RESUMEN
Tuberculosis (TB) infection was evaluated in Brazilian immunocompetent children and adolescents exposed and unexposed (control group) to adults with active pulmonary TB. Both groups were analysed by clinical and radiological assessment, TST, QFT-IT and T-SPOT.TB. The three tests were repeated after 8 weeks in the TB-exposed group if results were initially negative. Individuals with latent tuberculosis infection (LTBI) were treated and tests were repeated after treatment. Fifty-nine TB-exposed and 42 controls were evaluated. Rate of infection was 69·5% and 9·5% for the exposed and control groups, respectively. The exposed group infection rate was 61% assessed by TST, 57·6% by T-SPOT.TB, and 59·3%, by QFT-IT. No active TB was diagnosed. Agreement between the three tests was 83·1% and 92·8% in the exposed and control groups, respectively. In the exposed group, T-SPOT.TB added four TB diagnoses [16%, 95% confidence interval (CI) 1·6-30·4] and QFT-IT added three TB diagnoses (12%, 95% CI 0-24·7) in 25 individuals with negative tuberculin skin test (TST). Risk factors associated to TB infection were contact with an adult with active TB [0-60 days: odds ratio (OR) 6·9; >60 days: OR 27·0] and sleeping in the same room as an adult with active TB (OR 5·2). In Brazilian immunocompetent children and adolescents, TST had a similar performance to interferon-gamma release assays and detected a high rate of LTBI.
Asunto(s)
Ensayos de Liberación de Interferón gamma/métodos , Mycobacterium tuberculosis/aislamiento & purificación , Prueba de Tuberculina/métodos , Tuberculosis/epidemiología , Adolescente , Brasil/epidemiología , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Prevalencia , Factores de Riesgo , Tuberculosis/microbiologíaRESUMEN
Ataxia-telangiectasia, an autosomal recessive disorder caused by defect of the ataxia-telangiectasia mutated gene, is characterized by progressive neurologic impairment with cerebellar atrophy, ocular and cutaneous telangiectasia, immunodeficiency, heightened sensitivity to ionizing radiation and susceptibility to developing lymphoreticular malignancy. Supratentorial brain abnormalities have been reported only rarely. In this study, brain MRI was performed in 10 adults with ataxia-telangiectasia having stable neurologic impairment. Intracerebral telangiectasia with multiple punctate hemosiderin deposits were identified in 60% of subjects. These lesions were apparently asymptomatic. They are similar in appearance to radiation-induced telangiectasia and to cryptogenic vascular malformations. Also noted, in the 2 oldest subjects, was extensive white matter T2 hyperintensity, and in 1 of these a space-occupying fluid collection consistent with transudative capillary leak and edema as evidenced by reduced levels of metabolites on MR spectroscopic imaging. Asymptomatic supratentorial vascular abnormalities appear to be common in adults with ataxia-telangiectasia.
Asunto(s)
Ataxia Telangiectasia/patología , Edema Encefálico/patología , Malformaciones Vasculares del Sistema Nervioso Central/patología , Imagen por Resonancia Magnética/métodos , Adulto , Ataxia Telangiectasia/complicaciones , Edema Encefálico/complicaciones , Malformaciones Vasculares del Sistema Nervioso Central/complicaciones , Femenino , Humanos , Masculino , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto JovenRESUMEN
The objective of this study is to determine the best way to access and the position in which the patients must remain in order to obtain the best transversal section of the right internal jugular vein (RIJV) section during the catheterization by ultrasound, allowing a safer and precise access. The three possible ways to access the RIJV, anterior, lateral and posterior, from 57 healthy children, were examined by ultrasound in one similar sequence of positions: horizontal dorsal decubitus with the head centered in neutral position with and without the use of a pillow; horizontal dorsal decubitus with contralateral rotation of the head with and without the use of a pillow; horizontal dorsal decubitus with the head centered in neutral position and the patient in the Trendelenburg position without the use of a pillow. The relation between the different positions and punction regions in RIJV were established using analysis of variance. As a result, the lateral punction with the patient in the Trendelemburg position offered a largest area of the RIJV transversal section in comparison to all the other options (P<0.0001). In conclusion, this study demonstrated that the safer and precise way for the RIJV catheterization in pediatric patients is obtained in Trendelenburg position with lateral access and without a pillow.
Asunto(s)
Cateterismo/métodos , Venas Yugulares/diagnóstico por imagen , Punciones/métodos , Ultrasonografía Intervencional , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , MasculinoRESUMEN
OBJECT: Ataxia-telangiectasia (A-T) is a recessively inherited neurodegenerative disorder with prominent progressive ataxia and cerebellar degeneration, as well as manifest abnormalities of tone, posture, and movement suggesting extrapyramidal dysfunction. In this study, we tested the hypothesis that regional metabolite levels, as measured by proton magnetic resonance spectroscopic imaging, would be abnormal in patients with A-T in the posterior fossa and basal ganglia, reflecting the underlying neurodegenerative processes in these regions. METHODS: Spectroscopic images of N-acetyl aspartate (NAA), choline (Cho), and creatine (Cr) were obtained in 8 patients with A-T and 8 age-matched controls. Normalized metabolite levels were compared between A-T patients and control subjects in various regions of interest, including the cerebellum, brainstem, and basal ganglia. RESULTS: A-T patients were distinguished from controls by the profound loss of all metabolites in the cerebellar vermis (NAA, p < 0.01; Cr and Cho, p < 0.05) and a trend for decreased metabolites within the cerebellar hemispheres. No abnormalities were detected in the basal ganglia. CONCLUSIONS: Proton MR spectroscopic features in A-T closely correlate with the morphologic neuroimaging findings of posterior fossa atrophy. Although symptoms suggesting extrapyramidal dysfunction are part of the A-T phenotype, these are not associated with altered metabolite levels in the basal ganglia.
Asunto(s)
Ataxia Telangiectasia/diagnóstico , Espectroscopía de Resonancia Magnética , Protones , Adolescente , Adulto , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Ataxia Telangiectasia/metabolismo , Encéfalo/metabolismo , Encéfalo/patología , Mapeo Encefálico , Estudios de Casos y Controles , Niño , Colina/metabolismo , Creatina/metabolismo , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Masculino , Examen Neurológico/métodosRESUMEN
Ataxia telangiectasia is a rare, multiorgan neurodegenerative disorder with enhanced vulnerability to cancer and infection. Median survival in two large cohorts of patients with this disease, one prospective and one retrospective, is 25 and 19 years, with a wide range. Life expectancy does not correlate well with severity of neurological impairment.
Asunto(s)
Ataxia Telangiectasia/mortalidad , Adolescente , Adulto , Baltimore/epidemiología , Niño , Preescolar , Métodos Epidemiológicos , HumanosRESUMEN
We describe a 54-year-old man with X-linked agammaglobulinemia (XLA) and Helicobacter cinaedi bacteremia, who presented with tender, hyper-pigmented skin macules without increased local warmth or fever. We propose that this presentation may be a characteristic early sign of bacteremia caused by H. cinaedi and related organisms in otherwise healthy immunocompromised patients. This case demonstrates the importance of a high index of suspicion for H. cinaedi bacteremia in immunocompromised patients with unexplained skin lesions.
Asunto(s)
Agammaglobulinemia/genética , Agammaglobulinemia/microbiología , Bacteriemia/etiología , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades Genéticas Ligadas al Cromosoma X/microbiología , Infecciones por Helicobacter/etiología , Helicobacter/patogenicidad , Agammaglobulinemia/complicaciones , Bacteriemia/patología , Enfermedades Genéticas Ligadas al Cromosoma X/complicaciones , Infecciones por Helicobacter/patología , Humanos , Huésped Inmunocomprometido , Masculino , Persona de Mediana EdadRESUMEN
The objective of the present study was to identify the single photon emission computed tomography (SPECT) and magnetic resonance (MR) findings in juvenile systemic lupus erythematosus (JSLE) patients with CNS involvement and to try to correlate them with neurological clinical history data and neurological clinical examination. Nineteen patients with JSLE (16 girls and 3 boys, mean age at onset 9.2 years) were submitted to neurological examination, electroencephalography, cerebrospinal fluid analysis, SPECT and MR. All the evaluations were made separately within a period of 15 days. SPECT and MR findings were analyzed independently by two radiologists. Electroencephalography and cerebrospinal fluid analysis revealed no relevant alterations. Ten of 19 patients (53%) presented neurological abnormalities including present or past neurological clinical history (8/19, 42%), abnormal neurological clinical examination (5/19, 26%), and abnormal SPECT or MR (8/19, 42% and 3/19, 16%, respectively). The most common changes in SPECT were cerebral hypoperfusion and heterogeneous distribution of blood flow. The most common abnormalities in MR were leukomalacia and diffuse alterations of white matter. There was a correlation between SPECT and MR (P<0.05). We conclude that SPECT and MR are complementary and useful exams in the evaluation of neurological involvement of lupus.
Asunto(s)
Encefalopatías/diagnóstico , Encéfalo/diagnóstico por imagen , Lupus Eritematoso Sistémico/complicaciones , Imagen por Resonancia Magnética , Tomografía Computarizada de Emisión de Fotón Único , Adolescente , Encefalopatías/diagnóstico por imagen , Encefalopatías/etiología , Niño , Femenino , Humanos , Lupus Eritematoso Sistémico/diagnóstico por imagen , MasculinoRESUMEN
The objective of the present study was to identify the single photon emission computed tomography (SPECT) and magnetic resonance (MR) findings in juvenile systemic lupus erythematosus (JSLE) patients with CNS involvement and to try to correlate them with neurological clinical history data and neurological clinical examination. Nineteen patients with JSLE (16 girls and 3 boys, mean age at onset 9.2 years) were submitted to neurological examination, electroencephalography, cerebrospinal fluid analysis, SPECT and MR. All the evaluations were made separately within a period of 15 days. SPECT and MR findings were analyzed independently by two radiologists. Electroencephalography and cerebrospinal fluid analysis revealed no relevant alterations. Ten of 19 patients (53 percent) presented neurological abnormalities including present or past neurological clinical history (8/19, 42 percent), abnormal neurological clinical examination (5/19, 26 percent), and abnormal SPECT or MR (8/19, 42 percent and 3/19, 16 percent, respectively). The most common changes in SPECT were cerebral hypoperfusion and heterogeneous distribution of blood flow. The most common abnormalities in MR were leukomalacia and diffuse alterations of white matter. There was a correlation between SPECT and MR (P<0.05). We conclude that SPECT and MR are complementary and useful exams in the evaluation of neurological involvement of lupus
Asunto(s)
Humanos , Masculino , Femenino , Niño , Adolescente , Encéfalo , Lupus Eritematoso Sistémico , Tomografía Computarizada de Emisión de Fotón Único , Encefalopatías , Lupus Eritematoso Sistémico , Imagen por Resonancia MagnéticaRESUMEN
Skin tests and lymphocyte proliferation assays (LPA) were performed with Mycobacterium avium sensitin on patients with AIDS. Among 139 subjects, 13% had positive skin test results and 32% had positive LPA results. The LPA may be a more sensitive indicator of prior M. avium infection in this population.
Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Antígenos/inmunología , Infecciones por Mycobacterium/diagnóstico , Mycobacterium avium/aislamiento & purificación , Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Infecciones Oportunistas Relacionadas con el SIDA/inmunología , Antígenos Bacterianos/inmunología , División Celular/inmunología , Humanos , Linfocitos/citología , Linfocitos/microbiología , Infecciones por Mycobacterium/epidemiología , Infecciones por Mycobacterium/inmunología , Mycobacterium avium/inmunología , Factores de Riesgo , Sensibilidad y Especificidad , Pruebas CutáneasRESUMEN
Two patients with severe combined immunodeficiency and enterovirus infections were successfully treated with pleconaril. There were no adverse affects.
Asunto(s)
Antivirales/uso terapéutico , Infecciones por Enterovirus/tratamiento farmacológico , Oxadiazoles/uso terapéutico , Inmunodeficiencia Combinada Grave/tratamiento farmacológico , Infecciones por Enterovirus/complicaciones , Heces/virología , Femenino , Humanos , Lactante , Oxazoles , Reacción en Cadena de la Polimerasa , ARN Viral/análisis , Inmunodeficiencia Combinada Grave/complicacionesRESUMEN
Autoimmune diseases are rare in patients with severe combined immunodeficiency (SCID). The authors describe an 11-month-old infant girl with SCID with fatal warm autoimmune hemolytic anemia (AIHA) resulting from IgM autoagglutinins. Serologic evaluation revealed IgM autoantibodies that caused in vitro hemagglutination at 37 degrees C. The patient had clinical evidence of ongoing hemolysis and agglutination despite aggressive treatment. She had three strokes and died 6 weeks after unsuccessful bone marrow transplantation. Autoimmune disease is an unexpected complication of SCID. The presence of warm reactive IgM autoagglutinins in AIHA confers a dismal prognosis.
Asunto(s)
Anemia Hemolítica Autoinmune/etiología , Autoanticuerpos/inmunología , Enfermedades Autoinmunes/etiología , Hemaglutininas/inmunología , Inmunoglobulina M/inmunología , Inmunodeficiencia Combinada Grave/complicaciones , Anemia Hemolítica Autoinmune/terapia , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales de Origen Murino , Autoanticuerpos/biosíntesis , Enfermedades Autoinmunes/inmunología , Trasplante de Médula Ósea , Recambio Total de Sangre , Resultado Fatal , Femenino , Hemaglutininas/biosíntesis , Humanos , Inmunoglobulina M/biosíntesis , Lactante , Pronóstico , Recurrencia , Rituximab , Inmunodeficiencia Combinada Grave/inmunología , Inmunodeficiencia Combinada Grave/terapia , Accidente Cerebrovascular/etiología , Temperatura , Trasplante HomólogoRESUMEN
X-linked autoimmunity-allergic disregulation syndrome (XLAAD) is an X-linked recessive immunological disorder characterized by multisystem autoimmunity, particularly early-onset type 1 diabetes mellitus, associated with manifestations of severe atopy including eczema, food allergy, and eosinophilic inflammation. Consistent with the allergic phenotype, analysis of two kindreds with XLAAD revealed marked skewing of patient T lymphocytes toward the Th2 phenotype. Using a positional-candidate approach, we have identified in both kindreds mutations in JM2, a gene on Xp11.23 that encodes a fork head domain-containing protein. One point mutation at a splice junction site results in transcripts that encode a truncated protein lacking the fork head homology domain. The other mutation involves an in-frame, 3-bp deletion that is predicted to impair the function of a leucine zipper dimerization domain. Our results point to a critical role for JM2 in self tolerance and Th cell differentiation.
Asunto(s)
Enfermedades Autoinmunes/genética , Diabetes Mellitus Tipo 1/genética , Hipersensibilidad a los Alimentos/genética , Ligamiento Genético/genética , Proteínas Nucleares/genética , Factores de Transcripción/genética , Cromosoma X/genética , Secuencia de Aminoácidos , Enfermedades Autoinmunes/inmunología , Secuencia de Bases , Diferenciación Celular , Análisis Mutacional de ADN , Diabetes Mellitus Tipo 1/inmunología , Femenino , Hipersensibilidad a los Alimentos/inmunología , Factores de Transcripción Forkhead , Haplotipos , Humanos , Leucina Zippers , Masculino , Datos de Secuencia Molecular , Mutación/genética , Proteínas Nucleares/química , Proteínas Nucleares/inmunología , Linaje , Estructura Terciaria de Proteína , Sitios de Empalme de ARN/genética , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Síndrome , Células Th2/citología , Células Th2/inmunología , Factores de Transcripción/química , Factores de Transcripción/inmunología , Cromosoma X/inmunologíaRESUMEN
OBJECTIVES: To determine the immunogenicity and safety of heptavalent pneumococcal polysaccharide vaccine (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) conjugated to CRM(197) (7-valent conjugate pneumococcal vaccine [7VPnC]) among infants with sickle cell disease (SCD) and a comparison group of infants without SCD (non-SCD). DESIGN: Two cohorts of infants were enrolled and received open-label doses of 7VPnC vaccine; infants enrolled before 2 months of age received 7VPnC vaccine at 2, 4, and 6 months of age followed by 23-valent pneumococcal polysaccharide vaccine (PS-23) at 24 months of age for those infants with SCD (schedule A), and infants enrolled between 2 and 12 months of age received 7VPnC at 12 months of age followed by PS-23 at 24 months of age for infants with SCD (schedule B). Safety data were collected for 3 days after each dose of vaccine. Antibody concentrations were measured to each of the 7VPnC serotypes by enzyme-linked immunosorbent assay before each vaccine dose and 1 month after the last 7VPnC dose and the PS-23 vaccine dose. RESULTS: Forty-five infants (34 SCD and 11 non-SCD) were vaccinated according to schedule A and 16 infants (13 SCD and 3 non-SCD) according to schedule B. The 7VPnC vaccine was highly immunogenic for all serotypes among infants with and without SCD who received 3 doses of vaccine according to schedule A: depending on serotype, 89% to 100% achieved antibody concentrations above.15 microg/mL and 56% to 100% achieved antibody concentrations above 1.0 microg/mL. Among infants immunized according to schedule B, a single dose of 7VPnC vaccine resulted in antibody concentrations above.15 microg/mL in 53% to 92% by serotype and above 1.0 microg/mL in 31% to 71% by serotype. A single dose of PS-23 resulted in dramatic increases in the antibody concentrations to all serotypes regardless of 1- or 3-dose priming. There was no difference in the reactogenicity of the 7VPnC vaccine between those with and without SCD. There were no serious reactions to the 7VPnC or PS-23 vaccines, even among those with high antibody concentrations before immunization. CONCLUSIONS: Infants with SCD respond to 7VPnC vaccine with antibody concentrations that are at least as high as infants without SCD. Infants immunized with 7VPnC vaccine at 2, 4, and 6 months of age developed antibody concentrations in the same range as those achieved among infants without SCD enrolled in a large trial that demonstrated vaccine efficacy against invasive disease. Significant rises were seen in antibody concentrations to all 7VPnC serotypes after the PS-23 booster in children receiving schedule A or B.
Asunto(s)
Anemia de Células Falciformes/inmunología , Formación de Anticuerpos/inmunología , Toxina Diftérica/administración & dosificación , Vacunas Neumococicas/administración & dosificación , Neumonía Neumocócica/prevención & control , Preescolar , Toxina Diftérica/inmunología , Femenino , Humanos , Inmunización/métodos , Lactante , Masculino , Estudios Multicéntricos como Asunto , Vacunas Neumococicas/inmunología , Neumonía Neumocócica/inmunología , Rasgo Drepanocítico/inmunología , Streptococcus pneumoniae/clasificación , Streptococcus pneumoniae/inmunología , Vacunas Conjugadas/administración & dosificación , Vacunas Conjugadas/inmunologíaRESUMEN
Ataxia-telangiectasia (AT) is an uncommon genetic disorder characterized by cerebellar ataxia, oculocutaneous telangiectasias, progressive immunodeficiency, and a predisposition to lymphoid malignancy. The genetic defect in AT predisposes not only to malignancy but also to severe toxicity from anti-neoplastic therapies. It is important to consider the diagnosis of AT in any child with a lymphoid malignancy at a younger than expected age, or who has a pre-existing ataxia, to anticipate unusually severe toxicities from the antineoplastic therapy, to avoid confusing the development of ataxia with toxicity from therapy, and to provide appropriate genetic counseling. We describe two children at a young age with a lymphoid malignancy diagnosed before the diagnosis of AT. One patient had severe toxicity from his chemotherapy, requiring truncation of the planned course of treatment. The other child was able to tolerate his entire planned course of therapy, but ataxia that was initially interpreted as toxicity from chemotherapy rather than as a sign of his AT developed. Lymphoid malignancy may be the presenting sign of AT. Making this diagnosis may influence therapy of the malignancy. The neurologic manifestations of the disease can be misinterpreted as toxicities of the chemotherapy, and diagnosis of AT allows appropriate genetic counseling for the family.
Asunto(s)
Ataxia Telangiectasia/complicaciones , Leucemia/etiología , Linfoma/etiología , Ataxia Telangiectasia/genética , Preescolar , Asesoramiento Genético , Humanos , Lactante , MasculinoRESUMEN
BACKGROUND: Patients infected with HIV who experience increases in CD4(+) cell counts are at reduced risk for opportunistic infections. However, the safety of discontinuing prophylaxis against Mycobacterium avium complex has been uncertain. OBJECTIVE: To compare the rate of M. avium complex infection in patients with increased CD4(+) cell counts who receive azithromycin and those receiving placebo. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: 29 university-based clinical centers in the United States. PARTICIPANTS: 643 HIV-1-infected patients with a previous CD4(+) cell count less than 0.05 x 10(9) cells/L and a sustained increase to greater than 0.10 x 10(9) cells/L during antiretroviral therapy. INTERVENTION: Azithromycin, 1200 mg once weekly (n = 321), or matching placebo (n = 322). MEASUREMENTS: Mycobacterium avium complex cultures, CD4(+) cell counts, and clinical evaluations for AIDS-defining illnesses and bacterial infections were done every 8 weeks. Plasma HIV-1 RNA levels were measured at 16-week intervals. RESULTS: During follow-up (median, 16 months), 2 cases of M. avium complex infection were reported among the 321 patients assigned to placebo (incidence rate, 0.5 event per 100 person-years [95% CI, 0.06 to 1.83 events per 100 person-years]) compared with no cases among the 322 patients assigned to azithromycin (CI, 0 to 0.92 events per 100 person-years), resulting in a treatment difference of 0.5 event per 100 person-years (CI, -0.20 to 1.21 events per 100 person-years) for placebo versus azithromycin. Both cases were atypical in that M. avium complex was localized to the vertebral spine. Patients receiving azithromycin were more likely than those receiving placebo to discontinue treatment with the study drug permanently because of adverse events (8% vs. 2%; hazard ratio, 0.24 [CI, 0.10 to 0.57]). CONCLUSIONS: Prophylaxis against Mycobacterium avium complex can safely be withdrawn or withheld in adults with HIV infection who experience increases in CD4(+) cell count while receiving antiretroviral therapy.
Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/prevención & control , Antibacterianos/uso terapéutico , Azitromicina/uso terapéutico , Recuento de Linfocito CD4 , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Infección por Mycobacterium avium-intracellulare/prevención & control , Adulto , Antibacterianos/efectos adversos , Fármacos Anti-VIH/uso terapéutico , Azitromicina/efectos adversos , Progresión de la Enfermedad , Método Doble Ciego , Femenino , Infecciones por VIH/virología , VIH-1/genética , Humanos , Huésped Inmunocomprometido , Masculino , Complejo Mycobacterium avium , Placebos , Modelos de Riesgos Proporcionales , ARN Viral/sangre , Carga ViralRESUMEN
Lymphocyte proliferation assays (LPAs) are widely used to assess T-lymphocyte function of patients with human immunodeficiency virus infection and other primary and secondary immunodeficiency disorders. Since these assays require expertise not readily available at all clinical sites, specimens may be shipped to central labs for testing. We conducted a large multicenter study to evaluate the effects of shipping on assay performance and found significant loss of LPA activity. This may lead to erroneous results for individual subjects and introduce bias into multicenter trials.
Asunto(s)
Infecciones por VIH/inmunología , Linfocitos/inmunología , Manejo de Especímenes/efectos adversos , Candida/inmunología , División Celular , Infecciones por VIH/sangre , Humanos , Linfocitos/citología , Mitógenos de Phytolacca americana/inmunología , Manejo de Especímenes/métodos , Estreptoquinasa/inmunología , Toxoide Tetánico/inmunología , TransportesRESUMEN
Pneumococcal infections are an important cause of morbidity and mortality in children with sickle-cell disease (SCD). Pneumococcal conjugate vaccines (PCVs) are immunogenic in healthy infants <2 years of age but have not been evaluated in young children with SCD. Infants with SCD were immunized with a 7-valent PCV (Wyeth-Lederle Vaccines & Pediatrics) at 2, 4, and 6 months of age. A booster dose of 23-valent pneumococcal polysaccharide vaccine (PPV; Pnu-Immune) was administered at 24 months of age. Antipneumococcal type 6B and 14 serum opsonic activity was measured to assess the biologic function of the antibody. Following the administration of three doses of PCV, opsonic activity against serotype 6B increased from 4. 8% at 2 months to 33.5% at 7 months, with a subsequent decline to 8.1% at 12 months and 7.5% at 24 months and with an increase to 30.7% at 25 months after administration of a booster dose of PPV. Similar trends were seen with serotype 14 (opsonic activities were 9.4% at 2 months, 24.9% at 7 months, 16.5% at 12 months, and 12.6% at 24 months, and the opsonic activity was 27.3% 1 month after the administration of PPV). Serum opsonic activity correlated with antibody levels for both serotypes. PCV induces serum opsonic activity in infants with SCD. Antipneumococcal serum opsonic activity correlates with antibody levels.
Asunto(s)
Anemia de Células Falciformes/inmunología , Anticuerpos Antibacterianos/sangre , Vacunas Meningococicas/inmunología , Proteínas Opsoninas/sangre , Vacunas Neumococicas/inmunología , Polisacáridos Bacterianos/inmunología , Streptococcus pneumoniae/inmunología , Vacunas Conjugadas/inmunología , Anemia de Células Falciformes/sangre , Anemia de Células Falciformes/complicaciones , Anticuerpos Antibacterianos/inmunología , Vacuna Neumocócica Conjugada Heptavalente , Humanos , Inmunización , Lactante , Proteínas Opsoninas/inmunología , Infecciones Neumocócicas/prevención & controlRESUMEN
Several clinical investigations with adults suggest that the cerebellum may be critical for judgment of explicit time intervals; however, little work has been done in populations with lesions of the cerebellum acquired during development. We evaluated 17 individuals with ataxia-telangiectasia (AT), an autosomal recessive disorder with on-set in early childhood characterized by diffuse, almost selective, degeneration of the cerebellar cortex, and 21 normal controls, matched for age. Because patients with AT have motor impairment, verbal IQ (VIQ) was used to estimate intelligence; VIQ was significantly lower in the group with AT (p < .0001). Participants were tested using a test of judgment of duration that has been found to be impaired in adults with cerebellar lesions and a contrasting auditory control task (not impaired in adults with cerebellar lesions) involving judgment of pitch. After statistically controlling for VIQ, the 2 groups did not differ significantly on judgment of pitch, but those with AT performed significantly worse than controls on judgment of duration (p = .01). Children and adolescents with AT show deficits in judgment of duration but not of pitch, suggesting that the cerebellum may be critical for judgment of explicit time intervals at all ages.
Asunto(s)
Ataxia Telangiectasia/psicología , Cerebelo/patología , Cognición , Percepción del Tiempo , Adolescente , Adulto , Factores de Edad , Ataxia Telangiectasia/patología , Percepción Auditiva , Estudios de Casos y Controles , Niño , Humanos , InteligenciaRESUMEN
BACKGROUND: Ataxia telangiectasia (A-T) is a rare disorder with many distinctive neurologic features. Although there is substantial individual variation in the rate of progression of these features, their relationship to one another or to age has not been characterized. METHODS: We formulated and tested multiple elements that assess different neurologic functions known to be affected by A-T. The overall index was applied to 52 patients with A-T, 2 to 29 years of age. RESULTS: Seven elements items proved to be informative, and three elements were added based on face validity. In a linear regression model of individuals under 19 years of age, controlled for correlation within sibships, age accounted for 87% of the variation in the A-T Index. CONCLUSION: Despite substantial individual variability of the phenotypic elements of A-T, scores on this multidimensional index have a very high correlation with age, indicating that there is a characteristic rate of progression of the disease, although functional domains in the brain are differentially affected. The pattern of scores suggests that a severe and a mild form of A-T may be distinguished by this quantitative measure. With further development this index may become useful as an outcome measure for treatment studies and prognosis.
Asunto(s)
Ataxia Telangiectasia/diagnóstico , Pruebas Neuropsicológicas , Índice de Severidad de la Enfermedad , Adolescente , Adulto , Factores de Edad , Niño , Preescolar , Estudios de Cohortes , Interpretación Estadística de Datos , Progresión de la Enfermedad , Humanos , Lactante , Modelos Lineales , Variaciones Dependientes del Observador , Fenotipo , Valor Predictivo de las Pruebas , Estudios Prospectivos , Reproducibilidad de los ResultadosRESUMEN
OBJECTIVES: To ascertain if immunization results in the restoration of responses to recall antigens, in the development of responses to presumed neoantigens, and to identify the virologic and immunologic correlates of these responses in persons with HIV-1 infection. DESIGN AND SETTING: Open-label study carried out at three university-affiliated AIDS Clinical Trials Units in the United States. SUBJECTS AND METHODS: Thirty-one subjects participating in AIDS Clinical Trials Group Protocol 375 who had received zidovudine, lamivudine, and ritonavir for at least 48 weeks. Subjects were immunized with tetanus toxoid (TT) at entry and with inactivated hepatitis A vaccine (hep A) and keyhole limpet hemocyanin (KLH) at entry and 6 weeks. The development of antibody, lymphocyte proliferative assay (LPA), and delayed-type hypersensitivity (DTH) responses after immunization were monitored. RESULTS: The LPA and DTH responses to TT improved in 57 and 68% of participants, respectively; 73 and 65% developed enhanced LPA and DTH responses to KLH. Forty-eight percent of patients developed a four-fold increase in antibody concentration to tetanus. Seventy-three percent of patients without detectable hepatitis A antibodies at baseline developed antibodies after immunization. Eighty-three percent of patients experienced at least a four-fold rise in KLH antibody concentration. Immune activation and viral load predicted poor recall responses and the number of memory CD4+ T-cells predicted good responses to recall antigens. Naïve CD4+ T-cell numbers, decrease in viral load, increases in CD4+ and CD28+ cells, and decreases in immune activation were associated with responses to presumed neoantigens. CONCLUSIONS: Most HIV-infected patients treated with potent combination antiretrovirals develop responses to recall and presumed neoantigens after immunization. Functional immune restoration in response to immunization is related to control of viral replication, decreased immune activation as well as to both quantitative and qualitative restoration of circulating T- lymphocyte subpopulations.