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Biomedical subjects

C T Le

Publications and source records attributed to C T Le.

At least 37 records · Page 2Linked to original sources
PubMed1997

Significance of epidermoid formations in the middle ear in fetuses and children.

OBJECTIVE: To determine the incidence, size, and location of epidermoid formations (EFs), which have been suggested to be precursors of congenital cholesteatomas, in temporal bones from fetuses and children. DESIGN: We examined temporal bones from 226 fetuses and children up to the age of 10 years for the incidence, size, and location of EFs. RESULTS: Twenty-five EFs were identified in middle ears of 3 fetuses, 7 neonates, 9 infants, and 2 children aged 2 and 3 years. There was a male-female preponderance of 5:4. Generally, we saw EFs between the anterosuperior edge of the eardrum and the anterior limb of the tympanic ring, but 4 were below the level of the handle of the malleus. Their widths ranged from 25 to 300 microns. Keratinization was not observed in any EF. Contrary to previous reports, we found EFs not only in ears of fetuses, but also in ears of infants and children. CONCLUSION: Although EFs may persist in some ears, possibly developing into congenital cholesteatomas, our findings do not provide direct support for this concept.

Child↗
PubMed1997

Measuring health status in patients with skeletal metastases treated by surgery.

Since the introduction of the Functional Living Index-Cancer (FLIC) > 10 years ago, a variety of general as well as disease-specific quality of life (QOL) instruments have been developed and used as a means of assessing the success of clinical interventions. Clinicians faced with selecting an appropriate QOL measurement tool will need guidance in both the selection of the instrument and its evaluation for applicability to the patient group under study. In our examination of this issue, we analyzed the results of administering the FLIC and the more general SF-36 questionnaire to a group of 17 patients who had undergone orthopaedic surgery to correct problems associated with bone metastatic cancer. Because the SF-36 has been widely adopted as a general Health Status evaluation tool and because of its extensive validation it may be considered a gold standard providing a means of assessing the validity of disease-specific instruments such as the FLIC. Using multivariate regression, we built a model in which five of the eight health status dimensions of the SF-36 account for 77% of the variation in the FLIC scores for this group of patients (R2 = 0.77). The implication of this result is that most of the information (i.e., 77%) provided by the FLIC could be equivalently obtained using the more general, more widely validated SF-36. Despite the small sample size, half of the regression coefficients in this model achieved a high level of statistical significance (p < 0.001). In addition, when applied to new patients, the model showed good predictive capability with relative error 2-20%. If these results can be replicated for other patient disease groups and in larger study populations, it may be possible to use the SF-36 as the primary QOL evaluation tool for cancer patients. The burden of this disease could then be more easily compared with that of other disease groups and the resulting standardization of QOL analysis would be simpler and more cost effective.

Aged↗
PubMed1997

Effects of brain injury on college academic performance.

Brain injury, a leading cause of mortality, morbidity and disability in the United States, has serious consequences and substantial costs. Although previous studies have assessed a variety of outcomes subsequent to brain injury, documentation of performance prior to brain injury using a case-control approach has not been included; preinjury performance differences may confound the estimate of the effects of brain injury on performance. The primary objective of this study was to compare academic performance before and after brain injury in a population of university undergraduate students to determine the extent to which the academic career of the brain-injured person was altered from what would have been expected in the absence of such an injury. Cases included all undergraduate students in a major university, between the ages of 17 and 27, who incurred a brain injury requiring hospitalization between 1980 and 1984 (n = 99). Two comparison groups were used to determine whether changes in academic performance were specifically related to brain injuries or injuries in general: (1) injured controls, i.e. 121 students between the ages of 17 and 27 years, hospitalized for injuries other than to the central nervous system, and (2) uninjured academic controls, i.e. 198 students with out injuries requiring hospitalization during the study period, matched 2:1 to the brain-injured students by age, gender, and completed course credits categorized as < 90, > or = 90. Although there were no differences when the total groups, including both males and females, were compared, there was a significant pre- to postinjury decrease in the grade point average for female cases when compared to their uninjured academic controls (p < 0.02). This difference was related to the effects of brain injury, and not to the effects of injury in general. No such difference was observed for the males. There were also no differences when the total groups, including males and females, were compared relevant to return to school. However, a significantly higher proportion of the female cases, compared with their uninjured academic controls, did not return to school after their injury; similar findings were identified for the injured controls as well. Thus, these differences were not specific to brain injury but rather to injury in general. In spite of this observation, the difference between female cases who returned and those who did not return was associated with neurological deficits, especially upper left limb motor deficits, as the time of hospital discharge. The findings from this effort are suggestive of gender differences in the consequences of brain injury and serve as a basis for further studies to evaluate the magnitude of this problem.

Adolescent↗
PubMed1997

Evaluation of confounding effects in ROC studies.

In many clinical studies, it is clear that external forces can affect the performance of diagnostic tests, as these factors influence the distributions of separator variables. A new estimator for the receiver operating characteristic (ROC) function is proposed; this estimator converges to the ROC function uniformly on the interval [0,1]. Using this new estimator, the author proposes to use Cox's proportional hazards regression model for the evaluation of confounding effects in ROC studies. The method can be used even when concomitant information is only available for the cases, for example, disease severity. A textbook example on prostate cancer is described for illustration.

Aged↗
PubMed1996

Temporal bone study of Down's syndrome.

OBJECTIVE: To study temporal bone histopathologic characteristics of the inner ear and middle ear cleft of patients with Down's syndrome. DESIGN: Sixteen temporal bones from eight patients with Down's syndrome were studied. Ten temporal bones from subjects without pathologic ear lesions but with congenital heart disease served as controls. The two-dimensional graphic reconstruction method proposed by Guild and modified by Schuknecht was used to study the cochleas; measurement of the vestibules was based on Igarashi's method. SETTING: The temporal bone collection of the Otitis Media Research Center, Department of Otolaryngology, University of Minnesota School of Medicine, Minneapolis. RESULTS: Six bones showed short cochlea, and four of six had Mondini's cochlea. The overall cochlear lengths in this study group were notably shorter than those of the controls. The spiral ganglion cell population and two of three vestibular dimensions also were notably less than the controls. Middle ear findings included residual mesenchyme, stapes abnormality, otitis media, and large facial canal dehiscence. CONCLUSIONS: The difficulties encountered in rehabilitation of patients with Down's syndrome caused by mental retardation can be compounded by the hearing loss caused by middle and inner ear abnormalities. A complete evaluation of hearing loss and therapy before starting the rehabilitation gives the most favorable outcome.

Adolescent↗
PubMed1996

The family study of otitis media: design and disease and risk factor profiles.

Recurrent acute otitis media (RAOM) and chronic otitis media with effusion (COME) exhibit familial aggregation, but environmental risk factors (day care attendance, cigarette smoke exposure, and bottle feeding) are also important in their development. The Family Study of OM was designed to ascertain the RAOM/ COME status of families whose children participated in Otitis Media Research Center studies between 1978 and 1984. Probands were treated with tympanostomy tubes, and had their RAOM/COME status ascertained as criteria for entry into these studies. For the Family Study of OM parents were interviewed about their otitis media and risk factor history; mothers were interviewed about their children's history, and pertinent medical records were obtained. Members of 173 families were examined with otomicroscopy and multifrequency tympanometry; 19% of parents and 32% of siblings were classified as affected, which is substantially higher than RAOM/COME rates from previous reports. Risk factor profiles differed significantly (P < .001) between parents and their children. Younger generation (adjusted odds ratio [OR] = 4.18, 95% confidence interval [CI], 2.74, 6.36) day care attendance (OR = 1.96, 95% CI, 1.32, 2.91) and male gender (OR = 1.42, 95% CI, 1.03, 1.97) were significantly related to RAOM/ COME using logistic regression. Analyses confirm 1) higher disease rates in families with an affected member compared to existing studies of the general population, 2) increased risk of RAOM/COME associated with known risk factors, and 3) increased risk for parents irrespective of risk factors. Additional analyses will explore competing models of disease susceptibility using genetic models and known risk factors.

Adult↗
PubMed1996

Immunogenicity and efficacy of Streptococcus pneumoniae polysaccharide-protein conjugate vaccines against homologous and heterologous serotypes in the chinchilla otitis media model.

Cross-protection among pneumococcal serotypes within serogroups was measured in the chinchilla otitis media (OM) model because several serotypes that cause OM in children are closely related biochemically. Chinchillas were given tetravalent vaccine composed of pneumococcal capsular polysaccharides (PS; types 6B, 14, 19F, 23F) conjugated to an outer membrane protein complex, and 89% to 96% developed a > or = 2-fold serum IgG rise against vaccine PS. Vaccine efficacy was tested by inoculating middle ear hypotympanic bullae with Streptococcus pneumoniae types 6B, 6A, 19F, or 19A. OM severity in the vaccinated groups challenged with types 6B, 6A, and 19F but not 19A was significantly better than in the respective placebo groups. Culture-positive pneumococcal OM occurred in 38%, 62%, 0, and 78% of vaccinated chinchillas challenged with types 6B, 6A, 19F, and 19A, respectively, but in 88% of type 6B- and 100% of type 6A-, 19A-, and 19F-challenged placebo chinchillas.

Analysis of Variance↗
PubMed1996

High frequency hearing loss associated with otitis media.

OBJECTIVE: Long-term effects of otitis media (OM) on hearing in both conventional and high frequency (HF) regions in children were studied. DESIGN: Children with OM were enrolled in a prospective study of sequelae after tympanostomy tube insertion (intubation) and were examined serially at 6-mo intervals with audiometry and multifrequency tympanometry, and every 3 mo with tympanometry and otoscopy for at least 3, and up to 5 yr. Hearing thresholds in conventional and HF regions were compared with those of an age-matched control group of children who had 2 or fewer documented episodes of any type of OM since birth. Frequency of OM during follow-up, number of intubations, use of ototopical eardrops, age, and sex along with several other factors were analyzed for a relationship to HF hearing loss. RESULTS: Otitis media history was associated with poorer HF hearing, but the presence of subtle residual middle ear dysfunction was not associated with an additional effect on HF hearing. Active middle ear disease significantly affected both conventional and HF thresholds. The number of intubations and frequency of OM during follow-up were significantly and positively associated with poorer HF thresholds. Several other factors, including middle ear appearance at intubation, presence of tympanosclerosis, age, male gender, and use of ototopical eardrops, were also associated with poorer HF hearing but failed to reach significance after their intercorrelation with number of intubations and frequency of OM was considered. CONCLUSIONS: High frequency hearing loss was associated with OM after middle ear disease resolved and after middle ear dysfunction was excluded. Relatively poorer HF hearing thresholds found for older children with OM histories appeared to be attributable to time spent with ear disease. Children at greatest risk for HF hearing loss were those who required multiple intubations. Older children tended to have poorer hearing in both conventional and HF regions, suggesting that the effects of OM on hearing thresholds may be progressive.

Acoustic Impedance Tests↗
PubMed1996

Residual mesenchyme in temporal bones of children.

The role of mesenchyme in the temporal bone is still poorly understood. A microscopic study of residual mesenchyme was undertaken in temporal bones of children from birth to 5 years of age. Residual mesenchyme was found to be located in the mastoid antrum and epitympanum more often than in the mesotympanum. The amount of mesenchymal tissue remaining in the temporal bones decreased with increasing age. Persistence of mesenchyme in the temporal bone was related to congenital morphologic ear anomalies and syndromes. There was also an association evident with pulmonary disease, but not with congenital heart defects. Persistent mesenchyme was also found to be significantly associated with chronic middle ear inflammation, and in cases of unilateral otitis media the ear with otitis media had more residual mesenchyme than the non-otitis media ear.

Age Factors↗
PubMed1996

Roles of autolysin and pneumolysin in middle ear inflammation caused by a type 3 Streptococcus pneumoniae strain in the chinchilla otitis media model.

Streptococcus pneumoniae cell wall and pneumolysin are important contributors to pneumococcal pathogenicity in some animal models. To further explore these factors in middle ear inflammation caused by pneumococci, penicillin-induced inflammatory acceleration was studied by using three closely related pneumococcal strains: a wild-type 3 strain (WT3), its pneumolysin-negative derivative (P-1), and into autolysin-negative derivative (A-1). Both middle ears of chinchillas were inoculated with one of the three pneumococcal strains. During the first 12 h, all three strains grew in vivo at the same rate, and all three strains induced similar inflammatory cell responses in middle ear fluid (MEF). Procaine penicillin G was given as 12 h to one-half of the animals in each group, and all treated chinchillas had sterile MEF at 24 h. Penicillin significantly accelerated MEF inflammatory cell influx into WT3-and P-1-infected ears at 18 and 24 h in comparison with the rate for penicillin-treated A-1-infected ears. Inflammatory cell influx was slightly, but not significantly, greater after treatment of WT3 infection than after treatment of P-1 infection. Interleukin (IL)-1beta and IL-6, but not IL-8, concentrations in MEF at 24 h reflected the penicillin effect on MEF inflammatory cells; however, differences between treatment groups were not significant. Results suggest that pneumococcal otitis media pathogenesis is triggered principally by the inflammatory effects of intact and lytic cell wall products in the middle ear, with at most a modes additional pneumolysin effect. Investigation strategies that limit the release of these products or neutralize them warrant further investigation.

Animals↗
PubMed1995

Protection of myocytes against free radical-induced damage by accelerated turnover of the glutathione redox cycle.

The primary defence mechanism of myocytes against peroxides and peroxide-derived peroxyl and alkoxyl radicals is the glutathione redox cycle. The purpose of the present study was to increase the turnover rate of this cycle by stimulating the glutathione peroxidase catalysed reaction (2GSH-->GSSG), the glutathione reductase catalysed reaction (GSSG-->2GSH), or both. Neonatal rat heart cell cultures were subjected to a standardized protocol of oxidative stress using 80 mumol.l-1 cumene hydroperoxide (CHPO) for 0-90 min. The consequences of this protocol were described in terms of cellular concentrations of GSH, GSSG, NADPH and ATP, formation of malondialdehyde (MDA), release of GSSG and of ATP catabolites, depression of contraction frequency, cellular calcium overload, and enzyme release. Trolox-C, an analogue of vitamin E, accelerated the glutathione peroxidase reaction leading to lowering of GSH concentration and the GSH/GSSG ratio, less MDA formation, diminished negative chronotropy, delayed calcium overload, and less enzyme release. Glucose was used to accelerate the glutathione reductase reaction by supplying NADPH, leading to higher GSH concentration and a higher GSH/GSSG ratio, less MDA formation, diminished negative chronotropy, unchanged development of calcium overload, and less enzyme release. As a full turn of the glutathione redox cycle involves both the peroxidase and the reductase reactions, the combination of Trolox-C and glucose was superior to either of the two alone: 90 min following addition of CHPO together with Trolox-C and glucose, the GSH concentration and the GSH/GSSG ratio were almost normal, MDA formation was extremely low, calcium overload was markedly delayed, and enzyme release hardly occurred at all. Cells remained beating in the observation period of 30 min. We conclude that the capacity of the glutathione redox cycle to withstand oxidative stress can be increased by stimulation of either the peroxidase reaction or the reductase reaction, and that optimal redox cycling is achieved by stimulation of both reactions.

Adenosine Triphosphate↗
PubMed1995

Randomized trial of the efficacy of trimethoprim-sulfamethoxazole and prednisone in preventing post-tympanostomy tube morbidity.

This study was designed to determine whether treatment with prednisone and trimethoprim-sulfamethoxazole would reduce first year post-operative morbidity in children with chronic otitis media with effusion undergoing tympanostomy tube insertion (intubation). Eighty children ages 6 months to 8 years were enrolled at intubation and randomized from age strata to receive active drugs or placebos for 14 days after surgery. They were examined with pneumatic otoscopy and tympanometry preoperatively and at 3 weeks and 3, 6, 9 and 12 months after surgery. Active drug treatment significantly reduced tube obstruction or extrusion in the first 3 postoperative months compared with placebos (4% vs. 17%, P = .01). However, rates of repeat intubation, otorrhea and recurrence of otitis media did not differ significantly in the two groups. Children with chronic otitis media with effusion treated with intubation may benefit from a 2-week course of prednisone and trimethoprim-sulfamethoxazole at the time of surgery. However, there is no apparent long term benefit of this treatment.

Anti-Infective Agents↗
PubMed1994

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.

Child↗
PubMed1994

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.

Acoustic Impedance Tests↗
PubMed1994

Desferrioxamine protects myocytes against peroxide-induced myocyte damage without affecting glutathione redox cycle turnover.

The primary defense mechanism of myocytes against peroxide-derived free radicals is the glutathione redox cycle. The purpose of the present study was to investigate whether desferrioxamine protects myocytes against peroxide-induced cell damage, and if so, whether the turnover rate of the glutathione redox cycle is involved in this protection. Neonatal rat heart cell cultures were subjected to a standardized oxidative stress by a 90 min incubation with 80 mumol/l cumene hydroperoxide. The consequences of this stress protocol were described in terms of cellular concentrations of GSH, GSSG, ATP, ATP-catabolites, and Ca2+, formation of malondialdehyde to quantify lipid peroxidation, and enzyme release to quantify the relative number of irreversibly injured cells. Following pretreatment of cell cultures with 10 mmol/l desferrioxamine mesylate for 1 h, 80 mumol/l cumene hydroperoxide caused less malondialdehyde formation (at 90 min: 0.34 v 2.35 nmol), less ATP depletion (at 60 min: 16.7 v 3.6 nmol), less Ca2+ overload (at 30 min: 40 v 1500 nM) and less enzyme release (at 90 min: 4.6 v 60.5% of the cells) compared to cell cultures subjected to cumene hydroperoxide without pretreatment. However, in desferrioxamine pretreated cell cultures cumene hydroperoxide caused cellular GSH depletion (at 60 min: 19.5 v 20.8 nmol) and GSSG efflux (at 60 min: 6.3 v 6.0 nmol) which was not different from cell cultures subjected to cumene hydroperoxide without pretreatment. Added to the finding that in a cell-free system cumene hydroperoxide is a substrate for glutathione peroxidase, we conclude that desferrioxamine, by chelating free iron ions (1), prevented the formation of cumene alkoxyl and peroxyl radicals associated with protection of the myocytes, and (2) did not diminish rapid glutathione redox cycling leading to GSH depletion and GSSG efflux.

Adenosine Triphosphate↗
PubMed1994

Piecewise exponential survival curves with smooth transitions.

Several models of a population survival curve composed of two piecewise exponential distributions are developed. In one formulation the hazard rate changes at a point that is an unobservable random variable that varies between individuals. The population hazard function may decrease with age even when all individuals' hazards are increasing. In a second formulation, the population hazard function is modeled directly. Several models are fit to the survival history of a cohort of 5751 highly inbred male Drosophila melanogaster and the British coal mining disaster data.

Animals↗
PubMed1994

Comparison of two otitis media models for the study of middle ear antimicrobial pharmacokinetics.

We compared two models of acute otitis media that estimate middle ear antimicrobial pharmacokinetics. Using a crossover study design, we compared a systemic drug administration model with a diffusion model we devised that measures the disappearance of antimicrobials from the middle ear. We induced acute otitis media in 14 chinchillas by inoculating S. pneumoniae into the middle ear, then administered 3 antimicrobials: amoxicillin, trimethoprim, and sulfamethoxazole. Next we collected middle ear fluid samples to analyze drug concentrations and compare rate constants for the systemic and diffusion models by analysis of variance. We found that amoxicillin K values were not affected by model testing sequence (p = 0.827) or model type (systemic versus diffusion, p = 0.310), nor were sulfamethoxazole K values: model testing sequence (p = 0.917), model type (p = 0.963). Trimethoprim K values were also not affected by model testing sequence (p = 0/760), but were by model type (p = 0.0001). Trimethoprim elimination from the diffusion model was faster (K = 0.33 +/- 0.17 versus 0.57 +/- 0.09 hr-1) than from the systemic model, although it appears this was caused by sampling before drug distribution into the middle ear was complete. In conclusion, it appears K values derived from either systemic antimicrobial administration or direct middle ear instillation are similar for assessing middle ear antimicrobial pharmacokinetics, and these models can be used interchangeably to study factors affecting otitis media treatment response.

Amoxicillin↗