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Biomedical subjects

C T Le

Publications and source records attributed to C T Le.

At least 55 records · Page 3Linked to original sources
PubMed1994

Determining otitis media severity from middle ear fluid analysis.

Otitis media has a complex multifactorial pathogenesis, and the middle ear inflammatory response is typified by the accumulation of cellular and chemical mediators in middle ear effusion. However, specific biochemical and immunochemical factors that may be responsible for the severity or chronicity of otitis media have not been identified. Identification of factors involved in chronicity appears to be an essential step in the treatment and ultimate prevention of chronic otitis media. We analyzed 70 effusion samples from patients 1 to 10 years of age who had chronic otitis media with effusion for two cytokines (interleukin-1 beta and tumor necrosis factor alpha) and total collagenase. The highest concentrations of all three inflammatory mediators were found in purulent otitis media, and concentrations were higher in younger than in older patients. Mediator concentrations were similar in samples obtained from patients having their first myringotomy for otitis media with effusion and in those who had had multiple previous myringotomies. The multiresponse star, which incorporates several biochemical parameters in one graphic illustration, may best characterize the complex nature of middle ear inflammation.

Child↗
PubMed1994

Acute otitis media increases middle ear susceptibility to nasal injection of Pseudomonas aeruginosa.

Pseudomonas aeruginosa was injected intranasally into four groups of chinchillas to determine if these bacteria can invade the middle ear by way of the eustachian tube. One group completed penicillin treatment of bilateral penumococcal otitis media (POM), and the second group started penicillin treatment of bilateral POM at the time of P. aeruginosa injection. A third group had no POM, but completed a course of penicillin treatment before P. aeruginosa injection, and a fourth group had no POM and received no penicillin. Middle ear susceptibility to nasally injected P. aeruginosa was significantly higher in animals with POM (61%) than in animals without POM (32%, p = 0.001). Forced eustachian tube opening pressures did not correlate with P. aeruginosa susceptibility. Thus, P. aeruginosa, the principle pathogen of chronic suppurative otitis media, can invade the middle ear by way of the eustachian tube, and acute otitis media predisposes to middle ear infection by P. aeurginosa.

Acute Disease↗
PubMed1994

Association between survival time and ordinal covariates.

An application of the method of rank correlation is proposed for testing independence between a censored survival time and an ordinal covariate. The test statistic counts the number of concordances minus the number of discordances at each time with event(s) and adds across times; it is expressible as a score statistic within the proportional hazards framework. The proposed test includes, as a special case, a generalization of Jonckheere's test against ordered alternatives and as applied to the analysis of categorical data, it can be seen as a generalization of the Mantel-Haenszel procedure.

Analysis of Variance↗
PubMed1993

Buthionine sulfoximine reduces the protective capacity of myocytes to withstand peroxide-derived free radical attack.

Mammalian heart myocytes have a limited capacity to withstand the deleterious effects of free radical generating compounds. To assess the role of the glutathione redox cycle relative to this capacity, rat heart cell cultures were subjected for 90 min to 80 mumol/l cumene hydroperoxide (CHPO) without and with prior glutathione depletion by buthionine sulfoximine. Preincubation of cultures with 125 mumol/l buthionine sulfoximine for 2 h and 17 h caused a reduction of glutathione by 33% and 82%, respectively, without concomitant increase of glutathione disulfide. Subsequent incubation with CHPO for 90 min caused slowing of NADPH consumption (in the first 20 min 27 pmol vs 68 pmol without pretreatment with buthionine sulfoximine for 17 h), which indicates that glutathione depletion reduced the turnover rate of the glutathione redox cycle. Pretreatment with buthionine sulfoximine for 17 h exaggerated the negative chronotropic effects of CHPO: the time elapsed to 50% of baseline contraction frequency fell from 5.7 +/- 1.4 min without buthionine sulfoximine to 3.7 +/- 0.4 min after pretreatment with buthionine sulfoximine (P < 0.02). The severity of CHPO-induced lipid peroxidation as assessed by malondialdehyde formation (2.23 +/- 0.51 vs 0.99 +/- 0.05 nmol in the first 20 min; P < 0.05) was increased by buthionine sulfoximine pretreatment, as was the extent of cell necrosis as assessed by release of alpha-hydroxybutyrate dehydrogenase (39.5 +/- 5.1 vs 29.0 +/- 12.9% in the first 45 min). A "sublethal" dose of 10 microM CHPO for 60 min caused no substantial HBDH release, no formation of malondialdehyde, and no exhaustion of cellular GSH (35 nmol/U HBDHt = 0). However, following pretreatment with buthionine sulfoximine, 10 microM CHPO for 60 min produced 12% HBDH release and extensive lipid peroxidation (1.95 nmol malondialdehyde/U HBDHt = 0). As the deleterious effects of CHPO were aggravated by glutathione depletion, we conclude that the glutathione redox cycle plays a major role in the protection of myocytes against peroxide-induced free radical attack.

Animals↗
PubMed1993

Pneumococcal capsular polysaccharide-meningococcal outer membrane protein complex conjugate vaccines: immunogenicity and efficacy in experimental pneumococcal otitis media.

Vaccines composed of pneumococcal capsular polysaccharides (PS) conjugated to outer membrane protein complex (OMPC) from Neisseria meningitides group B bacteria were tested in the chinchilla otitis media model. Monovalent (types 6B and 23F), bivalent (6B+23F), and tetravalent (6B+14+19F+23F) PS-OMPC conjugate vaccines elicited significant total serum antibody responses against all four PS. Type 6B vaccine elicited IgG, IgM, and IgA antibodies after a single dose and an anamnestic IgG response after a second vaccine dose on day 28. Type 6B and 19F vaccines prevented or greatly attenuated pneumococcal otitis media after direct middle ear challenge with the immunizing serotype, type 14 vaccine was not protective by this challenge route, and type 23F pneumococci were not sufficiently virulent in chinchillas to test vaccine effectiveness. The promising results with two serotypes suggest the PS-OMPC conjugates may be useful in human infants.

Animals↗
PubMed1992

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.

Acoustic Impedance Tests↗
PubMed1992

Effects of glucose, Trolox-C, and glutathione disulphide on lipid peroxidation and cell death induced by oxidant stress in rat heart.

OBJECTIVE: The aim was to find effective protection of myocytes against peroxide induced damage in terms of preservation of contractile activity, protection against lipid peroxidation, and protection against cell death. METHODS: The components of the glutathione redox cycle, the production of malondialdehyde, cell contractions, and enzyme release from myocytes were measured in cultured neonatal rat heart cells before and after administration of cumene hydroperoxide, 80 mumol.litre-1. The protective action was tested of (1) glucose (10 mmol.litre-1) which stimulates the production of NADPH; (2) Trolox-C (0.16 mmol.litre-1) which is a water soluble analogue of alpha tocopherol and a scavenger of free radicals; and (3) GSSG (0.6 mmol.litre-1) which increases the intracellular concentrations of GSH and GSSG. RESULTS: Although the three substances tested were equally effective in reducing the formation of malondialdehyde, exogenous GSSG afforded only slight protection against cumene hydroperoxide induced cell death, whereas glucose and Trolox-C were highly effective protectors. The depressant effect of cumene hydroperoxide on beating frequency was not influenced by preincubation with GSSG, nor by coadministration of glucose, but Trolox-C was able to diminish the negative chronotropic action of cumene hydroperoxide. CONCLUSIONS: Effective protection against cumene hydroperoxide induced lipid peroxidation is not associated per se with effective protection against cumene hydroperoxide induced loss of beating frequency and cell death.

Animals↗
PubMed1991

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.

Age Factors↗
PubMed1991

Evaluation of ventilating tubes and myringotomy in the treatment of recurrent or persistent otitis media.

In a prospective controlled study of the efficacy and sequelae of ventilating tubes, 44 children with bilateral recurrent acute otitis media (greater than 6 episodes/year) and 13 children with bilateral persistent middle ear effusion (greater than 3 months) received unilateral ventilating tube insertion in a randomly selected ear. The contralateral ears were randomized to receive either myringotomy alone or no surgery. Clinical, otoscopic, tympanometric and audiologic examinations were performed before the study and 2 to 4 weeks later, then at 3-month intervals for up to 2 years and at 36 months after surgical randomization. Medical therapy and antibiotic prophylaxis were used whenever indicated. While the ventilating tubes remained functional (mean duration, 10 months) the ears with a tube had significantly fewer episodes of otitis media than their contralateral ear (P less than 0.001; 95% confidence intervals -0.7, -1.7) and had more hearing improvement (P = 0.005; 95% confidence intervals, -5.9, -1.2). After tube extrusion there was a tendency for surgically treated ears to have more otitis and worse hearing, but not at a significant level. Tympanosclerosis, retraction and atrophy were more common in ears that received tubes. The majority of ears treated medically also improved. There is need for a more cautious and selective use of ventilating tubes.

Acoustic Impedance Tests↗
PubMed1991

Resolution of otitis media with effusion with the use of a stepped treatment regimen of trimethoprim-sulfamethoxazole and prednisone.

This double blind, placebo-controlled trial was designed to determine whether intervention with a stepped regimen of trimethoprim-sulfamethoxazole (TMP-SMX) and prednisone would prevent high risk children from developing chronic otitis media with effusion (OME) and recurrent acute otitis media. Forty-two children were enrolled, assigned to treatment with active drug or placebo and then examined at 2-week intervals. They received TMP-SMX (or placebo) during the first 2 weeks, TMP-SMX and prednisone (or placebo) during Weeks 3 and 4 for persistent OME and TMP-SMX (or placebo) for Weeks 5 and 6 if OME was still unresolved. After treatment 48% of active drug and 14% of placebo subjects resolved OME bilaterally (P less than 0.05). Active drug subjects also had fewer acute otitis media episodes than placebo subjects while receiving study treatment (P less than 0.01). Although this treatment regimen produced short term OME resolution, long term benefits were not demonstrated.

Child↗
PubMed1991

Cellular changes in Reissner's membrane in endolymphatic hydrops.

A quantitative morphologic study of the cellular changes in human Reissner's membrane (RM) was performed under light microscopy on 30 normal temporal bones from 15 subjects, and on 20 temporal bones from 10 subjects with endolymphatic hydrops. The cellular density of the epithelial and mesothelial layers of normal RMs decreased with increasing age. In endolymphatic hydrops, cellular proliferation and decreased cellular density of a distended RM were observed, and these changes occurred more remarkably in epithelial cells. Decreased cellular density in RM was correlated to the degree of endolymphatic hydrops. These findings indicate an involvement of the epithelial cellular changes in the pathogenesis of endolymphatic hydrops. Our results suggest that cellular changes in RM may cause dysfunction of radial flow leading to ionic disturbance of endolymph, which provides a possible mechanism of hearing loss in endolymphatic hydrops.

Adolescent↗
PubMed1991

Relative value of diagnostic tests for small acoustic neuromas.

Auditory brainstem response is now widely employed as a screening test for acoustic neuromas because it is equally sensitive when standardized against computed tomography. We have detected eight small (less than 10 mm) acoustic neuromas using gadolinium enhanced magnetic resonance imaging. In three of these cases, the auditory brainstem response was falsely negative. In contrast, 19 patients with larger tumors (greater than or equal to 10 mm) were found to have no false negative auditory brainstem responses. Auditory brainstem response appears to be less sensitive for detecting small, symptomatic acoustic neuromas.

Adult↗
PubMed1991

Tests of homogeneity for the relative risk in multiply-matched case-control studies.

We examine several tests of homogeneity of the odds ratio in the analysis of 2 x 2 tables arising from epidemiologic 1:R matched case-control studies. The T4 and T5 statistics proposed by Liang and Self (1985, Biometrika 72, 353-358) are unable to detect obvious inhomogeneity in two numerical examples and in simulation studies. The null hypothesis is rejected by the chi-square statistic of Ejigou and McHugh (1984, Biometrika 71, 408-411) and by a new proposed method whose significance level must be simulated.

Biometry↗
PubMed1990

Statistical methods for determining risk factors of chronic otitis media with effusion.

We use logistic regression with paired Bernouilli outcomes to analyse data on subjects who have either one or two organs (e.g. ears) each of which may develop disease. In this model, subject-specific covariates are related to the probability of developing disease. The proposed method is applied to determine risk factors for chronic otitis media with effusion.

Analysis of Variance↗
PubMed1990

An experimental model for measuring middle ear antimicrobial drug penetration in otitis media.

Bacteria are an important cause of acute otitis media and successful treatment depends on achieving inhibitory or bacteriacidal antimicrobial drug concentrations in the middle ear. To evaluate further otitis media treatment success and failure, we developed a chinchilla model to study antimicrobial drug penetration through the middle ear mucosa. Using quantitative histomorphometry, we measured the middle ear space in 10 chinchillas and found a mean +/- SD volume of 2.09 +/- 0.08 ml and a mean +/- SD surface area of 14.41 +/- 1.48 cm2. To measure the apparent rate constant (Kc) of antibiotic elimination from the middle ear, through the middle ear mucosa, an antibiotic solution was inoculated into the middle ear cavity, and samples were aspirated between 1 and 8 hr later. In normal ears, the mean Kc +/- SD for amoxicillin was 0.118 +/- 0.013 hr-1, that for a trimethoprim 0.461 +/- 0.090 hr-1, and that for sulfamethoxazole 0.265 +/- 0.062 hr-1. In ears inoculated with type 7F Streptococcus pneumoniae to induce acute otitis media, the Kc +/- SD increased for all three drugs (P less than 0.05): amoxicilin to 0.286 +/- 0.089 hr-1, trimethoprim to 0.662 +/- 0.118 hr-1, and sulfamethoxazole to 0.411 +/- 0.056 hr-1. These values demonstrate that amoxicillin had the lowest apparent penetration rate constant of the three antibiotics but the greatest increase from normal to infected mucosa (142%). Trimethoprim had the highest apparent penetration rate constant of the three antibiotics but the smallest increase from normal to infected mucosa (44%), while the sulfamethoxazone apparent penetration rate constant increased from normal to infected mucosa by 55%.(ABSTRACT TRUNCATED AT 250 WORDS)

Amoxicillin↗
PubMed1990

A controlled trial comparing three treatments for chronic otitis media with effusion.

A randomized, controlled clinical trial was conducted in 76 children to evaluate the efficacy of trimethoprim-sulfamethoxazole for 4 weeks, prednisone for 2 weeks and aluminum ibuprofen suspension for 2 weeks in resolving chronic otitis media with effusion which had persisted for more than 8 weeks. After 2 weeks of treatment resolution rates of chronic otitis media with effusion in the prednisone and trimethoprim-sulfamethoxazole groups were significantly greater than those in the control (no treatment) and ibuprofen groups. After 4 weeks the differences in resolution rates between the control, trimethoprim-sulfamethoxazole and prednisone groups became smaller. After 12 months of follow-up, differences in hearing sensitivity among study groups were not statistically significant, although 83% of patients had a 15-dB or greater hearing loss. Therefore short term antimicrobial and antiinflammatory treatment did not appear to have a long lasting effect on chronic middle ear inflammation.

Analysis of Variance↗