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Biomedical subjects

W J Doyle

Publications and source records attributed to W J Doyle.

171 records · Page 10Linked to original sources
PubMedDate not supplied

Longitudinal study of the efficacy of ampicillin in the treatment of pneumococcal otitis media in a chinchilla animal model.

A chinchilla animal model was used to determine the effects of early antibiotic treatment with ampicillin or the local and systemic protective mechanisms during pneumococcal acute otitis media with effusion (AOME). The right bullae of 74 chinchillas were inoculated with 170 colony-forming units (CFU) of Streptococcus pneumoniae type 7F, and animals were randomly assigned to 1 of 2 groups: early (24 hours postinoculation) and late (12 days postinoculation) initiation of ampicillin treatment. During the first challenge, 52 chinchillas died within a 1-month period, apparently from suppurative complications of AOME. Following the resolution of AOME in their right ears, all surviving animals were challenged for the second time by bilateral bullar inoculations using 130 CFU of the same organism. All 10 animals in the early ampicillin treatment group developed severe bilateral AOME, whereas only 3 of the 12 animals in the late ampicillin treatment group developed a recurrence of AOME in the right ear. Significantly, 8 of the 12 animals in this group developed severe left AOME. These findings suggest the presence of a local middle ear defense system and support the results of previous similar studies in which S pneumoniae types 3 and 6A were used. The results of the present study also suggest that in the chinchilla the early administration of a systemic antibiotic (ampicillin) interferes with this defense mechanism.

Ampicillin↗
PubMedDate not supplied

Neuraminidase activity in middle ear effusions.

Analyses of Streptococcus pneumoniae culture filtrates and middle ear effusions (MEE) containing S pneumoniae for various hydrolytic enzymes have demonstrated substantial levels of neuraminidase activity when measured employing a sensitive fluorometric assay. S pneumoniae neuraminidase exhibits optimum activity near neutral pH (6.0 to 6.5), and catalyzes the cleavage of sialic acid residues from glycoproteins, gangliosides and mucopolysaccharides. S pneumoniae begins secreting large amounts of neutral neuraminidase (mean [means] = 43.3 units/mL culture filtrate) when cells enter the stationary phase. Nearly all (96%) human chronic MEEs yielding positive cultures for S pneumoniae contain neuraminidase activity (means = 0.200 units/mg protein), while only 21.1% to 45.5% of all other effusions contain the enzyme. Middle ear effusions obtained from S pneumoniae infected-chinchillas contained large amounts of neuraminidase activity (approximately 200 units/mL), which decayed exponentially in vivo with an apparent half-life of 8 1/2 days. Three neuraminidase isoenzymes (designated I-III) were identified in S pneumoniae culture filtrates, as well as in MEEs from chinchillas infected with the organism, using a combination of ion-exchange and gel filtration chromatography. With 4-methylumbelliferyl-N-acetylneuraminic acid serving as substrate, preparation I from both culture filtrates and MEEs was characterized by a high Michaelis constant (Km), while forms II and III had low Km values. Preferred substrates were orosomucoid and neuramin-lactose; gangliosides, thyroglobulin, and bovine submaxillary mucin were poorer substrates.

Animals↗
PubMedDate not supplied

Histopathology of otitis media in infants with cleft and high-arched palates.

The middle ear and the bony and cartilaginous portions of the eustachian tube (ET) were studied histopathologically in 20 temporal bones from 19 infants, aged 45 minutes to 12 months. Otitis media (OM) was observed in 17 of 20 bones, and 16 bones with OM had an effusion. Otitis media was more severe in the ears of cleft palate infants compared to those with high-arched palates. Inflammation was present in the bony portion of the ET in 15 of 17 temporal bones with OM, but appeared to be less marked than that present in the middle ear. In addition, inflammation of the cartilaginous portion of the ET appeared to be less severe than in its bony portion. Inflammation of the middle ear and the ET appeared to be more pronounced in older infants, particularly in those with cleft palates.

Cleft Palate↗
PubMedDate not supplied

A method for the histopathological analysis of the temporal bone and the eustachian tube and its accessory structures.

A very important contribution to the study of otitis media, one of the diseases most often seen in pediatric patients, is the collection, processing, and study of the specimens of the temporal bone and the entire eustachian tube. During the last few years, we have collected, processed, and studied 100 such specimens, and through these experiences our technique has become refined. We now have some important suggestions for otologists interested in the histological study of otitis media as well as in the pathology of the eustachian tube and its relation to middle ear abnormalities. This report details the most successful method for the study of eustachian tube abnormalities and their relationship to middle ear effusion.

Dissection↗
PubMedDate not supplied

Auditory brain stem responses in rhesus monkey with otitis media with effusion.

Auditory brain stem response (ABR) tests were conducted on 17 anesthetized juvenile rhesus monkeys. Recordings were obtained for 13 control ears without otitis media with effusion (OME) and seven experimental ears with OME. The results demonstrated an increase in response latencies for the experimental ears with OME at each of four stimulus presentation levels (80, 60, 40, and 20 dB hearing level). Interwave latencies were the same for both groups of ears. The results suggest an average 25-dB peripheral loss of predominantly middle ear origin associated with OME. The ABR appeared to be a viable technique for documenting auditory impairment associated with OME in this nonhuman primate model.

Acoustic Stimulation↗
PubMedDate not supplied

An animal model of acute otitis media consequent to beta-lactamase-producing nontypable Haemophilus influenzae.

A chinchilla model of acute otitis media with effusion consequent to beta-lactamase-producing nontypable Haemophilus influenzae was developed using the method of direct inoculation of 145 colony-forming units (CFU) or 252 CFU of beta-lactamase-producing nontypable H influenzae into the right superior bullae of 40 chinchillas. The course of the disease was documented longitudinally by otomicroscopy, tympanometry, and periodic culturing of the middle ears. Onset of the disease occurred in 100% of the animals between two and six days postinoculation and resolution was complete in all ears by day 36. Results of rechallenge with the same organism support the combined effect of a local and weaker systemic middle ear protective mechanism rendering resistance to reinfection with a homologous organism in the chinchilla.

Acute Disease↗
PubMedDate not supplied

Physiological modulation of eustachian tube function.

The effect of changing body position on the Eustachian tube opening time (TOT) and nasal conductance (NC) was investigated in 5 subjects. Eustachian tube function was evaluated using a sonotubometric technique and NC was determined by anterior or posterior rhinomanometry. The results showed that both the TOT and NC were decreased by changing the body position from erect to recumbent. On a different day, Eustachian tube function and rhinomanometry tests were repeated every 30 min over a 5-7 h period. The results documented a nasal cycle in all subjects. Moreover, TOT tracked the ipsilateral NC in 3 subjects and the contralateral NC in 2 subjects. Since TOT measures mucosal venous congestion, these findings suggest that the tubal mucosa also experiences autonomically modulated cyclic fluctuations.

Adult↗
PubMedDate not supplied

Experimental paralysis of tensor veli palatini muscle.

In an effort to study the effects of experimental paralysis of tensor veli palatini (TVP) muscle on Eustachian tube (ET) function and middle-ear (ME) status, botulinum toxin A (Oculinum) was injected into the TVP muscles of 8 Rhesus monkeys. Tubal function was tested longitudinally in 2 animals with tympanostomy tubes using the forced-response test, while in the remaining 6 animals; ME condition was documented daily using tympanometry. The postinjection tubal function was characterized by abolished active muscular function and decreased closing pressure. Activity associated with tubal dilations gradually reappeared by the fifth week. The lack of lumen constrictions following injection suggested that the TVP muscle is the cause of constriction as well as normal dilation. In 6 animals with intact tympanic membranes, 10 of the 12 ears developed flat tympanograms associated with otitis media with effusion (OME) within 8-30 days of injection and serous effusions were recovered by tympanocentesis in seven ears. These results show that a non-traumatic reversible functional obstruction of the ET was created by injecting botulinum toxin A into the TVP muscle. This functional obstruction was associated with the development of high negative ME pressure and serous effusion.

Acoustic Impedance Tests↗