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Biomedical subjects

T R Pasic

Publications and source records attributed to T R Pasic.

12 recordsLinked to original sources

Report of successful prolonged antifungal therapy for refractory allergic fungal sinusitis.

Allergic fungal sinusitis (AFS) is an increasingly recognized cause of refractory chronic sinusitis in the young immunocompetent host, analogous to allergic bronchopulmonary aspergillosis (ABPA), a related process in the lower respiratory tract. Most patients experience remittent disease despite corticosteroid therapy and aggressive sinus surgery. Because controlled trials have shown adjunctive antifungal therapy to be of benefit in treating ABPA, long-term oral itraconazole was used in a young man with remittent AFS, which was able to break the cycle of relapsing disease.

Adolescent↗

Influence of computed tomography on pretherapeutic tumor staging in head and neck cancer patients.

Refinements in radiographic techniques have resulted in increased use of radiographic studies in the evaluation of patients with head and neck cancer over the past 20 years. To assess the impact of such studies, we compared tumor clinical stages based solely on physical-examination findings with those obtained with the addition of CT findings. This study was accomplished through case review of 81 head and neck cancer patients who underwent CT after preliminary TNM-stage assignment as determined on the basis of physical examination alone. In this cohort, 44 patients (54%) had a change in assigned clinical stage. We reviewed individual anatomic sites to determine where CT was found to be most useful in modifying tumor stage. Changes in tumor and nodal stage were found across all major sites of the head and neck. Tumors of the hypopharynx were the most likely to change stage (90%) on the basis of CT findings, whereas tumors of the glottic larynx were least likely to undergo a change in stage (16%). The therapeutic implications of these findings are discussed in the context of the published literature.

Head and Neck Neoplasms↗

Development of Cat-301 immunoreactivity in auditory brainstem nuclei of the gerbil.

The developing brainstem auditory system has been studied in detail by using anatomical and physiological techniques. However, it is not known whether immature auditory neurons exhibit different molecular characteristics than those of physiologically mature neurons. To address this issue, we examined the distribution of Cat-301 immunoreactivity in the developing auditory brainstem of gerbils. Cat-301 is a monoclonal antibody that recognizes a 680-kD chondroitin sulfate proteoglycan similar to aggrecan, a high-molecular-weight chondroitin sulfate proteoglycan found in cartilage. In the central nervous system, Cat-301 immunoreactivity is localized to the extrasynaptic surface of neurons. It has been hypothesized by Hockfield and co-workers (Hockfield et al. [1990a]Cold Spring Harbor Symp. Quart. Biol. 55:504-514) that the Cat-301 proteoglycan is a molecular marker indicating that a neuron has acquired mature neuronal properties. In the current study, Cat-301 staining is first seen at 7 days after birth in the anterior ventral cochlear nucleus (AVCN), the posterior VCN (PVCN), and the medial nucleus of the trapezoid body (MNTB) shortly before the onset of sound-evoked activity. By 21 days after birth, neurons in the AVCN, the PVCN, and the lateral and medial superior olive have attained adult-like distributions of Cat-301 staining concomitant with the physiological maturation of these neurons. Neurons in MNTB attain adult-like distributions of Cat-301 immunoreactivity at 1 year. The maturation of Cat-301 immunoreactivity parallels the physiological maturation of gerbil auditory neurons, and the Cat-301 proteoglycan may play a role in the formation and/or stabilization of auditory synapses.

Animals↗

alpha-difluoromethylornithine ototoxicity. Chemoprevention clinical trial results.

OBJECTIVES: To determine the effects of low-dose oral eflornithine hydrochloride (difluoromethylornithine [DFMO]) administration on hearing and to identify factors that influence those effects. DESIGN: Combined data from 2 studies: a prospective, randomized phase 1 clinical trial of eflornithine (n = 26 subjects) and a prospective, randomized, placebo-controlled phase 2 clinical trial of eflornithine (n = 40 subjects). SETTING: Ambulatory academic tertiary care referral center. PARTICIPANTS: Sixty-six volunteer subjects who had previously treated bladder, prostate, or colon cancer with no current evidence of neoplastic disease, or who were healthy individuals at increased risk for colon cancer, all without need of hearing amplification. INTERVENTIONS: Subjects were randomized to receive oral eflornithine at daily doses between 0.5 and 3 g per square meter of body surface area (g/m2) for 6 to 12 months (phase 1 study) or randomized to receive placebo or eflornithine, 0.5 g/m2 for 12 months (phase 2 study). OUTCOME MEASURES: Auditory thresholds were measured before, during, and after eflornithine administration. Auditory thresholds and threshold shifts were evaluated with regard to eflornithine dose, serologic variables, and demographic factors. RESULTS: Predictable shifts in auditory thresholds occurred following administration of eflornithine. As the daily dose of eflornithine increased, the magnitude and incidence of threshold shift increased, and the time until onset of threshold shift decreased. Threshold changes were greater in the lower frequencies than in the higher frequencies. Subjects' sex, age, and renal function had no effect on eflornithine-associated threshold shifts. Threshold shifts were reversible after eflornithine treatment was discontinued. CONCLUSIONS: Administration of eflornithine is associated with a predictable shift in auditory thresholds. The magnitude and incidence of threshold shift correlate with the daily eflornithine dose.

Anticarcinogenic Agents↗

Effect of altered neuronal activity on cell size in the medial nucleus of the trapezoid body and ventral cochlear nucleus of the gerbil.

Activity-dependent transneuronal regulation of neuronal soma size has been studied in the medial nucleus of the trapezoid body and ventral cochlear nucleus of adolescent gerbils. Cochlear ablation or tetrodotoxin has been used to eliminate afferent electrical activity in auditory nerve fibers permanently or for 24 or 48 hours. Previous studies have shown that the cross-sectional area of spherical cell somata in the ipsilateral anteroventral cochlear nucleus decreases within 24 hours of electrical activity blockade with tetrodotoxin, which is fully reversible when activity is restored. The present findings extend this work by directly comparing the results of unilateral blockade of auditory nerve action potentials or unilateral cochlear ablation on the size of spherical and globular cell bodies in the ventral cochlear nucleus with changes produced by the same manipulations in third-order cells, principal neurons in the medial nucleus of the trapezoid body. Soma size in both ventral cochlear nucleus cell types decreases reliably by 24 hours after cochlear removal or eighth nerve activity blockade by tetrodotoxin. Soma size of neurons in the contralateral medial nucleus of the trapezoid body decreases 48 hours, but not 24 hours, after either manipulation. When activity in auditory nerve fibers is allowed to resume for 7 days following a 48-hour activity blockade, soma size fully recovers in the medial nucleus of the trapezoid body as well as in ventral cochlear nucleus neurons. We also report that the cross-sectional area of neuronal soma in the medial nucleus of the trapezoid body is larger in lateral regions of medial nucleus of the trapezoid body (low-frequency representation) than in the medial regions of the nucleus (high-frequency representation). We conclude that cell body size changes in brainstem auditory neurons are reversible and that the signals associated with the loss and subsequent recovery of soma size are activity related. However, the delayed effect of activity deprivation in the medial nucleus of the trapezoid body suggests that trophic substances released by afferent axons may contribute to the maintenance of anatomical characteristics.

Action Potentials↗

Hearing loss in Townes-Brocks syndrome.

Townes-Brocks syndrome is an autosomal dominant syndrome consisting of anomalies affecting the ear, hand, foot, anus, and kidney. Anomalies affecting the ear include lop ear, preauricular skin tags, ossicular abnormalities, and a mixed hearing loss. The hearing loss in Townes-Brocks syndrome is predominantly sensorineural, affects high-frequency thresholds more than low-frequency thresholds, and has a variable (usually small) conductive component. The sensorineural component of the hearing loss is slowly progressive. It is typically in the mild range (20 to 40 dB hearing level) during early childhood and progresses to the moderate hearing loss range (40 to 60 dB hearing level) by early adulthood. We present a description of the otologic manifestations and an analysis of audiologic findings in six members of a family with Townes-Brocks syndrome.

Abnormalities, Multiple↗

Physiologic chest sounds and helicopter engine noise.

To develop an amplification system for physiologic chest sounds during air medical transport in jet helicopters, we compared frequency spectra of physiologic chest sounds and Allison C-28 equipped jet helicopter noise. We found that the frequency spectrum of physiologic chest sounds is contained entirely within that of jet rotocraft noise. Attempts to amplify physiologic chest sounds or to filter jet rotorcraft noise will invariably fail to improve perception of chest sounds. Future research must focus on assessment of actual movement of the chest and of each hemithorax, as well as an carbon dioxide production, as indicators of adequate ventilation and proper endotracheal tube position.

Air Ambulances↗

Cochlear nucleus cell size is regulated by auditory nerve electrical activity.

Accumulating evidence suggests that sensorineural hearing loss in animals is rapidly followed by degenerative changes in central auditory neurons. For example, cochlear removal in birds and mammals results in a reduction in central auditory neuron cell size within 48 hours. A similar decrease in cell size after pharmacologic blockade of auditory nerve electrical activity with tetrodotoxin has been reported. In the present study, we evaluate the reversibility of central auditory changes after a profound sensorineural hearing loss caused by blockade of auditory nerve actions potentials. Tetrodotoxin, which blocks voltage-sensitive sodium channels, was embedded in a slow-release vehicle and placed next to the round window membrane of gerbils. Tetrodotoxin diffused into perilymph and unilaterally blocked electrical activity in auditory nerve axons. Electrical activity blockade was confirmed with recordings of auditory brainstem response. Animals were killed immediately after 24 hours of electrical blockade or 7 days after a transient 24- or 48-hour blockade. Large spherical cells of the anteroventral cochlear nucleus ipsilateral to manipulation were measured and compared to large spherical cells on the opposite, unmanipulated side of the brain. Animals killed immediately after a 24-hour blockade of electrical activity showed a mean decrease of 16% in cell size ipsilateral to the blockade (p less than 0.05). In animals allowed to recover for 7 days after blockade for 24 or 48 hours, cell size returned to previous levels. There was no longer a consistent difference in cell size between the two sides of the brain in these animals (p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

cis-platinum ototoxicity in children.

Despite the recognized ototoxicity of cis-platinum, a clinical outline for the audiologic evaluation of patients receiving this drug has not been clearly defined. In a practical approach to this problem, the audiograms of 48 pediatric patients referred for monitoring during planned cis-platinum therapy were reviewed. Eleven patients tested with auditory brain-stem response (ABR) audiometry demonstrated several limitations of this modality. Fourteen children underwent initial ABR testing followed by at least two pure-tone audiograms. The remaining 23 patients had their hearing evaluated by pure-tone audiometry only. Various factors such as patient age, cis-platinum dosage, and cranial radiation exposure were analyzed for apparent effect. Younger patients tended to be more susceptible to audiologic changes with the administration of cis-platinum. The proportion of patients who demonstrated a hearing loss increased with successive dosing as did the severity of the hearing loss. Prior exposure to cranial radiation was strongly linked to the development of hearing loss following cis-platinum therapy. Guidelines are presented regarding the use of clinical audiometry in the screening of these pediatric oncology patients.

Adolescent↗

Nasal schwannoma.

A 36-year-old man with a nasal septal mass is presented. The diagnosis of a benign neoplasm arising from peripheral nerve Schwann cells was made by excisional biopsy. A benign nerve sheath tumor may be either a schwannoma or neurofibroma. Schwannomas may be distinguished from neurofibroma by clinical and histologic criteria. Malignant degeneration and intracranial extension may complicate the course of a nasal schwannoma. Complete excision is the preferred therapy.

Adult↗

Rapid changes in cochlear nucleus cell size following blockade of auditory nerve electrical activity in gerbils.

Large spherical cells of the mammalian anteroventral cochlear nucleus (AVCN) receive direct excitatory input from auditory nerve axons. Trans-synaptic regulation of neuronal cell size and cell number after cochlear ablation has been previously demonstrated in neonates of several vertebrate species, including the gerbil. Such changes may be related to loss of spontaneous or evoked auditory nerve electrical activity or to loss of activity-independent factors. We have developed a method to chronically, yet reversibly, block auditory nerve electrical activity without violating the integrity of the inner ear. Tetrodotoxin (TTX) was embedded in an ethylene-vinyl acetate copolymer resin (Elvax). A small piece of Elvax containing TTX was placed next to the round window membrane, which allowed TTX to diffuse into the inner ear. As a measure of the effectiveness of manipulation, the onset, duration, and magnitude of the auditory threshold shift were measured by the auditory brainstem response. The sound-evoked response was abolished within 10 minutes of placement of TTX on the round window membrane. The duration of threshold shift was dose-dependent and lasted 24-46 hours. Implants of Elvax without TTX did not produce a significant threshold shift. TTX, which blocks voltage-gated sodium channels, did not abolish the potassium-based cochlear microphonic response. The consequence of blocking afferent electrical activity on gerbil AVCN large spherical cells was examined by measuring their cross-sectional area after each of four manipulations: unilateral auditory nerve action potential blockade with TTX; unilateral surgical cochlear ablation; ipsilateral TTX exposure/contralateral cochlear ablation; and unilateral sham operation (Elvax without TTX).(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗