Middle Ear Secretions Research Articles

Surface Tension of Secretions from Eustachian Tube and Middle Ear

The surface tension of secretions from the pharyngeal orifice of the eustachian tube in eight rabbits was analyzed with a modified maximum-bubble pressure method. Measurements were made before, during, and after intravenous injections of isoprenaline (10 micrograms/kg). Surface tension was found to be 57.6 +/- 0.9 (mean +/- SEM) mN/m before injections, and was not significantly changed by isoprenaline. The surface tension in middle-ear secretions from children with secretory otitis media was also determined, the serous type of secretion measuring 62.0 +/- 1.4 mN/m (n = 8), and the mucoid type 70.7 +/- 2.6 mN/m (n = 9). In another ten humans, measurements of tears were performed, and the surface tension was found to be 59.9 +/- 2.2 mN/m. This bubble technique promises to be useful for the evaluation of surface tension when the available sample volume is very small.

Cytological and bacteriological aspects of secretory otitis media

Bacteriological and cytological examinations were performed on 105 middle ear secretions from 66 children with middle ear effusion (MEE) of more than 3 months' duration. The secretions were searched for granulocytes and the activity of these cells was judged by their capacity for random locomotion and their ability to reduce nitroblue tetrazolium. The functional characteristics of the granulocytes were compared with the bacteriological findings on cultures from MEE. Bacteria commonly regarded as pathogens in middle ear infections (Hemophilus influenzae, Branhamella catarrhalis or Streptococcus pneumoniae) were found in 25% of the secretions. Granulocytes with activity or lacking activity, virtually dead, were found in all secretions where these bacteria were isolated. In secretions where bacteria commonly regarded as commensals, mainly staphylococci, were isolated, about two thirds of the secretions showed phagocytes with or without activity. No relation between bacterial growth and the functional state of the granulocytes was observed. In contrast, no phagocytes were found in over 60% of MEE lacking bacterial growth. These findings suggest a role for bacteria in the development and maintenance of secretory otitis media.

Serum antibodies against respiratory tract viruses: a prospective three-year follow-up from birth.

Acute otitis media (AOM) has been epidemiologically related to viral respiratory tract infections, and viral antigens have also been detected in middle ear secretion in some AOM episodes. Successive serum samples from children followed prospectively for three years from birth were analysed for IgG antibodies against respiratory syncytial virus (RSV), adenoviruses and influenza A virus. Values from serum antibody activity gradually decreased during the first six months of life, followed by a gradual increase. Various relationships were found to obtain between age and the increases of antibody activity against the different viruses. Thus, three quarters of those tested had manifested increased antibody activity against RSV by 18 months of age, and against adenoviruses by 30 months of age. No increase of antibody activity against influenza A was noted before 12 months of age, and then only seen in two thirds of those tested during the entire three-year observation period. With regard to age, however, the proportion of children with increased antibody activity to RSV, adenoviruses or influenza A virus did not differ between otitis-prone and non-otitis-prone children. Thus, as compared to non-otitis-prone children, development of the ability to produce antibodies against these viruses was not found to be delayed in otitis-prone children.

Drugs affecting clearance of middle ear secretions: a perspective for the management of otitis media with effusion.

Otitis media with effusion (OME) is characterized by the production and accumulation in the middle ear of mucus secretions, whose physicochemical properties are an important feature in the etiology and treatment of the disease. Many types of pharmaceutical agents, including anti-inflammatory agents, antihistamines, antibiotics, and mucolytics, have been used in attempts to improve the clinical status of patients with OME. This study critically reviews the literature from the point of view of possible changes induced by these agents in the physicochemical properties of the secretions and hence their clearance from the middle ear. In vitro studies on mucociliary clearance of respiratory (tracheobronchial) secretions and middle ear effusions are cited as the basis for analyzing the important parameters expected to govern middle ear clearance and to determine the rationale for use (or nonuse) of various classes of drugs. It is expected that this analysis will prove useful in the design of properly controlled trials of such agents.

Penetration of doxycycline in respiratory mucosa.

In order to study the penetration of doxycycline (Idocyklin) in respiratory mucosa 100 mg tablets were given in standard dosage to 58 patients with longstanding secretory otitis media, the "secretion-in-cavity" model, and to 37 patients with nasal polyposis, the tissue model. Myringotomy with aspiration of the middle ear secretion or polypectomy was performed at different intervals during the course of medication. Blood samples were drawn simultaneously. The concentration in secretion, tissue and serum was assessed by means of a microbiological agar well method. The mean concentration of doxycycline in respiratory mucosa and secretion was found to exceed the MICs of the common respiratory pathogens as soon as 3 hours after the first dose, and remained on a therapeutical level until 24 hours after the last dose. The results are in full agreement with those obtained from penetration studies in other parts of the respiratory tract, thereby lending support to the validity of the models used.

Failure to Detect Viral Antigens in the Middle Ear Secretions of Patients with Secretory Otitis Media

A solid-phase enzyme-immunoassay technique was used for the detection of respiratory virus antigens in middle ear and nasopharyngeal secretions of 96 children with secretory otitis media (SOM) in order to test the hypothesis of chronic viral infection as the cause of the SOM. In spite of the high sensitivity of the assays used (1 to 10 ng/ml of purified viral antigen), respiratory virus antigens were not detectable in any of the middle ear or nasopharyngeal secretions studied. The results do not offer evidence supporting the role of chronic viral infection as an etiopathogenic factor of SOM.

Tympanosclerosis

Tympanosclerosis is a disease which affects the tympanic membrane (TM) and middle ear. The locus for the essential pathology is in the connective tissue component of the drum which is the lamina propria. In the middle ear, the pathology is in the basement membrane. In the early stages there is a minimal involvement of the mesenchymal component, usually seen as a small white macula, or scar, in the drum. In advanced disease, the hyalinization of the mesenchymal component together with the attraction of the calcium ion leads to a thick, dense, calcified scar. The theory of pathogenesis for this disease entity is that the connective tissue component of these structures is stimulated by infection, inflammation, or trauma involving some degree of local immunological hypersensitivity. With severe middle ear infection, the mucosa of the inner surface of the drum becomes permeable, and the ground substance of the lamina propria becomes edematous taking up water together with components of complement from the middle ear disease. The abnormal middle ear secretions contain the immunoglobulin components capable of participating in the process. If there is any damage to the connective tissue, the adsorption and repair permits the body to react immunologically against the destroyed tissue, thereby sensitizing this area. Experiments were performed with the guinea pig in which the tympanic membrane was removed and the lamina propria isolated and prepared as an immunological antigen. When this material was injected into the rabbits, a high, satisfactory antiguinea pig tympanic membrane antibody was formed (anti-GPTM). It was then possible to remove this anti-GPTM antibody from the serum. The tissue specificity was determined by immunofluorescent staining which showed it to be adsorbed onto the TM, middle ear mucosa, as well as the basement membrane of the respiratory tract. The guinea pigs which were passively sensitized with anti-GPTM antiserum demonstrated the binding of the antibodies on the tympanic membrane when subject to trauma, infection, or cautery. The manifestation was in the anatomical area related to the injury. Complement fixation was, likewise, demonstrated. Controlled animals which were not traumatized, or were not passively sensitized, included those which were injected with IgG from rabbits not sensitized against GPTM. They showed no fixation of antibody or complement in the TM. Following injury the antibody and complement bound to the TM provide the necessary elements for the subsequent immunopathologic disease entity known at tympanosclerosis.

Local IgA-class antibodies against respiratory viruses in middle ear and nasopharyngeal secretions of children with secretory otitis media.

The presence of antibodies against some important respiratory viruses in the middle ear and nasopharyngeal secretions of 52 children with secretory otitis media (SOM) was investigated in order to find out about the role of these viruses in the development of SOM. The method employed was a sensitive radioimmunoassay test. Antibodies to adeno, syncytial, and parainfluenza 3 viruses were detected in about 50%, 50% and 20% of the patients, respectively. In eight patients the middle ear secretion/nasopharyngeal secretion titer ratio of antibodies to one virus was selectively increased in comparison with the other viruses tested, indicating an active local production of specific antibodies in the middle ear. Further studies are required to determine the cause of such an active antibody synthesis and its possible role in the etiopathogenesis of SOM.

Penetration of Erythromycin Through Respiratory Mucosa: A Study Using Secretory Otitis Media as a Model

This study is based upon the concept that the respiratory mucosa reacts in a uniform manner to an inflammatory stimulus. Secretory Otitis Media (SOM) may be used as a model to disclose some aspects of antibiotic penetration. Erythromycin was given for different periods of time to 108 cases of SOM where myringotomy was indicated. The middle ear effusion was aspirated and blood samples were obtained simultaneously. The concentration of erythromycin was determined by microbiological procedures. Erythromycin penetrated into the middle ear effusion. After the fourth dose the concentration was at the same level as the plasma peak level. The elimination of the drug from the middle ear secretion was considerably prolonged compared with the rapid elimination from plasma. This implies that erythromycin attains a steady state in the middle ear effusion with concentrations equal to the plasma peak level.

Penetration of Erythromycin into Middle Ear Secretions: A Preliminary Report

SummaryConcentrations of erythromycin in middle ear effusions and in plasma were measured at various periods of time in a total of 65 patients, with secretory otitis media requiring myringotomy, who had been treated with a standard dosage for up to 10 days. After an initial slow penetration into the effusion, the mean concentrations of erythromycin were equal in plasma and secretion at the steady state level, although higher concentrations in secretion than in plasma were measured in more than half the patients. Erythromycin remained at higher concentrations and for a longer time in middle ear secretions than in plasma when administration was stopped.

Experimentelle Untersuchungen zur anteiligen Hemmkapazit�t verschiedener Proteinasen-Inhibitoren bei der Cholesteatom- und Schleimhauteiterung

Among the three investigated proteinase inhibitors alpha-1-antitrypsin (“acute phase protein”) possesses the highest antiproteolytic capacity. Alpha-2-macroglobulin reaches as an average one fifth of the preoperative level of alpha-1-antitrypsin and postoperatively one quarter of this inhibitor level. The average concentrations of the low molecular acid stable proteinase inhibitor of the mucous membrane in the preoperative phase are about equivalent to the concentrations of alpha-2-macroglobulin. In the postoperative phase the concentrations of the low molecular acid stable inhibitor are a slightly lower than those of alpha-2-macroglobulin. The samples of the middle ear secretions from cases with chronic otitis media or with cholesteatoma do not differ essentially in their concentrations of the different proteinase inhibitors.

T Cells as Marked with Acid α-Naphthyl Acetate Esterase Staining in Secretory Otitis Media

Non-specific acid alpha-naphthyl acetate esterase (ANAE) activity of the lymphocytes was investigated in smears made of middle ear secretions and peripheral blood from 61 children with secretory otitis media. On the average, 20.1% (right ear) and 2.1% (left ear) of the lymphocytes in the ear samples showed distinctive ANAE-positive spots in their cytoplasms, by the method used. The mean percentage of ANAE-positive cells in the blood was 47.8 and it was significantly (P less than 0.001) higher than the respective percentages of the ear samples. In normal childrne, 54.9% of the lymphocytes, on the average, were ANAE-positive. This difference in blood between patients and control group was significant (P less than 0.001). Consequently, the present study suggests that the relationship of T- and non-T-lymphocytes, as a marked with ANAE, are disturbed in children suffering from secretory otitis media. The importance of this finding and the validity of the method are discussed.

Haemophilus influenzae in otitis media and sinusitis: Serotypes and susceptibility to ampicillin and amoxycillin in vitro

In order to obtain Haemophilus influenzae, other than Type b, with highly probable human pathogeniticy strains were collected that had been isolated in abundant numbers from middle ear or maxillary sinus secretions of 157 patients with otitis media or sinusitis. The distribution of serotypes was as follows: nontypable 33.8%, Type b 26.1% Type a 19.1%, Type c 7.6%, Type e 5.7%, Type f 5.1%, and Type d 2.5%. The type distribution did not depend on the source of the strains. All strains were susceptible to ampicillin and amoxycillin in vitro; the broth dilution minimum inhibitory concentrations (MIC) of both antibiotics varied only fourfold; typical MIC values were 0.125 microgram/ml and 0.25 microngram/ml, respectively. Susceptibility did not vary with the source or type of the strains nor with the presence or absence of concomitant penicillin therapy.

Azidocillin and Ampicillin Concentrations in Middle Ear Effusion

The penetration of azidocillin and ampicillin into the middle ear effusion after oral administration was studied and compared with blood levels of the drugs. In acute otitis media one hour after a single oral dose of azidocillin (15 mg/kg) 1.56 +/- 0.44 microgram/ml of the drug was found in the effusion fluid; after 2 hours the fluid contained 3.21 +/- 0.87 microgram/ml and after 12 hours,0.84 +/- 0.13 microgram/ml. The concentrations of ampicillin were 1.15 +/- 0.23 microgram/ml after one hour, 2.17 +/- 0.46 microgram/ml after 2 hours and 1.09 +/- 0.22 microgram/ml after 8 hours following a single oral dose of 10 mg/kg. Both drugs stay longer in the middle ear secretion than in the blood. This persistence supports the administration of azidocillin twice daily in acute otitis media. In contrast, the penetration of the drugs into the middle ear effusion fluid was poor in secretory otitis media, where the levels of the drugs were significantly lower.

Der Nachweis eines niedermolekularen Proteinasen-Inhibitors im Ohrsekret bei chronischer Mittelohreiterung

The proteolytic activity of different proteinases during chronic otitis media can be inhibited by alpha-2-macroglobulin and alpha-1-antitrypsin. A new low molecular, acid stable and polyvalent proteinase inhibitor could be investigated in the middle ear secretion. It is probable that this inhibitor is identical with the low molecular inhibitor of the bronchial mucus. We believe that this inhibitor in the middle ear secretion results from a limited proteolysis and splitting of inter-alpha-trypsin-inhibitor by a proteolytic enzyme, possibly by kallikrein.

Allergy and Secretory Otitis Media: Clinical and Immunologic Studies

The relationship of allergy to the etiology of secretory otitis media is very controversial. The authors' investigations re-examined the relationship between allergy and secretory otitis media utilizing (1) clinical studies, (2) immunologic analysis of middle ear secretions, and (3) immunohistologic examination of middle ear mucosa.

Experimentelle Untersuchungen zum Verhalten des Immunsystems bei chronischen Mittelohreiterungen

After the experimental demonstration of split-products of intact immun-globulins of the middle ear secretion the level of the intact immunglobulins IgG, IgA and IgM has been measured pre- and postoperatively. By these studies it could be demonstrated that particulary in cases of chronic otitis media associated with cholesteatoma the level of the intact immunglobulins is much more higher postoperatively than preoperatively. The liberation of serum proteinase inhibitors by injuring the bloodvessels during a tympanoplasty combined with appropriate antibiotic therapy causes a stabilisation of the inhibitory and immunological system. It is the purpose of further studies to inform about the capability of the split-products of the immunglobulins to attach and to absorb antigens and toxins during a chronic inflammation in the middle ear.

Penicillin concentration in middle ear secretion in otitis.

The author has examined the penicillin concentration in otitis and the relationship between penicillin concentration in serum and ear secretion. The series consists of 273 middle ear samples; 206 of these were acute cases, 22 catarrhal, and 45 chronic. Serum samples totalled 142. The results are presented by tables which show the following: In acute otitis, penicillin can be noted in the middle ear secretion as early as half an hour after parenteral administration of the drug. The penicillin concentration is highest 1 hour after administration. Penicillin disappears more slowly from the ear than from serum. In catarrhal otitis, penicillin appears very little in the ear secretion despite high serum concentrations. In chronic otitis, somewhat higher penicillin concentrations were noted than in the catarrhal inflammation. Compared with acute otitis, the concentrations were, however, low.

Proteins of middle ear secretion in serous ottitis. An electrophoretic and immunoelectrophoretic study.

The protein fractions of the middle ear secretions of 22 patients with true serous otitis were studied electrophoretically and immunoelectrophoretically. The total protein of the secretion varied from 0.4 to 10.5g/100cc, mean 4.5g/100cc. The electrophoretic protein pattern of the secretion was mostly similar to that of the serum. The relative albumin content seemed to be a little lower and that of gamma globulin a little higher than in serum. A very small amount or no γM immunoglobulin was present in the secretion, while γA was clearly demonstrable in little more than half of the cases.

EXPERIMENTAL STUDIES ON ALLERGIC OTITIS MEDIA

Experimental acute otitis media was produced by injecting various agents into the middle ear cavity of the guinea-pig and the animal was sacrificed for histological studies after 7 days of careful observation. The results are summarized as follows: 1) The introduction of bacteria suspension, egg albumin or milk into the healthy middle ear cavity produced the proliferation of the connective tissue and the infiltation of neutrophilic leucocytes in the mucosa, The secretion in the middle ear mostly consisted of the neutrophilic leucocytes. The introduction of egg albumin and milk produced a milder inflammation as compared with that of bacteria. No eosinophilic leucocytes were found in the lesion of these series. 2) In the guinea-pigs sensitized with egg albumin or milk, the introduction of the antigen agents into the middle ear cavity led to the allergic changes characterized by the edema, hemornhage, vascular dilatation, production of fibrin and the infiltration of eosinophilic leuco-cytes in the tympanic membrane or mucosa of fhe tympanic cavity. The secretion was also characterized by fibrin clots, blood, and eosinophilic cells. 3) When the egg albumin was employed as the antigen, the pathologic process was chara-cterized by high degree of edema, while with milk it is characterized by hemorrhage and fibrinous exudation. It is evident that different antigen gives rise to different histopathologic manifestations. 4) The injection of bacteria suspension into the tympanic cavity of the sensitized guinea-pig resulted in the edema, vascular dilatation, eosinophilic infiltration and hemorrhage, which are similar to the allergic response of the tympanic membrane or the mucosa of the cavity. However, these changes are much milder as compared with those produced by true antigen-antibody reaction. The edema, in some instances, was absent. Neutrophilic leucocytes are the chief constituent of the middle ear secretion, but in many instances, fibrin clots and eosinophilic cells were demonstrated. It is clear that the sensitized mucous membrane differs entirely in the reaction to bacteria from the intact membrane. 5) In non-allergic reaction, eosinophilic cells are scarcely detected in the tissue or secretion, but in allergic response, eosinophilic leucocytes are demonstrable in all instances. It is, therfore, considered that the presence of eosinophilic cells in case of acute otitis media is characteristic to the allergic nature of the inflammation.