Biomedical subjects
Publications and source records attributed to C D Bluestone.
Pharyngitis is one of the most common disorders seen by primary care physicians. Fortunately, most cases resulting from viral or bacterial infection respond well to symptomatic medications or antibiotics. However, aggressive treatment of pharyngitis due to group A beta-hemolytic streptococcus is crucial to avoid complications, such as rheumatic fever and acute poststreptococcal glomerulonephritis.
For children with acute otitis media, appropriate antibiotic therapy provides a modest improvement over the high rate of spontaneous recovery and, more importantly, has greatly reduced the incidence of serious complications. Prophylaxis with antibiotics is beneficial for patients with recurrent episodes. Otitis media with effusion also has a high rate of spontaneous resolution, and many physicians have adopted a "wait and see" approach to this problem. Modification of risk factors may be helpful. Antibiotic therapy is recommended for infants who have otitis media with effusion (since they cannot relate symptoms); patients with a coexisting purulent infection of the upper respiratory tract; patients who have significant hearing loss, vertigo, or structural changes in the tympanic membrane; and patients who have had effusion for more than 2 to 3 months. Referral to an otolaryngologist should be considered if medical therapy for recurrent acute otitis media or chronic otitis media with effusion has failed or been poorly tolerated, or if complications are present.
Congenital perilymphatic fistula (PLF) as a diagnosis for progressive, fluctuating, or sudden sensorineural hearing loss with or without vertigo is still controversial. Beta-2 transferrin is a protein that is unique to cerebrospinal fluid, aqueous humor, and perilymph. A recent pilot study demonstrated that beta-2 transferrin may be an objective test to determine the existence of a congenital PLF. The authors prospectively evaluated and recommended surgery for 43 children with suspected PLF over the past 3 years. A prospective, blinded study was performed by having the attending otolaryngologist evaluate the middle ear at the time of surgery for a PLF and any middle ear abnormalities. Samples of fluid were collected from the oval and round windows and were tested for beta-2 transferrin. Of 16 patients undergoing tympanoplasty or tympanomastoidectomy who served as controls, none were positive for beta-2 transferrin. Of the 43 patients undergoing exploratory tympanoplasty for PLF, 20 (46.5%) were considered to be negative for PLF on microscopic visualization; 23 (53.5%) were found to be positive. Of the 20 patients thought to be negative for PLF, 18 (90%) tested negative for beta-2, but 2 of these patients were positive for beta-2, and both had a congenital middle ear abnormality. Of the 23 patients found to have a PLF at surgery, 6 (26.1%) tested positive for beta-2, and all of these 6 had middle ear abnormalities. Of the 17 patients negative for beta-2, 9 had normal anatomy; 6 had middle ear abnormalities, and 2 had erosive changes. The authors conclude that beta-2 transferrin, an objective test, confirms the existence of congenital PLF in children, which is associated with middle ear abnormalities.
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The ability of aural acoustic immittance measures and validated pneumatic otoscopy to identify middle ear effusion (MEE) was determined for a group of children with chronic or recurrent otitis media. The measures were made immediately prior to surgery for placement of tympanostomy tubes, with the validating diagnosis of MEE made by the surgeons. Aural acoustic admittance measures were made by a certified and licensed clinical audiologist using an instrument that meets current standards and otoscopic examinations were made by a nurse practitioner validated for use of otoscopy in the identification of MEE. Logistic regression analyses were done to determine the ability of admittance variables, otoscopy, and their combination to discriminate between ears with and ears without MEE. Of the individual admittance variables, tympanometric width had the best performance. Otoscopy alone had good sensitivity but only fair specificity. Combining acoustic admittance data with the otoscopist's findings did not improve sensitivity greatly, but improved the specificity relative to that of the otoscopist. The criterion tympanometric width > 150 daPa or Ytm < 0.2, a criterion commonly used based on interim norms published in an appendix of ASHA guidelines for screening, had good sensitivity but very poor specificity in the group of children scheduled for surgery. Also, a comparison was made for tympanometric width measures from the children undergoing surgery with those from a group of children more representative of the general population. Three distributions were found; one for ears with MEE, one for ears with no MEE of children scheduled for otologic surgery and one for ears with no MEE from the group of children from the general population. The data illustrate the importance of the population characteristics on the test measure used and have implications for choosing test criteria. In addition, group estimates of performance of acoustic admittance variables were approximately the same when otoscopy was used as the gold standard for identification of MEE as when findings at surgery were used. However, when comparing the two diagnostic methods on a case-by-case basis, it was determined that the otoscopist's diagnosis disagreed with the diagnosis of the surgeons in over 21% of the ears.
beta 2-Transferrin is a protein that is unique to the cerebrospinal fluid and aqueous humor. On the basis of this information and a recent study from our institution that demonstrated that beta 2-transferrin was also unique to human perilymph, a prospective, double-blind study to evaluate perilymphatic fistula in children was performed. Attending otolaryngologists at Children's Hospital of Pittsburgh evaluated and recommended surgery for 10 children (10 ears) who were suspected of having a congenital perilymphatic fistula. During the operation, the surgeon decided whether a perilymphatic fistula existed, on the basis of otomicroscopic findings, and then separate pieces of gelatin sponge were placed on the oval and round windows, respectively, and sent to the immunopathology laboratory where they were analyzed for beta 2-transferrin. Ten patients (10 ears) undergoing tympanoplasty or tympanomastoidectomy were used as controls and tested in a similar fashion. During the study, both the surgeons and patients were blinded from the results of the test. Of the 10 control patients, none was observed to have a perilymphatic fistula, and all were negative for beta 2-transferrin. Of the 10 patients undergoing exploratory tympanotomy for perilymphatic fistula, 1 ear was thought to be negative for perilymphatic fistula on microscopic visual examination, whereas 9 were considered to be positive for perilymphatic fistula. No beta 2-transferrin was identified from the ear that was considered not to have a perilymphatic fistula, whereas six of the nine ears that were thought to have perilymphatic fistula tested positive for beta 2-transferrin.(ABSTRACT TRUNCATED AT 250 WORDS)
Congenital perilymphatic fistula is an abnormal communication between the inner ear and middle ear. Inner ear anomalies have been described on computed tomography scans. Middle ear anomalies have been found at surgery; the most frequent are anomalies of the stapes and round window. This retrospective study describes the appearance of the inner and middle ear on computed tomography scans, and of the middle ear at surgery, in 10 patients (15 ears) in whom perilymphatic fistula was found at surgery. Twelve of 15 stapes were abnormal at surgery; 4 of these 12 (33%) could be seen on computed tomography scans. Two stapes normal at surgery were normal on computed tomography. Three round windows were abnormal at surgery; none of these was seen on computed tomography scans. There were also four dysplastic cochleas, four dysplastic vestibules, and three dilated vestibular aqueducts. Computed tomography scans identified an abnormal inner ear, middle ear, or both in 8 (53%) of the 15 ears with perilymphatic fistula. An inner ear or middle ear anomaly on computed tomography may heighten clinical suspicion of congenital perilymphatic fistula.
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To specifically determine the frequency and type of middle ear abnormalities associated with perilymphatic fistula (PLF), a retrospective chart review was performed of 94 patients (117 ears) who underwent exploratory tympanotomy for PLF from 1980 to 1989. Of the 117 ears explored, 80 (68.4%) had a PLF, and in 65 (81.3%) of these ears, a middle ear malformation was associated with the PLF. Of these 65 ears in which a congenital middle ear abnormality was observed, a malformed stapes was the most common abnormality seen (39 ears, 60%), followed by a deformed round window (20 ears, 30.8%), a deformed incus (11 ears, 16.9%), and a deformed promontory (2 ears, 3%). Often these malformations coexisted amongst themselves or with inner ear abnormalities. Sixteen children (25 ears) had an inner ear malformation identified on computed tomography (CT); all of these children had a PLF found at the time of surgery. This study demonstrated that 86.3% of the ears found to have a PLF had a deformity of the middle ear, inner ear, or both. A malformation of the stapes, most frequently identified as a deformity of its superstructure (and presumably also the anterior footplate), was the most common congenital middle ear abnormality found to be associated with PLF in children.
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.
During the past decade there has been an increase in the percentage of resistant bacteria isolated from middle-ear effusions aspirated from infants and children who have had acute otitis media. At least nine oral antibiotics or combination agents are available for this indication. Cefixime, a third generation cephalosporin, has excellent in vitro activity against both beta-lactamase-negative and beta-lactamase-positive Haemophilus influenzae and Moraxella catarrhalis, good activity against Streptococcus pneumoniae and Streptococcus pyogenes but relatively poor activity against Staphylococcus aureus. In children cefixime is similar in effectiveness to amoxicillin and cefaclor, but diarrhea and stool changes are more common with cefixime. Amoxicillin is still preferred for initial empiric treatment of uncomplicated acute otitis media. Its major drawback is limited efficacy when beta-lactamase-producing bacteria are the causative organisms. Cefixime is a viable alternative to amoxicillin for infants and children with acute otitis media when: (1) a beta-lactamase-producing H. influenzae or M. catarrhalis is isolated from otorrhea or tympanocentesis; (2) the child has a history of delayed hypersensitivity to the penicillins but no history of hypersensitivity to the cephalosporins; (3) there is a high incidence of resistant bacteria in the community; (4) there is not clinical improvement with amoxicillin; or (5) once daily administration is more convenient.
In an earlier study of 214 children with acute otitis media (AOM) randomly assigned to a 14-day course of either cefaclor or amoxicillin, 55.7% of cefaclor-treated subjects were effusion-free compared with 41.2% of amoxicillin-treated subjects at the end of treatment. The present study was conducted to determine whether, in a 1-year period, subjects treated with cefaclor for each episode would have middle ear effusion for significantly less time than those treated with amoxicillin for each episode. One hundred fifty-seven subjects with AOM were enrolled. No statistically significant differences were found between the cefaclor-treated and amoxicillin-treated groups in number of subjects effusion-free immediately after first treatment (47.9% vs. 42.3%, respectively), average percent of time with effusion (22.2% vs. 23.4%, respectively), or in rate of new episodes of AOM (3.05 vs. 3.26, respectively). We conclude that there is no clinically significant advantage to the use of cefaclor rather than amoxicillin as the routine first line drug in the treatment of AOM.
In 1988, the authors reported their experience in medical treatment of 66 children who had chronic suppurative otitis media, including the administration of intravenous antimicrobial agents. At the time of their initial treatment, 89 percent were successfully treated with medical treatment only, and the remaining 11 percent required surgical intervention. This report presents the long-term follow-up of 51 of those children who were available for study. Of these 51 patients, 40 (78%) had resolution of their initial or recurrent otorrhea, whereas 11 (22%) had surgery either initially or at the time of a recurrence. Medical management is successful in most children who have chronic suppurative otitis media, but surgical intervention should be considered if a cholesteatoma is suspected, if medical treatment is not effective in rapidly improving the chronic infection, or if the patient has recurrent disease over a relatively short period.
Nontypeable Haemophilus influenzae (NTHi) is one of the leading causative agents of bacterial otitis media, and no vaccine has been shown to be effective against it. Three outer membrane lipoproteins of NTHi have been investigated extensively and are leading candidates for inclusion in a vaccine against this organism. Hi-PAL (P6), recombinant PCP (rPCP), and e (P4) proteins are antigenically conserved among NTHi strains and elicit bactericidal and protective antibodies. A genetic fusion of the rPCP and Hi-PAL proteins has also been reported. Mixtures of these proteins were used for active immunization experiments in the chinchilla model of otitis media. Chinchillas were immunized either with a mixture of all three lipoproteins or with the mixture of rPCP-PAL hybrid plus e protein. When these animals were challenged with a NTHi strain injected directly into the middle ears, no protection from infection or disease, as measured by otoscopy, was observed in either group. However, effusion and inflammation measured by tympanometry were significantly reduced in animals immunized with the three lipoproteins. Animals that had been immunized with either whole NTHi cells or total outer membranes and then challenged with the homologous strain were significantly protected from both infection and disease, as determined by tympanometry and otoscopy. Unlike other animals antisera, chinchilla antisera against the purified proteins had no bactericidal activity against NTHi but did fix complement on the cell surface. Thus, the chinchilla immune responses to mixtures of these lipoproteins differ from the immune responses observed in other animal species. Further evaluation of these proteins for their vaccine potential remains to be done.
A chart review was undertaken of 30 patients who were presented to Children's Hospital of Pittsburgh from 1983 to 1990 and underwent surgical management for suspected subperiosteal abscess of the orbit (SPA). All patients had preoperative computerized tomography (CT) scans. Twenty-seven of 30 CT scans were reevaluated, of which 20 (74%) demonstrated findings consistent with or suggestive of SPA. Opacified sinuses were seen in 100% of this study group. Abscess collections were found in 21 patients (70%). Predominant organisms included: Streptococcus pneumoniae (38%), Streptococcus pyogenes (33%), and Haemophilus influenzae (14%); Moraxella catarrhalis was not isolated and anaerobic bacteria were isolated from only one patient. CT scans were found to be accurate predictors of SPA in 16 (80%) of 20 patients. All patients did well following surgical intervention without visual or central nervous system sequelae. We conclude from this study that CT scans should be obtained when SPA is suspected, and antimicrobial therapy should be directed toward the bacteria isolated from these abscesses.
To better define the clinical course of congenital subglottic stenosis, the authors reviewed a cohort of 27 children managed with long-term tracheotomy and interval bronchoscopy. Rates of spontaneous resolution were 19% at 6 months, 39% at 12 months, and 69% at 18 months (Kaplan-Meier survival analysis). Children older than 4 months of age at tracheotomy tended to have more rapid resolution of their stenoses (P = .08). Overall, the median time to decannulation was 15.8 months (95% confidence interval, 13.9 to 17.6 months). One death was possibly tracheotomy-related, and 12 (44%) of the children experienced complications or sequelae resulting in new or extended hospitalization. Considering the prolonged cannulation necessary for spontaneous resolution of congenital subglottic stenosis, the role of long-term tracheotomy as the sole form of management may be limited. Once the need for intervention is apparent, the authors recommend early consideration of cricoid split or laryngotracheoplasty as alternatives to long-term tracheotomy.
Children who suffer from primary immunodeficiencies have long been thought to be subject to infections of the ears, nose, and throat due to unusual or resistant organisms. A retrospective chart review was undertaken at Children's Hospital of Pittsburgh from 1979 to 1989 to determine the types and frequency of infections of the ears, nose, and throat, and the bacteriologic findings from cultures of the sinuses, ears, and head and neck abscesses, when obtained. Seventy-five patients were identified with primary immunodeficiencies, and 80% suffered from infections of the ears, nose, and throat. Cultures obtained from 33% of the group showed the majority of the organisms commonly seen in ear and sinus infections. We conclude from this study that children with primary immunodeficiencies who require hospitalization frequently have an infection of the ears, nose, and throat, and that the infection is usually caused by community acquired bacteria. Empiric treatment may therefore be directed to common organisms causing these infections.