Yasuhiro Manabe

Long-term follow-up results of electrogustometry and subjective taste disorder after middle ear surgery

Objectives The present study compares the long‐term follow‐up results of electrogustometry with patient reports of taste dysfunction after middle ear surgery.

Morphological and Functional Study of Regenerated Chorda Tympani Nerves in Humans

It is still unclear whether the chorda tympani nerves in humans regenerate after being severed during middle ear surgery, although functional studies have demonstrated recovery of taste 1 to 2 years after surgery. To date, 12 cases of regenerated chorda tympani nerves have been found in our series of patients during secondary surgery. The regenerated nerves of 3 cases of the 12 were removed as samples during secondary surgery to detect regenerated myelinated axons. All regenerated nerves were in the submucosal connective tissue layer of the reconstructed eardrum. In the regenerated nerves, myelinated nerve fibers existed in a small fascicle or in connective tissue, but the number of myelinated axons was low compared with that in normal subjects (1,752 ± 78; n = 3), and the distribution was sparse. The total number of regenerated myelinated axons varied from 141 (8.3%) to 979 (55.9%). From a functional study using electrogustometry, incomplete recovery of electrogustation was observed in all 3 cases before secondary surgery, suggesting that chorda tympani nerves actually regenerate in the middle ear and do function.

OTOTOXICITY OF CARBOPLATIN IN GUINEA PIGS

Since carboplatin (CBDCA) is a platinum compound of second generation, its ototoxicity was investigated. In order to assess the ototoxicity, hearing acuity was measured based on the compound action potential (AP), and the organ of Corti was morphologically studied using scanning electron microscopy (SEM) and succinate dehydrogenase (SDH) staining in guinea pigs treated with CBDCA. CBDCA induced morphological changes in the organ of Corti when the guinea pigs received 50 mg/kg daily for 2 or 3 days. The threshold value of AP was elevated 10 to 25 dB in treated animals, as compared with the control value. The SEM study and SDH staining revealed that the administration caused scattered degeneration of the outer hair cells (OHCs), and the inner hair cells remained intact. These lesions were milder than those of OHCs treated with cisplatin (CDDP). The rapid elimination of CBDCA from the kidney and the inner ear seems to account for the low ototoxicity of this compound. Although CBDCA is less toxic than CDDP, it may affect hearing function if patients suffer from renal dysfunction or if the organ of Corti is vulnerable.

Intraoperative Identification of Regenerated Chorda tympani Nerve and Its Relationship to Recovered Taste Function

This study demonstrated a simple method of repairing the severed chorda tympani nerve and a method of intraoperative identification of regenerated nerves, and evaluated taste function of regenerated nerves. Seven patients who underwent staged tympanoplasty and whose chorda tympani nerve was severed during primary surgery were evaluated. When the chorda tympani nerve was severed during primary surgery, proximal and distal stumps were anastomosed or approximated almost in the original position and fixed with fibrin glue on the temporal muscle fascia used to reconstruct the eardrum by the underlay method. During primary surgery, end-to-end anastomosis was possible in 3 patients but nerve gap defects remained in the other 4 patients. In all 7 patients, regenerated nerves were identified during secondary surgery not in the tympanic cavity but in the submucosal layer of the previously reconstructed eardrum. In all patients, complete or incomplete recovery of taste perception was observed by both the filter paper disk method and electrogustometry, suggesting that the regenerated nerves had actual taste function. From these results, it was concluded that the severed chorda tympani nerve could regenerate in the reconstructed eardrum even if nerve gap defects remained between the proximal and distal cut ends, when repair or approximation of the nerve was properly completed.

Ototoxicity of the new platinum anticancer agent TRK-710 in comparison with cisplatin.

The pharmacokinetics and ototoxicity of the new platinum analogue TRK-710 (3, 9, 15 mg/kg x 3 days) were compared with those of cisplatin (1, 3, 5 mg/kg x 3). The perilymphatic concentration of TRK-710 was one seventh of that of cisplatin even 1 h after the administration. The N1 threshold of the compound action potential was elevated dose-dependently in both groups with a similar degree of hearing impairment. Morphological observation using phase contrast microscopy and scanning electron microscopy revealed the damage of the outer hair cells to almost the same degree mainly in the basal and second turns. Despite its usefulness against cisplatin-resistant tumors and a lesser degree of nephrotoxicity and myelosuppression, TRK-710 should be clinically used with caution similar to cisplatin.

Morphology of human fungiform papillae after severing chorda tympani nerve.

Objectives: We aimed to clarify the postoperative morphology of the fungiform papillae (FP) of the tongue in patients who recovered gustatory function after the chorda tympani nerve was severed during middle ear surgery. Methods: Fifty-four patients with normal preoperative gustatory function measured by electrogustometry (EGM) were included. The proximal and distal stumps of the severed nerves were re-adapted or re-approximated during surgery to promote regeneration of the nerve. The EGM thresholds over 2 years after surgery were compared with preoperative values. At the same time, the morphological characteristics of the FP in the midlateral region of the tongue were recorded with a digital microscope. Results: One month after surgery, EGM showed no response in any patients. At a time point of more than 2 years, the FP showed complete atrophy and no response to EGM on the surgical side in 21 of the 54 patients. In 16 patients who showed complete recovery of the EGM threshold (below 20 μA), the FP showed an almost normal appearance, and the mean number of FP was 77.5% (10 ± 4.1 papillae per square centimeter) of that on the contralateral side (12.9 ± 4.9 papillae per square centimeter; p > 0.05). Conclusions: The morphology of the FP was maintained in patients who recovered gustatory function after the chorda tympani nerve was severed. Because the results indicate regeneration of the taste buds, further observation is needed to detect regenerated taste buds in the FP.

Observation of regenerated fungiform taste buds after severing the chorda tympani nerve using confocal laser scanning microscopy in vivo.

Objective To evaluate whether regenerated fungiform taste buds after severing the chorda tympani nerve can be detected by confocal laser scanning microscopy in vivo. Study Design Retrospective study. Setting University hospital. Patients Six patients with a normal gustatory function (Group 1), 9 patients with taste function recovery after severing the CTN (Group 2), and 5 patients without taste function recovery (Group 3) were included. In Groups 2 and 3, canal wall up (closed) tympanoplasty or canal wall down with canal reconstruction tympanoplasty was performed in all patients. Intervention Diagnostic. Main Outcome Measures The severed nerves were readapted or approximated on the temporalis muscle fascia used to reconstruct the eardrum during surgery. Preoperative and postoperative gustatory functions were assessed using electrogustometry. Twelve to 260 months after severing the CTN, the surface of the midlateral region of the tongue was observed with a confocal laser microscope. Results EGM thresholds showed no response 1 month after surgery in all patients of Groups 2 and 3. In Group 2, EGM thresholds showed recovery 1 to 2 years after surgery and before confocal microscopy (−1.3 ± 6.5 dB). There was a significant difference between Group 1 (−5.7 ± 2.0 dB; p < 0.01) and Group 2. In Group 3, EGM thresholds showed no response for more than 2 years. In the control group (Group 1), 0 to 16 taste buds were observed in each FP, and 55 (79.7%) of 69 FP contained at least 1 taste bud. The mean number of taste bud per papilla was 3.7 ± 3.6. In patients with a recovered taste function (Group 2), 0 to 8 taste buds were observed in each FP. In this group, 54 (56.2%) of 94 FP contained at least 1 taste bud. The mean number of taste bud per papilla was 2.0 ± 2.2 (p < 0.01). In Group 3, without recovery, the FP was atrophied, and no taste bud was observed. Conclusion Regenerated fungiform taste bud could be observed in vivo using confocal laser scanning microscopy, indicating that regenerated taste bud can be detected without biopsy.

Light and Electron Microscopic Observation of Regenerated Fungiform Taste Buds in Patients with Recovered Taste Function after Severing Chorda Tympani Nerve

Objectives: The aim of this study was to evaluate the mean number of regenerated fungiform taste buds per papilla and perform light and electron microscopic observation of taste buds in patients with recovered taste function after severing the chorda tympani nerve during middle ear surgery. Methods: We performed a biopsy on the fungiform papillae (FP) in the midlateral region of the dorsal surface of the tongue from 5 control volunteers (33 total FP) and from 7 and 5 patients with and without taste recovery (34 and 29 FP, respectively) 3 years 6 months to 18 years after surgery. The specimens were observed by light and transmission electron microscopy. The taste function was evaluated by electrogustometry. Results: The mean number of taste buds in the FP of patients with completely recovered taste function was significantly smaller (1.9 ± 1.4 per papilla; p < 0.01) than that of the control subjects (3.8 ± 2.2 per papilla). By transmission electron microscopy, 4 distinct types of cell (type I, II, III, and basal cells) were identified in the regenerated taste buds. Nerve fibers and nerve terminals were also found in the taste buds. Conclusions: It was clarified that taste buds containing taste cells and nerve endings do regenerate in the FP of patients with recovered taste function.

Degeneration process of fungiform taste buds after severing the human chorda tympani nerve--observation by confocal laser scanning microscopy.

Objective To elucidate the degeneration process of fungiform taste buds after severing the chorda tympani nerve (CTN) by confocal laser scanning microscopy in vivo. Study Design Prospective study. Setting University hospital. Patients Seven consecutive patients whose CTN was severed during tympanoplasty for middle ear cholesteatoma. Intervention Diagnostic. Main Outcome Measures Preoperative and postoperative gustatory functions were assessed by electrogustometry (EGM). An average of 10 fungiform papillae (FP) in the midlateral region of the tongue were periodically observed, and the number of taste buds was counted using a confocal laser microscope. Among them, 2 to 3 reference FPs were scelected based on the typical form of the FP or characteristic arrangements of taste pores. Observation was performed before surgery, 1 or 2 days after surgery, 2 or 3 times a week until 2 weeks after surgery, once a week between 2 and 4 weeks, and every 2 to 4 weeks thereafter until all taste buds had disappeared. Results EGM thresholds showed no response within 1 month after surgery in all patients. The initial change in the degeneration process was the disappearance of taste pores. The surface of taste buds became covered with epithelium. Finally, taste buds themselves atrofied and disappeared. The time course of degeneration differed depending upon individuals, each FP, and each taste bud. By employing the generalized linear mixed model under the Poisson distribution, it was calculated that all taste buds would disappear at around 50 days after surgery. Conclusion Confocal laser scanning microscopy was useful for clarifying the degeneration process of fungiform taste buds.

Effect of Asian sand dust on Japanese cedar pollinosis

OBJECTIVE Asian sand dust (ASD), originating in the deserts of Mongolia and China, spreads over large areas and is associated with adverse effects on human health in East Asia, including asthma, heart disease, and some allergic diseases. However, the effect of ASD on patients with seasonal allergic rhinitis caused by Japanese cedar pollen (SAR-JCP), the most common form of allergic rhinitis, remains unclear. The aim of this study was to investigate the effect of ASD on SAR-JCP patients. METHODS A total of 41 patients with SAR-JCP recorded nasal and ocular allergic symptom scores in a diary. We assessed the influence of ASD events on patients with SAR-JCP during the JCP season and before and after the JCP season. RESULTS ASD events did not influence nasal and ocular allergy symptoms during the JCP season. Scores for sneezing and runny nose were significantly increased by ASD events in the pre-JCP season. Ocular symptom scores were significantly increased by ASD events in the post-JCP season. CONCLUSION Our results suggest that ASD may exacerbate allergy symptoms even before mass scattering of JCP, which usually does not cause allergic symptoms in patients with SAR-JCP. ASD also induced conjunctivitis symptoms after the JCP season. However, we did not observe any adverse effects of ASD on allergic symptoms during the JCP season.