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Biomedical subjects

D J Lim

Publications and source records attributed to D J Lim.

At least 181 records · Page 10Linked to original sources
PubMedDate not supplied

Microorganisms in chronic otitis media with effusion.

A total of 175 effusions obtained from 172 patients suffering from chronic otitis media with effusions was examined for bacterial smear and culture. Eighty percent showed positive bacterial smear, but only 49% yielded positive bacterial culture. The mucoid effusions had positive cultures in only 37%, whereas the bacterial culture rate was higher in serous (59%) and leukocytic (64%) types. The isolation of common pathogens accounted for about 50% of the isolates, and nonpathogens accounted for the remaining 50%. The high incidence of microorganisms in the middle ear effusions in the present series raises the possibility of bacterial contribution in many cases of OME.

Child↗
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Otosclerotic stapes: morphological and microchemical correlates. An electron microscopic and x-ray analytical investigation.

A total of 32 otosclerotic stapes is thin-sectioned without decalcification and examined using transmission and scanning electron microscopes, with a nondispersive x-ray analyzer attached to the latter. These otosclerotic stapes are classified as spongiotic, sclerotic, or preotosclerotic, accoring to their pathologic characteristics and state of mineralization. Either diffuse or patchy demineralization in the ground substance appears to be the initial stage of otosclerosis, and this area coincides with preotosclerotic lesions (also known as blue mantle) in light microscopy. Therefore, it is interpreted that demineralization precedes the destruction of ground substance in the preotosclerotic lesion. Bone mineral deposits in new otosclerotic bone appear to be related to the collagen fibrils that are embedded in the ground substance. No mineral deposit could be seen without the ground substance deposition; therefore, it is suggested that this ground substance is the single most important factor in the poor mineralization of the otosclerosis. The sclerotic lesions are well mineralized and show a typical pattern of hydroxyapatite by x-ray diffraction study. We could not confirm the notion that the sclerotic lesion is hypermineralized as compared to the normal stapes. The spongiotic lesions are poorly mineralized, with low calcium salt. Using the Ca/P ratio and x-ray diffraction pattern as criteria, it was determined that spongiotic lesions belong to unstable, immature bone.

Bone Marrow↗
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Immunoglobulin E in chronic middle ear effusions: conmparison of RIST, PRIST, and RIA techniques.

To investigate the possible role of allergy in otitis media with effusion (OME), the immunoglobulin E (IgE) content of 138 middle ear effusions (MEE) and paired serum samples from patients with chronic otitis media with effusion was determined. The initial 62 paired specimens were assayed for IgE by the radioimmunosorbent test (RIST), while the later 76 paired specimens were assayed for IgE by the paper radioimmunosorbent test (PRIST). When the results obtained by these two techniques were compared, it was noted that the PRIST procedure gave significantly lower IgE values for effusions than the RIST method. When the effusion-to-serum ratios (E/S ratios) were computed from the PRIST data, the E/S ratio was less than one, while RIST data gave an E/S ratio greater than one. The results obtained with the PRIST procedure were confirmed by double antibody radioimmunoassay for IgE. Thus, the PRIST procedure appears to measure the IgE content of MEE more accurately, and the results obtained by this procedure fail to support the concept of allergy as a major causative factor in OME.

Adolescent↗
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Antibody activity in otitis media with effusion.

Bacteria were isolated from a high percentage of the effusions from patients with otitis media with effusion (OME, serous otitis media). In an attempt to determine if the isolated bacteria were involved in the disease process, we analyzed the serum and effusion of 25 OME patients for the presence of antibacterial antibodies by the indirect immunofluorescence antibody method. Specific antibody activity was detected in 20 of 25 effusions (80%) and 19 of 22 sera (86%). IgG antibodies were the most frequently found class of antibodies in both sera and effusions, but IgA antibodies were detected more frequently in the effusions than in the sera. Hemophilus influenzae, Streptococcus pneumoniae, and diphtheroids were the most frequently isolated organisms, and antibody activity to all bacterial species isolated was detected. The results support the concept that the isolated bacteria are not contaminants but are actively involved in the disease process.

Antibodies, Bacterial↗
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Antibiotic-resistant bacteria in otitis media with effusion.

Eighty-two bacterial isolates recovered from the middle ear effusions (192) of children with otitis media with effusion (OME) were tested for antibiotic sensitivity. Nearly 50% of all bacteria isolated were found to be resistant to penicillin, and in particular, 61% of the Haemophilus isolates were penicillin-resistant; 48% of the Haemophilus isolates were ampicillin-resistant. In addition, we we compared the bacterial recovery rate from effusions of patients who were receiving antibiotics with those who were not. Among patients who were receiving antibiotics, 33% of the effusions were culture positive, while 82% of the effusions were culture positive in the patients who were not given antibiotics. These results are discussed with respect to the possible role of bacteria in the pathogenesis of OME.

Ampicillin↗
PubMedDate not supplied

Experimental otitis media in chinchillas.

Otitis media was induced in chinchillas by intrabullar injection of type 3 Streptococcus pneumoniae. It was found that the severity of a primary infection was related to the dose of bacteria injected, and animals that had recovered from a primary infection were resistant to reinfection with type 3 S pneumoniae. Middle ear effusions from infected animals contained antibodies to type 3 pneumococcal polysaccharide, whereas the sera of these animals lacked this antibody, suggesting that resistance to reinfectin was due to local immune mechanisms. This idea was tested by immunizing chinchillas by various routes. Animals immunized with formalin-killed type 3 S pneumoniae by intramuscular injection (to stimulate the systemic immune system) or by intranasal inoculation (to stimulate the secretory immune system) were found to be susceptible to infection with type 3 pneumonococcus, while animals immunized by inoculation of bacterial suspension directly into the middle ear were resistant to infection. In addition, we found that ampicillin treatment of a primary infection blocks the development of resistance since antibiotic-treated animals were susceptible to reinfection with the type 3 pneumococcus. These results indicate that chinchillas develop an immunity to pneumococcal otitis media following recovery from primary infection and that this immunity is mediated primarily by local immune mechanisms rather than systemic immune responses.

Ampicillin↗
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Selective induction of macrophages in the middle ear.

A method is described for inducing an influx primarily of macrophages into the middle ears of chinchillas using keyhole limpet hemocyanin (KLH, a strong immunogen) and mineral oil (a nonimmunogen) to provide adequate numbers of these cells for study. Although KLH and mineral oil both induced sterile otitis media in which macrophages were the predominant cell type present in the middle ear, the cytological and histological responses of the middle ears to these substances differed. KLH proved to be a much stronger inducer of actively phagocytic macrophages and also produced serous effusions in about 11% of the experimental animals. This experimental model provides an opportunity for the in vitro and in vivo study of the role of macrophages, the predominant cell type associated with human chronic otitis media with effusion, in the defense system of the middle ear.

Animals↗
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Experimental otitis media with effusion following middle ear inoculation of nonviable H influenzae.

In order to test the hypothesis that nonviable bacteria can induce middle ear inflammation leading to persistent middle ear effusion (MEE), we conducted an animal experiment using formalin-killed Hemophilus influenzae, the bacterium reported to be the most common pathogen isolated from chronic MEEs. Over 70% of the chinchillas injected with formalin-killed H influenzae type b or a nontypeable isolate developed sterile, straw-colored serous MEEs, and exhibited histological evidence of extensive inflammatory changes of the middle ear mucosal connective tissue and epithelium. Control animals injected with pyrogen-free sterile saline did not exhibit any inflammatory changes or effusions in the middle ears. Our data suggest that endotoxin on the surface of H influenzae, a gram-negative bacterium, may be responsible for the induction of the otitis media with effusion. It is suggested that endotoxin (even when the organisms are no longer viable) may be responsible for the production of serous MEE and inflammatory changes in the middle ear.

Animals↗
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Otoconia in health and disease. A review.

Mammalian otoconia are made up of inorganic calcium carbonate crystallites and organic substance, which is thought to be sulfated glycosaminoglycans and glycoprotein. Mouse otoconia are formed in situ, and the primitive otoconia assume spindle, trigonal, dumbbell, or quadrilobed forms. As the otoconia mature, they assume the typical barrel-shaped body with pointed tips formed by three surfaces. A variety of otoconial disorders have been reported. Otoconial degeneration can result from ototoxic drugs, infection, trauma, and aging. Abnormal otoconia are also known to occur as a result of genetic mutation, as well as ototoxicity. Otoconial deficiency may be genetic or caused by certain drugs, such as carbonic anhydrase inhibitors or tetracycline, or manganese deficiency during the critical period of gestation when the otoconia are formed in utero. Otoconial deficiency has been found to produce head tilting, swimming difficulty, and reduction or failure of the air-righting reflexes in animals.

Aging↗
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Cross-reactive antibodies in type b and nontypeable Hemophilus influenzae-induced experimental otitis media.

Cross-reactive antibodies directed against type b (TBHI) or serologically nontypeable (NTHI) strains of Hemophilus influenzae were investigated in experimental otitis media. Cross-reactive antibody to TBHI was demonstrated in sera and middle ears from chinchillas infected with an NTHI, and cross-reactive antibody to NTHI developed in sera and middle ears of chinchillas challenged with TBHI. The absorption test data presented indicate that the sera and middle ear effusions from chinchillas challenged with either TBHI or NTHI had not only specific antibody activity to the challenged strain but also antibody activities against the probable common cell antigens of H influenzae. These data indicate that it may be possible to develop a polyvalent vaccine effective against the various and divergent strains of H influenzae, including the serologically nontypeable isolates.

Absorption↗
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Experimental otitis media with effusion: an immune-complex-mediated response.

The possibility that immune complexes cause otitis media with effusion (OME) has been previously proposed. In order to test this hypothesis we developed an animal model in which immune complexes were injected into the middle ears of chinchillas and the animals killed at various time intervals thereafter. Moderate inflammatory changes were seen in animals killed four hours postinjection, whereas intense inflammation was observed in those killed at 24 hours. Inflammatory changes observed included capillary dilatation with increased capillary permeability, migration of polymorphonuclear leukocytes into the sub-mucosa, hemorrhage, and damage to and actual disruption of the subepithelial basement membrane. These changes are consistent with a complement-mediated acute inflammatory reaction. Although no definite conclusion can be made concerning the etiologic role of immune complex in OME, our findings show that immune complexes can cause acute inflammatory changes in the middle ear of the experimental animal.

Animals↗
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Surface-active substances of the guinea pig tubotympanum: a chemical and physical analysis.

An attempt to describe the nature of the surface-active substances of the eustachian tube lining layer that influence normal tubal function was undertaken. Under sterile conditions, guinea pig tubotympanic washings were collected, centrifuged, and pooled. Analysis of the pooled lavages using standard surface chemistry techniques confirmed the presence of significant surface-tension-lowering activity in the mucous lining layer of the eustachian tube, but the surface pressure obtained is neither as great nor displays the same degree of hysteresis as pulmonary surfactant. Following separation into aqueous and lipid fractions, measurable amounts of surface activity can be found in both isolates. The chemical composition and concentration of the lipid fraction, and its relative contribution to the surface activity of the tubotympanic washings, however, is smaller and radically different from the phospholipids found in surfactant. A significantly higher concentration of protein was recovered in comparison with the lipid portion, and it was observed that the surface activity of the total washings and the aqueous phase bore remarkable similarities. Although the surface-tension-lowering properties of the tubal lining layer may be the consequence of a combined synergistic action of the lipid and protein moieties, we believe that the current evidence points toward the proteins as being the primary tubal surface-tension-lowering substances.

Animals↗
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Macromolecular transport by the middle ear and its lymphatic system.

The macromolecular transport in the middle ear mucosa of the guinea pig was investigated by means of light and electron microscopy using tracer substances such as Evans blue, India ink, and horseradish peroxidase (HRP). HRP particles were readily taken up by the middle ear mucosa and Eustachian tube. They were absorbed by all cell types, including ciliated, secretory and nonsecretory cells. The particles were first taken up by the pinocytotic vesicles and then transported into the intercellular spaces by reverse pinocytosis. These particles were transported toward the connective tissue through the basilar membrane. Some of the tracer particles were engulfed by the tissue histiocytes, but most of the particles entered into lymphatic and blood capillaries. By Evans blue instillation of the bulla, the retroauricular and junctional lymph nodes were positively identified as those draining the middle ear and the Eustachian tube. When HRP was used, the tracer particles were detected in the ipsilateral retroauricular and junctional lymph nodes as early as 5 minutes following the tympanic instillation. HRP in these lymph nodes were mainly found in the specific granules of the macrophages.

Animals↗
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Active otosclerotic foci in the stapes. An electron microscopic study.

A total of 12 undecalcified and decalcified otosclerotic stapes containing active spongiotic lesions were examined using an electron microscope. Evidence of osteolytic osteolysis was seen in all specimens, but osteoclasts were observed in only four. The advancing front in the spongiotic lesion was 'moth-eaten' due to the demineralization of canaliculi and lacunae. The demineralizing process appeared to be initiated by degranulation of lysosomes by the degenerating osteocytes. As bone resorption continued, poorly mineralized new bone was laid down by osteoblasts which showed mitochondrial swelling. The possible implication of this mitochondrial swelling is discussed in relation to the pathology of the otosclerosis.

Ear Ossicles↗
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Fine morphology of the advancing front of cholesteatome--experimental and human.

The fine morphology of the advancing front of the cholesteatoma and the mucocutaneous juction of implanted skin in the feline bulla have been investigated. Inflammatory cell infiltration was frequently observed at the advancing front and the mucocutaneous junction. It is suggested that this frequent inflammation at this junction is due to the lack of a tight seal. In the advancing front, epidermal migrating cells appear to be lower spinous cells (or "suprabasalar" cells) rather than basal cells. It appears that the slender cell processes of the migrating cells make the initial attachment to the fibrin and/or basement membrane left behind by the degenerated epithelial cells as a result of inflammation and migrate along these structures, using them as a guide. Implanted skin in the cat's bulla failed to develop a pearl formation but frequently developed an epiboly, in which case the epidermis receded and was partly replaced by mucous membrane, and its stroma was heavily invaded by mucous epithelium, resembling tubular glands.

Animals↗
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Trauma of the ear from infrasound.

Twenty-eight chinchillas received continuous or intermittent infrasound (1, 10, 20 Hz) at 150, 160, or 170 dB SPL; there were 7 controls. Serial sections of the temporal bones were examined using light microscopy. Pathologies noted were tympanic membrane perforation, stapes subluxation, bleeding from the middle ear mucosa and tensor tympani, strial pathology, Reissner's membrane rupture, endolymphatic hydrops, saccular wall rupture, hair cell damage, and blood in the cochlear scalae. Continuous infrasound was more damaging than intermittent. Only continuous infrasound produced saccular pathology and perforations of the tympanic membrane. Of the other pathologies observed, continuous infrasound exposures produced 67% of the hair cell damage, 73% of the bleeding in the cochlear scalae, 83% of the strial pathology, and 78% of the cases of cochlear hydrops. 170-dB infrasound exposures produced the highest percentage of ears with pathologies of the three exposure intensities. As frequency increased the percentage of ears with pathologies decreased.

Animals↗
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Ultrastructural morphology of enzyme-dissociated cochlear sensory cells.

Enzyme-dissociated chinchilla cochlear sensory cells maintained excellent cellular integrity for two hours or more when kept in the tissue culture medium. The healthy appearing sensory cells maintained their refractile characteristics. Early signs of cell stress were shown by the aggregation of nuclear chromatin, clustering of cytoplasmic contents in the central portion of the supranuclear region of the outer hair cells, and Brownian motion of the mitochondria. The ultrastructural morphology of the enzyme-dissociated outer hair cells was generally well maintained, but with such subtle changes as increased vesicle formation, condensation of mitochondrial matrix, nuclear chromatin aggregation, and vacuole formation. Some of the vesicles present in the infranuclear region are interpreted to be neural synaptic vesicles that have accumulated in the cell, or they may be dilated microsomes or vesicles formed from the degenerating cytoplasmic membrane system (ER system) as a sign of cell stress or degeneration.

Animals↗