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T F DeMaria

Publications and source records attributed to T F DeMaria.

At least 55 records · Page 3Linked to original sources

Current concepts of pathogenesis of otitis media: a review.

A number of important factors singly or in combination contribute to the pathogenesis of otitis media. These are poor tubal function, upper respiratory viral infection, bacterial adherence and nasopharyngeal flora, and immune status of the host. One of the important functions of the tubotympanum is to protect the middle ear from invading microbes. The host has available a number of strategies for this function including mucociliary protection, antibacterial secretory products, and specific immunodefenses. The microbes also possess the capability of escaping host defenses by enhancing their ability to adhere to mucosal surfaces, impairing mucociliary function and evading phagocytosis. Once microbes gain entrance to the middle ear, the microbes must overcome phagocytosis and immunodefense of the host, leading to otitis media. Recent data further indicate that specific qualitative and quantitative deficiencies in the immune system of children may predispose certain children to develop otitis media. These deficiencies appear to be in part due to a lack of maturity of the child's developing immune system as well as functional defects that are attributable to genetic or other unknown factors.

Bacterial Adhesion↗

Phagocytosis and killing of bacteria by middle ear macrophages.

Because macrophage dysfunction has been suggested as one of the underlying pathogenic mechanisms for otitis media with effusion, we have examined macrophage-bacterial interactions using keyhole limpet hemocyanin-induced middle ear macrophages from chinchillas. Our data indicate that macrophages recruited to the middle ear were functional phagocytes capable of discriminate phagocytosis and intracellular killing of eight species of bacteria associated with otitis media, as determined by a fluorochrome microassay. Streptococcus pneumoniae types 14 and 19F, which are associated with the highest relapse frequency in cases of acute otitis media, were the most resistant to phagocytosis. The two organisms most often involved in chronic otitis media (Staphylococcus epidermidis and nontypable Haemophilus influenzae), however, were among the most readily phagocytized isolates. The relative importance of macrophage function in defense of the middle ear, therefore, may be dependent on the causative agent.

Animals↗

Effect of preopsonization on phagocytosis of Haemophilus influenzae.

Because bacteria are known to persist in middle ear effusions for extended periods of time despite the presence of increasing titers of specific antibody in both sera and middle ear fluids in humans, we examined the ability of postinfection serum to opsonize Haemophilus influenzae (nontypable and type b) for phagocytosis by middle ear macrophages in chinchillas. Our data indicated that preopsonization of both strains of H influenzae enhanced phagocytosis by macrophages recruited to the middle ear following intrabullar instillation of keyhole limpet hemocyanin. Both the total number of bacteria ingested and the percentage of macrophages phagocytizing were significantly greater in the presence of postinfection serum than preinfection serum for all animals tested.

Animals↗

Functional morphology of the tubotympanum related to otitis media: a review.

One of the important functions of the tubotympanum is to protect the middle ear from invading organisms. The host develops a number of strategies for this function (e.g., mucociliary protection, antibacterial secretory products, immunodefense, and phagocytosis). The bacteria also develop their strategy to evade the host protection by enhancing adherence to the mucosal surfaces, impairing mucociliary function, and evading phagocytosis.

Animals↗

Antibody response in experimental Haemophilus influenzae otitis media.

Because Haemophilus influenzae is one of the most common pathogens in otitis media with effusion, we have investigated the antibody response in the serum and middle ear effusion (MEE) in nontypable H influenzae-induced experimental acute otitis media in the chinchilla, using an enzyme-linked immunosorbent assay. During acute otitis media, a reasonable antibody titer was observed: local antibody titers in the MEEs were equal to or greater than those of the serum samples for four of five MEE samples obtained at one week after inoculation. By two weeks, titers in both serum and MEE samples were increased significantly. However, the bacteria persisted in the middle ear cavity, even in the presence of increasing antibody titers, for up to five weeks after infection. The reason for this persistence of the bacteria in the middle ear is unknown.

Animals↗

Rheumatoid factor in otitis media with effusion.

Because of the pathologic similarities between rheumatoid arthritis and otitis media with effusion (OME), rheumatoid factor (RF) was measured in 156 human middle ear effusion (MEE) and serum samples from patients with chronic OME. Using a quantitative latex agglutination test, we were able to demonstrate RF in the MEEs of 85% of patients with OME. Demonstrable RF titers were found in only 8% of the patients' serum samples. The titers of mucoid MEE samples were seven times higher than those observed in serous MEE samples. The presence of RF was not related to the age of the patient, the presence of viable bacteria in the MEEs, or history of OME.

Adolescent↗

Endotoxin in middle-ear effusions from patients with chronic otitis media with effusion.

Endotoxin concentrations were determined in middle-ear effusions (MEEs) from 89 children with chronic otitis media by using the Limulu's amoebocyte lysate assay. Mean concentrations of endotoxin in Haemophilus influenzae-positive and Streptococcus pneumoniae-positive MEEs were 157 and 21.8 ng/ml, respectively, and were significantly different (P less than 0.01). Endotoxin was also found in Gram stain-positive, culture-negative and Gram stain-negative, culture-negative MEEs, but the levels were not significantly different (P greater than 0.05). However, the endotoxin concentrations in both groups of culture-negative MEEs significantly lower than those found in MEEs that grew either H. influenzae or S. pneumoniae (P less than 0.05). These results show that endotoxin is present in a high percentage of human MEEs, including those that are culture negative, and may contribute to the pathogenesis of otitis media with effusion.

Adolescent↗

Biotypes of serologically nontypable Haemophilus influenzae isolated from the middle ears and nasopharynges of patients with otitis media with effusion.

A biotype analysis was performed on serologically nontypable Haemophilus influenzae isolates from the middle ear effusions and nasopharynges of 33 children with chronic otitis media with effusion (serous otitis media). Over 50% of the H. influenzae isolates from the middle ears belonged to biotype II. The incidence of beta-lactamase production was 17%. The results of this study indicate that future clinical or experimental investigations of chronic otitis media with effusion induced by serologically nontypable H. influenzae should focus on this clinically important biotype.

Child↗

Panel discussion: pathogenesis of otitis media. Bacteriology and immunology.

Three features of otitis media with effusion (OME) are important in understanding its pathogenesis: 1. it is most common among children, when the eustachian tube is poorly developed; 2. it is most common during the winter months, when the common cold is prevalent; and 3. bacteria are found in a large number of middle ear effusions from OME patients. Although middle ear effusions are conventionally thought to be sterile, numerous recent investigations favor a bacterial pathogenesis of OME. Four possibilities can be considered: 1. bacteria are modified by antibiotics or antibodies, causing a lingering inflammation; 2. early antibiotic treatment may interfere with the development of local immunity; 3. bacterial antigen trapped in the middle ear causes immune injury leading to OME; and 4. bacterial endotoxin and inflammatory mediators cause middle ear effusions.

Animals↗

Pulmonary infection of mice with Staphylococcus aureus.

The survival of Staphylococcus aureus in the lungs of mice was studied under various conditions. Doses of 10(7) to 10(9) washed staphylococci were quantitatively introduced into the lungs after intratracheal inoculation in mice under either ether or sodium pentobarbital anesthesia. Mice were sacrificed at intervals, the lungs were excised and homogenized, and the cocci were enumerated by plate count. The 50% lethal dose was 6 x 10(8) cocci per mouse, and mice died within 24 h but without proliferation of the inoculum. Mice given 10(8) cocci intratracheally under pentobarbital anesthesia regularly survived and eliminated the organisms over a 48-h period. The use of ether anesthesia resulted in persistence of the inoculum for up to 48 h, but the organisms were then eliminated. Inability to proliferate did not appear to result from a lack of iron because pretreatment of the mice with ferric ammonium citrate or Imferon did not alter inoculum survival. Staphylococci inoculated intratracheally in mice infected with influenza virus 3 to 21 days previously showed no enhanced persistence or multiplication. Cocci preclumped with fibrinogen, inocula mixed with 10 times the number of Formalin-killed staphylococci, or inocula of the encapsulated Smith strain did not survive any better than conventional inocula, suggesting that phagocytosis might not be the sole mechanism for elimination. However, a sedimentable fraction from normal or infected lung homogenates proved either inhibitory or cidal for staphylococci in vitro.

Animals↗

Quantitative cytologic and histologic changes in the middle ear after the injection of nontypable Hemophilus influenzae endotoxin.

This study was undertaken to investigate and quantify the morphologic changes in the middle ear mucosa and connective tissue after the inoculation of graded doses (0.001 to 100 micrograms) of endotoxin prepared from Hemophilus influenzae. Histopathologic changes were observed in the middle ear mucosa in all animals. Marked bleeding and new bone formation in the submucosa were prominent at days 4 through 14. These findings indicate that the endotoxin from nontypable H influenzae is capable of inducing inflammation or pathologic changes in the middle ear mucosa and may play an important role in the pathogenesis of otitis media with effusion and its sequelae.

Animals↗

Experimental otitis media with effusion induced by nonviable Hemophilus influenzae: cytologic and histologic study.

In an earlier study the authors demonstrated that formalin-killed Hemophilus influenzae induces serous-type middle ear effusion in chinchillas and provides an excellent model for the study of human otitis media with effusion. The present study was initiated to evaluate the morphologic and histologic changes that occur in the middle ear after injection of this organism. All of the experimental animals injected with formalin-killed H. influenzae in the present study had straw-colored serous-type effusions within four days after injection. The submucosal thickness, mononuclear cell density, and capillary permeability all increased dramatically in the experimental animals. Marked bleeding, tissue edema, and cellular infiltration in the submucosa were prominent findings after injection of the inactivated bacteria. Half of the experimental animals had histologic evidence of marked proliferation of epithelial cells resembling adhesive otitis media. These findings suggest that nonviable H. influenzae are capable of inducing severe inflammatory changes in the middle ear and may play an important role in the pathogenesis of otitis media with effusion and its sequelae.

Animals↗

The effect of antecedent influenza A virus infection on the adherence of Hemophilus influenzae to chinchilla tracheal epithelium.

The adherence of Hemophilus influenzae (type b and nontypable) to ciliated chinchilla respiratory epithelium was investigated using a whole organ perfusion technique. Nontypable H influenzae (NTHi) were shown to be more adherent than type b to these organized and differentiated tracheal organ cultures. Bacteria were found adhering to ciliated cells. Antecedent influenza A virus infection had no effect on adherence of NTHi for at least 48 hours. However, 72 hours after exposure to the virus, infected tissues demonstrated significantly fewer adherent bacteria than did controls. To summarize, influenza A virus infection was not found to augment the initiation of NTHi adherence to ciliated respiratory epithelium in this model.

Animals↗

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↗

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↗

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↗