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Biomedical subjects

D E Mattox

Publications and source records attributed to D E Mattox.

At least 37 records · Page 2Linked to original sources

The effects of polyamines and polyamine inhibitors on rat sciatic and facial nerve regeneration.

The effects of exogenous polyamines and polyamine biosynthetic pathway inhibitors on regenerating nerves were examined in adult male rats following nerve transection and surgical repair. Several studies have demonstrated the efficacy of exogenous polyamines in promoting the functional recovery of peripheral nerves following crush or freeze injuries in the rat. In order to simulate clinical peripheral nerve surgery, we studied these effects after complete nerve transection and evaluated regeneration by counting axons. There was no statistical difference in axon number with and without polyamines and in the presence of inhibitors and inhibitors with end product addition. Our study suggests that the difference in recovery seen in previous studies is not mediated by a change in axon number.

Animals↗

The effects of DFMO on polyamine metabolism in the inner ear.

Difluoromethylornithine (DFMO) is a novel antineoplastic agent that was associated with an unexpected hearing loss in Phase II clinical trials. DFMO interferes with polyamine synthesis by inhibition of the enzyme ornithine decarboxylase (ODC). The objective of the current study was to establish a methodology to determine the effect of DFMO on polyamine levels and ODC activity in the cochlea. Guinea pigs received DFMO in their drinking water and were tested for auditory brainstem response threshold shifts. The organ of Corti, the lateral wall, and the acoustic nerve were assayed for both ODC activity and polyamine levels. In DFMO treated animals there was an inhibition of ODC activity in cochlear tissues as well as in intestinal mucosa. In addition, a significant depletion of cochlear polyamines was observed in the treatment animals. This study suggests that systemically administered DFMO inhibits ODC activity and interferes with polyamine synthesis in the cochlea.

Animals↗

Transpalatal transsphenoidal approach to the sella in children.

The sublabial transseptal transsphenoidal approach provides excellent exposure for pituitary surgery in adults. However, sellar lesions in children are more difficult to approach because of the smaller size of the pyramidal aperture and because of the limited pneumatization of the sella. We resurrected the transpalatal transsphenoidal approach for the treatment of sellar lesions in three children (one adenoma and two cystic craniopharyngiomas). The advantages of this approach were a short working distance and a wide exposure that permitted extensive drilling of the poorly pneumatized sphenoid bone under direct vision. The technique successfully provided exposure for management of the sellar pathology in all three cases and resulted in no nasal or palatal defects.

Journal Article↗

Clivus chordoma: a report of 12 recent cases and review of the literature.

Twelve patients with histologically confirmed clivus chordoma were treated at the Johns Hopkins Hospital between 1971 and 1989. Eight of the patients were men and four were women. The mean age at first operation was 51 years (range, 10 to 80). The most common presenting symptoms were headache, diplopia, dysphagia and dysarthria, and facial sensory changes. Computed tomography, with and without contrast enhancement, proved adequate for tumor identification and localization. Magnetic resonance imaging and angiography were occasionally employed to localize the tumors further and to define tumor vascular supply and proximity to vascular structures. Twenty-two resections were performed in 11 patients, and another patient underwent biopsy only. Seven were also treated with radiation therapy. Tumors recurred in eight patients, six of whom underwent further operations. The mean time to first recurrence was 22 months (range 8 to 36 months). Six of the patients are still alive, with a mean follow-up of 31 months (range, 3 to 89 months) from first surgical resection. The mean survival time from first treatment was 31 months (range, 4 to 62 months) among those patients who died. There was no operative mortality. The 5-year cumulative survival rate was 20%. Six patients with long follow-up have had fair to good results, being free of recurrences for at least a year. However, none of the patients returned to their premorbid baseline of activities. Five of the patients had tumors with the histologic diagnosis of chondroid chordoma. Three of these patients are still alive. The mean age at first treatment was 44 (compared with 62 for typical chordomas). The mean time from symptoms to diagnosis was 29 months (typical chordomas, 18 months). The mean length of survival and time to tumor recurrence were not significantly different between chondroid and typical chordomas.

Journal Article↗

Central nervous system changes associated with noise-induced hearing loss: an electron microscopic and freeze-fracture study of the chick nucleus magnocellularis.

This investigation assessed the effects of noise-induced hearing loss on the avian nucleus magnocellularis, the homologue of the mammalian cochlear nucleus. Fifteen-day-old chicks were exposed to high-intensity broad-band noise (132 dBA) for 24 to 72 hours. Hearing loss was documented with auditory brain-stem response recordings and scanning electron microscopy of the basilar papilla. Nucleus magnocellularis was assessed with thin-section electron microscopy and freeze-fracture techniques. Freeze-fracture preparations of noise-exposed animals showed a decrease in synaptic vesicle fusion sites at the synaptic active zone, a decrease in re-uptake of presynaptic membrane by coated vesicles, and a shift of the preferential fracture plane at the synapse from the presynaptic membrane to the post-synaptic membrane. These findings support the hypothesis that the effects of noise are not limited to the auditory periphery, but that transneuronal changes extend into the auditory central nervous system.

Animals↗

Repair of peripheral nerves of unequal diameters.

Four techniques for anastomosis were investigated for the anastomosis of a large proximal segment to a smaller distal segment of rat peripheral nerve with a size disparity of approximately 3 to 1. The techniques were perineural sutures (group I), KTP laser annealing (group II), collagen tubes with a 5-mm gap between the nerve segments (group III), and collagen tubes without a gap between the nerve ends (group IV). At 6 weeks there were no gross nerve distractions in groups I or IV. There were two failures in group II and three in group III. The percentage of fibers that crossed intact anastomoses were: group I, 89%; group II, 75%; group III, 115%; group IV, 125% (P less than .05 for the collagen tube repairs). Our results indicate that the suture technique is still the most reliable method of nerve repair. However, collagen tubes were effective in increasing the percentage of axons crossing the anastomosis.

Anastomosis, Surgical↗

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Journal Article↗

Management of the facial nerve in skull base surgery.

The facial nerve presents a significant obstacle to adequate surgical exposure of lesions involving the skull base. The evolution of various surgical approaches to the jugular foramen, petrous apex, and lateral facial approaches to the skull base aimed at preserving the seventh cranial nerve are reviewed. Methods and techniques in management of the intratemporal and extratemporal facial nerve are discussed.

Facial Nerve↗

Experimental nerve regeneration. A review.

The aim of peripheral nerve repair is to restore motor and sensory function, which requires more than just 10-0 sutures and a good microscope. The past decade has seen an explosion in the understanding of how nerves grow, and this information is being used to develop better treatments for nerve injuries. In the future, treatment will not be limited to the operating room, because postoperative adjuvant therapies will become increasingly more important in the management of nerve repairs. At the same time, advancement in manufacturing techniques, a better understanding of biomaterials, and the use of the laser will replace the time-honored techniques of surgical repair in many clinical settings.

Animals↗

Southwest Oncology Group study of mitoxantrone for treatment of patients with advanced adenoid cystic carcinoma of the head and neck.

Eighteen patients are evaluable for response in a Phase II trial of Mitoxantrone for advanced adenoid cystic carcinoma of the head and neck. One patient had a complete response; there were no partial responses. Twelve patients had stable disease for 3 or more months. There was no significant anti-tumor activity of Mitoxantrone in the group of patients with adenoid cystic carcinoma, all of whom were previously heavily treated with surgery, chemotherapy and/or radiation therapy.

Adult↗

Cochlear damage and increased threshold in alpha-difluoromethylornithine (DFMO) treated guinea pigs.

Alpha-difluoromethylornithine (DFMO) inhibits polyamine synthesis and is used as an antineoplastic and antiparasitic drug. In early human trials DFMO unexpectedly caused a sensorineural hearing loss. In the current study DFMO was administered to guinea pigs to investigate its effects on organ of Corti histology and on auditory thresholds. Histologic examination revealed that DFMO caused greatest damage in the hook and first turn. Damage in the second and third turns was minimal. Animals treated for 12 weeks with DFMO differed significantly (P less than 0.05) from controls in the hook and first turn in that: 1) DFMO caused a loss of hair cells in all rows. Loss of inner hair cells was greater than that of outer hair cells. 2) The remaining outer hair cells were shorter and contained a greater number of Hensen bodies. 3) The Deiters' cell bodies were longer and this increased length was associated with the decreased length of the corresponding outer hair cells. Brainstem audiometry showed that DFMO produced a hearing loss and the magnitude of this loss increased over twelve weeks of DFMO administration.

Aminoglycosides↗

Endoscopic management of cerebrospinal fluid leaks and cephaloceles.

The excellent visualization and atraumatic surgical techniques of endoscopic sinus surgery have been applied to the management of five cerebrospinal fluid leaks and two nasal cephaloceles. In all cases, the exact site of the lesion was identified. Four cerebrospinal fluid leaks were grafted with a free or pedicled septal mucosal graft. The fifth cerebrospinal fluid leak came from a narrow sphenoethmoid recess and stopped after the mucosa was abraded. The two cephaloceles were reduced intranasally and covered with bone and mucosal grafts. Not all cases seen in the same time period were treated endoscopically; two additional cerebrospinal fluid leaks were treated with conventional techniques because of severe nasal inflammatory disease and intracranial complications. The technique and indications for endoscopic management of cerebrospinal fluid leaks and cephaloceles are discussed.

Adult↗

Uncommon tumors of the skull base and uncommon approaches to them.

The recognition of a number of uncommon tumors of the skull base is now relatively simple because of three-dimensional computed tomography and magnetic resonance imaging with enhancement. The radiographic classification of these tumors is reviewed, and their treatment is discussed. Although the basic approach to these tumors is the same--radical surgery with decompression of neural and vascular structures--the authors present various operative techniques for gaining access to and removing these tumors. They also examine the role of radiotherapy in supplementing surgical treatment.

Craniotomy↗

Tumors of the skull base.

Recognition of the many benign and malignant tumors that occur in the skull base is now simple, given three-dimensional CT scanning and MRI with enhancement. Recent developments in surgical technique have allowed these tumors to be approached, but only in the past two to three years has radical surgery been possible.

Chondroma↗

High-dose cisplatin for locally advanced or metastatic head and neck cancer. A phase II pilot study.

High-dose cisplatin (40 mg/m2 every day X5) was administered to 14 patients (11 men, three women) with locally advanced or metastatic head and neck cancer not curable by surgery or refractory to previous chemotherapy and/or radiation therapy. All 14 patients were evaluable for toxicity; one patient was inevaluable for response due to early death. A total of 24 courses of therapy were administered. The dose-limiting toxicity was myelosuppression with 73% of patients experiencing Grade III or IV neutropenia. Grade II or above thrombocytopenia occurred in 30% of the patients. Renal and neurologic toxicity was minimal. Two patients experienced laryngeal edema from vigorous hydration with one of them requiring a tracheostomy for respiratory compromise. Partial responses were seen in six patients (46%). Two of the six patients had received previous treatment with standard dose cisplatin. Two patients achieved long-term responses (54+, 44+ months, respectively). Both of these patients were previously untreated, inoperable (T4N3M0, T3N1M0), and subsequently received radiation therapy after two cycles of chemotherapy. Median duration of response in the remaining responders was 3 months (range, 3-10 months). High-dose cisplatin may benefit selected patients with inoperable, advanced head and neck tumors. However, further randomized trials need to be conducted before firm conclusions can be established.

Adult↗

An animal model of hearing loss from alpha-difluoromethylornithine.

alpha-Difluoromethylornithine is a new antineoplastic and antiparasitic drug that inhibits the synthesis of polyamines. It causes a sensorineural hearing loss in humans. We have established an animal model for alpha-difluoromethylornithine-induced hearing loss. The time course for onset and recovery of the hearing loss in animals was similar to that seen in humans. Electrophysiologic and histologic data suggest that the anatomic site of alpha-difluoromethylornithine-induced hearing loss is the organ of Corti. Unlike other drugs with ototoxic effects, the specific enzymatic site of action of alpha-difluoromethylornithine is known, making it a potentially important tool in auditory research.

Animals↗

Effects of fibrin glue on rat facial nerve regeneration.

Studies of nerve repair comparing fibrin glue with suture techniques have produced mixed results. To test the effect of fibrin glue on nerve regeneration without the confounding variables of distraction and/or movement of the anastomosis, nerve repairs were performed with and without fibrin glue on the intratemporal facial nerve of the rat. The location of the nerve transection was the same for control and experimental nerves, but on the experimental side the nerve was repaired with fibrin glue and on the control side of the nerve was reapproximated in the fallopian canal, without glue or sutures. Axon counts distal to the repair revealed no statistically significant difference between the two methods of repair. This result suggests that mechanical obstruction by the fibrin glue between the nerve ends has a negligible effect on nerve regeneration.

Animals↗

Endoscopic sinus surgery for mucoceles: a viable alternative.

Functional endoscopic surgery affords the potential for dramatically reducing operative morbidity of surgery for paranasal sinus mucoceles by offering a minimally invasive approach under local anesthesia. Following surgery, direct endoscopic visualization of the area enables accurate follow-up. Unlike sinus obliteration, the ability to accurately image the sinus by CT is also preserved. This paper presents our preliminary experience with 18 mucoceles in which endoscopic sinus surgery was attempted. Five patients had preoperative proptosis and diplopia, three had Pott's puffy tumor and five had erosion of the posterior table of the frontal sinus. Fifteen patients were satisfactorily treated endoscopically, two lesions could not be satisfactorily approached and required external surgery, and one patient had persistent disease. No disease recurrence has been noted to date with endoscopic follow-up of up to 42 months.

Adolescent↗