Safety of cetirizine in infants 6 to 11 months of age: a randomized,double-blind,placebo-controlled study

BACKGROUND: H(1)-antihistamines are widely used for symptom relief in allergic disorders in infants and children; however, there are few prospective, randomized, double-blind, controlled studies of these medications in young children, and to date, no such studies have been conducted in infants. OBJECTIVE: This prospective, randomized, parallel-group, double-blind, placebo-controlled study was designed to evaluate the safety of the H(1)-antihistamine cetirizine, particularly with regard to central nervous system and cardiac effects, in infants age 6 to 11 months, inclusive. METHODS: Infants who met the entry criteria for age and had a history of treatment with an H(1)-antihistamine for an allergic or other disorder were randomized to receive 0.25 mg/kg cetirizine orally or matching placebo twice daily orally for 1 week. RESULTS: The mean daily dose in cetirizine-treated infants was 4.5 +/- 0.7 mg (SD). No differences in all-cause or treatment-related adverse events were observed between the cetirizine- and placebo-treated groups. A trend was observed toward fewer adverse events and sleep-related disturbances in the cetirizine group compared with the placebo group. No prolongation in the linear corrected QT interval was observed in cetirizine-treated infants compared with either baseline values or with values in placebo-treated infants. CONCLUSIONS: We have documented the safety of cetirizine in this short-term investigation, the first randomized, double-blind, placebo-controlled study of any H(1)-antihistamine in infants. Additional prospective, randomized, double-blind, placebo-controlled, long-term studies of cetirizine and other H(1)-antihistamines are needed in this population.     

Incidence of systemic reactions during rush immunotherapy.

Rush immunotherapy (RIT) was administered on an outpatient basis to 11 patients. Of these, nine had asthma and four were steroid-dependent. All patients received extracts containing a mixture of antigens to which they were prick-sensitive. FEV1s were greater than 80% predicted before starting RIT. Four patients each required a 1 week steroid "burst" to accomplish this. A series of 8 subcutaneous injections were given starting with 0.3 mL of 1:100,000 (wt/vol) and ending with 0.10 mL of 1:100 (wt/vol) 1.5 days later. A dose of 0.15 mL of 1:100 was given weekly after that. All patients but one completed the RIT. Four had sore arms, four had pruritus and/or sneezing, four developed wheezing, and one experienced anaphylaxis with hypotension. Systemic reactions tended to occur at the higher doses and usually more than 30 minutes after a previous injection. Subsequent weekly injections were tolerated without reactions by seven of the patients. Rush immunotherapy is an effective method for administering a high dose of allergen in a very short time period. Due to the risk of systemic reactions it needs to be given under carefully controlled conditions.     

Continuous terbutaline nebulization for the treatment of severe exacerbations of asthma in children

Twelve children with severe asthma were treated in an intensive care unit with continuously nebulized terbutaline at doses between 1.0 and 12.0 mg/hour. All patients showed improvement in blood gases, pulse, and respiratory rates. None experience significant side effects. The duration of therapy ranged from 1 to 24 hours (mean = 8.3 hours), and all were able to leave the intensive care unit within one day. The use of continuously nebulized terbutaline appears to be safe and effective for the treatment of severe asthma in children in this limited experience.     

Epicoccum allergy: skin reaction patterns and spore/mycelium disparities recognized by IgG and IgE ELISA inhibition

Comparable degrees of skin reactivity were observed towards spore and mycelium extracts from two isolates of Epicoccum and to one preparation of Alternaria in 35 rural and 120 university patients. The best experimental extracts detected Epicoccum sensitivity in 70% of the group tested while the commercial extract detected sensitivity in only 6%. Skin reaction correlations were greatest within isolates (eg, spore-A/mycelium-A), then for specific fungus parts (eg, spore-A/spore-B), then between isolates and parts (spore-A/mycelium-B). High correlations were found between individual IgG and IgE ELISA values for all antigens using serum from Epicoccum skin-reactive patients. ELISA inhibition results suggested that significant cross-reactivity exists between Epicoccum and Alternaria antigens recognized by IgG but not by IgE. ELISA inhibition cross-reaction patterns among Epicoccum antigens were comparable to skin reactions while IgG patterns showed little variability. Further characterization of spore/mycelium and interstrain recognition patterns among different immunoglobulin isotypes will be necessary before complete standardization of extracts from different parts of fungi will be possible. The use of spore material for skin testing and treatment of Epicoccum sensitivity appears to be both premature and unnecessary at this time.     

A New Model for Environmental Assessment and Exposure Reduction

Environmental assessment and exposure reduction are a set of diagnostic and treatment techniques that work in tandem with the traditional medical approach by reducing a patient??s exposure to adverse environmental conditions as part of medical care. Assessment involves identifying the specific exposures to which a patient is sensitive and locating the corresponding contaminants in the patient??s environment. This provides a more complete diagnostic evaluation of a patient??s problem than could be obtained merely by examining the patient alone. Exposure reduction involves reducing the identified triggers to levels that are below thresholds that are associated with increased risk of sensitization and disease morbidity. Assessment of an environment for contaminants focuses on a chain of factors that include contaminant sources such as cockroaches, rodents, dust mites and fungi that excrete contaminants into an environment, facilitative factors such as moisture, food, water and shelter that help sources to thrive, and reservoirs where contaminants can accumulate prior to subsequent transport to occupants. By using this model to guide environmental assessments and their corresponding interventions, the root cause of health problems can be addressed, leading to improved quality of life for patients and reduced need for chronic medications.     

Intracellular methicillin selection of Listeria monocytogenes mutants unable to replicate in a macrophage cell line.

To dissect the determinants of Listeria monocytogenes that are required for pathogenicity, we designed an intracellular selection protocol based on penicillin selection to isolate mutants defective for intracellular growth. Eight independent mutants obtained by insertion of Tn916 were isolated that were resistant to methicillin treatment following internalization by the J774 macrophage-like cell line. Seven mutants were absolutely defective for intracellular growth, whereas one showed abortive intracellular growth. The majority of the mutants were nonhemolytic and lacked a secreted 58-kDa polypeptide thought to be the L. monocytogenes hemolysin, listeriolysin O. Southern blot analysis indicated that one mutant contained a Tn916 insertion in hlyA, the listeriolysin O structural gene, which resulted in a truncated listeriolysin O polypeptide, whereas another mutant contained an insertion immediately upstream of hlyA, which resulted in reduced expression of listeriolysin O. The other mutants contained Tn916 insertions in genes other than hlyA, although all but one were nonhemolytic. Revertants isolated by their ability to grow within tissue culture cells regained hemolytic activity. These data show that intracellular methicillin selection facilitates isolation of mutations in genes required for intracellular growth and strengthens the premise that listeriolysin O is essential for intracellular growth.     

In Vitro Resistance Studies with Bacteria That Exhibit Low Mutation Frequencies: Prediction of “Antimutant” Linezolid Concentrations Using a Mixed Inoculum Containing both Susceptible and Resistant Staphylococcus aureus

Bacterial resistance studies using in vitro dynamic models are highly dependent on the starting inoculum that might or might not contain spontaneously resistant mutants (RMs). To delineate concentration-resistance relationships with linezolid-exposed Staphylococcus aureus, a mixed inoculum containing both susceptible cells and RMs was used. An RM selected after the 9th passage of the parent strain (MIC, 2 μg/ml) on antibiotic-containing media (RM9; MIC, 8 μg/ml) was chosen for the pharmacodynamic studies, because the mutant prevention concentration (MPC) of linezolid against the parent strain in the presence of RM9 at 10² (but not at 10⁴) CFU/ml did not differ from the MPC value determined in the absence of the RMs. Five-day treatments with twice-daily linezolid doses were simulated at concentrations either between the MIC and MPC or above the MPC. S. aureus RMs (resistant to 2× and 4× MIC but not 8× and 16× MIC) were enriched at ratios of the 24-h area under the concentration-time curve (AUC₂₄) to the MIC that provide linezolid concentrations between the MIC and MPC for 100% (AUC₂₄/MIC, 60 h) and 86% (AUC₂₄/MIC, 120 h) of the dosing interval. No such enrichment occurred when linezolid concentrations were above the MIC and below the MPC for a shorter time (37% of the dosing interval; AUC₂₄/MIC, 240 h) or when concentrations were consistently above the MPC (AUC₂₄/MIC, 480 h). These findings obtained using linezolid-susceptible staphylococci supplemented with RMs support the mutant selection window hypothesis. This method provides an option to delineate antibiotic concentration-resistance relationships with bacteria that exhibit low mutation frequencies.     

Localized pericardial inflammation in systemic lupus erythematosus

Regional or localized pericarditis has been infrequently reported. We report a patient with systemic lupus erythematosus (SLE), who presented with retrosternal pleuritic-type chest pain without audible friction rub, electrocardiographic changes or detectable pericardial effusion on echocardiography. Computed tomography, however, revealed a circumscribed area of pericardial inflammation, suggesting a diagnosis of localized lupus-associated pericarditis. This case demonstrates that localized pericarditis may occur in SLE and that chest CT may be required as part of the work-up in the diagnosis of lupus pericarditis.