Characteristics of depressive disorders in patients with rheumatoid arthritis and some related factors.

OBJECTIVE: Rheumatoid arthritis (RA), a type of chronic arthritis, is common in Vietnam. It has severe consequences for patients, both physically and psychologically, including depressive disorders. Therefore, early detection of depressive disorders is of high importance to help provide comprehensive treatment and improve RA patients' quality of life. This cross-sectional study explored the prevalence of depressive disorders and their salient characteristics and related factors in RA patients in Vietnam. PATIENTS AND METHODS: We enrolled 156 patients diagnosed with RA using the ACR-1987 criteria. The Patient Health Questionnaire-9 (PHQ-9) was used to screen for depressive disorders. Patients' demographic characteristics and clinical and laboratory investigation results, such as the visual analog score, complete blood count, erythrocyte sedimentation rate, Disease Activity Score 28 for RA with C-reactive protein (DAS28-CRP), and quality-of-life score (based on the SF-36 test) were analyzed. Depressive disorders assessed on the first day of admission were reevaluated by a psychiatrist if the PHQ-9 score was ≥ 5. RESULTS: According to the PHQ-9 results, depression prevalence among RA patients was 76.3%. The majority of patients (49.4%) had moderate-to-severe depression and 91% experienced sleep disorder symptoms. Negative thoughts -- suicidal ideation or self-injury - were reported by 21.8% of patients. Depression severity had a moderately positive relationship with disease activity level and a moderately negative relationship with quality of life. CONCLUSIONS: Depression prevalence was high among RA patients. Depression severity increased with disease activity and decreased quality of life.

Increasing sample diversity in psychiatric genetics - Introducing a new cohort of patients with schizophrenia and controls from Vietnam - Results from a pilot study.

OBJECTIVES: Genome-Wide Association Studies (GWAS) of Schizophrenia (SCZ) have provided new biological insights; however, most cohorts are of European ancestry. As a result, derived polygenic risk scores (PRS) show decreased predictive power when applied to populations of different ancestries. We aimed to assess the feasibility of a large-scale data collection in Hanoi, Vietnam, contribute to international efforts to diversify ancestry in SCZ genetic research and examine the transferability of SCZ-PRS to individuals of Vietnamese Kinh ancestry. METHODS: In a pilot study, 368 individuals (including 190 SCZ cases) were recruited at the Hanoi Medical University's associated psychiatric hospitals and outpatient facilities. Data collection included sociodemographic data, baseline clinical data, clinical interviews assessing symptom severity and genome-wide SNP genotyping. SCZ-PRS were generated using different training data sets: (i) European, (ii) East-Asian and (iii) trans-ancestry GWAS summary statistics from the latest SCZ GWAS meta-analysis. RESULTS: SCZ-PRS significantly predicted case status in Vietnamese individuals using mixed-ancestry (R2 liability = 4.9%, p = 6.83 × 10-8), East-Asian (R2 liability = 4.5%, p = 2.73 × 10-7) and European (R2 liability = 3.8%, p = 1.79 × 10-6) discovery samples. DISCUSSION: Our results corroborate previous findings of reduced PRS predictive power across populations, highlighting the importance of ancestral diversity in GWA studies.

A modified comorbidity index for hematopoietic cell transplantation.

A recent validation analysis at our center among allogeneic hematopoietic cell transplant (HCT) recipients did not find the HCT-specific comorbidity index (HCT-CI) to clearly segregate patient's transplant-related risk. We hypothesized that the discriminating and predictive power of the HCT-CI for mortality could be improved by eliminating the assignment of categorical weights to comorbidities and instead replacing them with hazard ratios (HR) from a Fine and Gray adjusted regression model. This approach allowed us to look carefully at each component of the comorbidity index. We developed the modified comorbidity index (MCI) using a cohort of 444 adult allogeneic HCT recipients using a pure multiplicative model. Compared with low-risk patients, the HR for non-relapse mortality (NRM) using the HCT-CI was 1.3 (95% confidence intervals, 0.7-2.4) for intermediate risk and 1.6 (0.9-2.8) for high-risk patients, and with the MCI was 1.6 (0.9-2.8) and 2.7 (1.5-5.0), respectively. In conclusion, we are introducing the MCI which may have higher discriminating and predictive power for overall survival and NRM. Validation of the HCT-CI and the MCI in larger and separate cohorts of HCT recipients is still needed.

Monoclonal nicotine-specific antibodies reduce nicotine distribution to brain in rats: dose- and affinity-response relationships.

Vaccination against nicotine is being studied as a potential treatment for nicotine dependence. Some of the limitations of vaccination, such as variability in antibody titer and affinity, might be overcome by instead using passive immunization with nicotine-specific monoclonal antibodies. The effects of antibodies on nicotine distribution to brain were studied using nicotine-specific monoclonal antibodies (NICmAbs) with K(d) values ranging from 60 to 250 nM and a high-affinity polyclonal rabbit antiserum (K(d) = 1.6 nM). Pretreatment with NICmAbs substantially increased the binding of nicotine in serum after a single nicotine dose, reduced the unbound nicotine concentration in serum, and reduced the distribution of nicotine to brain. Efficacy was directly related to antibody affinity for nicotine. Efficacy of the highest affinity NICmAb, NICmAb311, was dose-related, with the highest dose reducing nicotine distribution to brain by 78%. NICmAb311 decreased nicotine clearance by 90% and prolonged the terminal half-life of nicotine by 120%. At equivalent doses, NICmAb311 was less effective than the higher affinity rabbit antiserum but comparable efficacy could be achieved by increasing the NICmAb311 dose. These data suggest that passive immunization with nicotine-specific monoclonal antibodies substantially alters nicotine pharmacokinetics in a manner similar to that previously reported for vaccination against nicotine. Antibody efficacy is a function of both dose and affinity for nicotine.

Combination vaccines: choices or chaos? A practitioner's perspective.

Combination vaccines are necessary and important for the continuing success of our immunization program, especially when more vaccines are added to the already crowded immunization schedule. However, the multiplicity of competing vaccine products, with various overlapping antigen menu and subtle immunologic differences, may be confusing to the busy practitioner. The cost-effectiveness of the use of combination vaccines will depend on a number of factors, including fair and competitive pricing, appropriate reimbursement for vaccine administration fees, and critical economic algorithms for vaccine selection and purchase.

A modified rapid method of nucleic acid isolation from suspension of matured virus: applied in restriction analysis of DNA from an adenovirus prototype strain and a patient isolate.

This report describes a method for the isolation of nucleic acid from a suspension of matured virus. Nucleic acid (DNA) was isolated from a prototype strain of adenovirus type 7 and a clinical isolate of adenovirus type 7. Instead of the usual method of ultracentifugation, a filtration method was applied to concentrate the virus rapidly and nucleic acid was then isolated by a standard phenol/chloroform/isoamyl-alcohol extraction procedure. The DNA was found to be sufficiently purified to generate a reproducible restriction endonuclease digestion pattern. The clinical isolate of adenovirus type 7 revealed loss of restriction site for the endonuclease HindIII when compared with the prototype strain.

Bordetella pertussis detection by spectrofluorometry using polymerase chain reaction (PCR) and a molecular beacon probe.

Bordetella pertussis was detected by spectrofluorometry following PCR incorporating a molecular beacon probe in the reaction. A DNA fragment from the tandem repeat sequence region (IS 481) of the genome of B. pertussis was amplified in presence of the probe complementary to an internal segment of the amplified DNA fragment. Fluorescein (FAM) and DABCYL were used as the fluorophore and quencher in the probe. The probe was characterized for its signal to noise ratio by homogeneous solution hybridization with a complementary oligonucleotide. Measurement of fluorescent signal at the emission maxima of FAM, immediately after a PCR was used to detect the B. pertussis target, with no additional steps. Presence of B. pertussis in a sample was also examined by agarose gel electrophoresis of the PCR product. A serial diluted stock of B. pertussis (ATCC strain #9797) and fourteen clinical isolates of B. pertussis were examined. The sensitivity of detection by fluorescent measurement was found to be at least in the range of 0.01-0.1 CFU per 10 microl of the sample and was equal to or better than that detected by agarose gel analysis.

Treatment of anal fissure with glyceryl trinitrate in patients referred for surgical management.

BACKGROUND: A number of recent studies indicate that anal fissure may be treated by applying glyceryl trinitrate (GTN) ointment. The present study aims to determine the effectiveness and patient acceptability of GTN treatment for patients referred to a consultant surgeon. METHODS: A prospective study of 65 consecutive patients referred to one surgeon (ALP) over a 12-month period was undertaken. All patients were offered 0.2% GTN ointment to be applied intra-anally four times daily for 4 weeks. Informed consent was obtained and review planned for 4 weeks. RESULTS: Fourteen patients declined treatment and nine of the 14 (64%) subsequently underwent lateral sphincterotomy. Twelve of the 51 patients (18.5%) who accepted treatment could not complete it due to headache or persisting severe anal pain. Thirty-nine of the 51 patients (77%) were able to complete 4 weeks of treatment. Twenty-two of the 39 reported an improvement in symptoms. A total of 22 patients (43%) who started GTN treatment subsequently underwent lateral sphincterotomy. CONCLUSIONS: Evidence from the present study suggests that GTN ointment has a place in the management of referred patients with severe and/or chronic anal fissure, but sphincterotomy remains an important treatment option for the majority.

Anti-inflammatory effect of adenovirus-mediated IkappaBalpha overexpression in respiratory epithelial cells.

Many studies into basic biological characteristics of inflammation and tissue injury have implicated pro-inflammatory cytokine-mediated tissue injury in the pathogenesis of inflammatory lung diseases. Because transcription of most proinflammatory cytokines is dependent on the activation of nuclear factor (NF)-kappaB, NF-kappaB could be a good potential target to suppress the cytokine cascade. Cytokine-induced activation of NF-kappaB requires phosphorylation and subsequent degradation of IkappaBa. Therefore, the blocking NF-kappaB activation by IkappaBalpha could inhibit the pro-inflammatory cytokine-induced tissue injury. To evaluate whether blocking of NF-kappaB activation shows an anti-inflammatory effect, this study investigated the effect of adenovirus-mediated overexpression of IkappaBalpha super-repressor (IkappaBalpha-SR) on the pro-inflammatory cytokine expression in respiratory epithelial cells. The transduction efficiency of adenovirus was >90% in both A549 and NCI-H157 cells. Ad5IkappaBalpha-SR-transduced cells expressed high levels of IkappaBalpha-SR, which was resistant to tumour necrosis factor (TNF)-alpha-induced degradation. Adenovirus-mediated overexpression of IkappaBalpha-SR blocked cytokine-induced nuclear translocation of p65 and NF-kappaB deoxyribonucleic acid binding activity without affecting total cellular expression level of NF-kappaB. Ad5IkappaBalpha-SR transduction suppressed cytokine-induced interleukin-8 and TNF-alpha expressions at both ribonucleic acid and protein levels. These results suggest that blocking the nuclear factor-kappaB pathway by adenovirus-mediated overexpression of IkappaBalpha-super-repressor shows an effective anti-inflammatory effect in respiratory epithelial cells.

Patient satisfaction after surgical treatment for fistula-in-ano.

PURPOSE: The surgical treatment of fistula-in-ano frequently results in recurrence of the fistula or postoperative anal incontinence. Despite these problems, most patients are satisfied with the results of their surgery. To clarify this apparent discrepancy, we attempted to identify factors that affect patient's lifestyles and may contribute to their satisfaction. METHODS: A questionnaire was mailed to 624 patients surgically treated for cryptoglandular fistula-in-ano at the University of Minnesota during a five-year period. Three hundred seventy-five patients returned their questionnaires. Patients who were followed up for a minimum of one year were included in this retrospective study. Associations between postoperative complications and patient satisfaction were identified by chi-squared tests and multiple logistic regression. Attributable fractions for patient dissatisfaction were calculated using study population dissatisfaction rates. RESULTS: Patient satisfaction was strongly associated with fistula recurrence, difficulty holding gas, soiling of undergarment, and accidental bowel movements. Effects of incontinence on patient quality of life were also significantly associated with patient satisfaction as was the number of lifestyle activities affected by incontinence. Patients with fistula recurrence reported a higher dissatisfaction rate (61 percent) than did patients with anal incontinence (24 percent), but the attributable fraction of dissatisfaction for incontinence (84 percent) was greater than that for fistula recurrence (33 percent). Patient satisfaction was not significantly associated with age, gender, history of previous fistula surgery, type of fistula, surgical procedure, time since surgery, or operating surgeon. CONCLUSION: Patient satisfaction after surgical treatment for fistula-in-ano is associated with recurrence of the fistula, the development of anal incontinence, and with the effects of anal incontinence on patient lifestyle. In our series of patients treated mainly with laying open of the fistula tract, patients with fistula recurrence had a higher dissatisfaction rate than did patients with anal incontinence. However, because anal incontinence was more prevalent than fistula recurrence, a higher fraction of dissatisfaction was attributable to anal incontinence.

Tympanic membrane and middle ear pathologic correlates in mucoid otitis media.

OBJECTIVE: The goal of this study was to correlate tympanic membrane (TM) and middle ear (ME) pathologies in mucoid otitis media (MOM). METHODS AND MATERIAL: Forty ears with MOM and 56 control ears were retrospectively evaluated for TM and ME pathologies. Comparisons of TM thicknesses in MOM versus control ears were correlated with the Student t test; chi(2) analysis was used to correlate pathologic findings of the TM and ME. RESULTS: Thicknesses in all quadrants except the umbo were increased in MOM because of infiltration of inflammatory cells and fibrosis. The most common ME pathologies were granulation tissue and fibrosis. Significant correlations included (1) TM retraction and ME granulation tissue and fibrosis and (2) pars flaccida, posterosuperior, and anteroinferior thickness and ME granulation tissue and fibrosis. CONCLUSION: TM changes are likely to occur in patients with otitis media with effusion (MOM), and their presence is a strong indication of underlying ME pathology.

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.

Identification of MUC5B mucin gene in human middle ear with chronic otitis media.

OBJECTIVES: To identify the mucin gene and its expressing cells in the middle ear mucosa with chronic otitis media (COM), and to study the correlation between infiltration of inflammatory cells in the submucosa and expression of the mucin gene in the mucosal epithelium with COM. STUDY DESIGN: Middle ear mucosal specimens removed from the inferior promontory area of 19 patients undergoing middle ear surgery for COM were studied. METHODS: Sections were stained with H&E, Alcian blue-periodic acid Schiff (AB-PAS), polyclonal MUC5B antibody, and specific MUC5B riboprobe for histological, histochemical, immunohistochemical, and mucin mRNA analyses. RESULTS: H&E staining revealed pseudostratified epithelia in 18 of the middle ear specimens with COM and cuboidal secretory epithelia in one. AB-PAS staining of epithelia revealed abundant secretory cells and their products (glycoconjugates). In situ hybridization and immunohistochemistry studies demonstrated that the secretory cells of the middle ear mucosa with COM expressed MUC5B mucin mRNA and its product MUC5B mucin. CONCLUSIONS: The MUC5B mucin gene and its product were identified in the middle ear secretory cells of patients with COM. Its expression was extensive in pseudostratified mucosal epithelia and related to infiltration of inflammatory cells in the submucosa of the middle ear cleft with COM, suggestive that inflammatory cell products are involved in the production of MUC5B.

Evaluation of the feasibility of and results of measuring health-status changes in patients undergoing surgical treatment for skeletal metastases.

The goal of treating patients with skeletal metastases is to decrease pain and improve or maintain physical function. Assessment of the effectiveness of treatment should therefore include evaluation of patient-rated measures of quality of life. The primary objective of the study was to determine the feasibility of studying the effect of surgical treatment of skeletal metastases on quality of life. The secondary objective was to provide data that begin to characterize this effect. The characteristics of patients with skeletal metastases are heterogeneous, patient enrollment in the study may be low, high attrition occurs secondary to death, and well accepted health-status measures (such as the Short Form-36) may be ineffective at detecting changes in health status; therefore, it is difficult to study these patients. High attrition and adjuvant treatment with radiation or chemotherapy made it impractical to draw firm conclusions about the effect of surgical treatment, but a trend toward improvement in selected health-status measures for both physical and mental health was noted. Analysis of patient-rated health-status scores as predictors of survival indicates that improvement in these scores 6 weeks after surgery is associated with an increase in the length of survival following surgery.

Histopathologic features of the temporal bone in patients with cystic fibrosis.

OBJECTIVES: To investigate the lower than expected incidence of otitis media in patients with cystic fibrosis (CF) through histopathologic evaluation of temporal bones and to document pathologic findings in the inner ears of patients with CF who received long-term administration of antibacterial and diuretic agents. DESIGN: Clinical records of patients who died of CF were reviewed. Their temporal bones were sectioned, stained with hematoxylin-eosin, and examined histologically. Additional sections were stained with Alcian blue and periodic acid-Schiff for comparison of goblet cell densities from middle ears and auditory tubes of patients with CF with those of control temporal bones. Results were analyzed using the t test. SUBJECTS: Twenty-one temporal bones from 11 patients with CF and 13 bones from 8 age-matched patients without CF were selected. RESULTS: All temporal bones with CF had well-pneumatized mastoids. Temporal bones from 2 patients (3 ears) revealed histological findings of chronic otitis media with effusion. There was a statistically significant reduction in the density of goblet cells in the medial (P = .002) and lateral (P = .05) walls in patients with CF who had no otitis media histologically compared with control temporal bones. Two patients with CF who had otitis media had increased densities of goblet cells. Inner ear damage, due to ototoxic drugs, was seen in most of the temporal bones from patients with CF. CONCLUSION: Low densities of goblet cells in temporal bones with CF may contribute reduced amounts of viscous mucus, which can lead to a low incidence of otitis media.

Residual mesenchyme persisting into adulthood.

PURPOSE: (1) To detect the presence of residual mesenchyme in temporal bones of adults and children above 5 years of age; (2) to evaluate its regression with increasing age, and; (3) to detect pathologic conditions associated with the presence of unresolved mesenchyme. MATERIALS AND METHODS: We examined 1,404 human temporal bones of donors from 5 to 94 years of age for histopathologic evidence of mesenchyme. The presence of stellate (star-shaped) cells with interdigitating processes and large nuclei embedded in a structureless ground substance was labeled as "pure mesenchyme." Temporal bones showing these features and focal areas of fibrosis, fibroblasts, and capillaries were classified as showing "transitional mesenchyme." Selected sections were stained with Gomori's trichrome. Pathological features indicating otitis media and congenital anomalies of the ear were also documented. Case histories were reviewed, and any otologic complaints were noted. Statistical analysis was performed with the Chi-square test, analysis of variance, regression analysis, and confidence interval. RESULTS: Mesenchyme was found in 2.07% of temporal bones of patients from 5 to 81 years of age. Of these, 92.1% had transitional mesenchyme, whereas 7.9% had pure mesenchyme. Seventy-six percent of the bones showed mesenchyme in the mastoid air cells. In all 3 bones with pure mesenchyme, it was present in the round window niche. Otitis media was associated with residual mesenchyme in 84.2% of the temporal bones. No pattern of regression of mesenchyme with increasing age was observed in temporal bones from patients over the age of 5 years. CONCLUSIONS: Residual mesenchyme can be present in patients older than 5 years of age and can persist into adulthood, especially in the mastoid air cells. Persistence of mesenchyme is closely associated with evidence of otitis media.

Effects of estrogen on the condylar cartilage of the rat mandible in organ culture.

PURPOSE: The effects of estrogen on bone have been well documented. However, very little is known about the regulatory role of estrogen on cartilage and, in particular, the secondary cartilage of the mandibular condyle. The aims of this study were to determine whether estrogen receptors are present in the condylar cartilage of the rat mandible and to assess the effect of varying 17beta-estradiol (E2) concentrations on the proteoglycan content of this tissue. MATERIALS AND METHODS: Mandibular condyles of 16 female Sprague-Dawley rats were resected. Eighteen of these condyles were divided into three groups and the condylar cartilage was removed and placed in organ culture for 4 days with media containing different concentrations of estrogen: 10(-11) mol/L, 10(-8) mol/L, and 10(-6) mol/L. The cartilage then was analyzed for proteoglycan content along with six specimens not passed through the organ culture. Six intact mandibular condyles also were resected and placed in organ culture with the same varying E2 concentrations, and the condylar cartilage was analyzed for estrogen receptors along with two condyles not passed through the culture system. RESULTS: Estrogen receptors were evenly distributed within the chondroblastic and hypertrophic zones in the control group and the group with 10(-11) mol/L E2. With E2 concentrations of 10(-8) mol/L and 10(-6) mol/L, there was a qualitative decrease in hypertrophic chondroblasts, thickness of the condylar cartilage, and a significant decrease in proteoglycan content. CONCLUSIONS: This study shows the presence of estrogen receptors in the secondary cartilage of the rat mandibular condyle. Estrogen has the potential to cause a decrease in extracellular matrix and thickness of this cartilage.

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.

Tympanic membrane/middle ear pathologic correlates in chronic otitis media.

OBJECTIVE: To correlate pathologic findings of the tympanic membrane with pathologic changes in the middle ear cleft in chronic otitis media. STUDY DESIGN: Retrospective. MATERIAL AND METHODS: One hundred-fifty temporal bones from 97 subjects with chronic otitis media (defined as middle ear pathologic changes including granulation tissue, fluid, cholesteatoma, cholesterol granuloma, tympanosclerosis, and ossicular changes) were selected to correlate the presence of these middle ear pathologies with histopathologic changes of the tympanic membrane. The tympanic membrane pathologies included perforation, myringosclerosis, retraction, hemorrhage, fluid-filled cystic spaces, or dilated vessels. Temporal bones were also assessed for atelectasis. Fifty-six normal temporal bones were taken as controls for measurements. RESULTS: Significant correlations between tympanic membrane and middle ear pathology included myringosclerosis and granulation tissue, myringosclerosis and ossicular pathology, retraction and cholesterol granuloma, retraction and cholesteatoma, retraction and ossicular pathology, perforation and ossicular pathology, and hemorrhage and granulation tissue. Additive effects of some pathologies were also observed. Almost half the bones with middle ear pathology had no associated tympanic membrane pathology, whereas multiple pathologic changes in the tympanic membrane generally showed underlying multiple pathologic changes in the middle ear. CONCLUSION: When tympanic membrane pathology is detected otoscopically, its presence, alone or in combination, can be a strong indicator of underlying middle ear pathology. However, a normal-appearing tympanic membrane does not exclude the possibility of middle ear pathology. These findings suggest the need for other diagnostic tools such as multifrequency tympanometry and otoacoustic emissions to complement otoscopy for diagnosis of middle ear pathology, especially in a tympanic membrane that appears "normal."

Middle ear fluid cytokine and inflammatory cell kinetics in the chinchilla otitis media model.

Streptococcus pneumoniae is the most frequent microbe causing middle ear infection. The pathophysiology of pneumococcal otitis media has been characterized by measurement of local inflammatory mediators such as inflammatory cells, lysozyme, oxidative metabolic products, and inflammatory cytokines. The role of cytokines in bacterial infection has been elucidated with animal models, and interleukin (IL)-1beta, IL-6, and IL-8 and tumor necrosis factor alpha (TNF-alpha) are recognized as being important local mediators in acute inflammation. We characterized middle ear inflammatory responses in the chinchilla otitis media model after injecting a very small number of viable pneumococci into the middle ear, similar to the natural course of infection. Middle ear fluid (MEF) concentrations of IL-1beta, IL-6, IL-8, and TNF-alpha were measured by using anti-human cytokine enzyme-linked immunosorbent assay reagents. IL-1beta showed the earliest peak, at 6 h after inoculation, whereas IL-6, IL-8, and TNF-alpha concentrations were increasing 72 h after pneumococcal inoculation. IL-6, IL-8, and TNF-alpha but not IL-1beta concentrations correlated significantly with total inflammatory cell numbers in MEF, and all four cytokines correlated significantly with MEF neutrophil concentration. Several intercytokine correlations were significant. Cytokines, therefore, participate in the early middle ear inflammatory response to S. pneumoniae.