Kenny H. Chan

Influence of Age and Nature of Primary Infection on Varicella-Zoster Virus—Specific Cell-Mediated Immune Responses

BACKGROUND Varicella-zoster virus (VZV)-specific cell-mediated immunity is important for protection against VZV disease. We studied the relationship between VZV cell-mediated immunity and age after varicella or VZV vaccination in healthy and human immunodeficiency virus (HIV)-infected individuals. METHODS VZV responder cell frequency (RCF) determinations from 752 healthy and 200 HIV-infected subjects were used to identify group-specific regression curves on age. RESULTS In healthy individuals with past varicella, VZV RCF peaked at 34 years of age. Similarly, VZV-RCF after varicella vaccine increased with age in subjects aged <1 to 43 years. In subjects aged 61-90 years, VZV RCF after zoster vaccine decreased with age. HIV-infected children had lower VZV RCF estimates than HIV-infected adults. In both groups, VZV RCF results were low and constant over age. Varicella vaccination of HIV-infected children with CD4 levels 20% generated VZV RCF values higher than wild-type infection and comparable to vaccine-induced responses of healthy children. CONCLUSIONS In immunocompetent individuals with prior varicella, VZV RCF peaked in early adulthood. Administration of varicella vaccine to HIV-infected or uninfected individuals aged >5 years generated VZV RCF values similar to those of immunocompetent individuals with immunity induced by wild-type infection. A zoster vaccine increased the VZV RCF of elderly adults aged <75 years to values higher than peak values induced by wild-type infection.

Antibiotic-resistant bacteria in pediatric chronic sinusitis.

Background. Limited information exists on emerging bacterial resistance patterns in pediatric chronic sinusitis. Methods. A retrospective review (1995 to 1998) of the aerobic microbiology of chronic sinusitis in children at a tertiary care children’s hospital was conducted. One hundred nineteen children (mean age, 4.9 years) with maxillary sinusitis of >8 weeks duration and no known immunodeficiency or cystic fibrosis who underwent antral irrigation were included. Results. One hundred sixty-one of 240 (67%) aerobic cultures were positive, yielding 274 isolates. Eighty-eight positive cultures were polymicrobial. The most frequent isolates were nontypable Haemophilus influenzae (24%), Streptococcus pneumoniae (19%), Moraxella catarrhalis (17%), coagulase-negative Staphylococcus (6%), alpha-streptococci (6%), diphtheroids (5%), Staphylococcus aureus (3%) and Neisseria spp. (3%). Rates of nonsusceptibility of Streptococcus pneumoniae were 64% for penicillin (24% high grade resistance), 40% for cefotaxime, 18% for clindamycin and 0% for vancomycin. Rates of nonsusceptibility of S. pneumoniae did not change significantly during the study period. Thirty-nine percent of H. influenzae isolates were beta-lactamase-positive and 44% were nonsusceptible to ampicillin (41% high grade resistance). Beta-lactamase positivity of H. influenzae decreased during the study period (P = 0.06). All M. catarrhalis isolates tested were beta-lactamase-positive. Conclusion. This study indicates that the aerobic pathogens in pediatric chronic sinusitis include bacteria typical of acute sinusitis as well as organisms more characteristic of chronic disease. Moreover it highlights the significant role of antibiotic-resistant aerobes, including multiply resistant S. pneumoniae, in pediatric chronic sinusitis.

Concentrations of azithromycin in human tonsillar tissue

Patients scheduled to undergo tonsillectomy were administered 500 mg oral azithromycin as two 250 mg capsules given 12 h apart. Between 9 h and one week after the second dose, tonsil samples were taken during surgery and assayed for azithromycin. Mean concentrations in tonsillar tissue, 12 and 24 h after the second of the two 250 mg doses given 12 h apart, were 4.5 and 3.9 µg/g, respectively. Concurrent mean serum concentrations were approximately 0.03 and 0.01 µg/ml, respectively. The mean concentration in tonsillar tissue 7.5 days after the last dose was 0.93 µg/g. The apparent half-life of drug in the tissue was 76 h. The ratio of mean concentration in tissue to that in serum was greater than 150-fold for all time intervals. The presence of high azithromycin concentrations in tonsillar tissue suggests that a once-daily regimen over five days or less may be effective in treating tonsillo-pharyngitis.

In Vivo Observation with Magnetic Resonance Imaging of Middle Ear Effusion in Response to Experimental Underpressures

In this study, magnetic resonance imaging (MRI) was used to define, in vivo, the effect of acute middle ear (ME) underpressures on vascular permeability and the development of effusion. The MEs of four cynomolgus monkeys were unilaterally inflated with oxygen and carbon dioxide on different occasions and followed for a period of approximately 4 hours by tympanometry and MRI scanning. Carbon dioxide inflations caused the rapid development of ME underpressures of less than −600 mm H2O by 10 minutes. The MRI scans showed a progressive brightening of the ME and all associated air cells, indicative of the accumulation of effusion in three of the four experiments. An MRI contrast agent was administered to the vascular compartment during the course of the experiment and was rapidly transferred to the ME space, indicating vascular permeability to the agent. The contralateral, control side did not develop significant underpressures, effusion, or increased vascular permeability. Inflation with oxygen caused lesser underpressures and no accompanying changes in the MRI scans. These data support the hydrops ex vacuo theory and confirm the usefulness of MRI for in vivo documentation of the development of ME effusions and changes in vascular permeability of the mucosa in the experimental setting.

Lack of efficacy of middle-ear inflation: treatment of otitis media with effusion in children.

A randomized controlled trial was conducted to evaluate the efficacy of autoinflation of the middle ear in the treatment of otitis media with effusion. Forty-one children with middle ear effusion not responsive to antimicrobial therapy enrolled in the study. Of these subjects, 75 percent had effusion duration over 3 months. A system consisting of a disposable anesthesia mask attached to a flowmeter was used to teach children to perform autoinflation based on a modified Valsalva technique. Subjects were stratified according to their ability to achieve tubal opening as assessed by tympanometry and tubosonometry. Subjects were randomly assigned to either treatment or observation group and were followed weekly for 2 weeks; subjects in the treatment group attempted inflation three times each day for 2 weeks. Of the 19 subjects who were in the autoinflation group, only one (5.3 percent) was effusion-free at the two-week endpoint and of the 21 subjects in the control, only two (9.5 percent) were without middle-ear effusion. Autoinflation was ineffective for treatment of children with otitis media with effusion in our study.

Clinical practice guidelines for the management of chronic sinusitis in children

Chronic sinusitis in children is a common and vexing disease for clinicians and the public. There are insufficient data in the literature to develop an evidence-based clinical guideline. Experience in managing pediatric chronic sinusitis has been gained through a multidisciplinary clinic at our institution during the past 3 years. A panel of experts was formed, and with the guidance of a guideline methodologist, the development of a rigorous outcome-based guideline was undertaken. Symptom-improvement and recurrence estimates for a variety of medical and surgical treatments were assessed. Wide probability estimates were made by the panelists in most cases. Although we refrained from making specific recommendations, we developed a ranked series of practical treatment options taking into account side effects and costs.

Incidence of acute mastoiditis in Colorado children in the pneumococcal conjugate vaccine era.

Background: Acute otitis media is among the most common reasons young children seek medical care, with Streptococcus pneumoniae the most common pathogen. Despite introduction of heptavalent pneumococcal conjugate vaccine (PCV7) in 2000, recent experience suggests an increase in complications of acute otitis media, particularly acute mastoiditis. Methods: We performed a retrospective review of acute mastoiditis in children from 1999 to 2008 using inpatient data from the Colorado Hospital Association and the Children’s Hospital Colorado. The study included patients with documentation of acute mastoiditis or mastoidectomy and excluded those with chronic mastoiditis, chronic otitis media or cholesteatoma. Results: The annual incidence of acute mastoiditis in children <2 years/100,000 population was 11.0 in 2001 before decreasing to 4.6 in 2002 and 4.5 in 2003. The incidence then increased to 12.0 in 2008 (total N = 242). The proportion of S. pneumoniae isolates nonsusceptible to penicillin increased from 0% (0/16) between 1999 and 2004 to 38% (5/13) between 2005 and 2008 (P = 0.03). Conclusions: The incidence of acute mastoiditis in Colorado children <2 years of age exhibited a dynamic pattern from 1999 to 2008: a significant decline early after introduction of PCV7 that paralleled initial vaccine uptake, followed by an increase in subsequent years to pre-PCV7 levels. Replacement with non-PCV7 pneumococcal serotypes and increased pneumococcal antibiotic resistance may be responsible for the increase in incidence to pre-PCV7 rates. Surveillance of mastoiditis incidence, pathogen distribution and resistance patterns following introduction of 13-valent PCV is warranted.

Comparative study of sultamicillin and amoxicillin-clavulanate: treatment of acute otitis media.

Sultamicillin is a mutual prodrug of ampicillin and sulbactam that is chemically linked by a diester bond. This investigational agent has beta-lactamase-inhibiting activity by virtue of sulbactam, a novel beta-lactamase inhibitor. A double blind randomized study was conducted to evaluate the safety, efficacy and tolerance of sultamicillin for treatment of acute otitis media compared with amoxicillin-clavulanate. A total of 144 subjects were included (96 randomly assigned to the sultamicillin and 48 to the amoxicillin-clavulanate groups). No safety concerns for sultamicillin were identified during the study. The clinical efficacy in effusion clearance between the two groups was found not to be statistically different at 10 days (P = 0.23) and 30 days (P = 0.72). Similar rates of side effects, primarily gastrointestinal, were reported in both study groups. Sultamicillin may be an alternative for the treatment of acute otitis media when persistence and recurrence of disease become an issue.

Temporomandibular joint dysfunction after mandibular fracture in children: a 10-year review.

OBJECTIVES To collect demographic and clinical data on pediatric mandibular fractures and to assess temporomandibular joint (TMJ) dysfunction in patients with condylar and subcondylar (C/SC) fractures. DESIGN Retrospective case series of pediatric mandibular fractures (1999-2009) with follow-up telephone questionnaire of patients with C/SC fractures. Collected data included age, gender, unilateral vs bilateral C/SC fracture, presence of concomitant fracture, velocity of injury, and treatment modality. SETTING Tertiary care childrens hospital. PATIENTS Of 164 patients with mandibular fractures, 83 (50.6%) had C/SC fractures, of which 45 (54.2%) completed the questionnaire. MAIN OUTCOME MEASURES Helkimo Anamnestic Dysfunction Index (A(i)) quantification of TMJ dysfunction after C/SC fracture and treatment modality of C/SC fractures. RESULTS Of the 164 patients, 122 (74.4%) were male (median age, 10.4 years; age range, 0.6-19.0 years). Of the 83 patients with C/SC fractures, 61 (73.5%) were male (median age, 9.1 years; age range, 1.1-18.7 years); 66 (79.5%) had unilateral fractures and 17 (20.5%) had bilateral fractures. The A(i) distribution of the 45 patients who completed the questionnaire was as follows: 15 (33.3%) none, 6 (13.3%) mild, and 24 (53.3%) severe. Females have more severe dysfunction than do males (95% confidence interval, 1.6-140.0; P = .02). No other significant predictors of treatment modality or TMJ dysfunction were identified. Patients with bilateral fracture are 8.1 times (95% confidence interval, 1.0-66.1 times; P = .05) more likely to have closed reduction than are those with unilateral fracture. CONCLUSIONS This is one of the largest series of pediatric C/SC fractures reported in the recent literature. Findings are significant for increased severity of TMJ dysfunction in females and higher incidence of closed reduction in patients with bilateral C/SC fracture.

Multilevel airway involvement in children with Wegener's granulomatosis: clinical course and the utility of a multidisciplinary approach.

OBJECTIVE To examine the prevalence of airway involvement in children with Wegeners granulomatosis (WG) at our institution and to evaluate the utility of a treatment paradigm involving a multidisciplinary team. DESIGN Retrospective medical chart review. SETTING Tertiary childrens hospital. PATIENTS Pediatric subjects with WG treated at a tertiary childrens hospital over the past 15 years. MAIN OUTCOME MEASURES The medical records of all subjects with airway lesions were reviewed for clinical characteristics of airway involvement and for the medical and surgical treatment regimens. RESULTS Seven of 28 pediatric patients with WG were identified to have airway lesions (25%), including vocal fold granuloma, subglottic stenosis, and multilevel stenoses. Three of these patients had isolated and limited lesions. The 4 remaining patients are the focus of this study. One patient underwent a cricotracheal resection. All patients underwent repeated surgical treatment from combined services (otolaryngology and pulmonology) with flexible and rigid endoscopy, dilatation, and corticosteroid injection to manage subglottic, tracheal, and bronchial stenoses. Operative findings were communicated to the rheumatology service for manipulation of medical therapy. The 3 most recent patients received the anti-CD20 chemotherapeutic agent rituximab. This treatment approach led to temporary remission in some of the patients. CONCLUSIONS Airway involvement in pediatric patients with WG is known to occur, but multilevel airway involvement is rare and clinically challenging. We advocate a combined surgical approach involving otolaryngology, pulmonology, and rheumatology in managing aggressive cases of multilevel airway involvement in WG.