Yu Saito

Clinical study of tympanostomy tube placement for patients with intractable Ménière's disease

OBJECTIVE To evaluate the effectiveness of tympanostomy tube placement in controlling symptoms of intractable Menieres disease. METHODS Fifteen patients with intractable Menieres disease underwent tympanostomy tube placement in the affected ear. Post-operative changes in vertigo attacks and hearing level were recorded, and were evaluated according to American Academy of Otolaryngology-Head and Neck Surgery criteria. RESULTS At 12 months after treatment, 3 patients (20 per cent) showed complete control of vertigo, 7 (47 per cent) showed substantial control and 2 (13 per cent) showed limited control; 3 patients (20 per cent) required other treatment. At 24 months after treatment, 7 patients (47 per cent) showed complete control of vertigo, 3 (20 per cent) showed substantial control and 1 (7 per cent) showed limited control; 1 patient required other treatment 15 months after tympanostomy tube placement. CONCLUSION There is no definite pathophysiological explanation for the effect of tympanostomy tube placement in reducing vertigo attacks. This treatment is not effective for all patients with intractable Menieres disease. However, tympanostomy tube placement might be an additional surgical therapeutic option to consider prior to contemplating other, more invasive treatments.

Amino acid starvation culture condition sensitizes EGFR-expressing cancer cell lines to gefitinib-mediated cytotoxicity by inducing atypical necroptosis

The maintenance of the intracellular level of amino acids is crucial for cellular homeostasis. This is carried out via the regulation of both the influx from the extracellular environment and the recycling of intracellular resources. Since epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors, including gefitinib (GEF) have been reported to induce the apoptosis of several cancer cell lines, in the present study, we examined whether the cytotoxic effects of GEF are further enhanced under amino acid starvation (AAS) culture conditions. Under AAS culture conditions, the cell killing effect of GEF was synergistically pronounced in the EGFR-expressing cell lines, namely, CAL 27, Detroit 562, A549 and PANC-1 cells compared with those treated with either GEF or AAS alone. The addition of essential amino acids, but not non-essential amino acids to the cell culture medium resulted in the cancellation of this pronounced cytotoxicity. The knockdown of L-type amino acid transporter 1 (LAT-1) by siRNA also enhanced GEF-induced cytotoxicity. Therefore, the shortage of the intracellular amino acid pool appears to determine the sensitivity to GEF. Notably, this enhanced cytotoxicity is not mediated by the induction of apoptosis, but is accompanied by the pronounced induction of autophagy. The presence of necrostatin-1, an inhibitor of receptor-interacting serine/threonine-protein kinase 1 (RIPK-1), but not that of Z-VAD-fmk, attenuated the cytotoxic effects of GEF under AAS culture conditions. Electron microscopy demonstrated that the CAL 27 cells treated with GEF under AAS culture conditions exhibited swelling of the cytosol and organelles with an increased number of autophagosomes and autolysosomes, but without chromatin condensation and nuclear fragmentation. Autophagic cell death was excluded as the inhibition of autophagy did not attenuate the cytotoxicity. These results strongly suggest the induction of necroptosis in response to GEF under AAS culture conditions. However, we could not detect any phosphorylation of RIPK-1 and mixed lineage kinase domain like pseudokinase (MLKL), as well as any necrosome formation. Therefore, the enhanced cytotoxic effect of GEF under AAS culture conditions is thought to be mediated by atypical necroptosis.

Type 3 Thyroplasty for a Patient with Female-to-Male Gender Identity Disorder

Objective In most cases, about the voice of the patient with female-to-male/gender identity disorder (FTM/GID), hormone therapy makes the voice low-pitched. In success cases, there is no need for phonosurgery. However, hormone therapy is not effective in some cases. We perform type 3 thyroplasty in these cases. Method Hormone therapy was started in 2008 but did not lower the speaking fundamental frequencies (SFFs). We therefore performed TP3 under local anesthesia. Results In our case, the SFF at the first visit was 146 Hz. The postoperative SFF was 110 Hz. Conclusions TP3 was performed under local anesthesia in a patient with FTM/GID in whom hormone therapy proved ineffective. With successful conversion to a lower-pitched voice, the patient could begin to live daily life as a male. QOL improved significantly with TP3. If hormone therapy proves ineffective, TP3 may be selected as an optional treatment and appears to show few surgical complications and was, in this case, a very effective treatment.