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5.
N Engl J Med ; 360(5): 447-58, 2009 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-19179314

RESUMO

BACKGROUND: We investigated the long-term outcome of gene therapy for severe combined immunodeficiency (SCID) due to the lack of adenosine deaminase (ADA), a fatal disorder of purine metabolism and immunodeficiency. METHODS: We infused autologous CD34+ bone marrow cells transduced with a retroviral vector containing the ADA gene into 10 children with SCID due to ADA deficiency who lacked an HLA-identical sibling donor, after nonmyeloablative conditioning with busulfan. Enzyme-replacement therapy was not given after infusion of the cells. RESULTS: All patients are alive after a median follow-up of 4.0 years (range, 1.8 to 8.0). Transduced hematopoietic stem cells have stably engrafted and differentiated into myeloid cells containing ADA (mean range at 1 year in bone marrow lineages, 3.5 to 8.9%) and lymphoid cells (mean range in peripheral blood, 52.4 to 88.0%). Eight patients do not require enzyme-replacement therapy, their blood cells continue to express ADA, and they have no signs of defective detoxification of purine metabolites. Nine patients had immune reconstitution with increases in T-cell counts (median count at 3 years, 1.07x10(9) per liter) and normalization of T-cell function. In the five patients in whom intravenous immune globulin replacement was discontinued, antigen-specific antibody responses were elicited after exposure to vaccines or viral antigens. Effective protection against infections and improvement in physical development made a normal lifestyle possible. Serious adverse events included prolonged neutropenia (in two patients), hypertension (in one), central-venous-catheter-related infections (in two), Epstein-Barr virus reactivation (in one), and autoimmune hepatitis (in one). CONCLUSIONS: Gene therapy, combined with reduced-intensity conditioning, is a safe and effective treatment for SCID in patients with ADA deficiency. (ClinicalTrials.gov numbers, NCT00598481 and NCT00599781.)


Assuntos
Adenosina Desaminase/genética , Antígenos CD34/genética , Terapia Genética , Transplante de Células-Tronco Hematopoéticas , Imunodeficiência Combinada Severa/terapia , Adenosina Desaminase/deficiência , Células da Medula Óssea/imunologia , Pré-Escolar , Terapia Combinada , Seguimentos , Vetores Genéticos , Humanos , Lactente , Contagem de Linfócitos , Retroviridae , Imunodeficiência Combinada Severa/imunologia , Transdução Genética , Condicionamento Pré-Transplante
6.
Blood ; 115(16): 3231-8, 2010 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-20173115

RESUMO

A large proportion of patients with mutations in the Wiskott-Aldrich syndrome (WAS) protein gene exhibit the milder phenotype termed X-linked thrombocytopenia (XLT). Whereas stem cell transplantation at an early age is the treatment of choice for patients with WAS, therapeutic options for patients with XLT are controversial. In a retrospective multicenter study we defined the clinical phenotype of XLT and determined the probability of severe disease-related complications in patients older than 2 years with documented WAS gene mutations and mild-to-moderate eczema or mild, infrequent infections. Enrolled were 173 patients (median age, 11.5 years) from 12 countries spanning 2830 patient-years. Serious bleeding episodes occurred in 13.9%, life-threatening infections in 6.9%, autoimmunity in 12.1%, and malignancy in 5.2% of patients. Overall and event-free survival probabilities were not significantly influenced by the type of mutation or intravenous immunoglobulin or antibiotic prophylaxis. Splenectomy resulted in increased risk of severe infections. This analysis of the clinical outcome and molecular basis of patients with XLT shows excellent long-term survival but also a high probability of severe disease-related complications. These observations will allow better decision making when considering treatment options for individual patients with XLT.


Assuntos
Trombocitopenia/complicações , Trombocitopenia/mortalidade , Proteína da Síndrome de Wiskott-Aldrich/genética , Adolescente , Adulto , Idoso , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/etiologia , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Genes Ligados ao Cromossomo X , Hemorragia/epidemiologia , Hemorragia/etiologia , Humanos , Incidência , Infecções/epidemiologia , Infecções/etiologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mutação , Neoplasias/epidemiologia , Neoplasias/etiologia , Fenótipo , Estudos Retrospectivos , Trombocitopenia/genética , Adulto Jovem
7.
Nat Commun ; 13(1): 700, 2022 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-35121733

RESUMO

SP7/Osterix is a transcription factor critical for osteoblast maturation and bone formation. Homozygous loss-of-function mutations in SP7 cause osteogenesis imperfecta type XII, but neomorphic (gain-of-new-function) mutations of SP7 have not been reported in humans. Here we describe a de novo dominant neomorphic missense variant (c.926 C > G:p.S309W) in SP7 in a patient with craniosynostosis, cranial hyperostosis, and long bone fragility. Histomorphometry shows increased osteoblasts but decreased bone mineralization. Mice with the corresponding variant also show a complex skeletal phenotype distinct from that of Sp7-null mice. The mutation alters the binding specificity of SP7 from AT-rich motifs to a GC-consensus sequence (typical of other SP family members) and produces an aberrant gene expression profile, including increased expression of Col1a1 and endogenous Sp7, but decreased expression of genes involved in matrix mineralization. Our study identifies a pathogenic mechanism in which a mutation in a transcription factor shifts DNA binding specificity and provides important in vivo evidence that the affinity of SP7 for AT-rich motifs, unique among SP proteins, is critical for normal osteoblast differentiation.


Assuntos
Doenças Ósseas/genética , Osso e Ossos/metabolismo , Regulação da Expressão Gênica , Mutação , Fator de Transcrição Sp7/genética , Animais , Doenças Ósseas/metabolismo , Diferenciação Celular/genética , Linhagem Celular , Células Cultivadas , Criança , Células HEK293 , Humanos , Hibridização In Situ , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Osteoblastos/citologia , Osteoblastos/metabolismo , Fator de Transcrição Sp7/metabolismo , Microtomografia por Raio-X
8.
Front Pediatr ; 10: 744182, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35601438

RESUMO

Background: Pediatric osteoarticular infections (POAIs) are serious diseases requiring early diagnosis and treatment. Methods: In this prospective multicenter cohort study, children with POAIs were selected from the European Union Childhood Life-threatening Infectious Diseases Study (EUCLIDS) database to analyze their demographic, clinical, and microbiological data. Results: A cohort of 380 patients with POAIs, 203 with osteomyelitis (OM), 158 with septic arthritis (SA), and 19 with both OM and SA, was analyzed. Thirty-five patients were admitted to the Pediatric Intensive Care Unit; out of these, six suffered from shock, one needed an amputation of the right foot and of four left toes, and two had skin transplantation. According to the Pediatric Overall Performance Score, 36 (10.5%) showed a mild overall disability, 3 (0.8%) a moderate, and 1 (0.2%) a severe overall disability at discharge. A causative organism was detected in 65% (247/380) of patients. Staphylococcus aureus (S. aureus) was identified in 57.1% (141/247) of microbiological confirmed cases, including 1 (0.7%) methicillin-resistant S. aureus (MRSA) and 6 (4.2%) Panton-Valentine leukocidin (PVL)-producing S. aureus, followed by Group A Streptococcus (18.2%) and Kingella kingae (8.9%). K. kingae and PVL production in S. aureus were less frequently reported than expected from the literature. Conclusion: POAIs are associated with a substantial morbidity in European children, with S. aureus being the major detected pathogen. In one-third of patients, no causative organism is identified. Our observations show an urgent need for the development of a vaccine against S. aureus and for the development of new microbiologic diagnostic guidelines for POAIs in European pediatric hospitals.

9.
J Clin Invest ; 118(9): 3132-42, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18688285

RESUMO

Previously, several individuals with X-linked SCID (SCID-X1) were treated by gene therapy to restore the missing IL-2 receptor gamma (IL2RG) gene to CD34+ BM precursor cells using gammaretroviral vectors. While 9 of 10 patients were successfully treated, 4 of the 9 developed T cell leukemia 31-68 months after gene therapy. In 2 of these cases, blast cells contained activating vector insertions near the LIM domain-only 2 (LMO2) proto-oncogene. Here, we report data on the 2 most recent adverse events, which occurred in patients 7 and 10. In patient 10, blast cells contained an integrated vector near LMO2 and a second integrated vector near the proto-oncogene BMI1. In patient 7, blast cells contained an integrated vector near a third proto-oncogene,CCND2. Additional genetic abnormalities in the patients' blast cells included chromosomal translocations, gain-of-function mutations activating NOTCH1, and copy number changes, including deletion of tumor suppressor gene CDKN2A, 6q interstitial losses, and SIL-TAL1 rearrangement. These findings functionally specify a genetic network that controls growth in T cell progenitors. Chemotherapy led to sustained remission in 3 of the 4 cases of T cell leukemia, but failed in the fourth. Successful chemotherapy was associated with restoration of polyclonal transduced T cell populations. As a result, the treated patients continued to benefit from therapeutic gene transfer.


Assuntos
Cromossomos Humanos X , Terapia Genética/efeitos adversos , Terapia Genética/métodos , Leucemia de Células T/etiologia , Imunodeficiência Combinada Severa/terapia , Proteínas Adaptadoras de Transdução de Sinal , Antineoplásicos/farmacologia , Aberrações Cromossômicas , Ciclina D2 , Ciclinas/genética , Proteínas de Ligação a DNA/genética , Gammaretrovirus/metabolismo , Humanos , Lactente , Janus Quinase 3/genética , Proteínas com Domínio LIM , Leucemia de Células T/complicações , Leucemia de Células T/terapia , Metaloproteínas/genética , Modelos Biológicos , Mutação , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas , Receptores de Interleucina-2/genética , Imunodeficiência Combinada Severa/complicações
10.
Mycoses ; 54(6): e785-8, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21623951

RESUMO

Mucormycosis is associated with high morbidity and mortality and is perceived as an emerging fungal infection. However, contemporary paediatric data are limited. We present a series of paediatric cases of mucormycosis reported from Germany and Austria collected within a voluntary epidemiological survey through standardised, anonymized case report forms. Twelve cases were reported between January 2004 and December 2008 (six men; mean age: 12.6 years, range: 0.1-17 years). Mucormycosis was proven in nine, and probable in three cases. Isolates included Lichtheimia (syn. Absidia pro parte, Mycocladus) (five), Rhizopus (three) and Mucor (one) species. Infection was limited to soft tissue in three cases, the lung in two cases, and an infected thrombus in one case; rhinocerebral disease was found in three cases, and pulmonary-mediastinal, pulmonary-cerebral and soft tissue-cerebral involvement in one case each. All three patients with isolated soft tissue infection were cured, whereas seven of the remaining patients died (one patient without follow-up). The overall mortality rate was 67%. While these data cannot provide conclusive data on incidence and disease burden of mucormycosis in paediatric patients, they reflect the continuing threat of these infections to immunocompromised patients and the need for improved diagnosis and management.


Assuntos
Mucorales/isolamento & purificação , Mucormicose/epidemiologia , Mucormicose/microbiologia , Adolescente , Áustria/epidemiologia , Criança , Demografia , Feminino , Alemanha/epidemiologia , Humanos , Lactente , Masculino , Mucorales/classificação , Mucormicose/tratamento farmacológico , Mucormicose/patologia , Fatores de Risco , Análise de Sobrevida , Resultado do Tratamento
11.
J Pediatr Endocrinol Metab ; 23(3): 297-302, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20480731

RESUMO

AIM: To discuss the overlapping clinical spectrum of encephalopathy due to Addison's disease and HIV infection. PATIENT: We report a 2.5-year-old boy from Uzbekistan with recurrent episodes of encephalopathy and seizures, triggered by infection or vaccinations, in whom adrenal insufficiency and infection with HIV and HCV was diagnosed. Presumably, Addisonian crises prompted hypovolemic shock and blood transfusions, which were responsible for horizontal HIV infection. The combination of adrenal insufficiency and HIV infection eventually led to progressive severe encephalopathy. Despite highly active antiretroviral therapy (which led to substantial reduction of blood viral load), the neurological condition did not improve. DISCUSSION: The interactions of Addison's disease and HIV in the pathogenesis of encephalopathy are discussed.


Assuntos
Complexo AIDS Demência/complicações , Doença de Addison/complicações , Infecções por HIV/complicações , HIV-1 , Complexo AIDS Demência/patologia , Terapia Antirretroviral de Alta Atividade , Pré-Escolar , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/transmissão , HIV-1/imunologia , Humanos , Masculino , Choque/etiologia , Choque/terapia , Reação Transfusional , Resultado do Tratamento , Uzbequistão/etnologia
12.
HIV Med ; 10(10): 591-613, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19878352

RESUMO

PENTA Guidelines aim to provide practical recommendations for treating children with HIV infection in Europe. Changes to guidance since 2004 have been informed by new evidence and by expectations of better outcomes following the ongoing success of antiretroviral therapy (ART). Participation in PENTA trials of simplifying treatment is encouraged. The main changes are in the following sections: 'When to start ART': Treatment is recommended for all infants, and at higher CD4 cell counts and percentages in older children, in line with changes to adult guidelines. The number of age bands has been reduced to simplify and harmonize with other paediatric guidelines. Greater emphasis is placed on CD4 cell count in children over 5 years, and guidance is provided where CD4% and CD4 criteria differ. 'What to start with': A three-drug regimen of two nucleoside reverse transcriptase inhibitors (NRTIs) with either a nonnucleoside reverse transcriptase inhibitor (NNRTI) or a boosted protease inhibitor (PI) remains the first choice combination. Lamivudine and abacavir are the NRTI backbone of choice for most children, based on long-term follow-up in the PENTA 5 trial. Stavudine is no longer recommended. Whether to start with an NNRTI or PI remains unclear, but PENPACT 1 trial results in 2009 may help to inform this. All PIs should be ritonavir boosted. Recommendations on use of resistance testing, therapeutic drug monitoring and HLA testing draw from data in adults and from European paediatric cohort studies. Recently updated US and WHO paediatric guidelines provide more detailed review of the evidence base. Differences between guidelines are highlighted and explained.


Assuntos
Antirretrovirais/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Infecções por HIV/tratamento farmacológico , HIV-1 , Adolescente , Adulto , Fatores Etários , Anti-Infecciosos/uso terapêutico , Criança , Pré-Escolar , Farmacorresistência Viral , Europa (Continente) , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/transmissão , Sobreviventes de Longo Prazo ao HIV , Hepatite Viral Humana/complicações , Hepatite Viral Humana/tratamento farmacológico , Humanos , Lactente , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Educação de Pacientes como Assunto , Pneumonia por Pneumocystis/prevenção & controle , Gravidez , RNA Viral/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto , Falha de Tratamento , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Tuberculose/complicações , Tuberculose/tratamento farmacológico , Adulto Jovem
13.
J Pediatr ; 154(6): 888-94, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19230900

RESUMO

OBJECTIVE: To characterize common variable immunodeficiency disorder (CVID) in childhood. STUDY DESIGN: We retrospectively investigated clinical findings in 32 children with primary CVID by questionnaire and file review. RESULTS: Clinical presentation included recurrent or chronic respiratory tract infections (88%), sinusitis (78%), otitis media (78%), and intestinal tract infections (34%), mainly with encapsulated bacteria. Meningitis was found in 25%, sepsis in 16%, and pyelonephritis in 16% of patients. Poliomyelitis after vaccination occurred in 2 patients and opportunistic infections occasionally. Allergic disorders were present in 38%, and autoimmune disease in 31% of patients. Eighty percent of the patients underwent surgical procedures because of recurrent infections. Growth retardation was seen in 28% of patients, and 16% showed retarded mental development. Bronchiectasis developed in 34%, and lymphoid proliferative disease in 13%. Incidence of allergic and autoimmune diseases was increased in first-degree relatives with normal immunologic findings. Mean time between symptoms and induction of immunoglobulin substitution therapy was 5.8 years (0.2-14.3). CONCLUSIONS: CVID in children presents with comparable symptoms and disorders as in adults. We found a significant influence on growth and development. The marked delay of diagnosis may be due to overlap with common pediatric disorders, while also reflecting insufficient awareness of these disorders.


Assuntos
Imunodeficiência de Variável Comum/diagnóstico , Adolescente , Doenças Autoimunes/complicações , Doenças Autoimunes/imunologia , Criança , Pré-Escolar , Imunodeficiência de Variável Comum/complicações , Feminino , Humanos , Hipersensibilidade/complicações , Hipersensibilidade/imunologia , Lactente , Infecções/complicações , Infecções/imunologia , Masculino , Recidiva , Inquéritos e Questionários
14.
Pediatr Diabetes ; 10(4): 289-93, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18828793

RESUMO

To demonstrate that the 2-yr clinical follow-up of our patient strongly suggests that long-term therapy with posaconazole (POS) is safe and beneficial in treatment and prevention of relapses of, otherwise fatal, central nervous system mucormycosis. Mucormycosis is a very rare opportunistic mycotic infection of diabetic children. We present the 30-month follow-up of a 12-yr-old girl affected by diabetic ketoacidotic coma, complicated by rhinocerebral mucormycosis and successfully treated with POS at the initial daily dose of 5 mg/kg t.i.d. with fatty food for 3 wk, followed by a daily dose of 10 mg/kg in four doses for 2 months and then 20 mg/kg/d in four doses for 16 months and in two doses for further 5 months. The previous amphotericin B, granulocyte colony-stimulating factor, hyperbaric oxygen and nasal and left maxillary sinus surgical debridement therapy was ineffective in stopping the progression of the infection to the brain. The patient improved within 10 d with reduced ocular swelling and pain, and 6 months after therapy stop, she is in good health and cultures are sterile. This article demonstrates that POS may be a useful drug in mucormycosis in children. We also strongly draw the attention to the main preventive procedure against invasive fungal infection that is the correct management of antidiabetic therapy that prevents the predisposing temporary neutrophils activity deficit, contributing to a better survival rate of diabetic children.


Assuntos
Diabetes Mellitus Tipo 1/complicações , Cetoacidose Diabética/complicações , Mucormicose/tratamento farmacológico , Triazóis/uso terapêutico , Antifúngicos/efeitos adversos , Antifúngicos/uso terapêutico , Doenças do Sistema Nervoso Central/complicações , Doenças do Sistema Nervoso Central/tratamento farmacológico , Criança , Diabetes Mellitus Tipo 1/tratamento farmacológico , Cetoacidose Diabética/tratamento farmacológico , Feminino , Seguimentos , Humanos , Mucormicose/complicações , Doenças Nasais/complicações , Doenças Nasais/tratamento farmacológico , Doenças Orbitárias/complicações , Doenças Orbitárias/tratamento farmacológico , Fatores de Tempo , Resultado do Tratamento , Triazóis/efeitos adversos
15.
J Allergy Clin Immunol ; 121(2): 375-382.e9, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18155283

RESUMO

BACKGROUND: Chronic granulomatous disease (CGD) is the most common inherited disorder of neutrophil function, is caused by mutations in the reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and results in recurrent bacterial infections. OBJECTIVE: We sought to investigate the expression and function of innate immune receptors on neutrophils in patients with CGD. METHODS: We quantified mRNA and protein expression of Toll-like receptors (TLRs), complement receptors, and chemokine receptors on neutrophils from 15 patients with CGD compared with that seen in healthy control subjects (n = 15) and control patients with bacterial pneumonia (n = 15). Phagocytosis, chemotaxis, and TLR function of isolated neutrophils were analyzed. The effect of NADPH oxidase inhibition on receptor expression and function was analyzed in control neutrophils. RESULTS: Neutrophils from patients with CGD had lower expression levels of TLR5, TLR9, CD11b, CD18, CD35, and CXCR1 compared with those from healthy control subjects, whereas similar or increased receptor expressions were found in patients without CGD but with bacterial pneumonia. Reduced TLR5 expression resulted in impaired neutrophil activation by bacterial flagella, reduced CD11b/CD18 expression was associated with impaired phagocytosis of Staphylococcus aureus, and reduced CXCR1 expression was associated with decreased chemotaxis. TLR5 and CD18 expression levels correlated with disease severity in patients with CGD. TLR5 and TLR9 expression were greater in patients with residual NADPH oxidase activity. Inhibition of the NADPH oxidase in control neutrophils in vitro decreased TLR5 and TLR9 expression and impaired TLR5 function. CONCLUSION: These results provide the first evidence that innate immune receptors are dysregulated in patients with CGD.


Assuntos
Doença Granulomatosa Crônica/imunologia , Doença Granulomatosa Crônica/metabolismo , Imunidade Inata , Neutrófilos/metabolismo , Receptores Imunológicos/metabolismo , Adolescente , Adulto , Quimiotaxia de Leucócito , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Ativação de Neutrófilo , Fagocitose , Pneumonia Bacteriana/metabolismo , RNA Mensageiro/metabolismo , Receptores de Complemento/metabolismo , Receptores Imunológicos/genética , Receptores de Interleucina-8A/metabolismo , Índice de Gravidade de Doença , Staphylococcus aureus , Receptores Toll-Like/metabolismo
17.
AIDS ; 19(18): 2103-8, 2005 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-16284459

RESUMO

OBJECTIVE: In HIV-infected adults Pneumocystis jirovecii pneumonia (PCP) prophylaxis can be safely withdrawn after immune reconstitution due to the introduction of highly active antiretroviral therapy (HAART). With regard to children only a small amount of data has been published. The present study investigated whether the withdrawal of PCP prophylaxis after immune reconstitution is safe in HIV-infected children. METHODS: A retrospective analysis at 10 European centers belonging to the Pediatric European Network on the treatment of AIDS (PENTA) using a standardized questionnaire. RESULTS: A total of 113 questionnaires were received. In 82 children the indication for PCP prophylaxis was provided following Centers for Disease Control (CDC) guidelines (72 primary and 10 secondary). Prophylaxis was withdrawn after the CD4 cell count increased above the age-related CDC thresholds. The observation period off prophylaxis was 335 years (300 years for primary and 35 years for secondary prophylaxis) and the median time per patient off prophylaxis was 4.1 years (range, 0.3-7.7 years). No episode of PCP occurred during the study period. In comparison with the incidence rate from historical data before the introduction of PCP prophylaxis and HAART, this was a significant reduction (P < 0.05). CONCLUSIONS: The increase in CD4 cell count provides functional reconstitution of the immune system in children. Our data suggests that the risk of developing a PCP after immune reconstitution is sufficiently low to withdraw PCP prophylaxis.


Assuntos
Antifúngicos/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Pneumocystis carinii , Pneumonia por Pneumocystis/prevenção & controle , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Infecções por HIV/complicações , Humanos , Lactente , Pneumonia por Pneumocystis/complicações , Estudos Retrospectivos , Fatores de Risco , Carga Viral
18.
Eur J Med Res ; 10(12): 527-31, 2005 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-16356868

RESUMO

Focal viral encephalitis in childhood is a rare but life-threatening disease. Animal experiments and case reports suggest a positive effect of an additional therapy with interferon-beta on the course of the disease. Therefore, we initiated a prospective, double-blind placebo-controlled study to investigate the benefit of a combination therapy of Aciclovir (ACV) and recombinant interferon-beta (rIFN-beta) in juvenile focal viral encephalitis. - Initial inclusion criterium was suspicion of focal viral encephalitis. Diagnosis was proven by demonstration of characteristic focal lesions in cerebral imaging or virological evidence of HSV in cerebrospinal fluid. Patients were treated with ACV plus rIFN-beta or ACV plus placebo. Neurological outcome was determined 21 days and 3 months after onset of the disease. - Initially 59 patients were enrolled in the study. Encephalitis was proven in 14 patients (7 ACV + rIFN-beta, 7 ACV + placebo). The study groups were balanced in terms of important prognostic criteria. 10 patients (5 ACV + rIFN-beta, 5 ACV + placebo) were cured or had slight defects, 4 patients (2 ACV + rIFN-beta, 2 ACV + placebo) showed moderate to severe defects. There was no significant difference in favour of the additive therapy with rIFN-beta.


Assuntos
Aciclovir/uso terapêutico , Antivirais/uso terapêutico , Encefalite Viral/tratamento farmacológico , Infecção Focal/tratamento farmacológico , Herpes Simples/tratamento farmacológico , Interferon beta/uso terapêutico , Adolescente , Criança , Pré-Escolar , Método Duplo-Cego , Quimioterapia Combinada , Encefalite Viral/patologia , Encefalite Viral/fisiopatologia , Feminino , Infecção Focal/patologia , Herpes Simples/patologia , Humanos , Lactente , Masculino , Sistema Nervoso/patologia , Sistema Nervoso/fisiopatologia , Proteínas Recombinantes/uso terapêutico , Recuperação de Função Fisiológica/efeitos dos fármacos , Resultado do Tratamento
19.
AIDS ; 18(10): 1473-5, 2004 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-15199327

RESUMO

Five heavily pretreated HIV-infected children were put on amprenavir and delavirdine plus two nucleoside inhibitors to reverse transcriptase to boost amprenavir levels and to use the antiretroviral activity of a non-nucleoside reverse transcriptase inhibitor. No data are available about this combination in children. It w;as well tolerated, and the median reduction in viral load was 1.5 log after 18 months. Delavirdine boosted amprenavir trough levels more than 10-fold, and delavirdine trough levels remained i several fold above susceptible HIV strains.


Assuntos
Fármacos Anti-HIV/farmacocinética , Delavirdina/farmacocinética , Infecções por HIV/tratamento farmacológico , Inibidores da Transcriptase Reversa/farmacocinética , Sulfonamidas/farmacocinética , Adolescente , Área Sob a Curva , Carbamatos , Criança , Combinação de Medicamentos , Furanos , Humanos
20.
Pediatr Pulmonol ; 38(4): 344-8, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15334514

RESUMO

We report on a patient with the hitherto undescribed combination of chronic granulomatous disease, pulmonary hemosiderosis, and celiac disease. The hemosiderosis resolved with a gluten-free diet and glucocorticosteroid pulse therapy, but the restrictive lung function pattern remained unchanged. Lung function improved markedly by immunosuppression with daily glucocorticosteroid and azathioprine treatment.


Assuntos
Aconitina/análogos & derivados , Doença Celíaca/terapia , Doença Granulomatosa Crônica/terapia , Hemossiderose/terapia , Pneumopatias/terapia , Aconitina/uso terapêutico , Adjuvantes Imunológicos/uso terapêutico , Doença Celíaca/patologia , Tosse/etiologia , Dieta , Feminino , Glucocorticoides/uso terapêutico , Doença Granulomatosa Crônica/patologia , Hemossiderose/patologia , Humanos , Recém-Nascido , Pulmão/diagnóstico por imagem , Pulmão/patologia , Pneumopatias/complicações , Pneumopatias/patologia , Linfócitos T/metabolismo , Tomografia Computadorizada por Raios X , Capacidade Pulmonar Total , Resultado do Tratamento
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