysiology remains unclear. We describe two pediatric patients with AHLE with partial complement factor I (FI) deficiency whose successful treatment included the interleukin-1 (IL-1) receptor antagonist, anakinra, implicating a role for FI and IL-1 in this disorder. METHODS: Extensive clinical workup of two patients presenting with AHLE revealed complement abnormalities, specifically related to the alternative pathway and its regulator, FI. Aggressive management with steroids, immunoglobulin, and anakinra ultimately led to improvement of clinical status and near return to neurologic baseline in both patients. Genetic sequencing of the FI coding regions of the patients and their families was performed. In vitro protein expression studies and immunohistochemistry of fixed brain tissue was used to investigate pathogenic mechanisms. RESULTS: Two novel mutations in FI were identified in our patients, which result in failure to secrete FI. Immunohistochemical evaluation of brain tissue demonstrated positive staining for C3, membrane attack complex (MAC) and IL-1. CONCLUSIONS: We propose AHLE is an unreported, rare phenotype for partial FI deficiency. The upregulation of C3, MAC and IL-1 with subsequent demyelination support a pathologic role for complement activation in AHLE, and suggest anakinra as an important adjunctive therapy in this disease.


Assuntos
Fator I do Complemento/genética , Leucoencefalite Hemorrágica Aguda/genética , Leucoencefalite Hemorrágica Aguda/imunologia , Mutação de Sentido Incorreto/imunologia , Neurônios/imunologia , Neurônios/patologia , Adolescente , Adulto , Criança , Ativação do Complemento/genética , Ativação do Complemento/imunologia , Complemento C3/fisiologia , Fator I do Complemento/deficiência , Fator I do Complemento/metabolismo , Complexo de Ataque à Membrana do Sistema Complemento/fisiologia , Feminino , Células HEK293 , Humanos , Imunofenotipagem , Inflamação/genética , Inflamação/imunologia , Inflamação/patologia , Interleucina-1/fisiologia , Leucoencefalite Hemorrágica Aguda/patologia , Masculino , Neurônios/metabolismo , Linhagem
2.
Pediatrics ; 127(2): e489-93, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21220401

RESUMO

The recurrence of fever in a child with a history of Kawasaki syndrome (KS) poses a dilemma for clinicians who must consider the possibility of recurrent KS. In this report we present the cases of 4 patients who presented with classical symptoms of KS, were successfully treated with intravenous immunoglobulin, and later experienced a reappearance of inflammatory symptoms in a pattern consistent with a recurrent fever syndrome. The association of these syndromes within the same patient suggests that some patients may have a genetic propensity toward altered immune responses and autoinflammatory syndromes. We propose that these 2 syndromes exist within a family of febrile disorders related to innate immune dysregulation.


Assuntos
Febre/diagnóstico , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Recuperação de Função Fisiológica , Pré-Escolar , Feminino , Febre/tratamento farmacológico , Febre/etiologia , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Lactente , Masculino , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Recuperação de Função Fisiológica/efeitos dos fármacos , Recuperação de Função Fisiológica/fisiologia , Recidiva
3.
J Dev Behav Pediatr ; 32(1): 75-7, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21206360

RESUMO

CASE: Gerardo is an 8-year-old Latino boy who saw his primary care pediatrician with a second asthma exacerbation this year. His frustration with his illness was immediately apparent when he said, "I hate having to go to the nurse's office to take my albuterol!" His mother expressed concern that her son frequently refused to take his prevention medication for asthma, montelukast, each morning. When questioned about compliance with his inhaled steroid, his mother hesitated and then admitted that she discontinued the controller medication because she is afraid to "poison his body with so many chemicals." She consistently gave her son the inhaled steroid for 12 months, until care by the allergy specialist was unexpectedly transferred to a Spanish-speaking allergist. She complained that the new doctor is "cold and acts like a veterinarian, not a pediatrician." Gerardo is a first generation Mexican-American who was born in the United States to Spanish-speaking parents. There is no family history of asthma, although his mother fears that she may have contributed to Gerardo's condition. She explained that during pregnancy, she worked cleaning houses where she was exposed to many toxic household cleaners. She has always worried that by inhaling these fumes during pregnancy, she induced her son's asthma. Gerardo presented with his first episode of reactive airway disease at 9 months of age. His mother vividly recalled his high temperature, rapid breathing, and their ambulance ride to the hospital. He was hospitalized for 3 days, and he has not been hospitalized since. Allergy testing revealed sensitivity to weed pollen only. Gerardo sleeps with a nonallergenic pillow and bed cover. Gerardo's mother explained that 3 days before his current exacerbation, he was playing at an amusement park with his friends on a hot day. Gerardo and his friends ran through a large fountain. His mother reported that he was soaked in water and stated, "He knows that he will get sick with asthma if he gets wet!" She recalled that 3 years ago at a friend's birthday party, Gerardo abstained from running through the sprinklers with the other children without instruction from his parents. Since that event, she has trusted Gerardo to care for his "weak lungs." She is frustrated now with his regression in self-care.


Assuntos
Asma/tratamento farmacológico , Comportamento Infantil/psicologia , Características Culturais , Comportamento Materno/etnologia , Adesão à Medicação/psicologia , Mães/psicologia , Asma/fisiopatologia , Asma/psicologia , Criança , Comportamento Infantil/etnologia , Humanos , Masculino , Adesão à Medicação/etnologia , Americanos Mexicanos , Autocuidado/psicologia
4.
J Allergy Clin Immunol ; 126(6): 1198-204.e4, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21047675

RESUMO

BACKGROUND: Increased numbers of mast cells are present in the esophageal epithelium in patients with eosinophilic esophagitis (EE). However, mast cell infiltration into the esophageal lamina propria (LP) and smooth muscle (SM) and the effects of their products on SM function has not been determined. OBJECTIVE: We investigated mast cell localization and characterization in esophageal SM, the functional significance of mast cell TGF-ß1 expression to contraction of human esophageal smooth muscle (HESM) cells in vitro, and the effect of topical corticosteroids on the number of tryptase-positive (MC(T)) and chymase-positive (MC(C)) mast cells in patients with EE. METHODS: MC(T)- and MC(C)-positive mast cell numbers were quantitated in the epithelium, the LP before and after topical corticosteroid therapy, and the muscularis mucosa in patients with EE and control subjects by using immunohistology. Double immunofluorescence was used to assess mast cell production of TGF-ß1. The ability of TGF-ß1 to influence HESM cell contractility was assessed in vitro. RESULTS: In the SM in patients with EE, significantly increased numbers of MC(T)- and TGF-ß1-positive cells (but only low levels of eosinophils) were detected compared with those seen in control subjects. MC(T) expressed TGF-ß1, which increased the contractility of cultured primary HESM cells in vitro. Topical corticosteroid therapy in patients with EE significantly reduced epithelial MC(T) numbers but not LP tryptase-chymase-positive mast cell numbers. CONCLUSIONS: MC(T) numbers, rather than eosinophil numbers, are increased in the SM in patients with EE, express TGF-ß1, and increase the contractility of HESM cells in vitro. As such, mast cells localized to SM in patients with EE might modulate esophageal contractility.


Assuntos
Corticosteroides/administração & dosagem , Esofagite Eosinofílica/imunologia , Esôfago/metabolismo , Mastócitos/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Adolescente , Contagem de Células , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Criança , Pré-Escolar , Quimases/biossíntese , Esofagite Eosinofílica/tratamento farmacológico , Esofagite Eosinofílica/patologia , Esofagite Eosinofílica/fisiopatologia , Esôfago/patologia , Feminino , Humanos , Lactente , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Mastócitos/patologia , Mucosa/patologia , Contração Muscular/efeitos dos fármacos , Músculo Liso/fisiologia , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/imunologia , Triptases/biossíntese
5.
Ann Allergy Asthma Immunol ; 103(5): 401-6, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19927538

RESUMO

BACKGROUND: Eosinophilic esophagitis (EE) is an increasingly recognized allergic disease entity that is difficult to distinguish clinically from other causes of esophagitis, especially gastroesophageal reflux disease (GERD). To our knowledge, there are no prospectively analyzed or validated symptom scoring tools for pediatric patients with EE and no prospective evaluation correlating symptoms with tissue inflammation. OBJECTIVES: To prospectively analyze a symptom scoring tool's ability to distinguish pediatric patients with EE from those with GERD and from control patients with and without allergies and to correlate symptoms with tissue inflammation. METHODS: A prospective study of a symptom scoring tool given to patients with EE (n = 35 not receiving EE targeted therapy), patients with GERD (n = 27 not undergoing acid suppression), allergic control patients (n = 24), and nonallergic control patients (n = 14) at an academic pediatric hospital. Histology and endoscopy scores were correlated with symptom complaints. RESULTS: The total symptom score was higher among patients with EE (mean, 6.51; 95% confidence interval [CI], 5.50-7.53) and GERD (mean, 5.44; 95% CI, 4.64-6.25) than in allergic (mean, 0.92; 95% CI, 0.28-1.55) and nonallergic (mean, 1.00; 95% CI, 0.40-1.60) patients (P < .001). Patients with EE and GERD complained of more nausea/vomiting, abdominal pain, heartburn/regurgitation, and nocturnal awakening than control groups (P < .001). Only dysphagia (mean, 0.9 [95% CI, 0.7-1.2] in EE patients vs 0.4 [95% CI, 0.2-0.7] in GERD patients) and anorexia/early satiety (mean, 1.4 [95% CI, 1.2-1.6] in EE patients vs 0.8 [95% CI, 0.5-1.1] in GERD patients) discriminate EE from GERD (P < .01). These symptoms also correlated with the severity of histologic and endoscopic findings (P < .05). CONCLUSION: Dysphagia and anorexia/early satiety identify pediatric patients with EE and correlate symptoms with tissue inflammation.


Assuntos
Anorexia/diagnóstico , Transtornos de Deglutição/diagnóstico , Eosinofilia/diagnóstico , Esofagite/diagnóstico , Resposta de Saciedade , Anorexia/patologia , Anorexia/fisiopatologia , Criança , Transtornos de Deglutição/patologia , Transtornos de Deglutição/fisiopatologia , Diagnóstico Diferencial , Eosinofilia/patologia , Eosinofilia/fisiopatologia , Esofagite/patologia , Esofagite/fisiopatologia , Feminino , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/patologia , Refluxo Gastroesofágico/fisiopatologia , Humanos , Masculino , Estudos Prospectivos
6.
Pediatr Infect Dis J ; 27(5): 377-83, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18398382

RESUMO

Kawasaki syndrome (KS) is the most common cause of acquired pediatric heart disease in the developed world. There have been 2 distinctive patterns for the emergence of KS that are likely related to several factors including exposure to the causative agent(s) and host genetics. In Europe and North America where we presume the genetic susceptibility seems to be low, KS has existed in the pediatric population for more than a century and is associated with relatively low incidence. In Japan where genetic susceptibility is presumed to be high, KS seems not to have existed before the early 1950s. This relatively recent exposure has resulted in 3 nationwide epidemics and a high current endemic rate of 200 per 100,000 in children less than 5 years. If our history of alternative patterns of the emergence of KS is valid, it may prove useful as a predictive tool for countries including India, where clusters of KS cases have been recently reported. This article examines the historical evidence in support of a 2-tiered emergence of KS in Euro-America and Japan and then returns briefly to discuss its implications for the pediatric populations of India and the health care delivery systems in the developing world.


Assuntos
Síndrome de Linfonodos Mucocutâneos/epidemiologia , Criança , Pré-Escolar , Países em Desenvolvimento , Doenças Endêmicas , Europa (Continente)/epidemiologia , Feminino , História do Século XX , História do Século XXI , Humanos , Índia/epidemiologia , Lactente , Japão/epidemiologia , Masculino , Síndrome de Linfonodos Mucocutâneos/história , América do Norte/epidemiologia
7.
Am J Gastroenterol ; 102(10): 2271-9; quiz 2280, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17581266

RESUMO

BACKGROUND: Eosinophilic esophagitis (EE) is a disorder characterized typically by pan-esophageal eosinophilia. We evaluate a palatable, long-acting topical corticosteroid preparation for the treatment of EE. STUDY DESIGN: This is a retrospective analysis of symptoms, endoscopic and histologic findings, efficacy, and safety of treatment in children with EE receiving oral viscous budesonide. Response to therapy was determined histologically by the number of eos/hpf. Patients were classified by histology into responders (0-7 eos/hpf), partial responders (8-23 eos/hpf), and nonresponders (>/=24 eos/hpf). A symptom score (max. 14) and an EE endoscopy score (max. 8) were used to compare data. RESULTS: In 20 children (mean age 5.5 yr, median age 4.1 yr) the mean highest eosinophil count was 87 eos/hpf (range 30-170) before and 7 eos/hpf (range 0-50, P < 0.0001) after therapy. There were 16 (80%) responders, 1 partial responder, and 3 nonresponders. Commonest pretreatment symptoms were nausea, vomiting, pain, and heartburn. The mean symptom score fell from 4.4 to 0.8 (P < 0.0001) and the mean endoscopy score from 3.6 to 0.8 (P < 0.0001). No significant adverse events were reported. Morning cortisol levels were within normal limits. CONCLUSIONS: Topical viscous budesonide is a safe and effective therapy for EE in young children.


Assuntos
Budesonida/administração & dosagem , Eosinofilia/tratamento farmacológico , Esofagite/tratamento farmacológico , Glucocorticoides/administração & dosagem , Administração Oral , Adolescente , Criança , Pré-Escolar , Eosinofilia/complicações , Eosinofilia/patologia , Esofagite/etiologia , Esofagite/patologia , Feminino , Seguimentos , Humanos , Lactente , Masculino , Estudos Retrospectivos , Suspensões , Resultado do Tratamento , Viscosidade
8.
Pediatr Infect Dis J ; 26(3): 256-60, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17484225

RESUMO

BACKGROUND: A diagnosis of Kawasaki syndrome is based on clinical criteria with nonspecific laboratory findings, and there is a substantial risk of coronary artery aneurysms if treatment with intravenous immunoglobulin is delayed. In this study, we examined the contributions of sociodemographic factors and parent and physician behavior to the development of coronary artery aneurysms in children with Kawasaki syndrome. METHODS: We performed a retrospective, case-control chart review of Kawasaki syndrome patients treated at our institution during an 11-year period (1991-2002). Of 324 patients, 21 patients had coronary artery aneurysms and were matched with 81 Kawasaki syndrome control patients without coronary artery aneurysms. RESULTS: Patients who developed coronary artery aneurysms were more likely to have had their diagnosis established after 10 days of fever as a result of a delay in physician recognition of Kawasaki syndrome. In addition, these patients were also more likely to have been hospitalized at an outside facility with an erroneous diagnosis, to have had a greater number of healthcare visits before diagnosis, to have sought medical care in Mexico, to lack medical insurance and to speak Spanish as a primary language. Independent predictors of delayed diagnosis included incomplete clinical signs of Kawasaki syndrome, seeking health care in Mexico, and being hospitalized at an outside facility with a different diagnosis. CONCLUSIONS: Increased risk of coronary artery aneurysms is associated with a delay in diagnosis by physicians and not with a delay in seeking medical consultation by parents. Sociodemographic factors influence the likelihood that patients will have a delayed diagnosis.


Assuntos
Aneurisma Coronário/complicações , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Médicos , Estudos Retrospectivos , Fatores de Tempo
9.
J Clin Gastroenterol ; 41(3): 252-6, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17426462

RESUMO

GOALS: To determine the clinical, endoscopic, and histologic criteria that distinguish children with eosinophilic esophagitis (EE) from those with non-EE diagnoses. BACKGROUND: EE is a disease of escalating incidence. Distinguishing children with EE from those with non-EE diagnosis can be difficult before endoscopy. STUDY: A retrospective case-control study was performed for children with any degree of esophageal eosinophilic inflammation who underwent esophageal biopsy at Children's Hospital San Diego from January 1998 to December 2002. A database containing children who met histologic criteria for EE and an equivalent number of children who had milder esophageal eosinophilia (non-EE patients) was created to compare the 2 groups. RESULTS: The number of EE cases increased from 15 in 1998 to 35 in 2002. EE patients were predominantly school-aged boys; 5 of 102 were suspected to have EE before biopsy. Although EE and non-EE patients complained of vomiting and abdominal pain at equivalent rates, EE patients were 3 times more likely to complain of dysphagia [odds ratio (OR)=3.11, 95% confidence interval (CI) 1.55-6.65] and twice as likely to have stricture formation (OR=2.43, 95% CI 0.72-11.75). On endoscopy, patients with EE were 19-times more likely than non-EE patients to have endoscopic abnormalities (OR=19, 95% CI 9.0-45.88). Histologically, EE patients were more likely to have basal zone hyperplasia and degranulated eosinophils (OR=45 and 157, respectively). CONCLUSIONS: We demonstrate that school-aged children, particularly boys, who complain of dysphagia should raise the index of suspicion for EE. We also suggest that EE-associated strictures are more common than peptic strictures in children.


Assuntos
Eosinofilia/diagnóstico , Esofagite/diagnóstico , Adolescente , Biópsia , Criança , Pré-Escolar , Transtornos de Deglutição/etiologia , Estenose Esofágica/etiologia , Esofagite/imunologia , Esofagite/patologia , Esofagoscopia , Feminino , Humanos , Masculino , Estudos Retrospectivos
10.
J Allergy Clin Immunol ; 119(1): 206-12, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17208603

RESUMO

BACKGROUND: Eosinophils are associated with airway remodeling in asthma, but studies have not yet determined whether eosinophilic esophagitis (EE) is associated with esophageal remodeling. OBJECTIVE: We performed quantitative immunohistochemical analysis of remodeling changes in esophageal biopsy specimens from children with and without EE to evaluate if there were changes in the esophagus of pediatric patients with EE akin to airway remodeling. In addition, we determined whether the esophagus of patients with EE had increased levels of expression of TGF-beta(1) and its signaling molecule, phosphorylated SMAD2/3 (phospho-SMAD2/3). METHODS: To determine esophageal levels of eosinophilic inflammation, fibrosis, and vascular activation, endoscopically obtained esophageal biopsy specimens from 7 patients with EE (5 strictured, 2 nonstrictured), 7 with gastroesophageal reflux disease, and 7 normal patients were processed for immunohistology, trichrome staining, and assessment of levels of expression of TGF-beta(1), phospho-SMAD2/3, and vascular cell adhesion molecule 1. RESULTS: Esophageal biopsies in patients with EE demonstrated increased levels of subepithelial fibrosis and increased expression of TGF-beta(1) and its signaling molecule phospho-SMAD2/3 compared with gastroesophageal reflux disease and normal control patients. In addition, esophageal biopsies in patients with EE demonstrated an increased vascular density and an increased expression of the vascular endothelial adhesion molecule, vascular cell adhesion molecule 1. CONCLUSION: Previously unrecognized esophageal remodeling changes analogous to aspects of airway remodeling are detectable in the subepithelial region of the esophagus in pediatric patients with EE. CLINICAL IMPLICATIONS: Pediatric patients with EE demonstrate increased fibrosis, vascularity, and vascular activation in the esophagus that may contribute to stricture formation and potentially provide a basis for stratifying patients with EE on the basis of disease severity and/or prognosis.


Assuntos
Eosinofilia/patologia , Esofagite/patologia , Esôfago/patologia , Adolescente , Criança , Pré-Escolar , Eosinofilia/complicações , Eosinofilia/metabolismo , Esofagite/complicações , Esofagite/metabolismo , Esôfago/irrigação sanguínea , Esôfago/metabolismo , Feminino , Fibrose/etiologia , Fibrose/patologia , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/metabolismo , Refluxo Gastroesofágico/patologia , Humanos , Masculino , Proteínas Smad Reguladas por Receptor/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
11.
Curr Allergy Asthma Rep ; 6(6): 468-74, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17026873

RESUMO

Primary immunodeficiency disorders (PIDs) continue to illuminate mechanisms of human immunity and hypersensitivity. New discoveries in common variable immunodeficiency, the most enigmatic of PID syndromes, reveal molecular pathways of importance in human antibody production. FOXP3 mutations demonstrate the essential role that T-regulatory cells play in controlling autoantibody formation and disease. Interleukin-1 receptor-associated kinase 4 deficiency emphasizes the key role that innate immunity plays in the defense of bacterial disease occurring early in life. With respect to therapy, subcutaneous immunoglobulin treatment may indeed be a better treatment than intravenous immunoglobulin for many patients with antibody deficiency. Finally, PIDs remain in the vanguard for the treatment of inherited disorders by gene therapy. Gene therapy has cured patients with chronic granulomatous disease and severe combined immunodeficiency, but not without morbidity and mortality. Into the 21st century, PIDs continue to instruct us in human health and disease.


Assuntos
Formação de Anticorpos/genética , Imunodeficiência de Variável Comum/genética , Fatores de Transcrição Forkhead/genética , Imunidade Inata/genética , Quinases Associadas a Receptores de Interleucina-1/deficiência , Formação de Anticorpos/imunologia , Autoanticorpos/genética , Autoanticorpos/imunologia , Criança , Pré-Escolar , Imunodeficiência de Variável Comum/imunologia , Imunodeficiência de Variável Comum/terapia , Feminino , Fatores de Transcrição Forkhead/imunologia , Terapia Genética/métodos , Terapia Genética/mortalidade , Doença Granulomatosa Crônica/genética , Doença Granulomatosa Crônica/imunologia , Doença Granulomatosa Crônica/mortalidade , Doença Granulomatosa Crônica/terapia , Humanos , Imunidade Inata/imunologia , Masculino , Imunodeficiência Combinada Severa/genética , Imunodeficiência Combinada Severa/imunologia , Imunodeficiência Combinada Severa/mortalidade , Imunodeficiência Combinada Severa/terapia , Linfócitos T Reguladores/imunologia
13.
J Exp Med ; 202(2): 209-15, 2005 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-16009720

RESUMO

Golden color imparted by carotenoid pigments is the eponymous feature of the human pathogen Staphylococcus aureus. Here we demonstrate a role of this hallmark phenotype in virulence. Compared with the wild-type (WT) bacterium, a S. aureus mutant with disrupted carotenoid biosynthesis is more susceptible to oxidant killing, has impaired neutrophil survival, and is less pathogenic in a mouse subcutaneous abscess model. The survival advantage of WT S. aureus over the carotenoid-deficient mutant is lost upon inhibition of neutrophil oxidative burst or in human or murine nicotinamide adenine dinucleotide phosphate oxidase-deficient hosts. Conversely, heterologous expression of the S. aureus carotenoid in the nonpigmented Streptococcus pyogenes confers enhanced oxidant and neutrophil resistance and increased animal virulence. Blocking S. aureus carotenogenesis increases oxidant sensitivity and decreases whole-blood survival, suggesting a novel target for antibiotic therapy.


Assuntos
Carotenoides/genética , Regulação Bacteriana da Expressão Gênica , Estresse Oxidativo/genética , Infecções Estafilocócicas/genética , Staphylococcus aureus/genética , Staphylococcus aureus/patogenicidade , Abscesso/metabolismo , Abscesso/microbiologia , Abscesso/patologia , Adolescente , Animais , Antioxidantes/metabolismo , Carotenoides/biossíntese , Modelos Animais de Doenças , Feminino , Regulação Bacteriana da Expressão Gênica/genética , Humanos , Camundongos , Camundongos Knockout , Neutrófilos/metabolismo , Neutrófilos/microbiologia , Neutrófilos/patologia , Pele/metabolismo , Pele/microbiologia , Pele/patologia , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/patologia , Staphylococcus aureus/metabolismo , Streptococcus pyogenes/genética , Streptococcus pyogenes/patogenicidade , Virulência/genética
14.
J Pediatr ; 146(5): 662-7, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15870671

RESUMO

OBJECTIVE: To evaluate the use of tumor necrosis factor (TNF)-alpha blockade for treatment of patients with Kawasaki syndrome (KS) who fail to become afebrile or who experience persistent arthritis after treatment with intravenous gamma globulin (IVIG) and high-dose aspirin. STUDY DESIGN: Cases were retrospectively collected from clinicians throughout the United States who had used infliximab, a chimeric murine/human immunoglobulin (Ig)G1 monoclonal antibody that binds specifically to human TNF-alpha-1, for patients with KS who had either persistent arthritis or persistent or recrudescent fever > or =48 hours following infusion of 2 g/kg of IVIG. RESULTS: Response to therapy with cessation of fever occurred in 13 of 16 patients. C-reactive protein (CRP) level was elevated in all but one patient before infliximab infusion, and the level was lower following infusion in all 10 patients in whom it was re-measured within 48 hours of treatment. There were no infusion reactions to infliximab and no complications attributed to infliximab administration in any of the patients. CONCLUSION: The success of TNF-alpha blockade in this small series of patients suggests a central role of TNF-alpha in KS pathogenesis. Controlled, randomized clinical trials are warranted to determine the role of anti-TNF-alpha therapy in KS.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Aspirina/uso terapêutico , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adolescente , Criança , Pré-Escolar , Feminino , Febre/tratamento farmacológico , Humanos , Imunoglobulinas Intravenosas , Lactente , Infliximab , Masculino , Síndrome de Linfonodos Mucocutâneos/fisiopatologia , Estudos Retrospectivos , Resultado do Tratamento
15.
Pediatr Infect Dis J ; 23(8): 789-91, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15295237

RESUMO

To learn about physician practices in diagnosing Kawasaki disease, we surveyed general pediatricians and pediatric infectious disease physicians by questionnaire. A high proportion of general pediatricians (>50%) and infectious disease subspecialists (25%) did not consider the diagnosis of Kawasaki disease in children younger than 6 months and older than 8 years. Failure to consider the diagnosis at the extremes of the pediatric age range puts children at risk because coronary artery abnormalities occur more often in young infants and adolescents with Kawasaki disease.


Assuntos
Síndrome de Linfonodos Mucocutâneos/diagnóstico , Pediatria/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Fatores Etários , Criança , Pré-Escolar , Doença da Artéria Coronariana/etiologia , Diagnóstico Diferencial , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Lactente , Recém-Nascido , Masculino , Fatores de Risco
16.
Bull Hist Med ; 78(2): 410-39, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15211054

RESUMO

Kawasaki disease is a rash/fever illness of early childhood in which coronary artery aneurysms (CAA), sometimes fatal, may develop in up to 25 percent of untreated children. Because its etiology and pathophysiology are unknown and no diagnostic laboratory test exists, diagnosis is made via a list of clinical signs; however, a significant number of children fail to meet the clinical criteria and go on to develop CAA. We suspected a connection between these missed cases and the continuing difficulty in identifying the etiological agent(s) and mechanisms for CAA. In search of that connection, we launched a historical investigation into the institutionalization of the clinical criteria, and explored how this process influenced the framing of research questions. Our findings suggest that the canonization of the Kawasaki disease case definition was as much due to the enshrinement of the historical narrative as to compelling scientific findings. The Kawasaki disease narrative encompasses interrelated issues of definition, discovery, and naming; these, in turn, have profoundly influenced diagnosis, treatment, and research. "Atypical" cases, despite being at risk for CAA, often fail to receive prompt diagnosis and treatment; consequently, research has been limited to the population that meets the diagnostic criteria for Kawasaki disease, rather than including those who are at risk of CAA. Although clinical concerns prompted this investigation, it nevertheless has important implications for the history of medicine: it provides an illustration of how a historical interrogation of a syndrome's construction can free medical researchers to pursue novel approaches. Equally important, it demonstrates how historians can make unique contributions as collaborators in clinical care and medical research.


Assuntos
Pesquisa Biomédica/história , Síndrome de Linfonodos Mucocutâneos/história , Criança , Aneurisma Coronário/etiologia , Aneurisma Coronário/história , História do Século XX , Humanos , Japão , Síndrome de Linfonodos Mucocutâneos/classificação , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/fisiopatologia , Política , Síndrome , Estados Unidos
17.
Perspect Biol Med ; 46(2): 216-33, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12721522

RESUMO

This paper describes the historical evolution of the Kawasaki disease (KD) case definition and its limitations for identification and treatment of children at risk for coronary artery aneurysms (CAA). The dominant view of pathogenesis is that an unknown agent infects infants and children, who then develop the signs of KD. Some of the infected infants and children then develop CAA, and a few die from myocardial infarction. Because the etiologic agent remains unknown, diagnosis of KD relies on observation and recognition of the clinical signs that comprise the KD case definition criteria. This approach has been successful in identifying and treating many children at risk for CAA. Unfortunately, however, it has delayed the effective treatment of children who fail to meet the KD case definition criteria but who, nevertheless, develop CAA. The original case definition was developed before the general acceptance of CAA as sequelae of KD, the availability of the echocardiogram, and effective treatment with intravenous immunoglobulin. Despite an evolution in awareness, detection, and treatment of possible CAA sequela, the case definition has not been altered so as to incorporate this knowledge. Our investigation explores the transformation of the case definition from an epidemiological instrument to a diagnostic tool. We urge the construction of a more sensitive KD case definition that includes signs and laboratory findings associated with CAA.


Assuntos
Síndrome de Linfonodos Mucocutâneos/diagnóstico , Criança , Aneurisma Coronário/etiologia , Anomalias dos Vasos Coronários/etiologia , Diagnóstico Diferencial , História do Século XX , História do Século XXI , Humanos , Lactente , Japão , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/história , Poliarterite Nodosa/diagnóstico , Síndrome de Stevens-Johnson/diagnóstico , Estados Unidos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA