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Biomedical subjects

C M Alper

Publications and source records attributed to C M Alper.

28 records · Page 2Linked to original sources
PubMed1998

Treatment of chronic suppurative otitis media with topical ciprofloxacin.

To date, only ofloxacin has been approved by the US Food and Drug Administration for treatment of ears with a nonintact tympanic membrane. The purpose of this study was to determine the safety and efficacy of topical ciprofloxacin hydrochloride in the treatment of experimental chronic suppurative otitis media caused by Pseudomonas aeruginosa infection in cynomolgus monkeys. Forty adult cynomolgus monkeys were divided into 4 equal groups, and their ears were challenged with P aeruginosa, drained for 3 weeks, then treated twice daily for 4 weeks with 1 of 4 randomly assigned agents: 1) ciprofloxacin, 2) saline, 3) Cortisporin, or 4) vehicle. The animals were followed up with auditory brain stem response testing, culture, otoscopy, and histopathology. Both ciprofloxacin and Cortisporin treatment resulted in a significantly more rapid rate of clearance of P aeruginosa as compared to treatment with saline (100% versus 20%). Eradication was not associated with resolution of otorrhea after a 4-week period of treatment. There were no significant changes in auditory brain stem response wave latencies for any of the treatment groups. Histopathologic data revealed that there was no statistically significant difference in the amount of outer hair cell loss for the ciprofloxacin group as compared to the control ear and other treatment groups. We conclude, therefore, that topical ciprofloxacin is not ototoxic and is effective in sterilizing the otorrhea, but does not promote resolution of the drainage, in this animal model.

Administration, Topical↗
PubMed1997

Magnetic resonance imaging of the development of otitis media with effusion caused by functional obstruction of the eustachian tube.

In this study, magnetic resonance imaging (MRI) was used to define in vivo the effect of experimental functional obstruction of the eustachian tube (ET) on vascular permeability and the development of middle ear (ME) effusion. After collection of baseline data for ME pressure and MRI, the right tensor veli palatini muscle of 10 cynomolgus monkeys was injected with botulinum toxin A to induce ET obstruction. The left tensor veli palatini muscle was injected with saline in 4 monkeys. Right and left ME pressures and compliances were measured twice daily over a follow-up period of 36 days, and MRI scanning sessions including administration of a contrast agent, gadopentetate dimeglumine, were repeated on days 3, 6, 11, 15, 21, 29, and 36 in 6 animals and on days 15, 21, 29, and 36 in 4 animals. Two right ears did not develop underpressures, 5 developed persistent underpressures, and 3 developed underpressures that resolved. No changes in MRI parameters were noted for the ears that did not develop underpressures, but a progressive brightening of the ME on T2-weighted images, indicative of the development of inflammation and effusion, was noted for the others. Also, an increasing rate of transfer of the contrast agent between the vascular and ME compartments, indicative of increasing vascular permeability, was observed to track the temporal changes in ME pressure. These results support a causal relationship between ET dysfunction, ME underpressures, increased vascular permeability, and otitis media with effusion

Acoustic Impedance Tests↗
PubMed1996

Prechallenge antibodies: moderators of infection rate, signs, and symptoms in adults experimentally challenged with rhinovirus type 39.

This study determined the influence of serum neutralizing antibody titers on infection rate, symptom manifestations, and provoked signs and pathophysiologies in adults experimentally exposed to rhinovirus type 39 (RV-39). Antibody status was determined for 151 healthy volunteers who were then cloistered in a hotel for 6 days. At the end of the first cloister day, the volunteers were challenged with RV-39 in a median tissue culture infective dose of 100. On each of the 6 days, a nasal examination was performed, symptoms were scored, and objective tests of nasal mucociliary function, nasal airway patency, secretion production, and middle ear pressures were completed. Both subjects and investigators were blinded to the prechallenge serum homotypic antibody titers of the subjects. Four subjects presented with a wild virus and were excluded from the analysis. Of the 147 included subjects, prechallenge serum antibody titers to RV-39 were low (under 2) in 56 subjects, intermediate (2 to 8) in 51 subjects, and high (above 16) in 40 subjects. The high-titer group was significantly different from the low-titer group with respect to viral shedding, symptom load, subjective extent of illness, and secretion production, as well as in the frequency of subjects with abnormal nasal mucociliary clearance and positive middle ear pressures. The study results document that for experimental RV-39 exposure, high levels of homotypic serum neutralizing antibody titers are associated with protection from infection and a lessened degree of disease expression, but not with a reduction of otologic complications.

Adolescent↗
PubMed1996

Efficacy of clarithromycin treatment of acute otitis media caused by infection with penicillin-susceptible, -intermediate, and -resistant Streptococcus pneumoniae in the chinchilla.

Because of the increasing frequencies of recovery of penicillin-resistant Streptococcus pneumoniae from the middle ears of children with acute otitis media, non-beta-lactam antibiotics are being explored as treatment alternatives to amoxicillin. In this study, the efficacy of a 10-day course of clarithromycin was evaluated with chinchillas. After the pharmacokinetic profiles for clarithromycin were established, 180 animals were assigned to one of three susceptibility groups (n = 60/group; penicillin-susceptible, -intermediate, and -resistant S. pneumoniae), and the right middle ear was infected with the appropriate strain of S. pneumoniae. Equal numbers of animals in each group were treated orally beginning on day 2 with a 10-day course of clarithromycin (15 mg/kg of body weight; given twice a day) or amoxicillin as a control (20 mg/kg twice a day). On days 4, 9, and 13, otomicroscopy and tympanometry were performed, and on day 13, the middle ears were cultured for bacteria. The results showed 100% eradication of the challenge organism in both treatment groups for the susceptible strains of S. pneumoniae. Cultures were negative in 87 and 74% (P > 0.05) of the animals challenged with the intermediate resistant strains and in 100 and 56% (P < 0.05) of the animals challenged with the resistant strains and treated with clarithromycin and amoxicillin, respectively. There were no differences between treatments in the diagnosis of effusion for any group. These results support the use of the chinchilla to evaluate drug efficacy in the treatment of acute otitis media and show clarithromycin to be effective in sterilizing the middle ears of animals challenged with penicillin-susceptible, -intermediate, and -resistant strains of S. pneumoniae.

Amoxicillin↗
PubMed1995

Gas exchange across the middle ear mucosa in monkeys. Estimation of exchange rate.

OBJECTIVE: To estimate the rate of exchange of selected gases across the middle ear (ME) mucosa and define the exchange limitations. DESIGN: At separate sessions, the ME was inflated via the eustachian tube with a bolus of pure nitrogen, carbon dioxide, oxygen, or nitrous oxide, and ME pressures were recorded by tympanometry at selected intervals for up to 4 hours. The slope of the function relating pressure change to pressure was calculated by least squares regression and used as an estimate of the rate constant for exchange of that gas (experiment 1). Because of the slow rate of nitrogen exchange, a second experiment was performed in which the tensor veli palatini muscle was unilaterally paralyzed. The ME was inflated with nitrogen, and the slope of the rate-pressure function for measurements at 24-hour intervals was used to estimate the rate constant. SUBJECTS: Ten juvenile cynomolgus monkeys, six for experiment 1 and four for experiment 2. RESULTS: The relative, average rate constants for carbon dioxide, nitrous oxide, oxygen, and nitrogen were 1, 10.7, 18.6, and greater than 700, respectively. Comparisons of these rates with those predicted by theory show that oxygen and carbon dioxide exchange is diffusion limited, and nitrous oxide and nitrogen is perfusion limited. CONCLUSIONS: The perfusion limitation for nitrogen suggests that its exchange rate is notably increased by inflammation from increased mucosal blood flow. Targeting inflammation for therapy of persistent ME effusions may decrease the rate of nitrogen exchange and reestablish normal ME pressure regulation.

Acoustic Impedance Tests↗
PubMed1995

Influenza A virus--induced acute otitis media.

To better understand the significance of viral upper respiratory tract infections in the pathogenesis of acute otitis media (OM), 27 adults underwent intranasal inoculation with influenza A virus. Monitoring consisted of antibody titer determination, tympanometry, and otoscopy. Microbiologic analysis consisted of cultures and polymerase chain reaction (PCR)-based detection for influenza A virus, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. All subjects became infected with the challenge virus. By day 4, 16 (59%) developed middle ear pressures of -100 mm H2O or below and 4 (25%) of them developed OM. One subject (4%) developed purulent OM requiring myringotomy for pain relief. Middle ear effusion cultures were negative. PCR analysis of that subject's middle ear effusion and nasal washes were positive for influenza A virus and S. pneumoniae. These findings support a causal role for viral upper respiratory tract infections in the pathogenesis of OM, possibly mediated by middle ear underpressures and viral and bacterial middle ear infection.

Acute Disease↗
PubMed1995

In vivo observation with magnetic resonance imaging of middle ear effusion in response to experimental underpressures.

In this study, magnetic resonance imaging (MRI) was used to define, in vivo, the effect of acute middle ear (ME) underpressures on vascular permeability and the development of effusion. The MEs of four cynomolgus monkeys were unilaterally inflated with oxygen and carbon dioxide on different occasions and followed for a period of approximately 4 hours by tympanometry and MRI scanning. Carbon dioxide inflations caused the rapid development of ME underpressures of less than -600 mm H2O by 10 minutes. The MRI scans showed a progressive brightening of the ME and all associated air cells, indicative of the accumulation of effusion in three of the four experiments. An MRI contrast agent was administered to the vascular compartment during the course of the experiment and was rapidly transferred to the ME space, indicating vascular permeability to the agent. The contralateral, control side did not develop significant underpressures, effusion, or increased vascular permeability. Inflation with oxygen caused lesser underpressures and no accompanying changes in the MRI scans. These data support the hydrops ex vacuo theory and confirm the usefulness of MRI for in vivo documentation of the development of ME effusions and changes in vascular permeability of the mucosa in the experimental setting.

Animals↗
PubMed1995

Effects of dopamine, dobutamine and phentolamine on middle ear pressure and blood flow in cynomolgus monkeys.

To test the hypothesis that changes in mucosal perfusion could influence gas exchange and thus, middle ear pressure, the effects of systemically administered drugs showing alpha adrenergic effects on mucosal perfusion and middle ear pressure were evaluated in 4 cynomolgus monkeys. Two drugs with well characterized sympathomimetic effects, dopamine and dobutamine, were studied, and dopamine was combined with an antagonist, phentolamine. For each experiment, the monkeys were anesthetized with pentobarbital and followed for a 90 min baseline period. Then, the drug was administered for 60 min with follow-up extending through that period and for an additional 60 min. Data consisted of repeated measurements of rectal temperature, heart rate, blood pressure, left middle ear pressure and right mucosal blood velocity, volume and flow. The results documented an increase in middle ear pressure after intravenous infusion of either dopamine or dobutamine and an attenuation of the response by concurrent administration of phentolamine. Laser Doppler measurements documented a variable, non-directional change in blood volume, velocity and flow. The changes in the middle ear pressure observed following systemic administration of autonomic drugs are consistent with the rapid establishment of a transmucosal pressure gradient secondary to changes in the supply and/or metabolism of gases.

Animals↗
PubMed1995

Effects of intranasal challenge with histamine, bradykinin and prostaglandin on middle ear pressure and blood flow in cynomolgus monkeys.

Previous studies documented a significant increase in middle ear pressure following intranasal challenges with ascaris antigen or histamine in sensitized cynomolgus monkeys. To confirm that effects and investigate the mechanism, 4 monkeys were intranasally challenged at separate sessions with histamine (10 mg), bradykinin (1, 10 mg) and prostaglandin D2 (PgD2, 0.5, 1.0 mg) and followed for 90 min. Before and after challenge, middle ear pressure, mucosal blood flow, heart rate, blood pressure, body temperature and the partial pressures of O2 and CO2 in the venous blood were measured. The results showed that while bradykinin challenge had no effect on these measures, PgD2 provoked increased middle ear pressure, and histamine resulted in a biphasic pattern of increasing pressures followed by decreasing pressures. The pattern of change in middle ear pressure after histamine challenge was explicable by a mechanism involving transmucosal gas exchange, while that for PgD2 was related to increased mucosal inflammation. These results document the development of positive middle ear pressures during provoked nasal inflammation and may have relevance to similar observations in the clinical setting.

Administration, Intranasal↗