Palivizumab reduces respiratory syncytial virus (RSV) hospitalisations in high-risk infants. Those with severe bronchopulmonary dysplasia may require two seasons of prophylaxis. There is concern that this humanised antibody might cause an... more
Palivizumab reduces respiratory syncytial virus (RSV) hospitalisations in high-risk infants. Those with severe bronchopulmonary dysplasia may require two seasons of prophylaxis. There is concern that this humanised antibody might cause an adverse immune response in a second season of use. To evaluate and compare the occurrence of anti-palivizumab antibodies and clinical adverse events in subjects receiving monthly palivizumab injections for a first and second season, and to assess frequency and severity of RSV disease in the two groups. Subjects aged <or=2 years at severe risk for RSV disease were designated as first season (no previous palivizumab exposure) or second season subjects (received palivizumab in previous RSV season). Palivizumab injections (15 mg/kg) were administered monthly for up to 5 months. Anti-palivizumab antibody titres and serum palivizumab concentrations were measured; adverse events were recorded. No first (n = 71) or second (n = 63) season subjects experienced a significant anti-palivizumab antibody response (titre >or=1 : 80). Serum palivizumab concentrations were similar for the two groups. Nine (12.7%) first season and 8 (12.7%) second season subjects experienced one or more serious adverse events; most were respiratory and all were considered to be not or probably not related to palivizumab. No deaths occurred during the study. Monthly palivizumab injections were not associated with adverse immune responses or adverse events in young children receiving palivizumab for one or two seasons. Children receiving palivizumab for a second season did not experience more severe adverse events than those receiving it for the first time.
Research Interests: Pediatrics, Nonparametric Statistics, Medicine, Drug, Humans, and 15 moreFemale, Male, Infant, Monoclonal Antibodies, Respiratory Syncytial Virus, Palivizumab, Newborn Infant, Drug Safety, Drug evaluation, Chi Square Distribution, Risk Factors, Pharmacologie, Respiratory Syncytial Virus Infections Industry, Adverse effect, and Pharmacology and pharmaceutical sciences
Research Interests: Pediatrics, Epidemiology, Adolescent, Medicine, Seasonality, and 15 moreDisease Outbreaks, Prospective studies, Humans, Child, Infant, Incidence, Respiratory Syncytial Virus, Seasonal variation, Adult, Seasons, Outbreak, Metropolitan Area, Child preschool, Paediatrics and reproductive medicine, and Population surveillance
5-Androstene-3β, 17β-diol (AED) is a naturally occurring member of the androstene series of steroids. In models of chemotherapy and radiation-induced mylosuppression, AED expanded hematopoietic stem and progenitor cells (HSPC), decreased... more
5-Androstene-3β, 17β-diol (AED) is a naturally occurring member of the androstene series of steroids. In models of chemotherapy and radiation-induced mylosuppression, AED expanded hematopoietic stem and progenitor cells (HSPC), decreased need for clinical support and increased survival. We studied hematopoietic activity of AED vs. Placebo in healthy adult (20–64 years, n=9) and elderly (65–72 years, n=9) subjects. AED was safe and well tolerated. Complete blood counts were serially obtained between study days 1–56. Bone marrow (BM) samples were obtained on days -1 and 7. AED produced significant increases in average neutrophil counts (NT) and platelet counts (PLT) as compared to placebo. Adult NT significantly increased between days 2–7 (40–73%, p=0.05) and persisted through day 28 (41.5%); adult PLT increased (19.9%) by day 14, and achieved significance by day 21 (15.6%, p=0.01) and increases persisted through day 28 (19.4%, p=0.02). In elderly subjects, NT significantly increased by 56–96% (days 4–6, p=0.05) which persisted through day 28 (30.7%). Fewer elderly subjects demonstrated robust PLT responses; maximum increase in PLT was seen on day 14 (31.5%) and persisted through day 28. BM samples at day 7 showed increased cellularity in AED but not placebo-treated subjects which was consequently reflected as an increase in peripheral blood NT and PT in AE-treated subjects. BM phenotype changes and maturation potential were estimated from immunophenotyping and CFU assay in vitro. BM precursor populations were elevated in most treated subjects on day 7; this reflected an activity of AED on precursor cells that resulted in a decrease in the CD34+CD38− and CFU-F populations and an increase in erythrocyte (BFU-E, CFU-E), and granulocyte (CFU-GM) precursors and megakaryocytes. Elderly patients (but not adults) had increased levels of two angiogenic factors; vascular endothelial growth factor and plasminogen activator inhibitor-1 in plasma (day 5) and in BM (day 7). These findings suggest that AED has a regenerative role in elderly BM and that the stimulation of angiogenic factors precedes an increase in BM cellularity which in turn leads to an increase in circulating terminally differentiated blood elements.
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Ninety-one normal infants were followed longitudinally for varying periods from November 1975 to April 1977 to assess the correlation between tympanometry and pneumatic otoscopy and to study the pathogenesis of acute and chronic otitis... more
Ninety-one normal infants were followed longitudinally for varying periods from November 1975 to April 1977 to assess the correlation between tympanometry and pneumatic otoscopy and to study the pathogenesis of acute and chronic otitis media early in life. Type A (normal) tympanograms correlated with normal otoscopic findings in 92% of instances. Type B tympanograms, indicating reduced drum compliance with a relatively flat pressure curve, were associated with abnormal otoscopic findings in 93% of cases. The A8 (reduced compliance, normal pressure) and C (normal compliance, negative pressure) tympanograms were less consistent predictors of otoscopic findings. The correlation of tympanometric and otoscopic findings were similar in infants above and below 7 months of age. Tympanometry provided some insight into the natural history of otitis in 71 infants followed 12 to 17 months. Infants who failed to develop otitis had type B curves in only one of 240 determinations (0.4%). This pattern did not appear in those who developed acute otitis media (AOM) until the month preceding the first attack; nine of 29 tests (31%) made under these circumstances were type B. When a type B curve appeared in an asymptomatic study infant who had not previously had otitis, AOM developed within a month in nine of ten instances. At the time of diagnosis of first AOM, 87% of tympanograms were type B with the remainder type A8 or C. Sixty-three percent of tympanograms obtained from 25 infants during the six months following first AOM were type B, indicating that abnormal middle ear function was often prolonged. Fifteen of these 25 developed recurrent otitis during follow-up.
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Research Interests: Clinical Trial, Medicine, Prevention, Genetic Engineering, Humans, and 15 moreInfant, Palivizumab, Clinical Sciences, North America, Intensive Care Medicine, Bronchopulmonary Dysplasia, Monoclonal Antibody, Chronic lung disease, Food and Drug Administration, Lower Respiratory Tract Infection, Adverse effect, Nosocomial infection, High risk, Cardiovascular medicine and haematology, and Cross Infection
OBJECTIVE To assess the impact of multiple births and crowded homes on the severity of respiratory syncytial virus illness in preterm infants with bronchopulmonary dysplasia. RESEARCH DESIGN Retrospective case-control chart review from a... more
OBJECTIVE To assess the impact of multiple births and crowded homes on the severity of respiratory syncytial virus illness in preterm infants with bronchopulmonary dysplasia. RESEARCH DESIGN Retrospective case-control chart review from a prospective longitudinal respiratory illness study. SETTING Neonatal High-Risk Follow-Up Clinic (outpatient setting) and tertiary care hospitals (inpatient setting). PARTICIPANTS Fourteen sets of twins and two sets of triplets followed up between 1983 and 1989 and matched with 34 singleton infants for date of birth (within 3 months) and gestational age (within 1 month). MEASUREMENTS/MAIN RESULTS The risk of developing respiratory syncytial virus illness was significantly higher in multiple-birth infants than in singletons (53% vs 24%; P = .01). Multiple-birth infants were also at greater risk for developing pneumonia (24% vs 6%; P = .05) and requiring hospitalization (32% vs 18%; P = .05) than were singletons. Additional risk factors for developing pneumonia and bronchiolitis were examined in all 68 children. Multiple birth (P = .05), gestational age of less than 30 weeks (P = .02), and crowded homes (defined as more than one person living in 19 m2 of living space [P = .002] or more than one child living in 22 m2 of living space [P = .004]) were additional risk factors for developing pneumonia. CONCLUSION Multiple-birth preterm infants are at a higher risk of developing pneumonia than are singletons. Additional risk factors for developing pneumonia in preterm infants with bronchopulmonary dysplasia include gestational age of less than 30 weeks and crowded homes. At-risk infants with any of these risk factors should be targeted for prophylactic and therapeutic interventions against respiratory syncytial virus.
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Research Interests: Immunology, Infectious Diseases, Medicine, Biological Sciences, Prospective studies, and 15 moreHumans, Placebo, Hospitalization, Respiratory Syncytial Virus, Infectious, Newborn Infant, Bronchopulmonary Dysplasia, Seasons, Immunogenicity, Respiratory Syncytial Virus Infections Industry, immunoglobulin G, Child preschool, Neutralization tests, Medical and Health Sciences, and Influenza vaccines
Little is known about the risk of severe illness from respiratory syncytial virus infection in children with bronchopulmonary dysplasia. A prospective study was done of the natural history of respiratory syncytial virus infection in 30... more
Little is known about the risk of severe illness from respiratory syncytial virus infection in children with bronchopulmonary dysplasia. A prospective study was done of the natural history of respiratory syncytial virus infection in 30 children less than 2 years of age with bronchopulmonary dysplasia who were in a home oxygen program. Surveillance to identify children with acute respiratory symptoms was done by weekly telephone interview. Symptomatic children were examined, oxygen saturation was determined by oximetry, and nasopharyngeal lavage fluid was collected for virus cultures and rapid respiratory syncytial virus antigen tests. During the 4-month study period (December to April), 27 children had one or more acute respiratory illnesses, and respiratory syncytial virus developed in 16/27 (59%). Passive smoking and greater than or equal to four members in the home increased the risk of symptomatic respiratory syncytial virus (P less than .01 and P less than .03, respectively). Of 16 children, 11 (69%) required hospitalization. Of the 11 hospitalized children with respiratory syncytial virus, nine were either still receiving oxygen at home or required oxygen therapy within the previous 3 months v none of five nonhospitalized children (P less than .005). Five of the hospitalized children were greater than 12 months of age and five had respiratory syncytial virus infection previously that had been confirmed by culture results. Hospitalizations were prolonged and complicated. Seven of 11 children were hospitalized for greater than 1 week; four were admitted to the intensive care unit; four were treated with ribavirin aerosol, and two needed mechanical ventilation. There were no deaths.(ABSTRACT TRUNCATED AT 250 WORDS)
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Children who experience respiratory syncytial virus (RSV) lower respiratory tract infections (LRTIs) early in life have high rates of subsequent recurrent wheezing. Palivizumab, an anti-RSV monoclonal antibody, has 78% to 80% efficacy in... more
Children who experience respiratory syncytial virus (RSV) lower respiratory tract infections (LRTIs) early in life have high rates of subsequent recurrent wheezing. Palivizumab, an anti-RSV monoclonal antibody, has 78% to 80% efficacy in preventing RSV hospitalization in premature infants without chronic lung disease. We hypothesized that palivizumab, by ameliorating or preventing early RSV LRTI in preterm infants, might decrease later recurrent wheezing. A cohort of preterm infants who had received palivizumab and were not hospitalized for RSV (n = 191) or who never received palivizumab (n = 230; 76 who were hospitalized for RSV and 154 who were not), were prospectively followed for 24 months beginning at a mean age of 19 months. The subjects were assessed for recurrent wheezing by caretaker or physician report. The incidences of recurrent wheezing and physician-diagnosed recurrent wheezing were significantly lower in the 191 palivizumab-treated subjects (13% and 8%, respectively) compared with all 230 untreated subjects (26%, P = .001 and 16%, P = .011, respectively) and with the 154 patients in the subgroup not hospitalized for RSV LRTI (23%, P = .022 and 16%, P = .027, respectively). The effect of palivizumab treatment remained significant after adjustment for potential confounding variables. Our study suggests that preventing RSV LRTI with palivizumab may reduce subsequent recurrent wheezing in premature infants.
Research Interests: Pediatrics, Medicine, Probability, Multivariate Analysis, Prospective studies, and 15 moreHumans, Hospitalization, Female, Male, Monoclonal Antibodies, Respiratory Syncytial Virus, Palivizumab, Newborn Infant, Human Respiratory Syncytial Viruses, Reference Values, Logistic Models, Respiratory Sounds, Antiviral Agents, Paediatrics and reproductive medicine, and Infant Premature
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Research Interests:
Research Interests: Medicine, Biological Sciences, Safety, Prospective studies, Humans, and 15 moreFemale, Male, Infant, Vaccine, Risk factors, Newborn Infant, influenza A virus, Risk Factors, Immunogenicity, Seroconversion, High risk, Immunization Schedule, Medical and Health Sciences, Influenza vaccines, and Infant Premature
Influenza is an important cause of serious illness in very young children with cardiopulmonary disease. A 4-year study was conducted at two centers to assess immunogenicity and safety of influenza split-product vaccine in children aged 3... more
Influenza is an important cause of serious illness in very young children with cardiopulmonary disease. A 4-year study was conducted at two centers to assess immunogenicity and safety of influenza split-product vaccine in children aged 3 to 18 months with bronchopulmonary dysplasia and congenital heart disease. A total of 113 children were studied: 62 children 3 to 5 months of age and 51 children 6 to 18 months of age. Sera were drawn prior to first and second immunization and 3 weeks after second immunization and were tested by hemagglutination inhibition; protection was defined as greater than 1:32. Ninety-five children were surveyed for adverse reactions. Seroresponses were age and antigen specific. Best responses for all ages were to A/Mississippi (H3N2) (97%). Children older than 6 months of age had better seroresponses to A/Leningrad (H3N2) (73%, P less than .03) and B/Victoria (62%, P less than .02) than did children younger than 6 months of age. Seroconversion rates to the remaining antigens were low. Only 9% of children experienced adverse reactions; all but one were mild. The immunologic mechanisms responsible for preventing serious influenzal disease and more effective immunization strategies need to be defined for very young high-risk children.
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Research Interests: Pediatrics, Medicine, Congenital Heart Defects, Prospective studies, Humans, and 15 moreFemale, Male, Infant, The, Respiration, Newborn Infant, Human Respiratory Syncytial Viruses, Time Factors, Viral Infection, Oximetry, Bronchopulmonary Dysplasia, Ribavirin, Child preschool, High risk, and Paediatrics and reproductive medicine
5-androstenediol (5-AED) has been advanced as a possible countermeasure for treating the haematological component of acute radiation syndrome (ARS). It has been used in animal models to stimulate both innate and adaptive immunity and... more
5-androstenediol (5-AED) has been advanced as a possible countermeasure for treating the haematological component of acute radiation syndrome (ARS). It has been used in animal models to stimulate both innate and adaptive immunity and treat infection and radiation-induced immune suppression. We here report on the safety, tolerability and haematologic activity of 5-AED in four double-blinded, randomized, placebo-controlled studies on healthy adults including elderly subjects. A 5-AED injectable suspension formulation (NEUMUNE) or placebo was administered intramuscularly as either a single injection, or once daily for five consecutive days at doses of 50, 100, 200 or 400 mg. Subjects (n = 129) were randomized to receive NEUMUNE (n = 95) or the placebo (n = 34). NEUMUNE was generally well-tolerated; the most frequent adverse events were local injection site reactions (n = 104, 81%) that were transient, dose-volume dependent, mild to moderate in severity, and that resolved over the course of the study. Blood chemistries revealed a transient increase (up to 28%) in creatine phosphokinase and C-reactive protein levels consistent with intramuscular injection and injection site irritation. The blood concentration profile of 5-AED is consistent with a depot formulation that increases in disproportionate increments following each dose. NEUMUNE significantly increased circulating neutrophils (p < 0.001) and platelets (p < 0.001) in the peripheral blood of adult and elderly subjects. A dose-response relationship was identified. Findings suggest that parenteral administration of 5-AED in aqueous suspension may be a safe and effective means to stimulate innate immunity and alleviate neutropenia and thrombocytopenia associated with ARS.
Research Interests: Innate immunity, Medicine, Humans, Placebo, Adaptive Immunity, and 15 moreFemale, Male, Animal Model, Aged, Middle Aged, C reactive protein, Dose Response Relationship, Adult, Adverse Event, Blood Chemistry, Immune Suppression, Adverse effect, neutropenia, acute radiation syndrome, and Peripheral blood
Research Interests: Pediatrics, Medicine, Humans, Hospitalization, Female, and 15 moreMale, Infant, Patient Compliance, Monoclonal Antibodies, Palivizumab, Newborn Infant, Gestational Age, Observational Study, Regimen, Respiratory Syncytial Virus Infections Industry, Home Care Services, Antiviral Agents, Child preschool, Paediatrics and reproductive medicine, and Infant Premature
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Research Interests: Japan, Medicine, Genetic Engineering, Humans, Infectious Disease, and 15 moreAnimals, Infection, Monoclonal Antibodies, Respiratory Syncytial Virus, Palivizumab, Rats, Young Children, Bronchopulmonary Dysplasia, Monoclonal Antibody, Chronic lung disease, Antiviral Agents, Randomized Controlled Trials as Topic, Lower Respiratory Tract Infection, High risk, and Pharmacology and pharmaceutical sciences
Research Interests: Immunology, Asthma, Medicine, Disease susceptibility, Allergy, and 15 moreHumans, Female, Male, Infant, Monoclonal Antibodies, Palivizumab, Newborn Infant, Human Respiratory Syncytial Viruses, Bronchiolitis, Age Factors, Atopy, Antiviral Agents, Clinical Allergy and Immunology, Child preschool, and food hypersensitivity
Humoral and cellular immune responses to two doses of influenza antigens were measured in children 6-48 months of age. These vaccinees comprised a previously unimmunized cohort of 18 healthy full-term children and 15 sick preterm children... more
Humoral and cellular immune responses to two doses of influenza antigens were measured in children 6-48 months of age. These vaccinees comprised a previously unimmunized cohort of 18 healthy full-term children and 15 sick preterm children with bronchopulmonary dysplasia and an additional 30 ex-preterm children who were reimmunized. Half of the reimmunized cohort were recovered from bronchopulmonary dysplasia and half had active bronchopulmonary dysplasia. Antibody response was measured by haemagglutination inhibition (HI) and ELISA, and cellular immunity was measured by enumerating memory T cells. Six weeks after immunization, ELISA antibody levels were significantly higher in previously unimmunized full-term vaccinees than in previously unimmunized sick preterm infants (p less than 0.002). No difference was found between sick and recovered reimmunized children. By HI testing greater than 90% of children in both cohorts developed titres greater than or equal to 1:32, and these were generally maintained for at least 20 weeks. T-cell proliferative responses to influenza antigen were greater in the full-term children than in the preterm children (p less than 0.02), irrespective of state of health or prior immunization status. Split-product vaccine was immunogenic in all the cohorts studied; however, factors such as prematurity, health status and previous influenza immunization played important roles in the magnitude of some responses.
Research Interests: Immunology, Immune response, Medicine, Biological Sciences, Prospective studies, and 14 moreHumans, Infant, Immunization, Vaccine, Newborn Infant, T lymphocytes, Immune system, Young Children, Influenza Vaccine, Bronchopulmonary Dysplasia, Enzyme Linked Immunosorbent Assay, Medical and Health Sciences, Influenza vaccines, and Infant Premature
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Research Interests:
Research Interests: Medicine, Conjunctiva, Prospective studies, Humans, Female, and 15 moreMale, Infant, Otitis Media, Prospective Study, Positive predictive value, Haemophilus influenzae, Child preschool, Conjunctivitis, Negative predictive value, Antibiotic treatment, Clinical Pediatrics, Acute Otitis Media, Nasopharynx, Paediatrics and reproductive medicine, and Otitis
Respiratory syncytial virus (RSV) is the leading cause of lower respiratory illness in children. Prevention of this infection is available with the use of intravenous immunoglobulin or an intramuscular humanized monoclonal antibody... more
Respiratory syncytial virus (RSV) is the leading cause of lower respiratory illness in children. Prevention of this infection is available with the use of intravenous immunoglobulin or an intramuscular humanized monoclonal antibody (palivizumab). Palivizumab has been available in Puerto Rico since 1999. The objective of this study was to follow-up infants who received RSV prophylaxis with palivizumab in Puerto Rico to assess its efficacy and safety. A total of 230 infants who received RSV prophylaxis during the 2000-2001 and 2001-2002 seasons were followed-up. Adverse events from injections were minimal including erythema (2%), fever (5%), pain (4%), and rash (2%). In none of the patients prophylaxis was discontinued due to side effects. Forty-four infants (19%) had at least one respiratory hospitalization throughout the season, with RSV confirmed in seven (3%). Most hospitalizations occurred in the month of August when infants had received only one dose of palivizumab and on December, a peak month for RSV infections. Five infants (2.2%) required admission to an intensive care unit. In none of them, RSV was confirmed. This study confirms that monthly intramuscular administration of palivizumab is effective in preventing serious RSV infections in high risk infants.
Research Interests: Pain, Puerto Rico, Medicine, Humans, Hospitalization, and 15 moreFemale, Animals, Male, Infant, Immunization, Monoclonal Antibodies, Respiratory Syncytial Virus, Newborn Infant, Human Respiratory Syncytial Viruses, Fever, Respiratory System, Prognosis, Respiratory Syncytial Virus Infections Industry, Antiviral Agents, and Paediatrics and reproductive medicine
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Serious respiratory syncytial virus (RSV) disease requiring hospitalization occurs primarily in infants younger than 12 months. The incidence, risk factors, and clinical features in older children have not been studied extensively. Of 282... more
Serious respiratory syncytial virus (RSV) disease requiring hospitalization occurs primarily in infants younger than 12 months. The incidence, risk factors, and clinical features in older children have not been studied extensively. Of 282 children hospitalized at our institution with severe RSV disease during a 3-year period, 62 (22%) were older than 12 months. These 62 older children were matched for sex, onset of illness, and hospital location with 62 hospitalized children younger than 12 months with proved RSV infection. Older children had underlying chronic disease more commonly than younger children (47 of 62 vs 24 of 62). Chronic illnesses in older children included bronchopulmonary dysplasia and/or reactive airway disease (34 of 47), congenital heart disease (9 of 47), gastrointestinal disease (7 of 47), and genetic disorders (7 of 47). Three of the four deaths from RSV infection occurred in older children; all four had underlying disease (three with congenital heart disease and one with biliary atresia). We conclude that children older than 12 months with underlying disease are at increased risk for serious or fatal RSV infection and are not always protected by previous RSV disease. Such older children should be considered candidates for passive or active immunoprophylaxis against RSV infection as such agents become available.
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Research Interests: Incidence Geometry, Medicine, Congenital Heart Defects, Humans, Low Dose, and 15 moreFemale, Male, Infant, Newborn Infant, Human Respiratory Syncytial Viruses, Otitis Media, Bronchopulmonary Dysplasia, Congenital Heart Disease, Neutralizing antibodies, Acute Disease, Lower respiratory tract, Acute Otitis Media, High risk, Paediatrics and reproductive medicine, and Infant Premature
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To evaluate the safety and efficacy of respiratory syncytial virus immune globulin (RSVIG) in the prevention of severe respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) in infants born prematurely with or without... more
To evaluate the safety and efficacy of respiratory syncytial virus immune globulin (RSVIG) in the prevention of severe respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) in infants born prematurely with or without bronchopulmonary dysplasia (BPD). Data from a prospective, blinded, randomized, multicenter trial during three consecutive RSV seasons involving 249 children. This analysis comprises 162 preterm children, of whom 102 had BPD. The 87 children with congenital heart disease (CHD) were excluded from this analysis. Children were randomized to receive monthly infusions of RSVIG 750 mg/kg (high dose), RSVIG 150 mg/kg (low dose), or no RSVIG: Results from the preterm infants with and without BPD who received RSVIG 750 mg/kg are contrasted with control infants who did not receive RSVIG: As compared with controls, high-dose RSVIG administration significantly reduced the incidences of RSV LRTI (P = .01) and moderate-to-severe LRTI (P = .006). RSV-associated ho...
Research Interests: Pediatrics, Treatment Outcome, Medicine, Prospective studies, Humans, and 9 morePubmed, Newborn Infant, Human Respiratory Syncytial Viruses, Bronchopulmonary Dysplasia, Respiratory Syncytial Virus Infections Industry, Lower Respiratory Tract Infection, Psychology and Cognitive Sciences, Medical and Health Sciences, and Infant Premature
Infants with cardiopulmonary disease develop severe illness from respiratory syncytial virus (RSV) infection. Safety, feasibility, and pharmacokinetics of intravenous gamma globulin (IVIG) to prevent RSV illness were studied in 23... more
Infants with cardiopulmonary disease develop severe illness from respiratory syncytial virus (RSV) infection. Safety, feasibility, and pharmacokinetics of intravenous gamma globulin (IVIG) to prevent RSV illness were studied in 23 high-risk infants in a phase I trial. IVIG with an RSV neutralizing antibody titer of 1:1,100 in 5% solution was given monthly over a 2- to 4-h period in a clinical setting during the RSV season. The first group (n = 7) received 500 mg/kg of body weight, the second group (n = 9) received 600 mg/kg, and the third group (n =7) received 750 mg/kg. Serum was drawn prior to infusion and 2, 14, and 30 days after infusion. Total immunoglobulin G and RSV A2 and RSV B neutralizing antibody levels were obtained after the first IVIG infusion. Two children developed mild reversible pulmonary edema (group receiving 600 mg/kg per dose), and one developed hives and wheezing during one infusion (group receiving 500 mg/kg per dose). Twelve children developed subsequent RSV...
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Research Interests: Pediatrics, Medicine, Clinical Practice, Humans, Hospitalization, and 15 moreFemale, Male, Cohort Study, Infant, Cohort, International Classification of Diseases, First Year, Bronchiolitis, Linear Regression, Age Groups, Confidence Interval, Antiviral Agents, Cohort Studies, Lower Respiratory Tract Infection, and chronological age
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We performed a randomized, controlled trial of intravenous immune globulin (respiratory syncytial virus [RSV] neutralizing [Nt] antibody titer of 1:950 in 5% solution) to evaluate protection against RSV-induced disease over two... more
We performed a randomized, controlled trial of intravenous immune globulin (respiratory syncytial virus [RSV] neutralizing [Nt] antibody titer of 1:950 in 5% solution) to evaluate protection against RSV-induced disease over two respiratory virus seasons. Forty-nine children (mean age at enrollment, 4.5 months) with severe congenital heart disease or bronchopulmonary dysplasia were randomized as follows. Twenty-four patients were followed as controls and received no immune globulin. Twenty-five patients received monthly infusions of immune globulin at a dose of 500 mg/kg of body weight. There was a similar distribution between groups of patients with heart disease and bronchopulmonary dysplasia. There were 12 culture-proven RSV infections, 6 in the prophylaxis group and 6 in the control group. There was a trend toward less severe RSV illness in immune globulin recipients, as measured by length of hospitalization. Four of the six immune globulin recipients were hospitalized for a tota...
Research Interests: Microbiology, Medical Microbiology, Medicine, Humans, Infant, and 12 moreRisk factors, Newborn Infant, Human Respiratory Syncytial Viruses, Immune system, Antibody, Respiratory Tract Infections, Antimicrobial agents, Risk Factors, Bronchopulmonary Dysplasia, Gamma Globulin, Immunoglobulin A, and Pharmacology and pharmaceutical sciences
We read with interest the palivizumab review article by Shadman and Wald that was published in Expert Opinion on Biological Therapy in the November 2011 issue [1]. There were several factual errors in the text that should be brought to... more
We read with interest the palivizumab review article by Shadman and Wald that was published in Expert Opinion on Biological Therapy in the November 2011 issue [1]. There were several factual errors in the text that should be brought to the attention of your readers. The purpose of this letter is to list the errors and offer corrective information. In the “Areas covered” section the authors mention the use of palivizumab in patients with cystic fibrosis (CF), compromised immune systems or as treatment for respiratory syncytial virus (RSV) disease. Synagis is not approved by the FDA for the prevention of severe RSV disease in CF or immune-compromised patients or as treatment for RSV disease. Also, it is incorrect to state that motavizumab was “denied FDA approval.” MedImmune withdrew the RSV prophylaxis biologics license application from the FDA in December 2010 [2]. In Section 2.1.1, second paragraph, the text incorrectly states that the results of the IMpact trial “ showed a 55% reduction in hospitalization” for BPD and “premature less than 35 weeks” subjects. In fact, there was a 55% reduction in the rate of hospitalizations for all subjects combined. In addition, premature children born 35 wGA or less and £ 6 months of age were in fact eligible for the IMpact study [3]. In Section 2.2.2, it should be noted that Synagis has not been approved by the FDA for the prevention of asthma subsequent to severe RSV disease. In Section 3.1, third paragraph and in Table 3, the text incorrectly states that a Phase II trial is underway to study a “ liquid formulation of palivizumab.” This trial (NCT00240929) evaluated the safety, efficacy and bioavailability of an injectable liquid palivizumab preparation [4]. There is no oral liquid formulation of palivizumab under investigation. Table 3 from Shadman and Wald indicates that there are active trials for motavizumab and incorrectly cites Clinicaltrials.gov study NCT00435227 that has been completed [5]. There are no active studies ongoing with motavizumab at this time [6]. Finally, in Section 5 (Expert opinion) the authors state that palivizumab “has a clear role” in infants “ less than 32 weeks of gestation, those with chronic lung disease and those with congenital heart disease.” While this is in the “opinion” section, a balanced treatment would indicate that safety and efficacy have been demonstrated in premature infants who were born £ 35 wGA and £ 6 months of age prior to the start of the RSV season [7].
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Research Interests: Immunology, Clinical Trial, Adolescent, Humans, Child, and 15 moreHospitalization, Female, Animals, Disease, Heart Disease, Disease Outbreak, DNA vaccine, Congenital Heart Disease, Immunoglobulin, Antiviral Agents, immunoglobulin G, Clinical Trials as Topic, Child preschool, chronological age, and Immunization Schedule
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Research Interests: Pediatrics, Congenital Heart Defects, Pregnancy, Humans, Female, and 12 moreAnimals, Infant, Respiratory Syncytial Virus, Newborn Infant, Human Respiratory Syncytial Viruses, Bronchopulmonary Dysplasia, Immunoglobulins, Respiratory Syncytial Virus Infections Industry, Multicenter Studies as Topic, Randomized Controlled Trials as Topic, High risk, and Paediatrics and reproductive medicine
Respiratory secretions for viral diagnosis are often collected with nasopharyngeal (NP) swabs, although many laboratories recommend NP aspirates or washings. We compared results using NP washings and NP swabs in three diagnostic RSV... more
Respiratory secretions for viral diagnosis are often collected with nasopharyngeal (NP) swabs, although many laboratories recommend NP aspirates or washings. We compared results using NP washings and NP swabs in three diagnostic RSV tests, a rapid ...
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To evaluate the efficacy of high titer respiratory syncytial virus (RSV) immune globulin (RSVIG) in the treatment of previously healthy children hospitalized with proven RSV lower tract infection (LRI). Infants and young children... more
To evaluate the efficacy of high titer respiratory syncytial virus (RSV) immune globulin (RSVIG) in the treatment of previously healthy children hospitalized with proven RSV lower tract infection (LRI). Infants and young children </=2 years of age with RSV LRI of </=4 days duration, and respiratory scores >/=2. 5 were enrolled. One hundred and one previously healthy children hospitalized with RSV LRI received either 1500 mg/kg of RSVIG (RespiGam, MedImmune Inc, Gaithersburg, MD) or albumin placebo in a randomized, double-blind, placebo-controlled trial. Forty-six RSVIG and 52 recipients of placebo met all eligibility criteria. Demographic characteristics of the two groups were similar. More RSVIG recipients (46% vs 29%) had an SaO2 </=85% at entry than did placebo recipients, but a higher proportion of placebo recipients required intensive care unit (ICU) care and mechanical ventilation at study entry. The mean RSV hospital stay was 5.52 +/- 0.69 days (SE) for placebo and 4.58 +/- 0.40 days for RSVIG. Additionally, there was an interaction between treatment group and entry respiratory score, which led to subgroup analysis. Children with modest respiratory illness did not receive any benefit from RSVIG therapy. RSVIG recipients with more severe illness (entry respiratory scores >/=3.0) had 1.6 fewer hospital days and 2.7 days less ICU stays. RSVIG infusions seemed safe and generally well tolerated. Although some beneficial effect trends were seen for those with more severe disease who were treated there was no evidence that treatment with RSVIG resulted in reduced hospitalization and reduced ICU stays in all children with RSV disease.
Research Interests: Pediatrics, Treatment Outcome, Humans, Hospitalization, Female, and 10 moreMale, Infant, Respiratory Syncytial Virus, Length of Stay, Bronchiolitis, Respiratory Syncytial Virus Infections Industry, Severity of Illness Index, Lower Respiratory Tract Infection, Psychology and Cognitive Sciences, and Medical and Health Sciences
Page 1. PEDIATRICS Vol. 63 No. 3 March 1979 435 Otitis Media in Infancy: Tympanometric Findings Jessie R. Groothuis, MD, Sarah HW Sell, MD, Peter F. Wright, MD, Judith M. Thompson, RN, and William A. Altemeier Ill, MD ...
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Infants or children who had congenital or neonatal infection with cytomegalovirus (CMV) or herpes simplex virus (HSV) have fewer than 1:30,000 mononuclear cells in their blood lymphocytes preparations that proliferate in cultures... more
Infants or children who had congenital or neonatal infection with cytomegalovirus (CMV) or herpes simplex virus (HSV) have fewer than 1:30,000 mononuclear cells in their blood lymphocytes preparations that proliferate in cultures stimulated with the corresponding viral antigens. CMV and HSV responder cell frequencies in children and adults whose immunity followed postnatal infection with these viruses are 1:10,000 to 1:20,000. The low precursor frequency after congenital or neonatal infection is not associated with defective antigen processing by monocytes or nonspecific immunosuppression. Phenotypic changes in T cell subsets and the presence of antibody in the subjects suggests that the virus(es) do indeed elicit an immune response, but that this response is quantitatively deficient.
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To ascertain whether live attenuated or inactivated vaccines can be considered equivalent, we examined the primary antibody response of children following vaccination with influenza virus antigens in three different formulations. Nine... more
To ascertain whether live attenuated or inactivated vaccines can be considered equivalent, we examined the primary antibody response of children following vaccination with influenza virus antigens in three different formulations. Nine children received cold recombinant vaccine (CRV) containing A/Korea/82 (H3N2) and A/Dunedin/83 (H1N1) variants. Eight of these children responded to HA of the H3N2 subtype and the major portion of the elicited antibody was in the IgG1 subclass. Antibody of low titer in the IgG2 and IgG3 subclasses was detected in two and six serum specimens, respectively. Six of the nine children administered with CRV responded to the H1 antigen and only IgG1 antibody was detected. Serum specimens from eight children less than one year of age (5 less than 6 months of age) who had developed an antibody response to trivalent inactivated vaccine (TIV) vaccination were examined. High levels of IgG1 antibody to purified H3 were detected in all eight children. Low titers of antibody in IgG2 and IgG3 subclasses were detected in two and five children, respectively. Antibody responses to purified H1 showed a similar subclass distribution. In order to examine secondary response, eight children primed by immunization with TIV vaccine were subsequently given a single booster dose of purified hemagglutinin (HA) conjugated to diphtheria toxoid (HA-D). In 6/8 specimens antibody rises were detected to purified H3 and H1 antigens. Prior to the HA-D immunization, low levels of HA specific IgG1 antibody were detected in all serum specimens and vaccine induced responses were primarily of the IgG1 subclass.(ABSTRACT TRUNCATED AT 250 WORDS)
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The cocirculation in several parts of the world of influenza viruses B/Yamagata/16/88 and B/Victoria/2/87, which are genetically and antigenically divergent, has prompted the question of whether immunization with one viral antigen is... more
The cocirculation in several parts of the world of influenza viruses B/Yamagata/16/88 and B/Victoria/2/87, which are genetically and antigenically divergent, has prompted the question of whether immunization with one viral antigen is sufficient for protection against both strains. Twenty-three high-risk infants and young children were immunized with a commercial trivalent influenza vaccine containing the antigens of influenza virus B/Yamagata/16/88. When antibodies against influenza viruses B/Yamagata/16/88 and B/Victoria/2/87 were determined, increases developed uniformly to both in the sera of primed children previously exposed to influenza virus B/Victoria/2/87 by immunization or infection. Antibodies against B/Yamagata/16/88 developed in the sera of unprimed children with titers similar to those of the primed children. However, antibodies to B/Victoria/2/87 were not detected in the sera of the unprimed children. These data suggest that children without appropriate immunologic priming may not be protected against an infection with a B/Victoria/2/87 strain after vaccination with a B/Yamagata/16/88 strain. Immunization with more than one influenza B virus strain may be desirable in some high-risk pediatric patients if divergent influenza B viruses circulate.
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Page 1. Severe Respiratory Syncytial Virus Infection in Older Children Jessie R. Groothuis, MD; Carol K. Salbenblatt, RN; Brian A. Lauer, MD ... Respiratory syncytial virus in-fections. Postgrad Med J. 1973;49:788-791. 7. Mufson MA,... more
Page 1. Severe Respiratory Syncytial Virus Infection in Older Children Jessie R. Groothuis, MD; Carol K. Salbenblatt, RN; Brian A. Lauer, MD ... Respiratory syncytial virus in-fections. Postgrad Med J. 1973;49:788-791. 7. Mufson MA, Krause HE, Mocega HE, Daw-son FW. ...