Assuntos
Imunização Passiva/efeitos adversos , Imunoglobulinas/administração & dosagem , Imunoglobulinas/efeitos adversos , Infusões Subcutâneas/efeitos adversos , Ensaios Clínicos Fase III como Assunto , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Imunoglobulinas Intravenosas/efeitos adversos , Estudos ProspectivosRESUMO
The importance of serum immunoglobulin (Ig)G concentration in IgG replacement therapy for primary immunodeficiency diseases is established in certain settings. Generally, IgG is infused via the intravenous (IVIG) or subcutaneous (SCIG) route. For IVIG infusion, published data demonstrate that higher IgG doses and trough levels provide patients with improved protection from infection. The same conclusions are not yet accepted for SCIG; data from two recent Phase III studies and a recent post-hoc analysis, however, suggest the same correlation between higher SCIG dose and serum IgG concentration and decreased incidence of infection seen with IVIG. Other measures of clinical efficacy have not been considered similarly. Thus, combined analyses of these and other published SCIG studies were performed; a full comparison of the 13 studies was, however, limited by non-standardized definitions and reporting. Despite these limitations, our analyses indicate that certain clinical outcomes improve at higher SCIG doses and associated higher serum IgG concentrations, and suggest that there might be opportunity to improve patient outcomes via SCIG dose adjustment.
Assuntos
Imunização Passiva , Imunoglobulina G/administração & dosagem , Síndromes de Imunodeficiência/terapia , Infecções Bacterianas/etiologia , Humanos , Imunização Passiva/efeitos adversos , Imunoglobulina G/sangue , Síndromes de Imunodeficiência/complicações , Infusões Subcutâneas , Resultado do TratamentoRESUMO
BACKGROUND: The placebo-controlled study International Multicentre Prospective Angioedema C1-INH Trial 1 (I.M.P.A.C.T.1) demonstrated that 20 U/kg C1 esterase inhibitor (C1-INH) concentrate (Berinert®; CSL Behring, Marburg, Germany) is effective in treating acute abdominal and facial Hereditary Angioedema (HAE) attacks. METHODS: I.M.P.A.C.T.2 was an open-label extension study of I.M.P.A.C.T.1 to evaluate the safety and efficacy of long-term treatment with 20 U/kg C1-INH for successive HAE attacks at any body location. Efficacy outcomes included patient-reported time to onset of symptom relief (primary) and time to complete resolution of all symptoms (secondary), analysed on a per-patient and per-attack basis. Safety assessments included adverse events, vital signs, viral safety and anti-C1-INH antibodies. RESULTS: During a median study duration of 24 months, 1085 attacks were treated in 57 patients (10-53 years of age). In the per-patient analysis, the median time to onset of symptom relief was 0.46 h and was similar for all types of attacks (0.39-0.48 h); the median time to complete resolution of symptoms was 15.5 h (shortest for laryngeal attacks: 5.8 h; 12.8-26.6 h for abdominal, peripheral and facial attacks). Demographic factors, type of HAE, intensity of attacks, time to treatment, use of androgens and presence of anti-C1-INH antibodies had no clinically relevant effect on the efficacy outcomes. There were no treatment-related safety concerns. No inhibitory anti-C1-INH antibodies were detected in any patient. CONCLUSIONS: A single dose of 20 U/kg C1-INH concentrate is safe and provides reliable efficacy in the long-term treatment of successive HAE attacks at any body location.
Assuntos
Angioedemas Hereditários/tratamento farmacológico , Proteína Inibidora do Complemento C1/uso terapêutico , Adolescente , Adulto , Anticorpos/imunologia , Criança , Proteína Inibidora do Complemento C1/administração & dosagem , Proteína Inibidora do Complemento C1/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
Subcutaneous administration of intravenous immunoglobulin G (IgG) preparations provides an additional level of patient convenience and more options for patients with poor venous access or a history of intravenous IgG reactions. An open-label, pharmacokinetic trial (n = 32) determined the non-inferiority of the subcutaneous versus intravenous route of 10% caprylate/chromatography purified human immune globulin intravenous (IGIV-C; Gamunex®) administration by comparing the steady-state area under the concentration-versus-time curve (AUC) of total plasma IgG in patients with primary immunodeficiency disease. Patients on stable IGIV-C received two intravenous infusions (administered 3 or 4 weeks apart). Seven to 10 days after the second intravenous infusion, all patients switched to a weekly infusion of subcutaneous IGIV-C, with the dose equal to 137% of the previous weekly equivalent intravenous dose, for up to 24 weeks. Samples for pharmacokinetic analysis were collected during steady state for intravenous and subcutaneous IGIV-C treatments. The AUC(0-) τ geometric least-squares mean ratio was 0·89 (90% confidence interval, 0·86-0·92) and met the criteria for non-inferiority. The overall mean steady-state trough concentration of plasma total IgG with subcutaneous IGIV-C was 11·4 mg/ml, 18·8% higher than intravenous IGIV-C (9·6 mg/ml). Subcutaneous IGIV-C was safe and well tolerated. Subcutaneous IGIV-C infusion-site reactions were generally mild/moderate and the incidence decreased over time. No serious bacterial infections were reported. Weekly subcutaneous IGIV-C infusion using 137% of the weekly equivalent intravenous immunoglobulin dose provides an AUC comparable to intravenous administration, thus allowing patients to maintain the same IgG preparation/formulation if switching between intravenous and subcutaneous infusions.
Assuntos
Imunoglobulina G/sangue , Imunoglobulinas Intravenosas/farmacocinética , Síndromes de Imunodeficiência/tratamento farmacológico , Adolescente , Adulto , Idoso , Área Sob a Curva , Diarreia/induzido quimicamente , Relação Dose-Resposta a Droga , Esquema de Medicação , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Imunoglobulinas Intravenosas/efeitos adversos , Síndromes de Imunodeficiência/metabolismo , Síndromes de Imunodeficiência/patologia , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/farmacocinética , Fatores Imunológicos/uso terapêutico , Infusões Intravenosas , Infusões Subcutâneas , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Infecções Respiratórias/induzido quimicamente , Sinusite/induzido quimicamente , Resultado do Tratamento , Adulto JovemRESUMO
Immunoglobulin (Ig) administration via the subcutaneous (s.c.) route has become increasingly popular in recent years. The method does not require venous access, is associated with few systemic side effects and has been reported to improve patients' quality of life. One current limitation to its use is the large volumes which need to be administered. Due to the inability of tissue to accept such large volumes, frequent administration at multiple sites is necessary. Most studies conducted to date have investigated the use of subcutaneous immunoglobulin (SCIg) in patients treated previously with the intravenous (i.v.) formulation. New data now support the use of s.c. administration in previously untreated patients with primary immunodeficiencies. SCIg treatment may further be beneficial in the treatment of autoimmune neurological conditions, such as multi-focal motor neuropathy; however, controlled trials directly comparing the s.c. and i.v. routes are still to be performed for this indication. New developments may further improve and facilitate the s.c. administration route. For example, hyaluronidase-facilitated administration increases the bioavailability of SCIg, and may allow for the administration of larger volumes at a single site. Alternatively, more concentrated formulations may reduce the volume required for administration, and a rapid-push technique may allow for shorter administration times. As these developments translate into clinical practice, more physicians and patients may choose the s.c. administration route in the future.
Assuntos
Imunoglobulina G/administração & dosagem , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Antígenos de Neoplasias/administração & dosagem , Esquema de Medicação , Portadores de Fármacos , Histona Acetiltransferases/administração & dosagem , Humanos , Hialuronoglucosaminidase/administração & dosagem , Imunoglobulina G/uso terapêutico , Infusões Subcutâneas , Proteínas Recombinantes/administração & dosagem , Resultado do TratamentoRESUMO
Currently, patients have to keep track of doses to determine when to replace their metered-dose inhalers (MDIs). This study evaluated the performance and patient satisfaction of a novel MDI with an integrated dose counter. In an open-label study at 38 outpatient centres, patients > or =12 years old with asthma or chronic obstructive pulmonary disease (COPD) received two actuations of fluticasone propionate/salmeterol 125/25 microg (115/21 microg ex-actuator) hydrofluoroalkane (ADVAIR) HFA) via MDI with counter twice a day until all 120 actuations were completed. Concordance between counter and diary recordings in patients who reported use of > or =90% of labelled actuations (completer population, n = 228) was high (discrepancy rate of 0.94%) and the incidence of device firing without changes in counter readings was low (0.13%). Mean expected actuations based on canister weights (114) were slightly lower than mean counter (121) and diary reported actuations (120). Upon study completion, 95% of patients were satisfied with the dose counter and 92% agreed it would help prevent them from running out of medication. Safety assessments (intent-to-treat population, n = 237) indicated that the drug was well tolerated. This integrated MDI counter may help patients maintain better disease control by enabling them to accurately track their medication supply.
Assuntos
Albuterol/análogos & derivados , Androstadienos/administração & dosagem , Antiasmáticos/administração & dosagem , Asma/tratamento farmacológico , Broncodilatadores/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração por Inalação , Adolescente , Adulto , Idoso , Albuterol/administração & dosagem , Feminino , Fluticasona , Humanos , Hidrocarbonetos Fluorados , Masculino , Inaladores Dosimetrados , Pessoa de Meia-Idade , Satisfação do Paciente , Pós , Xinafoato de Salmeterol , Resultado do TratamentoRESUMO
We report two unrelated infants with cephaloskeletal dysplasia or Taybi-Linder syndrome, also referred to as osteodysplastic primordial dwarfism Type III. They presented with peculiar facial features, microcephaly and skeletal and cerebral abnormalities documented radiographically and with cranial MRI and/or CT. Some dissimilarities were observed in the skeletal findings between the two patients, most likely reflecting phenotypic variability within the same disorder. Some radiographic features were shown to evolve with time in both patients. Also of interest is the unusually long survival of these patients, more than 4 years in the first and of over 6 years in the second.
Assuntos
Nanismo/diagnóstico , Fatores Etários , Osso e Ossos/diagnóstico por imagem , Pré-Escolar , Nanismo/classificação , Nanismo/diagnóstico por imagem , Nanismo/mortalidade , Feminino , Humanos , Lactente , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Prognóstico , Crânio/diagnóstico por imagem , Síndrome , Tomografia Computadorizada por Raios XRESUMO
Antibody deficiency syndromes are an important cause of recurrent infections in children. Today it is possible to perform a complete evaluation of antibody-mediated immunity leading to a definitive diagnosis of either normal or abnormal immunity in most patients. However, the interpretation of the results of IgG subclass determinations and specific antibody responses is still being defined. At this time our recommendation is that patients who meet the criteria for an evaluation of antibody-mediated immunity be referred to subspecialists trained in this evaluation until better criteria for normal have been developed. The possibility that protective amounts of antibodies against pneumococcal serotypes may develop only transiently must be considered in patients with recurrent infections after initial improvement after immunization, especially if IgG2 subclass deficiency is also present. In the future it may be possible to use a faster and more economical approach to evaluate patients with recurrent infections by immunization with pneumococcal vaccine and then measuring IgM, IgG and IgA along with postimmunization specific antipneumococcal antibody titers 4 to 6 weeks later. For this approach to become feasible, further studies comparing the information obtained from the evaluation of pre- and postimmunization antibody concentrations with that obtained from the evaluation of postimmunization concentrations alone are needed.
Assuntos
Vacinas Bacterianas/imunologia , Imunização , Síndromes de Imunodeficiência/imunologia , Polissacarídeos Bacterianos/imunologia , Infecções Respiratórias/imunologia , Formação de Anticorpos , Vacinas Bacterianas/administração & dosagem , Criança , Pré-Escolar , Humanos , Imunoglobulinas Intravenosas/imunologia , Síndromes de Imunodeficiência/complicações , Lactente , Polissacarídeos Bacterianos/administração & dosagem , Infecções Respiratórias/complicações , Infecções Respiratórias/prevenção & controleRESUMO
OBJECTIVE: To determine the efficacy of endoscopic sinus surgery in pediatric patients with chronic sinusitis and asthma. SETTING: Patients were selected from the tertiary care practice of a pediatric pulmonologist (R.S.) and immunologist (R.L.W.); all underwent sinus surgery at Children's Medical Center at Dallas (Tex). PATIENTS: Fourteen pediatric patients aged 3.5 to 13 years with severe asthma requiring at least intermittent systemic steroid therapy. All patients had a history of sinusitis aggravating asthma and all had computed tomographic evidence of chronic sinus disease. INTERVENTION: All patients underwent endoscopic sinus surgery consisting of bilateral total ethmoidectomies and middle meatus antrostomies at a minimum. MAIN OUTCOME MEASURES: The period 12 months prior to surgery was compared with 12 months postoperatively with regard to total hospitalization days for asthma treatment, number of school days missed, pulmonary function test results, and systemic glucocorticoid medication requirements. Symptom scores for asthma and sinusitis were assessed via parental questionnaire both preoperatively and postoperatively. RESULTS: No significant difference was found for pulmonary function test results. Eleven of 14 patients demonstrated a significant reduction in hospitalization and school days missed. Twelve of 14 patients experienced a reduction in glucocorticoid requirements. Eleven of 14 and 13 of 14 patients experienced a significant improvement in asthma and sinusitis symptom scores. CONCLUSION: Endoscopic sinus surgery was effective in reducing sinusitis and improving the overall management of asthma in a majority of study patients.
Assuntos
Asma/complicações , Endoscopia , Sinusite Etmoidal/cirurgia , Sinusite Maxilar/cirurgia , Absenteísmo , Adolescente , Asma/tratamento farmacológico , Asma/fisiopatologia , Criança , Pré-Escolar , Doença Crônica , Sinusite Etmoidal/complicações , Sinusite Etmoidal/fisiopatologia , Feminino , Seguimentos , Volume Expiratório Forçado/fisiologia , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Hospitalização , Humanos , Masculino , Sinusite Maxilar/complicações , Sinusite Maxilar/fisiopatologia , Fluxo Máximo Médio Expiratório/fisiologia , Instituições Acadêmicas , Resultado do TratamentoAssuntos
Imunoglobulinas Intravenosas/efeitos adversos , Adolescente , Adulto , Criança , Pré-Escolar , Tolerância a Medicamentos , Feminino , Glucose/administração & dosagem , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Injeções , Masculino , Pessoa de Meia-Idade , Segurança , ÁguaRESUMO
Chronic meningoencephalitis due to enterovirus infection can occur in patients with antibody deficiencies. A modified polymerase chain reaction technique demonstrated persistent echovirus 11 infection in such a patient, despite negative routine viral cultures and negative routine nucleic acid hybridization. Although the sequence of echovirus 11 has not yet been determined, genomic conservation among the enteroviruses is significant, permitting detection of echovirus 11 with a primer pair and probe derived from enterovirus serotypes that have been fully sequenced. This study provides the first definitive evidence for the persistence of enterovirus infection with negative viral cultures.
Assuntos
Infecções por Echovirus/diagnóstico , Enterovirus Humano B/genética , Meningoencefalite/diagnóstico , RNA Viral/análise , Agamaglobulinemia/complicações , Sequência de Bases , Criança , Infecções por Echovirus/líquido cefalorraquidiano , Infecções por Echovirus/complicações , Eletroforese em Gel de Ágar , Enterovirus Humano B/isolamento & purificação , Amplificação de Genes , Humanos , Masculino , Meningoencefalite/líquido cefalorraquidiano , Meningoencefalite/complicações , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , Reação em Cadeia da Polimerase , RNA Viral/genéticaRESUMO
The possibility of transmission of the human immunodeficiency virus (HIV) from infected children to their contacts has been confronted in households, schools, day-care centers, and other child care settings. Cases reported to the Centers for Disease Control and several studies of close contacts of HIV-infected patients suggested that the risk of transmission in these settings is extremely low. However, most of these studies involved infected adults or older children. Younger children, who drool, bite, mouth toys, and are incontinent, may be more likely to transmit HIV in these settings. To assess this possibility, the authors tested 89 members of households in which 25 children with HIV infection, most of whom were preschool-aged, resided. Household members had close personal contact with the infected children. They shared many items likely to be soiled with blood and body fluids, such as toys, toothbrushes, eating utensils, toilets, and bathtubs. Hugging, kissing, sharing a bed, and bathing together were common. Household members were tested no sooner than 4 months after initial contact with the infected child, to allow adequate time for sero-conversion. All 89 participating household members were anti-HIV seronegative, and 78 who were tested were serum p24 antigen negative. It was concluded from this study and other evidence that the risk of transmission from children to their contacts is extremely low and has not been clearly documented in the household setting.
Assuntos
Síndrome da Imunodeficiência Adquirida/transmissão , Família , Adolescente , Criança , Características da Família , Feminino , Soropositividade para HIV , Utensílios Domésticos , Humanos , Lactente , Masculino , Fatores de Risco , Fatores de TempoRESUMO
The complete amino acid and nucleotide sequences of the variable regions of the heavy and light polypeptide chains of a human neutralizing IgGl anti-cytomegalovirus (CMV) antibody reveal a striking homology to IgM rheumatoid factors (RFs) of the Wa idiotypic family. The anti-CMV antibody and Wa RFs have in common VKIIIb, JKl, and VHIa gene segments but use different DH and JH gene segments. The anti-CMV antibody does not have RF activity and does not express the Wa idiotype. The Wa RFs do not have anti-CMV activity. A subset of Wa RFs, however, and the anti-CMV antibody do share several idiotypes on the VHIa and VKIIIb polypeptides. Since there are major differences in the antigen binding characteristics and some of the other expressed idiotypes, these data suggest that the D and J region amino acids are crucial to such specificities. Although the use of such highly homologous gene segments in different immune responses is well-documented in murine systems, these data represent the first such example in the human.
Assuntos
Anticorpos Antivirais/genética , Citomegalovirus/imunologia , Imunoglobulina G/genética , Região Variável de Imunoglobulina/genética , Fator Reumatoide/genética , Sequência de Aminoácidos , Especificidade de Anticorpos , Sequência de Bases , Citomegalovirus/genética , DNA/genética , Epitopos , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Idiótipos de Imunoglobulinas/genética , Cadeias Leves de Imunoglobulina/genética , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , Homologia de Sequência do Ácido NucleicoRESUMO
Production of useful human monoclonal antibodies has been limited by the inability to reliably generate and isolate antigen-specific B cells by in vivo immunization. An in vitro culture system employing antigen and mitogen to stimulate lymphocytes derived from solid lymphoid organs has been developed. Human tonsilar or splenic lymphocytes were stimulated in vitro with antigen and mitogen in short term culture and then fused with either of two enzyme deficient human B cell lines. This approach appears to expand antigen-specific B cell clones prior to fusion resulting in the production of a significant number of antigen-binding human hybridoma antibodies. The system has been effective in the production of human monoclonal antibodies following stimulation with KLH-ARS, a soluble antigen, and intact group B streptococcus, a particulate antigen. Hybridomas have been produced by fusion with two distinct parental human B cell lines supporting the previously reported observation that human B lymphoblastoid cell lines representing different stages of B cell differentiation may be useful fusion partners. The utility of the in vitro stimulation system in producing human-human hybridomas secreting antibody directed against two distinct classes of antigens establishes this approach as a generally useful method for the production of human monoclonal antibodies.
Assuntos
Antígenos/imunologia , Hibridomas/imunologia , Ativação Linfocitária , Anticorpos Monoclonais/biossíntese , Fusão Celular , Células Cultivadas , Hemocianinas/imunologia , Humanos , Linfócitos/imunologia , Streptococcus agalactiae/imunologiaRESUMO
Ataxia-telangiectasia and sarcoidosis are diseases characterized by abnormalities of the immune system. We examined a 13-year-old female with ataxia-telangiectasia who developed atrophic, violaceous plaques of the skin and a destructive, polyarticular arthritis. The histologic features of both skin and synovium were most consistent with a diagnosis of sarcoidosis. Interaction of these two immunologic disorders may have resulted in the unusual features of this patient's disease.
Assuntos
Ataxia Telangiectasia/complicações , Sarcoidose/complicações , Adolescente , Ataxia Telangiectasia/imunologia , Ataxia Telangiectasia/patologia , Criança , Feminino , Granuloma/patologia , Humanos , Sarcoidose/imunologia , Sarcoidose/patologia , Pele/patologia , Membrana Sinovial/patologiaRESUMO
Caustic and corrosive substance ingestions are a significant cause of early and late morbidity and may cause esophageal carcinoma after a long latent period. Initial management should be directed at the assurance of adequate ventilation and cardiovascular stability as well as the prevention of vomiting. Early esophagoscopy (to the level of first lesion, if present) is useful to identify those patients who do not need hospitalization or treatment. Esophagoscopy and contrast esophagram are useful to define the full extent of esophageal injury, but should be withheld until after the acute phase. Glucocorticoids are probably useful in limiting the extent and severity of esophageal stricture, the most frequent and significant long-term sequela. Colon interposition is used in those situations in which dilation of a stricture has been unsuccessful, and may prevent the subsequent development of esophageal carcinoma.