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Papers by Robert Welliver

Journal of Infectious …, 2003

To determine the role of leukotrienes in a mouse model of respiratory syncytial virus (RSV) infec... more To determine the role of leukotrienes in a mouse model of respiratory syncytial virus (RSV) infection, we correlated the quantity of leukotrienes in lung lavage fluids of infected mice with respiratory rates and measures of outflow obstruction and then determined the ...

Dendritic cells (DCs) are important cells of our innate immune system. Their role is critical in ... more Dendritic cells (DCs) are important cells of our innate immune system. Their role is critical in inducing adaptive immunity, tolerance, or allergic response in peripheral organs-lung and skin. The lung DCs are not developed prenatally before birth. The DCs develop after birth presumably during the first year of life; exposures to any foreign antigen or infectious organisms during this period can significantly affect DC developmental programming and generation of distinct DC phenotypes and functions. These changes can have both short-term and long-term health effects which may be very relevant in childhood asthma and predisposition for a persistent response in adulthood. An understanding of DC development at molecular and cellular levels can help in protecting neonates and infants against problematic environmental exposures and developmental immunotoxicity. This knowledge can eventually help in designing novel pharmacological modulators to skew the DC characteristics and immune responses to benefit the host across a lifetime.

The Journal of Infectious Diseases, 1998

BALB/c mice inoculated intranasally with respiratory syncytial virus (RSV) were studied in a whol... more BALB/c mice inoculated intranasally with respiratory syncytial virus (RSV) were studied in a whole-body plethysmograph to determine if signs of respiratory illness similar to those observed in human infants could be detected. Also, responsiveness to methacholine was assessed. RSV-infected mice showed significantly higher respiratory rates than did controls (409.2 vs. 305.2 breaths/min, P õ .0001). Significantly increased airway responsiveness to methacholine was noted, infected mice responding to a 100-fold lower dose than controls (P Å .003). Together, these data provide the first objective evidence of respiratory illness in the mouse model of RSV infection, which enhances the value of this model for evaluating effects of vaccines, antivirals, and other drugs acting on respiratory tract disease caused by RSV. cin B, and 5% (vol/vol) fetal calf serum. Cells and media were Respiratory syncytial virus (RSV) is the most important viral harvested when 80%-90% cytopathic effect was observed, sonipathogen causing respiratory tract disease in infants and young cated for 2 min with a high-output sonicator (Sonic 2000; Braun children [1-5]. Despite the clear importance of RSV in both Instruments, Burlingame, CA), and centrifuged for 10 min at 500 acute and chronic respiratory diseases of childhood, the underg. The supernatant was divided into small aliquots and quickly

AJP: Lung Cellular and Molecular Physiology, 2013

Respiratory syncytial virus (RSV) infection of the lower respiratory tract is the leading cause o... more Respiratory syncytial virus (RSV) infection of the lower respiratory tract is the leading cause of respiratory failure among infants in the United States of America and annually results in >300,000 deaths worldwide. Despite the importance of RSV, there is no licensed vaccine, and no specific form of therapy. This is largely due to the absence of an appropriate animal model for the evaluation of vaccines and therapeutic agents. We inoculated anesthetized infant (4 wk) baboons ( Papio anubis) with a human strain of RSV intranasally or intratracheally. Baboons were monitored daily for clinical changes. Anesthetized baboons were intubated at various intervals, and bronchoalveolar lavage (BAL) was performed for viral culture and determination of leukocyte counts. Sham-infected baboons served as controls. Necropsies were performed on infected baboons on days 1, 3, 5, 8, or 13 after inoculation, with pathological analysis and immunohistochemical staining of lung tissues to detect RSV an...

AJP: Lung Cellular and Molecular Physiology, 2013

Respiratory syncytial virus (RSV) infection of the lower respiratory tract is the leading cause o... more Respiratory syncytial virus (RSV) infection of the lower respiratory tract is the leading cause of respiratory failure among infants in the United States of America and annually results in >300,000 deaths worldwide. Despite the importance of RSV, there is no licensed vaccine, and no specific form of therapy. This is largely due to the absence of an appropriate animal model for the evaluation of vaccines and therapeutic agents. We inoculated anesthetized infant (4 wk) baboons ( Papio anubis) with a human strain of RSV intranasally or intratracheally. Baboons were monitored daily for clinical changes. Anesthetized baboons were intubated at various intervals, and bronchoalveolar lavage (BAL) was performed for viral culture and determination of leukocyte counts. Sham-infected baboons served as controls. Necropsies were performed on infected baboons on days 1, 3, 5, 8, or 13 after inoculation, with pathological analysis and immunohistochemical staining of lung tissues to detect RSV an...

The Pediatric Infectious Disease Journal, 2000

Pediatric Critical Care Medicine, Dec 1, 2010

J Allerg Clin Immunol, 1999

Background: An imbalance of production of T-helper lymphocyte cytokines, favoring overproduction ... more Background: An imbalance of production of T-helper lymphocyte cytokines, favoring overproduction of IL-4, is believed to be important in the pathogenesis of allergic asthma. However, less is known about the cytokine response in virus-induced wheezing, which is a major cause of morbidity in asthma. Objective: We undertook this study to determine the magnitude of IFN-γ, IL-4 and IL-10, and leukotriene (LT) responses in infants and children with virus-induced wheezing. Methods: We measured the concentrations of IFN-γ, IL-4 and IL-10, and cysteinyl LTs in respiratory secretions of 82 infants and young children during acute episodes of virus-induced wheezing. Control subjects were 47 infants and children with uncomplicated upper respiratory infections and 18 normal healthy infants. Results: Ratios of IFN-γ to IL-4 were higher (due to increased quantities of IFN-γ) in subjects with wheezing than in those with upper respiratory infection alone (P = .003). Quantities of LTs were also increased in wheezing subjects in comparison with those with upper respiratory infections (P = .009). There was a significant correlation between measured concentrations of IFN-γ and LTs (correlation coefficient = .451, P = .007). Quantities of IL-4 were slightly suppressed in the wheezing groups. Conclusions: An imbalance favoring overproduction of IFN-γ appears to be associated temporarily with virus-induced wheezing. A possible mechanism is the enhanced release of LTs from eosinophils or mast cells after sensitization by IFN-γ. (J Allergy Clin Immunol 1999;103:630-6.)

Antimicrobial Agents and Chemotherapy, May 1, 1999

We conducted a multicenter, double-blind, placebo-controlled, randomized trial of a humanized mon... more We conducted a multicenter, double-blind, placebo-controlled, randomized trial of a humanized monoclonal antibody against a respiratory syncytial virus (RSV) fusion protein (SB 209763) to evaluate its safety, pharmacokinetics, and fusion inhibition and neutralization titers. Forty-three infants who were either delivered prematurely (<35 weeks' gestation) or exhibited bronchopulmonary dysplasia were administered either single or repeat (two doses, 8 weeks apart) intramuscular injections of SB 209763 at a concentration of 0.25, 1.25, 5.0, or 10.0 mg/kg or of a placebo. Four of 229 adverse events were considered related to the study drug, including purpura (n ‫؍‬ 3) and thrombocytosis (n ‫؍‬ 1). No subject developed a detectable level of anti-SB 209763 antibody. Approximately 1 week after administration of the second dose of SB 209763 at 10 mg/kg, the mean plasma concentration (n ‫؍‬ 9) was 68.5 g/ml. The terminal half-life (T 1/2 ) determined by noncompartmental analysis ranged from 22 to 50 days. The population pharmacokinetics for SB 209763 following intramuscular administration was appropriately described by a one-compartment model with first-order input and elimination. Higher values for clearance and volume of distribution at steady state were observed for younger patients, with values decreasing to 0.143 (ml/h)/kg and 161 mL/kg, respectively, by a mean age of 298 days (ϳ10 months). The mean T 1/2 of SB 209763 for the study population was 32.5 days. No other factor (dose, weight, gender, race, premature birth, or bronchopulmonary dysplasia) was observed to alter the population pharmacokinetics of SB 209763 in this study of infants and young children. The mean neutralization titer on day 6 was 286, and the mean fusion inhibition titer was 36. At least 57% of subjects dosed at 1.25 to 10.0 mg of SB 209763 per kg of body weight who were seronegative at baseline experienced a fourfold or greater increase in fusion inhibition titer. Nine RSV infections were documented during the 16-week course of the study; the numbers of RSV infections were similar for the different regimens, including the placebo. The doses of SB 209763 studied may have been insufficient to confer protection against RSV lower respiratory tract disease; these results suggest that additional trials using higher doses of monoclonal antibody for immunoprophylaxis should be considered.

ABSTRACT Purpose Inhaled halogenated anesthetics have been used for general anesthesia for decade... more ABSTRACT Purpose Inhaled halogenated anesthetics have been used for general anesthesia for decades and for sedation in the pediatric intensive care unit (PICU) sporadically. They also have anti-inflammatory effects in ischemia-reperfusion injury. We wished to determine if the halogenated anesthetic, Sevoflurane, reduced inflammation in respiratory syncytial virus (RSV) infection, a common viral infection requiring PICU admission. Methods We studied Sevoflurane in a mouse model of severe RSV infection using 4-week old New Zealand White mice. Mice were randomized into 5 groups (Pretreatment, Postexposure treatment, RSV controls, Sevoflurane Controls and Sham Controls). Animals assigned to treatment and Sevoflurane control groups were exposed to Sevoflurane at 1% for 1h either before inoculation with RSV on day 0 (Pretreatment) or daily after inoculation (days 1-5 – Postexposure) with anesthetic concentration monitored during exposure. Mice were weighed daily and observed for general appearance, behavior, and mortality. Plethysmography was performed to determine respiratory rate and enhanced pause, or Penh. On day 3 or day 5 mice had tracheal cannulation under intraperitoneal anesthesia followed by sacrifice in CO2 chamber. Lung mechanics were studied using FlexiVent, and lungs were processed for histology scoring. Samples were scored on a scale from 0 to 4 based on the amount of infiltrates in lung tissue. Results In contrast to healthy-looking and active mice in the Sham and Sevoflurane Control groups, mice in the RSV-infected groups had progressively decreased activity, labored breathing and wasting noticeable from day 3 (Table). Mortality abWeight change, % from Day 0 Day 3 / Day 5 abPenh, Day 0 / Day 3 / Day 5 abCdyn, ml/cmH2O Day 3 / Day 5 aMedian Histology Score, Day 3 / Day 5 Sevoflurane Pretreatment 2 / 15 -12% / -23% 0.62 / 3.45 / 4.83 0.022 / 0.0094 3 / 3 Sevoflurane Postexposure 2 / 20 -12% / -26% 0.58 / 3.41 / 5.44 0.020 / 0.011 3 / 4 RSV controls 1 / 25 -13% / -23% 0.71 / 3.62 / 4.91 0.018 / 0.011 3 / 4 Sevoflurane Controls 0 / 10 0% / 4% 0.58 / 0.49 / 0.48 0.033 0 Sham Controls 0 / 10 2% / 9% 0.60 / 0.85 / 0.59 0.031 0 ap&lt;0.05 for RSV vs. non-RSV infected mice and bfor day 3 vs. day 5 RSV-infected mice in all groups, including Sevoflurane treatment groups, demonstrated significantly greater weight loss, increased Penh, decreased dynamic compliance (Cdyn) and higher histology score than controls. Conclusion The NZW mouse is an excellent model for severe RSV disease. Sevoflurane exposure at 1% for 1h did not produce clinical benefit in our model. Longer exposure time or a different halogenated anesthetic may be more effective in decreasing inflammation in RSV infection.

Antimicrobial agents and chemotherapy, 1999

We conducted a multicenter, double-blind, placebo-controlled, randomized trial of a humanized mon... more We conducted a multicenter, double-blind, placebo-controlled, randomized trial of a humanized monoclonal antibody against a respiratory syncytial virus (RSV) fusion protein (SB 209763) to evaluate its safety, pharmacokinetics, and fusion inhibition and neutralization titers. Forty-three infants who were either delivered prematurely (</=35 weeks' gestation) or exhibited bronchopulmonary dysplasia were administered either single or repeat (two doses, 8 weeks apart) intramuscular injections of SB 209763 at a concentration of 0.25, 1.25, 5.0, or 10.0 mg/kg or of a placebo. Four of 229 adverse events were considered related to the study drug, including purpura (n = 3) and thrombocytosis (n = 1). No subject developed a detectable level of anti-SB 209763 antibody. Approximately 1 week after administration of the second dose of SB 209763 at 10 mg/kg, the mean plasma concentration (n = 9) was 68.5 micrograms/ml. The terminal half-life (T1/2) determined by noncompartmental analysis ran...

Vaccine, 1994

In a previous study, children 18 to 36 months of age and seropositive for respiratory syncytial v... more In a previous study, children 18 to 36 months of age and seropositive for respiratory syncytial virus (RSV) were vaccinated with an RSV subunit vaccine (PFP-1) consisting of the viral fusion protein. Vaccines developed substantial increases in anti-fusion and neutralizing antibody and exhibited protection against RSV infection through one RSV epidemic, in comparison to controls. This present study of the same cohort was undertaken to determine the persistence of antibody responses and immunity to reinfection, as well as to monitor for enhanced disease upon subsequent RSV infection during the second RSV season after vaccination. Vaccinees continued to have greater ELISA specific anti-fusion (F) antibody responses than controls up to 18 months after vaccination. Neutralizing antibody titres were not as durable, and the attack rates for RSV in the second winter season after vaccination (25% in vaccines versus 42% in controls) were not significantly different (p = 0.23). Nevertheless, &...

American journal of diseases of children (1960), 1981

Studies of cell-mediated immunity (CMI) to measles were carried out in patients with natural meas... more Studies of cell-mediated immunity (CMI) to measles were carried out in patients with natural measles infection, in recipients of live measles vaccine, and in umbilical cord blood specimens from infants of mothers who were seropositive for measles. Evidence of CMI to measles was found in 100% of patients with natural infection but in only 62% of vaccine recipients and, interestingly, in 40% of umbilical cord blood specimens. Eight of these infants were subsequently studied at 4 to 5 months of age, at which time evidence of measles CMI was still detectable in three. Sufficient stimulation of cell-mediated immune mechanisms may be a prerequisite for the development of life-long immunity to measles. The effect of congenitally acquired CMI to measles on the outcome of immunization or of exposure to natural measles during the first year of life remains to be determined.

The Pediatric Infectious Disease Journal, 1996

Journal of Infectious …, 2003

To determine the role of leukotrienes in a mouse model of respiratory syncytial virus (RSV) infec... more To determine the role of leukotrienes in a mouse model of respiratory syncytial virus (RSV) infection, we correlated the quantity of leukotrienes in lung lavage fluids of infected mice with respiratory rates and measures of outflow obstruction and then determined the ...

Dendritic cells (DCs) are important cells of our innate immune system. Their role is critical in ... more Dendritic cells (DCs) are important cells of our innate immune system. Their role is critical in inducing adaptive immunity, tolerance, or allergic response in peripheral organs-lung and skin. The lung DCs are not developed prenatally before birth. The DCs develop after birth presumably during the first year of life; exposures to any foreign antigen or infectious organisms during this period can significantly affect DC developmental programming and generation of distinct DC phenotypes and functions. These changes can have both short-term and long-term health effects which may be very relevant in childhood asthma and predisposition for a persistent response in adulthood. An understanding of DC development at molecular and cellular levels can help in protecting neonates and infants against problematic environmental exposures and developmental immunotoxicity. This knowledge can eventually help in designing novel pharmacological modulators to skew the DC characteristics and immune responses to benefit the host across a lifetime.

The Journal of Infectious Diseases, 1998

BALB/c mice inoculated intranasally with respiratory syncytial virus (RSV) were studied in a whol... more BALB/c mice inoculated intranasally with respiratory syncytial virus (RSV) were studied in a whole-body plethysmograph to determine if signs of respiratory illness similar to those observed in human infants could be detected. Also, responsiveness to methacholine was assessed. RSV-infected mice showed significantly higher respiratory rates than did controls (409.2 vs. 305.2 breaths/min, P õ .0001). Significantly increased airway responsiveness to methacholine was noted, infected mice responding to a 100-fold lower dose than controls (P Å .003). Together, these data provide the first objective evidence of respiratory illness in the mouse model of RSV infection, which enhances the value of this model for evaluating effects of vaccines, antivirals, and other drugs acting on respiratory tract disease caused by RSV. cin B, and 5% (vol/vol) fetal calf serum. Cells and media were Respiratory syncytial virus (RSV) is the most important viral harvested when 80%-90% cytopathic effect was observed, sonipathogen causing respiratory tract disease in infants and young cated for 2 min with a high-output sonicator (Sonic 2000; Braun children [1-5]. Despite the clear importance of RSV in both Instruments, Burlingame, CA), and centrifuged for 10 min at 500 acute and chronic respiratory diseases of childhood, the underg. The supernatant was divided into small aliquots and quickly

AJP: Lung Cellular and Molecular Physiology, 2013

Respiratory syncytial virus (RSV) infection of the lower respiratory tract is the leading cause o... more Respiratory syncytial virus (RSV) infection of the lower respiratory tract is the leading cause of respiratory failure among infants in the United States of America and annually results in >300,000 deaths worldwide. Despite the importance of RSV, there is no licensed vaccine, and no specific form of therapy. This is largely due to the absence of an appropriate animal model for the evaluation of vaccines and therapeutic agents. We inoculated anesthetized infant (4 wk) baboons ( Papio anubis) with a human strain of RSV intranasally or intratracheally. Baboons were monitored daily for clinical changes. Anesthetized baboons were intubated at various intervals, and bronchoalveolar lavage (BAL) was performed for viral culture and determination of leukocyte counts. Sham-infected baboons served as controls. Necropsies were performed on infected baboons on days 1, 3, 5, 8, or 13 after inoculation, with pathological analysis and immunohistochemical staining of lung tissues to detect RSV an...

AJP: Lung Cellular and Molecular Physiology, 2013

Respiratory syncytial virus (RSV) infection of the lower respiratory tract is the leading cause o... more Respiratory syncytial virus (RSV) infection of the lower respiratory tract is the leading cause of respiratory failure among infants in the United States of America and annually results in >300,000 deaths worldwide. Despite the importance of RSV, there is no licensed vaccine, and no specific form of therapy. This is largely due to the absence of an appropriate animal model for the evaluation of vaccines and therapeutic agents. We inoculated anesthetized infant (4 wk) baboons ( Papio anubis) with a human strain of RSV intranasally or intratracheally. Baboons were monitored daily for clinical changes. Anesthetized baboons were intubated at various intervals, and bronchoalveolar lavage (BAL) was performed for viral culture and determination of leukocyte counts. Sham-infected baboons served as controls. Necropsies were performed on infected baboons on days 1, 3, 5, 8, or 13 after inoculation, with pathological analysis and immunohistochemical staining of lung tissues to detect RSV an...

The Pediatric Infectious Disease Journal, 2000

Pediatric Critical Care Medicine, Dec 1, 2010

J Allerg Clin Immunol, 1999

Background: An imbalance of production of T-helper lymphocyte cytokines, favoring overproduction ... more Background: An imbalance of production of T-helper lymphocyte cytokines, favoring overproduction of IL-4, is believed to be important in the pathogenesis of allergic asthma. However, less is known about the cytokine response in virus-induced wheezing, which is a major cause of morbidity in asthma. Objective: We undertook this study to determine the magnitude of IFN-γ, IL-4 and IL-10, and leukotriene (LT) responses in infants and children with virus-induced wheezing. Methods: We measured the concentrations of IFN-γ, IL-4 and IL-10, and cysteinyl LTs in respiratory secretions of 82 infants and young children during acute episodes of virus-induced wheezing. Control subjects were 47 infants and children with uncomplicated upper respiratory infections and 18 normal healthy infants. Results: Ratios of IFN-γ to IL-4 were higher (due to increased quantities of IFN-γ) in subjects with wheezing than in those with upper respiratory infection alone (P = .003). Quantities of LTs were also increased in wheezing subjects in comparison with those with upper respiratory infections (P = .009). There was a significant correlation between measured concentrations of IFN-γ and LTs (correlation coefficient = .451, P = .007). Quantities of IL-4 were slightly suppressed in the wheezing groups. Conclusions: An imbalance favoring overproduction of IFN-γ appears to be associated temporarily with virus-induced wheezing. A possible mechanism is the enhanced release of LTs from eosinophils or mast cells after sensitization by IFN-γ. (J Allergy Clin Immunol 1999;103:630-6.)

Antimicrobial Agents and Chemotherapy, May 1, 1999

We conducted a multicenter, double-blind, placebo-controlled, randomized trial of a humanized mon... more We conducted a multicenter, double-blind, placebo-controlled, randomized trial of a humanized monoclonal antibody against a respiratory syncytial virus (RSV) fusion protein (SB 209763) to evaluate its safety, pharmacokinetics, and fusion inhibition and neutralization titers. Forty-three infants who were either delivered prematurely (<35 weeks' gestation) or exhibited bronchopulmonary dysplasia were administered either single or repeat (two doses, 8 weeks apart) intramuscular injections of SB 209763 at a concentration of 0.25, 1.25, 5.0, or 10.0 mg/kg or of a placebo. Four of 229 adverse events were considered related to the study drug, including purpura (n ‫؍‬ 3) and thrombocytosis (n ‫؍‬ 1). No subject developed a detectable level of anti-SB 209763 antibody. Approximately 1 week after administration of the second dose of SB 209763 at 10 mg/kg, the mean plasma concentration (n ‫؍‬ 9) was 68.5 g/ml. The terminal half-life (T 1/2 ) determined by noncompartmental analysis ranged from 22 to 50 days. The population pharmacokinetics for SB 209763 following intramuscular administration was appropriately described by a one-compartment model with first-order input and elimination. Higher values for clearance and volume of distribution at steady state were observed for younger patients, with values decreasing to 0.143 (ml/h)/kg and 161 mL/kg, respectively, by a mean age of 298 days (ϳ10 months). The mean T 1/2 of SB 209763 for the study population was 32.5 days. No other factor (dose, weight, gender, race, premature birth, or bronchopulmonary dysplasia) was observed to alter the population pharmacokinetics of SB 209763 in this study of infants and young children. The mean neutralization titer on day 6 was 286, and the mean fusion inhibition titer was 36. At least 57% of subjects dosed at 1.25 to 10.0 mg of SB 209763 per kg of body weight who were seronegative at baseline experienced a fourfold or greater increase in fusion inhibition titer. Nine RSV infections were documented during the 16-week course of the study; the numbers of RSV infections were similar for the different regimens, including the placebo. The doses of SB 209763 studied may have been insufficient to confer protection against RSV lower respiratory tract disease; these results suggest that additional trials using higher doses of monoclonal antibody for immunoprophylaxis should be considered.

ABSTRACT Purpose Inhaled halogenated anesthetics have been used for general anesthesia for decade... more ABSTRACT Purpose Inhaled halogenated anesthetics have been used for general anesthesia for decades and for sedation in the pediatric intensive care unit (PICU) sporadically. They also have anti-inflammatory effects in ischemia-reperfusion injury. We wished to determine if the halogenated anesthetic, Sevoflurane, reduced inflammation in respiratory syncytial virus (RSV) infection, a common viral infection requiring PICU admission. Methods We studied Sevoflurane in a mouse model of severe RSV infection using 4-week old New Zealand White mice. Mice were randomized into 5 groups (Pretreatment, Postexposure treatment, RSV controls, Sevoflurane Controls and Sham Controls). Animals assigned to treatment and Sevoflurane control groups were exposed to Sevoflurane at 1% for 1h either before inoculation with RSV on day 0 (Pretreatment) or daily after inoculation (days 1-5 – Postexposure) with anesthetic concentration monitored during exposure. Mice were weighed daily and observed for general appearance, behavior, and mortality. Plethysmography was performed to determine respiratory rate and enhanced pause, or Penh. On day 3 or day 5 mice had tracheal cannulation under intraperitoneal anesthesia followed by sacrifice in CO2 chamber. Lung mechanics were studied using FlexiVent, and lungs were processed for histology scoring. Samples were scored on a scale from 0 to 4 based on the amount of infiltrates in lung tissue. Results In contrast to healthy-looking and active mice in the Sham and Sevoflurane Control groups, mice in the RSV-infected groups had progressively decreased activity, labored breathing and wasting noticeable from day 3 (Table). Mortality abWeight change, % from Day 0 Day 3 / Day 5 abPenh, Day 0 / Day 3 / Day 5 abCdyn, ml/cmH2O Day 3 / Day 5 aMedian Histology Score, Day 3 / Day 5 Sevoflurane Pretreatment 2 / 15 -12% / -23% 0.62 / 3.45 / 4.83 0.022 / 0.0094 3 / 3 Sevoflurane Postexposure 2 / 20 -12% / -26% 0.58 / 3.41 / 5.44 0.020 / 0.011 3 / 4 RSV controls 1 / 25 -13% / -23% 0.71 / 3.62 / 4.91 0.018 / 0.011 3 / 4 Sevoflurane Controls 0 / 10 0% / 4% 0.58 / 0.49 / 0.48 0.033 0 Sham Controls 0 / 10 2% / 9% 0.60 / 0.85 / 0.59 0.031 0 ap&lt;0.05 for RSV vs. non-RSV infected mice and bfor day 3 vs. day 5 RSV-infected mice in all groups, including Sevoflurane treatment groups, demonstrated significantly greater weight loss, increased Penh, decreased dynamic compliance (Cdyn) and higher histology score than controls. Conclusion The NZW mouse is an excellent model for severe RSV disease. Sevoflurane exposure at 1% for 1h did not produce clinical benefit in our model. Longer exposure time or a different halogenated anesthetic may be more effective in decreasing inflammation in RSV infection.

Antimicrobial agents and chemotherapy, 1999

We conducted a multicenter, double-blind, placebo-controlled, randomized trial of a humanized mon... more We conducted a multicenter, double-blind, placebo-controlled, randomized trial of a humanized monoclonal antibody against a respiratory syncytial virus (RSV) fusion protein (SB 209763) to evaluate its safety, pharmacokinetics, and fusion inhibition and neutralization titers. Forty-three infants who were either delivered prematurely (</=35 weeks' gestation) or exhibited bronchopulmonary dysplasia were administered either single or repeat (two doses, 8 weeks apart) intramuscular injections of SB 209763 at a concentration of 0.25, 1.25, 5.0, or 10.0 mg/kg or of a placebo. Four of 229 adverse events were considered related to the study drug, including purpura (n = 3) and thrombocytosis (n = 1). No subject developed a detectable level of anti-SB 209763 antibody. Approximately 1 week after administration of the second dose of SB 209763 at 10 mg/kg, the mean plasma concentration (n = 9) was 68.5 micrograms/ml. The terminal half-life (T1/2) determined by noncompartmental analysis ran...

Vaccine, 1994

In a previous study, children 18 to 36 months of age and seropositive for respiratory syncytial v... more In a previous study, children 18 to 36 months of age and seropositive for respiratory syncytial virus (RSV) were vaccinated with an RSV subunit vaccine (PFP-1) consisting of the viral fusion protein. Vaccines developed substantial increases in anti-fusion and neutralizing antibody and exhibited protection against RSV infection through one RSV epidemic, in comparison to controls. This present study of the same cohort was undertaken to determine the persistence of antibody responses and immunity to reinfection, as well as to monitor for enhanced disease upon subsequent RSV infection during the second RSV season after vaccination. Vaccinees continued to have greater ELISA specific anti-fusion (F) antibody responses than controls up to 18 months after vaccination. Neutralizing antibody titres were not as durable, and the attack rates for RSV in the second winter season after vaccination (25% in vaccines versus 42% in controls) were not significantly different (p = 0.23). Nevertheless, &...

American journal of diseases of children (1960), 1981

Studies of cell-mediated immunity (CMI) to measles were carried out in patients with natural meas... more Studies of cell-mediated immunity (CMI) to measles were carried out in patients with natural measles infection, in recipients of live measles vaccine, and in umbilical cord blood specimens from infants of mothers who were seropositive for measles. Evidence of CMI to measles was found in 100% of patients with natural infection but in only 62% of vaccine recipients and, interestingly, in 40% of umbilical cord blood specimens. Eight of these infants were subsequently studied at 4 to 5 months of age, at which time evidence of measles CMI was still detectable in three. Sufficient stimulation of cell-mediated immune mechanisms may be a prerequisite for the development of life-long immunity to measles. The effect of congenitally acquired CMI to measles on the outcome of immunization or of exposure to natural measles during the first year of life remains to be determined.

The Pediatric Infectious Disease Journal, 1996