Utilización y farmacovigilancia de inmunoglobulina G endovenosa en un hospital pediátrico de alta complejidad / Intravenous immunoglobulin G use and pharmacovigilance in a tertiary care children's hospital

Introducción. La inmunoglobulina G endovenosa (IGEV) es un medicamento hemoderivado de inmunoglobulina G polivalente y policlonal. Posee un amplio espectro de indicaciones como inmunomodulador o como terapia de reemplazo. Asimismo, si bien se considera un tratamiento seguro, la incidencia de reacciones adversas reportadas en la literatura varía del 1 % al 81 %. Este trabajo tuvo como objetivo evaluar la utilización de IGEV y describir los acontecimientos adversos por la medicación en un hospital pediátrico de alta complejidad.Población y métodos. Se realizó un estudio de farmacoepidemiología, observacional y prospectivo. Se evaluaron pacientes que recibieron IGEV durante 7 meses, en 6 áreas de un hospital pediátrico de alta complejidad de la Ciudad Autónoma de Buenos Aires. La unidad de análisis fue cada infusión de IGEV, y la principal variable de estudio fue la presencia de reacciones adversas.Resultados. Se analizaron 305 infusiones en 111 pacientes. El 81,6 % de las indicaciones fueron de tipo supletorio. La dosis máxima utilizada fue 1 g/kg. En el 99,6 % de las infusiones, se indicó algún tipo de premedicación; la difenhidramina fue la droga más utilizada, aunque con diferentes posologías. Se registraron 12 reacciones adversas (el 3,9 % de las infusiones), tres de las cuales se consideraron graves: dos meningitis asépticas y una crisis comicial. Todas se resolvieron ad integrum.Conclusiones. La tasa de reacciones adversas de la IGEV en nuestro medio fue baja, con mayoría de reacciones leves e inmediatas y evolución favorable en todos los pacientes.

Introduction. Intravenous immunoglobulin G (IVIG) is a blood product from polyvalent and polyclonal immunoglobulin G. It covers a broad range of indications as immunomodulator or replacement therapy. In addition, although it is considered a safe therapy, the incidence of adverse reactions reported in the bibliography ranges from 1 % to 81 %. The objective of this study was to assess IVIG use and describe related adverse events in a tertiary care children's hospital.Population and methods. This was a pharmacoepidemiological, observational, and prospective study. Patients receiving IVIG for 7 months in 6 areas of a tertiary care children's hospital in the Autonomous City of Buenos Aires were assessed. The analysis unit was each IVIG infusion, and the main variable was the presence of adverse reactions.Results. A total of 305 infusions in 111 patients were analyzed. In 81.6 % of cases, the indication was for replacement. The maximum dose was 1 g/kg. In 99.6 % of infusions, some type of premedication was indicated; diphenhydramine was the most common drug, with varying dosages. A total of 12 adverse reactions (3.9 % of infusions) were recorded; 3 were severe: aseptic meningitis (2 cases) and seizures (1 case). All resolved to normal.Conclusions. The rate of IVIG adverse reactions in our setting was low; most reactions were mild and immediate and resolved favorably in all patients

Eficacia y seguridad de pembrolizumab en el tratamiento de pacientes con diagnóstico de melanoma maligno con enfermedad metastásica o irresecable, sin tratamiento sistémico previo / Efficacy and safety of pembrolizumab in the treatment of patients with malignant melanoma with metastatic or unresectable disease without previous systemic treatment

INTRODUCCIÓN: Antecedentes: El Instituto de Evaluación de Tecnologias en Salud e Investigaciones (IETSI) ha recibido la solicitud de evaluar el uso de pembrolizumab para su uso en pacientes con diagnóstico de melanoma maligno con enfermedad metastásica o irresecable, sin tratamiento sistémico previo, dentro del sistema de EsSalud, indicación actualmente no contemplada en el Petitorio Farmacológico de EsSalud. Generalidades: Los melanomas a nivel mundial representam un problema de salud pública vigente y creciente. De hecho su incidencia no sólo ha aumentado en las últimas décadas sino que también ha aumentado su mortlidad, comparado con otros tipos de cáncer. Tecnología Sanitaria de Interés: Pembrolizumab: Pembrolizumab es un anticuerpo monoclonal humanizado de tipo inmunoglobulina G4 (IgG4) (HuMAb) que actúa sobre la via del receptor de muerte programada 1 (PD-1) bloqueando su interación con PD-L1 y PD-L2. Dado que el receptor PD-1 es un regulador negativo de la actividad de los linfocitos T, al bloquearlo permite la reactivación de la inmunidad anti-tumor. METODOLOGÍA: Estrategia de Búsqueda: El protocolo de esta revisión sistemática y revisado coon el equipo técnico de IETSI. Las siguientes fuentes han sido revisadas y consultadas con la intención de buscar la mejor evidencia disponible: Canadian Agency for Drugs and Technologies in Health (CADTH), Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, European Society for Medical Oncology (ESMO) de Europa, Medline/Pubmed, National Comprehensive Cancer Network (NCCN) de los Estados Unidos, National Guideline Clearinghouse (NCG) de los Estados Unidos, Nationa Institute for Health and Care Excellence (NICE) del Reino Unido, Scopus, Scottish Medicines Consortium (SMC) de Escocia, Sociedad Española de Oncologia Médica (SEOM) de Espanã, Translating Research into Practice (TRIP Database), Web of Science. RESULTADOS: Luego de revisar un total de 77 referencias resultados de nuestra búsqueda bibliográfica, se filtraron 35 estudios, de los cuales sólo seis fueron finalmente seleccionados para nuestro análisis, incluyendo dos ensayos clínicos, tres guías clínicas y uuna evaluación de tecnología. Sinopsis de la Evidencia: Al realizar la búsqueda amplia de guías de prática clínica en Googl Académico así como en las bases de datos revisadas se encontró una gran varidad de guías específicas para el maenejo de pacientes con melanoma maligno. Sin embargo, entre las guías revisadas sólo se encontró tres en las cuales se listó pembrolizumab como una alternativa de tratamiento para el maenjo de pacientes con melanoma maligno irresecable o metastásico, elaboradas respectivamente por SEOM de España, ESMO de Europa y NCCN de los Estados Unidos por lo que a continuación resumiremos lo que plantea esta guía. CONCLUSIONES: A la fecha no se dispone de evidencias que sustenten el uso de pembrolizumab como uma alternativa más eficaz y segura a la quimioterapia con dacarbacina (DTIC) en el tratamiento de los pacientes con diagnóstico de melanoma maligno irresecable o metastásico, sin tratamiento sistémico previo. El Instituto de Evaluación de Tecnologías en Salud e Investigaciones-IETSI, no aprueba el uso de pembrolizumab como tratamiento para los pacientes con diagnóstico de melanoma maligno irresecable o metastásico, sin tratamiento sistémico previo.

Early effects of tumor necrosis factor inhibition on bone homeostasis after soluble tumor necrosis factor receptor use

BACKGROUND/AIMS: Our aim was to assess whether short-term treatment with soluble tumor necrosis factor (TNF) receptor affects circulating markers of bone metabolism in rheumatoid arthritis (RA) patients. METHODS: Thirty-three active RA patients, treated with oral disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids for > 6 months, were administered etanercept for 12 weeks. Serum levels of bone metabolism markers were compared among patients treated with DMARDs at baseline and after etanercept treatment, normal controls and naive RA patients not previously treated with DMARDs (both age- and gender-matched). RESULTS: Bone-specific alkaline phosphatase (BSALP) and serum c-telopeptide (CTX)-1 levels were lower in RA patients treated with DMARDs than in DMARD-naive RA patients. After 12 weeks of etanercept treatment, serum CTX-1 and sclerostin levels increased. In patients whose DAS28 improved, the sclerostin level increased from 1.67 +/- 2.12 pg/mL at baseline to 2.51 +/- 3.03 pg/mL, which was statistically significant (p = 0.021). Increases in sclerostin levels after etanercept treatment were positively correlated with those of serum CTX-1 (r = 0.775), as were those of BSALP (r = 0.755). CONCLUSIONS: RA patients treated with DMARDs showed depressed bone metabolism compared to naive RA patients. Increases in serum CTX-1 and sclerostin levels after short-term etanercept treatment suggest reconstitution of bone metabolism homeostasis.

Síndrome de Kawasaki. Persistencia de la fiebre luego del tratamiento / Kawasaki syndrome. Fever persistence after treatment

El síndrome de Kawasaki es un trastorno multisistémico, de etiología desconocida, que afecta a niños menores de 5 años. Presentamos el caso de un niño de 2 años con síndrome de Kawasaki, que recibió tratamiento con inmunoglobulina en infusión única y ácido acetilsalicílico, con respuesta rápida y favorable del cuadro cutáneo pero persistencia de la fiebre y reaparición del exantema a las 72 horas, por lo que se debió repetir la administración de inmunoglobulina. El ecocardiograma inicial revelaba dilatación de la arteria coronaria izquierda de 1,6 vez el diámetro del vaso adyacente.

Rubéola, soroprevalência de anticorpos em puérperas e recém-nascidos durante a campanha de vacinação de 2008, em Botucatu, Brasil / Rubella: seroprevalence of antibodies among puerperae and newborns during the 2008 vaccination campaign in Botucatu, Brazil

Objetivo: Avaliar o estado sorológico contra rubéola de uma amostra, representativa e randomizada de puérperas e seus filhos durante a campanha de vacinação. Métodos: Estudo transversal de amostr representativa e randomizada de puérperas e recém-nascidos, durante campanha de vacinação e inquérito sobre antecedente de doença e vacinas. Nas crianças, a dosagem em IgG contra rubéola foi repetida aos 9 meses de vida. Resultados: Noventa e duas, puérperas e 51 recém-nascidos foram avaliados. A menor positividade (66,6%), foi encontrada entre as mulheres com menos de 20 anos, e a maior (90,4%), entre as com 30 ou mais anos de idade. Houve forte correlação entre IgG da mãe e do recém-nascido. Entre as mulheres com antecedentes de doença exantemática, os valores médios de IgG foram significativamente maiores. A maioria das mães (62,0%) não sabia informar se tinha recebido vacina anteriormente. Aos nove meses, nenhuma das crianças avaliada apresentou IgG detectável.

Anti-TNF-alpha Therapy for Ankylosing Spondylitis

BACKGROUND: This review evaluated the safety and efficacy of etanercept in patients with ankylosing spondylitis (AS). METHODS: Of 59 patients with AS, this study reviewed 11 patients who were refractory to conventional therapy and treated with etanercept from September 2005 to January 2008. The mean follow-up duration was 13.6 months. The general improvement was evaluated by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and adverse effects, complications and inflammatory markers were also assessed. RESULTS: The mean BASDAI decreased from 7.1 +/- 1.6 before treatment to 4.2 +/- 1.8 at 3 months after the etanercept treatment (p = 0.001). The mean erythrocyte sedimentation rate and C-reactive protein were decreased significantly by the etanercept treatment. The greatest improvement in symptoms was enthesitis, followed by skin involvement and morning stiffness. There was a significant difference in the improvement in BASDAI along with the follow up duration (p = 0.04). A serious infection was observed as a complication in 1 case. CONCLUSIONS: These results suggest that etanercept can induce significant improvement in most patients with less damage. A trial of tumor necrosis factor inhibition is indicated in all AS patients who do not achieve adequate disease control with disease-modifying antirheumatic drugs, such as methotrexate, leflunomide etc. The patients treated with etanercept should be educated about the possibility of infection and monitored closely.

Antibodies against electronegative LDL inhibit atherosclerosis in LDLr-/- mice

In order to determine the effect of antibodies against electronegative low-density lipoprotein LDL(-) on atherogenesis, five groups of LDL low receptor-deficient (LDLr-/-) mice (6 per group) were immunized with the following antibodies (100 µg each): mouse anti-LDL(-) monoclonal IgG2b, rabbit anti-LDL(-) polyclonal IgG or its Fab fragments and mouse irrelevant monoclonal IgG and non-immunized controls. Antibodies were administered intravenously one week before starting the hypercholesterolemic diet (1.25 percent cholesterol) and then every week for 21 days. The passive immunization with anti-LDL(-) monoclonal IgG2b, polyclonal antibody and its derived Fab significantly reduced the cross-sectional area of atherosclerotic lesions at the aortic root of LDLr-/- mice (28.8 ± 9.7, 67.3 ± 17.02, 56.9 ± 8.02 µm² (mean ± SD), respectively) compared to control (124.9 ± 13.2 µm²). Vascular cell adhesion molecule-1 protein expression, quantified by the KS300 image-analyzing software, on endothelium and the number of macrophages in the intima was also decreased in aortas of mice treated with anti-LDL(-) monoclonal antibody (3.5 ± 0.70 per field x 10) compared to controls (21.5 ± 3.5 per field x 10). Furthermore, immunization with the monoclonal antibody decreased the concentration of LDL(-) in blood plasma (immunized: 1.0 ± 1.4; control: 20.5 ± 3.5 RLU), the amount of cholesterol oxides in plasma (immunized: 4.7 ± 2.7; control: 15.0 ± 2.0 pg COx/mg cholesterol) and liver (immunized: 2.3 ± 1.5; control: 30.0 ± 26.0 pg COx/mg cholesterol), and the hepatic content of lipid hydroperoxides (immunized: 0.30 ± 0.020; control: 0.38 ± 0.15 ng/mg protein). In conclusion, antibodies against electronegative LDL administered intravenously may play a protective role in atherosclerosis.

The importance of the interaction between leukocyte integrin Mac-1 and platelet glycoprotein Ib-a for leukocyte recruitment by platelets and for the inflammatory response to vascular injury / Importância da interação entre a integrina Mac-1 dos leucócitos e a glicoproteína Iba das plaquetas para o recrutamento de leucócitos pelas plaquetas e para a resposta inflamatória à lesão vascular

OBJETIVO: Avaliar a importância da interação entre a integrina Mac-1 dos leucócitos (a Mb 2) e a glicoproteína (GP) Iba das plaquetas para o recrutamento de leucócitos após a lesão vascular e o efeito da neutralização da interação Mac-1-GPIba sobre a proliferação celular e a hiperplasia neointimal desencadeadas por lesão vascular. MÉTODOS: Um peptídeo denominado M2 ou anticorpo anti-M2 foi desenvolvido para bloquear a interação Mac-1-GPIba . Esse peptídeo foi injetado e comparado com anticorpo-controle em camundongos C57B1/6J submetidos a lesão vascular da artéria femoral com corda-guia. Um, cinco ou 28 dias após a lesão vascular, as artérias femorais foram retiradas para a realização de morfometria e imuno-histoquímica. RESULTADOS: O bloqueio da interação Mac-1-GPIba promoveu uma redução estatisticamente significativa do número de leucócitos na camada média no primeiro dia após a lesão vascular (controle: 7,9±5,0 por cento do total de células versus anti-M2: 2,0±1,6 por cento, p=0,021), bem como determinou uma diminuição estatisticamente significativa do acúmulo de leucócitos na neoíntima em cinco e 28 dias (controle: 42,3±12,9 por cento versus anti-M2: 24,6±10,8 por cento, p=0,047 e controle: 7,9±3,0 por cento versus anti-M2: 3,3±1,3 por cento, p=0,012; respectivamente). A proliferação celular na camada média do vaso em cinco dias pós-lesão foi reduzida com o bloqueio da interação Mac-1-GPIba (controle: 5,0±2,9 por cento do total de células versus anti-M2: 1,8±0,5 por cento; p=0,043), assim como houve diminuição significativa da proliferação celular na camada íntima do vaso em 28 dias (controle: 3,8±1,7 por cento versus anti-M2: 2,0±1,2 por cento; p=0,047). O bloqueio da interação Mac-1-GPIba também determinou uma redução estatisticamente significativa do espessamento intimal em 28 dias pós-lesão (controle: 10.395±3.549 µm² versus anti-M2: 4.561±4.915 ...

OBJECTIVE: To assess the importance of the interaction between leukocyte integrin Mac-1 (a Mb 2) and platelet glycoprotein (GP) Ib-a for leukocyte recruitment after vascular injury and the effect of the neutralization of the Mac-1-GPIba interaction on cell proliferation and the neointimal hyperplasia triggered by the vascular injury. METHODS: A peptide called M2 or anti-M2 antibody was developed to block the Mac-1-GPIba interaction. This peptide was injected and compared to a control-peptide in C57B1/6J mice submitted to vascular injury of the femoral artery with a guide wire. One, five or 28 days after the vascular injury, the femoral arteries were removed for morphometric and immunohistochemical analyses. RESULTS: The blocking of the Mac-1-GPIba interaction promoted a statistically significant reduction in the number of leukocytes in the neointimal layer on the first day after the vascular injury (control: 7.9±5.0 percent of the cell total versus anti-M2: 2.0±1.6 percent, p=0.021), as well as determined a statistically significant decrease in leukocyte accumulation in the neointimal layer on days 5 and 28 (control: 42.3±12.9 percent versus anti-M2: 24.6±10.8 percent, p=0.047 and control: 7.9±3.0 percent versus anti-M2: 3.3±1.3 percent, p=0.012; respectively). Cell proliferation in the neointimal layer of the vessel five days post-injury was reduced with the blocking of the Mac-1-GPIba interaction (control: 5.0±2.9 percent of the cell total versus anti-M2: 1.8±0.5 percent; p=0.043), along with a significant decrease in cell proliferation in the vessel neointimal layer 28 days post-injury (control: 3.8±1.7 percent versus anti-M2: 2.0±1.2 percent; p=0.047). The blocking of the Mac-1-GPIba interaction also determined a statistically significant decrease of the intimal thickening 28 days post-injury (control: 10,395±3,549 µm² versus anti-M2: 4,561±4,915 µm²; ...

Hemophagocytic syndrome in Dengue hemorrhagic fever with severe multiorgan complications.

A 46 year old woman who presented with severe multiorgans involvement including liver brain, cardio-pulmonary failure, gastrointestinal bleeding, progressive cytopenia, DIC and hemophagocytic syndrome during the convalescent phase of Dengue type II has been successfully treated primarily with pulse methyl prednisolone and high dose intravenous immunoglobulin G. The authors believe that HPCS are not infrequently seen with high mortality and recommended early diagnosis and treatment with the regimen. This is the first complete report of hemophagocytic syndrome in adult dengue hemorrhagic fever in Thailand. The literature of HPCS in DHF was reviewed and discussed.

Neuromuscular respiratory failure in Guillain-Barre Syndrome: evaluation of clinical and electrodiagnostic predictors.

Guillain-Barre Syndrome (GBS) has an unpredictable clinical course with up to 30% of patients requiring assisted ventilation during the course of their illness. Successful management mandates anticipation, prompt recognition and optimal treatment of neuromuscular respiratory failure in GBS. AIMS: To identify clinical and electrodiagnostic predictors of neuromuscular respiratory paralysis in GBS. MATERIALS AND METHODS: Forty six patients of GBS were studied over a 6 year period, the study being 2 year retrospective and 4 year prospective. Clinical and electrodiagnostic data were compared between ventilated (28) and non-ventilated (18) patients. The clinical parameters assessed were median age, gender, antecedent infection, prior lung disease, time to peak disability, bifacial weakness, upper limb weakness, bulbar paralysis, neck weakness and autonomic dysfunction. Electrodiagnostic studies included motor nerve conduction studies in 11 ventilated and 13 non-ventilated patients, done prior to maximum disability in each group. Multiple logistic regression analysis was used to compare the two groups. RESULTS: Comparing the clinical data in the ventilated and non-ventilated groups, 'early peak disability', autonomic dysfunction and bulbar weakness predicted the onset of respiratory paralysis. Age, gender, neck or bifacial weakness, upper limb paralysis, or preceding infection did not influence the development of neuromuscular respiratory weakness. Electrodiagnostic testing revealed abnormal H reflex and F waves to be the commonest abnormality in either group. Although data was not sufficient for statistical analysis, the presence of markedly attenuated Compound Muscle Action Potentials inexcitable motor nerves and denervation changes on the electromyography, was commoner in the ventilated group. Thirty six patients received treatment with either plasmapheresis (12) or intravenous immunoglobulin (24). Overall mortality was 5, all 5 patients being on assisted ventilation. CONCLUSION: Early progression to peak disability, bulbar dysfunction and autonomic instability predicted the development of neuromuscular respiratory paralysis in GBS. Early electrodiagnostic studies in this series suggest axonopathic GBS as a predictor of respiratory paralysis, a finding that needs to be evaluated with sufficient data to permit statistical analysis.

Common variable immunodeficiency: experience in Puerto Rico

Common variable immunodeficiency (CVI) is a primary immunodeficiency characterized by hypogammaglobulinemia and an increased susceptibility to infections. The degree and the type of deficiency of serum immunoglobulins, as well as, the clinical course vary from patient to patient, hence the term [quot ]variable[quot ]. The aim of this report is to describe the clinical characteristics and the response to gammaglobulin therapy of a group of patients with CVI followed at the University Hospital of the Puerto Rico Medical Center. To our knowledge, no data on primary immunodeficiencies in Puerto Rico has been reported in the literature. The study group exhibits specific characteristics as compared to other reported series.

Clinical Aspects of Pregnancy and Delivery in Patients with Chronic Idiopathic Thrombocytopenic Purpura (ITP)

BACKGROUND: Idiopathic thrombocytopenic purpura (ITP) is a condition that often develops in young women and, consequently, physicians should frequently manage and monitor pregnant patients with this disorder. METHODS: We reviewed the charts of 30 women with chronic ITP delivered in 31 pregnancies from January 1995 to December 2003. RESULTS: Fifteen patients were diagnosed with ITP before pregnancy and sixteen patients were diagnosed during pregnancy. The mean platelet counts before pregnancy, during pregnancy, and at delivery were 70, 040/mm3, 83, 960/mm3, and 62, 680/mm3, respectively. The symptoms of hemostatic impairment were not noted in most of the pregnancies (77%, 24/31). During pregnancy and at delivery, most of the women (61%, 19/31) received various kinds of treatment to raise platelet counts. At delivery, the most commonly used therapy was platelet transfusion (48.4%, 15/31). Seven pregnancies (22.6%) were treated with corticosteroids during pregnancy and at delivery. Five pregnancies (16.1%) were treated with IV IgG during pregnancy and at delivery. Fifteen deliveries (51.7%) were performed by cesarean section and fourteen (48.3%) with vaginal delivery. Bleeding was uncommon at delivery. There were no cases of infants with any clinical signs of hemorrhage. CONCLUSION: Our current results suggest that ITP in pregnancy can proceed safely with low hemorrhagic risk in both infants and mothers, and that mothers with ITP can deliver healthy infants without serious hemorrhagic complications.

Cunatificación de IgG anti-D por micro ELISA / IgG anti-D cuantification by micro ELISA

Se estandarizó un ensayo inmunoenzimático en microplacas para la cuantificación de IgG anti-D en suero. Se utilizó antiinmunoglobulina humana conjugada con fosfatasa alcalina y paranitrofenil fosfato como sustrato. La densidad óptica del producto final de la reacción fue linealmente proporcional a la concentración de anti-D incubado con células rojas. Los experimentos intraensayos e interensayos realizados mostraron que el método es preciso y específico. Los valores de concentración determinados son comparables a los obtenidos por el método de hemaglutinación automatizada.

Metabolic and hematologic changes occurring after rapid intravenous infusion of gammaglobulin in patients with antibody deficiency syndromes

We wished to investigate whether increased IgG infusion rates are associated with metabolic and hematologic changes in pediatric patients with antibody deficiency syndromes. Methods: We studied 7 patients (2-16 years old) with primary antibody deficiencies who had been on regular IgG replacement treatment, 350-600 mg/kg/dose every 3 weeks with a 3 per cent IVIG preparation, for periods ranging from 6 months to 4 years. Initially, the IgG concentration of IVIG preparations was increased to 6, 9 and 12 per cent in consecutive infusions at a constant IgG infusion rate of 4 mg/kg/min. Subsequently the infusion rates were increased to 8, 12, and 16 mg/kg/min using the IVIG 12 per cent preparation. Results: Clinically, all patients tolerated increases in IVIG concentrations white the infusion rate was 4 mg/kg/min. However, 3 patients presented side effects when the infusion rate was increased to 8 and 16 mg/kg/min. Conclusion: We conclude that metabolic and hematologic sides effects, occur with rapid infusion of IVIG even in patients who tolerate the increased infusion rate clinically. The advantages of using high infusion rates have to be re-evaluated.

Sequential study of IgG antibody response in immunized rabbit and development of immunization protocol for raising monospecific antibody.

The present study was planned to develop an immunization protocol to decide the bleeding modalities for harvesting anti IgG antibody from the immunized rabbit. A fourteen dose immunization protocol (four primary and ten boosters) of the purified human IgG spread over the one calendar year was executed. The antibody titre estimated by Reverse Single Radial Immunodiffusion displayed a six-phased pattern. The titre following the initial immunization ranged between nil to 1.02, characteristic of the primary response while the titres after 7th and 8th boosters (phase V) ranged between 0.5 to 3.87 consistent with secondary response. Phase II, III, IV had moderately elevated titres. The antibody titre amongst the six phases reached to its peak generally by the 12th day after the last dose of protocol and it took about 60 days to reach to its basal level. Administration of antigen with the higher levels of residual antibody did not produce high titre antibody and is probably ascribed to elimination of antigen through an immunecomplex mechanism. Based on the data we recommend that 15 batches. (3 per phase, phase I to phase V) with a total yield of 100 to 120 ml of serum can be procured from one immunised animal over the span of one calendar year and that should make the programme cost effective.

Dosagem seriada de IgG e subclasses nas infecçöes recorrentes da hipogamaglobulinemia comum variável: contribuiçäo à terapêutica com imunoglobulinas venosas / Serial dosage of IgG class and subclasses in the recurent infections of common variable immunodeficiency: contribution to the therapeutics with intra venous immunoglobulins

As imunoglobulinas endovenosas (IGIV) constituem o tratamento de escolha nas imunodeficiências humorais, sendo habitualmente utilizadas nas doses de 100 a 400 mg/kg em intervalos de aproximadamente 25 dias. Tal posologia é ajustada individualmente segundo parâmetros clínicos. A presente investigaçäo objetiva rever o esquema terapêutico clássico, com base no conhecimento dos níveis de anticorpos dosados em quatro ocasiöes. Com isso pretende-se verificar se há associaçöes entre os valores obtidos e o quadro cliínico, para determinar se os mesmos constituem parâmetro para monitorizaçäo da terapêutica, e se há associaçöes entre o quadro clínico e deficiências específicas, notadamente das subclasses de IgG. Foram examinados dez pacientes portadores de hipogamaglobulinemia comum variável, em uso de IGIV. Dosaram-se os anticorpos antes da infusäo de IGIV, 30 minutos após a infusäo, 14 e 28 dias após a infusäo. Os valores absolutos näo tiveram associaçäo evidente com a evoluçäo dos pacientes, desautorizando sua aplicaçäo para o seguimento dos mesmos.

Effect of allerglobuline injection on serum immunoglobulin levels in ENT patients.

Allerglobuline is a human gammaglobulin preparation which has been reported to have a protective effect against Type I allergic diseases and chronic infection of the upper respiratory tract both in adults and children. This study included 64 patients suffering from perennial allergic rhinitis and/or chronic infection of the nose, paranasal sinuses and pharynx. All patients received Allerglobuline 10 ml intramuscular injection once a week for 5 times then once a month for another 3 times. Blood samples were taken before the first and after the last injections to assay for the levels of Igs G, A, M and E. The therapeutic responses were evaluated after the fifth injections by dividing into 5 grades (from Grade I = excellent to Grade V = no response). Statistical analysis revealed that there was no significant difference between the pre- and post-treatment levels of Igs, G, A and M. But the level of IgE decreased significantly after 8 injections (p less than 0.001). There was no correlation between the level of immunoglobulins and grade of therapeutic responses. But the number of patients who respond satisfactorily to Allerglobuline treatment increased from 62.26% after 5 injections to 77.36% after 8 injections. This difference does not reach the statistically significant level but is noteworthy.

Intravenous immunoglobulin prophylaxis for infection in very low birth-weight infants.

The effectiveness of intravenous immunoglobulin for prevention of sepsis in very low birth weight infants was studied on 102 neonates at the Children Hospital, Bangkok from February 1988 to February 1990. Infants were randomly allocated into 3 groups of 35 each. Group I and group II received 250 mg/kg and 500 mg/kg of immunoglobulin intravenously respectively within four hours of life. Group III was not given immunoglobulin and served as the control group. It was found that during the early neonatal period the infection rate of group I (14.7%) and group II (14.7%) was significantly lower than that of group III (38.2%). There was no difference in the infection rate of group I and group II. The mortality rate was also higher in group III than in group I and group II. It suggested that the intravenous immunoglobulin dosage of 250 mg per kilogram body weight is effective as well as dosage of 500 mg per kilogram body weight in prevention of sepsis in very low birth weight infants during the early neonatal period.