Low cord blood pneumococcal antibody concentrations predict more episodes of otitis media.

OBJECTIVE: To determine if cord blood anticapsular polysaccharide pneumococcal IgG antibody concentration was related to the number of otitis media (OM) and acute OM episodes during the first year of life. DESIGN: Prospective study following infants from birth to 24 months. SETTING: Health maintenance organization. PATIENTS: The study population consisted of 415 infants whose mothers volunteered for the study during pregnancy. Cord blood samples were collected and infants were followed up for OM in the health maintenance organization. Ninety-seven percent of the infants were white, 49% male, 3% from households with annual incomes of less than $20 000, and 30% from households with annual incomes of more than $60 000. MAIN OUTCOME MEASURE: Number of physician-diagnosed OM episodes, including both OM with effusion and acute OM, and acute OM episodes from birth to 12 months. RESULTS: With univariate analysis, low cord blood antibody concentrations against serotypes 3 and 19F predicted more acute OM episodes (P =.04 and P =.05, respectively), and low antibody concentrations against serotypes 19F and 23F predicted more OM episodes (P =.04 and P =.05, respectively) over the first year of life. With Poisson regression, which adjusted for variables related to the recurrence of OM and having low cord blood antibody concentrations, serotype 19F remained significantly related to the number of OM episodes (relative risk for lowest quartiles vs upper 3 quartiles 1.23; 95% confidence interval, 1.02-1.50; P =.03). CONCLUSIONS: Low cord blood antibody concentrations to serotype 19F predicted more OM episodes over the first 12 months of life. These results suggest the potential benefit of maternal immunization to raise neonatal antipolysaccharide pneumococcal antibody concentration and delay the onset and reduce the number of OM episodes.

The relationship between clinical and MRI findings in patients with unilateral temporomandibular joint pain.

BACKGROUND: With the advent of magnetic resonance imaging, or MRI, clinicians and researchers have sophisticated techniques by which to assess the anatomy of the temporomandibular joint, or TMJ. Imaging is indicated when the results will affect the patient's care beyond that which can be gained from a complete clinical assessment. One of the primary indications for treatment of patients with temporomandibular disorders, or TMDs, is jaw pain, including TMJ pain. Therefore, it is necessary to assess whether MRI-depicted TMJ findings are associated with TMJ pain. This study assessed the relationship between TMJ pain and clinical and MRI findings. METHODS: Subjects consisted of 85 patients with unilateral jaw pain in the area of the TMJ. The contralateral, nonpainful TMJ served as the matched control. All patients underwent a complete stomatognathic examination that included palpation of both TMJs. No care was given and no anti-inflammatory medications were prescribed until bilateral MRIs were obtained within one week. RESULTS: The authors found significant relationships between the side of reported jaw pain and the patient's report that palpation of the TMJ was painful and between the side of reported pain and the presence of MRI-detected effusions. The authors found no relationship between the side of reported pain and the presence of a disk displacement, or DD, or between the presence of effusions and DD on either side of the jaw. CONCLUSION: Although MRI-depicted effusions of the TMJ were associated with reports of TMJ pain, there was a high level of false-positive and false-negative findings. The results indicate that palpation of the TMJ is more accurate than MRI-depicted effusions in identifying the TMJ as the source of pain for patients with unilateral jaw pain. CLINICAL IMPLICATIONS: The results of this study suggest that palpation of the TMJ is superior to MRI in identifying the joint as the source of pain. Therefore, the most cost-effective and valid test to determine if the TMJ is a source of jaw pain is a complete clinical assessment.

Low cord blood type 14 pneumococcal IgG1 but not IgG2 antibody predicts early infant otitis media.

Type-specific IgG1 and IgG2 antibodies to Streptococcus pneumoniae capsular polysaccharides 14 and 19F were measured in cord blood samples from 425 neonates, to determine which antibody subclass was most strongly associated with otitis media (OM) during the first 6 months of life (early OM). Early OM was significantly associated with type 14 IgG1 antibody in the lowest antibody quartile (P=.055) but not with type 19F IgG1 antibody or with either IgG2 antibody. IgG1 and IgG2 antibodies were significantly intercorrelated for type 14 (r=.52, P<.001) and type 19F (r=.38, P<.001). Multivariate analysis revealed that having type 14 IgG1 antibody in the lowest quartile, child care attendance, and sibling and maternal OM history were independent risk factors for early OM. Although type-specific pneumococcal IgG2 antibody concentrations were significantly higher than IgG1 concentrations, IgG2 antibodies apparently are not protective against OM during early infancy.

Epidemiology of otitis media onset by six months of age.

OBJECTIVE: Although early otitis media (OM) onset predicts later recurrent and chronic OM, little research has been directed at illuminating the role of prenatal exposures in early OM. This prospective study examined prenatal, innate, and early environmental exposures associated with acute otitis media (AOM) onset and recurrent OM (ROM) by age 6 months. DESIGN AND METHODS: Prospective study of 596 infants from a health maintenance organization followed from birth to 6 months. Mothers completed monthly forms on prenatal exposures (diet, medications, and illnesses) and infant risk factors (eg, smoke exposure and child care) during pregnancy and until infants were 6 months old. Urine samples were collected when infants were 2 months of age and analyzed for cotinine and creatinine. Physicians and nurse practitioners examined infants at each clinic visit and completed standard ear examination forms. RESULTS: Thirty-nine percent had an episode of AOM and 20% had ROM by age 6 months. Using Cox's regression models to control for confounding, respiratory tract infection (relative risk [RR] 7.5), day care (RR 1. 7), >1 sibling (RR 1.4), maternal, paternal, and sibling OM history (RR 1.6, 1.5, and 1.7, respectively) were significantly related to early OM onset. ROM was related to respiratory tract infection (RR 9. 5), day care (RR 1.9), conjunctivitis (RR 2.0), maternal OM history (RR 1.9), and birth in the fall (RR 2.6). Among prenatal exposures, only high prenatal dietary vitamin C intake was significantly inversely related to early AOM with univariate but not multivariate analysis. CONCLUSION: Prenatal factors were not linked to early AOM onset with multivariate analysis, but environmental and innate factors play an important role in early AOM onset. Strategies to reduce exposure to environmental variables could reduce rates of early AOM, which could potentially result in declining rates of ROM and chronic OME.

Relationships between otitis media sequelae and age.

OBJECTIVES: To explore relationships between age and sequelae in two groups of children treated with tympanostomy tubes for chronic otitis media with effusion (OME). STUDY DESIGN: Cross-sectional study of sequelae among children, adolescents, and adults at 4 years and 9 to 23 years after tympanostomy tube treatment. METHODS: Group I was examined with otomicroscopy, tympanometry, and audiometry two to four times a year as part of a prospective study, and they were evaluated 4 years after initial tube treatment for this study. Group II received tubes while participating in a chronic OME study, but participants were not followed prospectively after treatment. Nine to 23 years after tube treatment, they were examined with otomicroscopy, tympanometry, and hearing screening. RESULTS: Among the 5- to 28- year-old subjects, cholesteatoma (< or = 1%) and perforation (< or = 2%) were rare. In Group I, tympanosclerosis increased with age (P < .01), and OME (flat tympanograms) decreased with age in Group II (P < .01). The older cohort was more likely to have severe retractions (18% vs. 4%, P = .02), hearing loss (21% vs. 10%, P < .01), and severe atrophy (24% vs. 0%, P < .01) than the younger cohort, but they were less likely to have flat tympanograms (2% vs. 12%, P < .01). CONCLUSIONS: Although OME became less prevalent with age, important sequelae (severe atrophy, severe tympanic membrane retraction, hearing loss, cholesteatoma, and chronic perforation) may develop in children with chronic OME as they become adolescents and young adults. Long-term prospective studies are important in defining the progression of sequelae in these children.

Determination of reliability and validity in home monitoring data of pulmonary function tests following lung transplantation.

Electronic spirometry units were used to monitor lung transplantation recipients upon their return home. The data from 77 participants were used to develop methods to verify that the pulmonary function measurements, forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1), were reliable and valid. The standard deviation was calculated for the best daily effort on consecutive days of home spirometry. An acceptable upper limit for the standard deviation, as the measure of day-to-day reliability, was 0.20 for FVC and 0.15 for FEV1. Validity was determined by examining the mean difference (bias) between the spirometry done in the pulmonary function laboratory and the home monitoring results. The clinic values were slightly higher, with an average difference of 0.15 for FVC and 0.12 for FEV1. Therefore, the home spirometry measurements have a high degree of reliability and validity and can now be used for early detection of serious complications.

Low cord blood pneumococcal immunoglobulin G (IgG) antibodies predict early onset acute otitis media in infancy.

Low maternally derived serum immunoglobulin G (IgG) antibodies to Streptococcus pneumoniae capsular polysaccharides (PS) combined with the inability of infants to produce anti-PS antibody may explain onset of otitis media in the first 6 months of life. To explore this relation, cord blood samples were assayed for anti-PS IgG antibodies from 414 of 592 infants enrolled in a study of early onset otitis media between 1991 and 1994. Infants' ears were examined at health supervision and illness visits for the first 6 months of life in a large Minneapolis-St. Paul, Minnesota, health maintenance organization. Antibodies to seven common pneumococcal serotypes (3, 4, 6B, 14, 18C, 19F, and 23F) were measured by enzyme-linked immunoabsorbent assay (ELISA). Cox's regression analysis revealed that among infants with a sibling otitis media history, those with low concentrations of type 14 or 19F anti-PS cord blood antibody had earlier otitis media onset than those with higher cord blood antibody concentrations (relative risks (RR) (95% confidence intervals (CI)) = 1.77 (1.05-2.99) and 1.89 (1.11-3.23), respectively). Day care attendance also increased risk (RR = 1.56, 95% CI 0.96-2.52). Breastfeeding, parental smoking, and low anti-PS antibody to pneumococcal serotypes 3, 4, 6B, 18C, and 23F did not significantly affect the risk of early otitis media.

Temporomandibular joint iontophoresis: a double-blind randomized clinical trial.

This double-blind study evaluated the short-term effect of iontophoretic delivery of dexamethasone on the signs and symptoms of temporomandibular disorders in patients who had concurrent temporomandibular joint disc displacement without reduction and capsulitis. Twenty-seven patients with this clinical diagnosis were randomized to one of three groups: treatment group (dexamethasone sodium phosphate and lidocaine hydrochloride); control group (lidocaine hydrochloride); and placebo group (pH-buffered saline). Pretreatment and posttreatment data included items to calculate Helkimo's Anamnestic Dysfunction index, Helkimo's Clinical Dysfunction index, the Symptom Severity Index, and the Craniomandibular Index (CMI). The CMI is composed of the Dysfunction index (DI) and Muscle index. Analysis of variance showed no baseline differences on these measures between the three groups. Pretreatment and posttreatment values were compared with the paired t tests. Posttreatment, the treatment group had an increased mean maximal active mandibular opening of 6 mm (P = .02), increased mean lateral excursion of 1.2 mm to the noninvolved side (P = .05), and reduced mean DI scores of 0.51 to 0.39 (P = .01); no statistically significant decrease in pain symptoms was reported. Analysis of variance showed a significant difference in the DI scores (P = .04) between groups from pretreatment to posttreatment, with the treatment group showing the greatest improvement in the DI scores relative to the other two groups. No other questionnaire items, exam items, or resultant indexes showed changes in any of the groups at P < or = .05. These results suggest that iontophoretic delivery of dexamethasone and lidocaine was effective in improving mandibular function, but not in reducing pain, in temporomandibular disorders patients who had concurrent temporomandibular joint capsulitis and disc displacement without reduction.

Duration of ventilating tubes: a test for comparing two clustered samples of censored data.

A study of otitis media that requires a test for the comparison of two clustered samples of censored data is described. A method is proposed taking into account the within-subject correlation in the formation of the log-rank statistic.

Prediction of functional capacities.

OBJECTIVE: This study explores the hypothesis that clients with low back injury can estimate their own functional capacities for waist-level lifting, lifting from the floor, and standing tolerance prior to formal functional capacity testing. SUMMARY OF BACKGROUND DATA: The frequent use of functional capacity evaluations for clients with industrial injuries and health care cost containment prompted research on the appropriateness and need for ohjective functional capacity evaluations. STUDY DESIGN/METHODS: All clients referred to the Sister Kenny Institute Work Injury Program for functional capacity evaluations from July 1991 to May 1992 were screened for eligibility and willingness to participate. Seventy-five subjects participated in the study. These subjects predicted their capacities prior to formal functional capacities testing; formal testing results were then compared to the predictions. RESULTS: RESULTS indicated the majority of low back injured clients' actual test scores were not within 20 tests. CONCLUSION: The outcome of this study indicates it is difficult for clients to accurately predict their own functional capacities following low back injuries. Therefore, when functional capacities remain in question, functional capacity evaluations continue to be a valuable and cost-effective route to promote a safe return to work.

Expression of p53, transforming growth factor alpha, epidermal growth factor receptor, and c-erbB-2 in endometrial carcinoma and correlation with survival and known predictors of survival.

Abnormal expression of p53, transforming growth factor alpha (TGF alpha), epidermal growth factor receptor (EGFR), and c-erbB-2 occurs in a variety of cancers and in some cases is associated with poor prognosis. Immunoperoxidase staining using these markers in formalin-fixed, paraffin-embedded endometrial carcinoma tissue was performed to determine whether immunoreactivity correlates with survival and known prognostic variables. Cases included 84 endometrioid adenocarcinomas, five adenoacanthomas, 12 adenosquamous carcinomas, 11 serous carcinomas, 15 clear cell carcinomas, and one carcinosarcoma for a total of 128 cases. Frequencies of immunoreactivity were as follows: p53, 37 of 128 (29%); TGF alpha, strong (2+) 23 of 128 (18%) and intermediate (1+) 26 of 128 (20%); EGFR, strong (3+) 21 of 128 (16%) and intermediate (2+ or 1+) 83 of 128 (65%); and c-erbB-2, strong (2+) four of 128 (2%) and intermediate (1+) three of 128 (1%). p53 and TGF alpha staining showed statistically significant correlations with decreased length of survival (P < .0017 and P < .0013, respectively, generalized Savage [Mantel Cox]). p53 immunoreactivity correlated with tumor types, grade, and stage. Transforming growth factor alpha staining correlated with increased depth of invasion and presence of vascular invasion. Epidermal growth factor receptor staining did not correlate with length of survival or known prognostic variables. c-erbB-2 staining correlated with tumor type. In the multivariate analysis p53 and TGF alpha staining were not independent predictors of survival when other variables were taken into account, including grade, stage, tumor type, presence of vascular invasion, and depth of invasion. Grade and stage were the only independent predictors of survival when used in combination in a Cox proportional hazards model.

A clinical profile of otitis media without an intact tympanic membrane.

An otitis media with effusion algorithm developed by Paradise et al has become the basis for many studies of otitis media. However, it has been shown to be too ambitious (low specificity) and too optimistic (absence of fluid does not necessarily mean normal ears). We developed a four-point profile to characterize the condition of the middle ear, but it cannot be used when the eardrum is perforated (with a functioning tube or chronic perforation). We propose a three-point profile for use without an intact tympanic membrane, and we report the validation of the profile by findings at myringotomy and by the preoperative profile. This postoperative profile and the previously described profile for ears with an intact tympanic membrane should increase the accuracy of middle ear assessment in following the course of otitis media over time.

Treatment evaluation in otitis media research.

OBJECTIVE: An application of the clinical otitis media profile is proposed for the evaluation of treatments in clinical studies of otitis media. METHODS: Methods include a statistical test of significance and measures of "treatment difference." This article focuses on the method, not any particular study; however, an example is given to illustrate the ideas. CONCLUSIONS: The proposed method substantially increases powers of statistical tests, as compared with the use of a two-point scale algorithm, when applied to study changes of the middle ear condition over time or to compare treatment effects. The proposed evaluation method is applicable to any medical drug treatment for groups that may not be comparable, even with randomization, for baseline severity. Applied to surgical treatment, it can be used for long-term evaluation; however, short-term evaluation is impossible because the needed tympanometric, static admittance, and width measurements cannot be obtained in the presence of functioning tubes. To achieve this objective, it is necessary to use another profile or diagnostic procedure.

Contrasting clinical and statistical significance within the research setting.

When designing a clinical trial or study, the value of the following interrelated parameters should be determined prior to collecting data: clinical significance, statistical significance, power, and sample size. Too often, clinical importance and the other design issues are ignored and only statistical significance dictates the conclusions of the study. In order to evaluate the frequency that each of these design parameters is addressed in the published literature, the topic of pulmonary function tests (specifically forced vital capacity) was chosen, and all relevant articles for one year (1990) were identified using Minnesota MEDLINE. A total of 121 articles met the selection criteria and were reviewed. Of all the articles, 13.2% discussed clinical significance, 21.5% discussed sample size, and only 5.0% addressed statistical power. As expected, the majority of the articles (92.6%) discussed statistical significance (P values). None of the articles mentioned all four factors. When choosing the level of clinical significance several methods may be used. Such might be well established in certain clinical areas or available from previous publications and references or they may be attainable from pilot study data and, in the absence of any prior information, a clinician may use personal experience. To minimize subjectivity, the clinical effect-size can be based on the population distribution of the measurement of interest.

The relationship between level of mandibular pain and dysfunction and stage of temporomandibular joint internal derangement.

Temporomandibular joint internal derangement (TMJ ID) is the most common intra-articular TM disorder and can progress from TMJ ID with reduction to TMJ ID without reduction. It is not known whether this anatomical progression is associated with increasing levels of mandibular dysfunction. The objective of this study was to determine whether the level of clinically detectable mandibular dysfunction was related to the stage of TMJ ID. Two clinicians examined 42 subjects prior to bilateral TMJ arthrographic evaluation. The level of mandibular dysfunction was calculated by Helkimo's Clinical Dysfunction Index (Di) and the Craniomandibular Index (CMI). Statistical analysis revealed that the level of mandibular dysfunction as determined by the Di and CMI was not related to the arthrographic presence or absence of TMJ ID. Therefore, the clinician cannot assume that the level of mandibular dysfunction is directly related to the absence or presence of TMJ ID. Epidemiologically, the CMI and Di can be used only for estimation of the degree of mandibular dysfunction, since they do not provide direct information on a specific TM disorder.

A clinical profile of otitis media.

An otitis media with effusion algorithm developed by Paradise et al and tested by Cantekin et al has become the basis for many studies of otitis media. However, a two-point scale algorithm (otitis media with effusion-no otitis media with effusion) may be too ambitious (ie, low specificity) and too optimistic (ie, absence of fluid does not necessarily mean normal ear). We propose a four-point profile that characterizes the condition of the middle ear, and we report the validation of the profile against findings at myringotomy. Statistically, a four-point scale profile would substantially increase powers of statistical tests, compared with a two-point scale algorithm (in studies of the same size), when used to study changes of the middle-ear condition over time or to compare treatment effects.

Homogeneity of the relative risk in cohort studies.

We propose a statistical method to test the homogeneity of relative risk in cohort studies. We illustrate its application to an original data set from a low-risk group of end-stage renal disease patients on haemodialysis. The use of the method is as a global test against the omnibus alternative.

Effects of cilazaprilat and enalaprilat on experimental dermatitis in guinea pigs.

Two non-sulfur containing ACE-inhibitors were tested concerning their local effect on experimental dermatitis in ovalbumin-sensitized guinea pigs. Enalaprilat but not cilazaprilat potentiated the ovalbumin-evoked inflammatory response. Furthermore, enalaprilat clearly enhanced the erythema evoked by substance P, whereas cilazaprilat did not. Concerning, the bradykinin-evoked erythema, enalaprilat significantly potentiated the response, whereas cilazaprilat only caused a slight increase. Our results suggest that different affinities for peptidases involved in degradation of inflammatory peptides can explain differences between the pro-inflammatory properties of enalaprilat and cilazaprilat.

Enalaprilat, but not cilazaprilat, increases inflammatory skin reactions in guinea-pigs.

The inflammatory effects of enalaprilat and cilazaprilat were tested in an experimental model of ovalbumin-sensitised guinea-pigs. Enalaprilat, but not cilazaprilat, enhanced the ovalbumin-induced inflammatory skin responses. The effect of enalaprilat was dose-dependent. Enalaprilat significantly increased the skin content of substance P and histamine. Cilazaprilat did not alter the level of these inflammatory mediators. Enalaprilat, applied locally, but not cilazaprilat, enhanced the inflammatory reactions caused by intradermal injections of allergen and substance P. Both angiotensin converting enzyme (ACE) inhibitors enhanced the inflammatory skin response evoked by bradykinin. Our study strongly indicates that enalaprilat has pro-inflammatory properties, whereas the new long-acting ACE inhibitor cilazaprilat does not. This might give a better safety profile of cilazaprilat.