Acyclovir improves recovery rate of facial nerve palsy in Ramsay Hunt syndrome.

OBJECTIVE: Although the antiviral agent, acyclovir, is currently employed for the treatment in Ramsay Hunt syndrome, the benefit of acyclovir on facial nerve is still unknown and remains controversial. This study was designed to evaluate the effect of acyclovir in facial nerve recovery in Ramsay Hunt syndrome. METHODS: To evaluate drug effect on facial nerve function, evaluation of the facial voluntary movement and nerve excitability testing were performed. We have used an infusion therapy of acyclovir in combination with a high dose of steroid (AS), which was started within 7 days of onset of facial nerve palsy in 91 patients with Ramsay Hunt syndrome. The results were compared with those of 47 patients whose therapy was steroid alone started within 7 days of onset. RESULTS: Out of 91 patients treated with AS, nerve exitability was good in 68 (75%), while it was poor in 17 and absent in six. Of 47 patients treated with steroid alone, nerve exitability was good in 25 (53%), while it was poor in 11 and absent in 11. There was statistically significant difference between AS and steroid therapy in the posttreatment degree of nerve function. Complete recovery to grade I in facial voluntary movement was attained in 82 of 91 patients (90%) in the AS therapy, while out of 47 patients treated with steroid alone complete recovery to grade I was attained in only 30 (64%). A statistically significant difference in the recovery rate of facial nerve function was induced between AS and steroid therapy. CONCLUSION: The AS therapy was proved to keep good degree of nerve function indicated with nerve excitability testing and improve recovery rate of facial nerve in Ramsay Hunt syndrome. Based on this study, we now believe that the AS therapy is an advisable treatment modality to improve the recovery rate of facial nerve function in Ramsay Hunt syndrome.

[Mechanism for producing a neoglottal fricative [h] in tracheoesophageal speech].

BACKGROUND: Over the past 24 years, we have been performing the tracheoesophageal (TE) fistulization for voice restoration following a total laryngectomy. The principle of this technique is to divert the exhaled air through the TE fistula into the hypopharynx, where the thyropharyngeus muscle forms the retropharyngeal prominence on which the neoglottis is located. In TE speech, the electromyographic (EMG) activity of the thyropharyngeus muscle decreases for voiceless positive production. This neoglottic articulatory adjustment plays an important role in opening the neoglottis. It has been previously reported that the glottis is open for the glottal fricative ([h]) sound produced with laryngeal articulatory adjustment and that turbulence through the glottis produces the [h] sound in laryngeal speech. Of all the voiceless consonants in the Japanese language, [h] is the most difficult to produce in TE speech. This suggests that other adjustments in addition to the neoglottic articulatory adjustment are necessary to produce the [h] sound in TE speech. This study was designed to clarify the mechanism by which the neoglottal fricative ([h]) sound is produced. SUBJECTS AND METHODS: Eight speakers who could pronounce [h] were included in this investigation, a fiber optic examination of the neoglottis, aerodynamic study, and an EMG examination of the thyropharyngeus muscle during the production of words containing voiceless fricative [h] and [s] sounds were performed in each subject. The two groups were classified according to the subject's success or failure in producing words with initial [h] and medial [h] sounds. Out of 80 TE speakers who could not pronounce [h], 4 subjects were selected as the control group. RESULTS: Fibroptic examination revealed a transient neogottal opening during the production of [h] and [s] sounds. The median of the average opening time was 0.26 seconds for initial [h] sounds and 0.19 seconds for medial [h] sounds. No significant difference in opening time was observed for [h] and [s] sounds. The aerodynamic investigation demonstrated a transient increase in supraneoglottal pressure and airflow through the neoglottis and a transient decrease in subneoglottal pressure for [h] production, while no changes were observed in the control group. The EMG study demonstrated that the activity of the thyropharyngeus muscle decreases in cooperation with a transient decrease in subneoglottal pressure only for [h] production. As a result of the transient decrease in subneoglottal pressure, the EMG activity for [h] decreased more strongly than that for [s]. CONCLUSIONS: These findings indicate that both neoglottic adjustment and pulmonary adjustment are required for [h] production in TE speech.

[Differentiation and proliferation of mast cells in nasal mucosa].

We determined the distribution of mast cells in nasal mucosa and studied their proliferation. Inferior turbinate mucosa was sampled in 13 patients with allergic rhinitis (allergic group) and 5 without (non allergic group) and stained immunohistochemically using anti mast cell tryptase antibody, anti-c-kit antibody, anti-PCNA antibody, and anti mast cell chymase antibody. Tissue sections stained with anti tryptase antibody revealed a higher degree of infiltration of tryptase-positive cells, i.e., mast cells, in the allergic group than in non allergic group. In the allergic group, the number of tryptase-positive cells, c-kit-positive cells, and PCNA-positive cells was significantly greater in the epithelium and shallow lamina propria than that in the deep lamina propria. Tryptase-positive, c-kit-positive cells, i.e., c-kit-positive mast cells, and tryptase-positive, PCNA-positive cells, i.e., PCNA-positive mast cells, were also abundunt in the epithelium and shallow lamina propria. The stem cell factor and c-kit receptor are reported to play a primary role in mast cell differentiation and proliferation. PCNA-positive cells represent actively proliferating cells. Based on the above, we concluded that mast cells in the epithelium and shallow lamina propria in the allergic group differentiated and proliferated more actively than those in the deep lamina propria.

Significance of retropharyngeal node dissection at radical surgery for carcinoma of the hypopharynx and cervical esophagus.

OBJECTIVES: To clarify the efficacy of dissection of retropharyngeal lymph nodes (RPLNs) in the surgical treatment of carcinoma of the hypopharynx and cervical esophagus. STUDY DESIGN: We started planned dissection of the RPLN during initial radical surgery in patients with squamous cell carcinoma of the hypopharynx or the cervical esophagus in 1988. Until 1997, we performed this procedure as a standard operation in 82 consecutive patients. METHODS: Mortality resulting from RPLN metastasis was compared between 82 patients who underwent RPLN dissection and 69 patients who did not undergo the procedure. RESULTS: Of 82 patients, 16 patients (20%) had positive RPLNs. These patients were at high risk of recurrence unless the node(s) were dissected. Although RPLN dissection did not improve the cumulative 5-year survival rate, it significantly decreased the number of patients who died of RPLN metastasis (chi2 = 3.68, P <.1). Four of the 16 patients who had positive RPLNs survived without any recurrence. CONCLUSION: Bilateral dissection of the RPLN during initial surgery is highly recommended in every surgical case of carcinoma of the hypopharynx and cervical esophagus.

Further experience with tracheojejunal shunt speech after pharyngolaryngoesophagectomy.

Over the past 10 years, 16 patients have undergone the tracheojejunal shunt operation for voice reconstruction after undergoing pharyngolaryngoesophagectomy with free jejunum reconstruction for advanced hypopharyngeal cancer. For the purpose of voice reconstruction, a 2-cm inferiorly based tracheal flap is obtained from the membranous part of the trachea by removing 4 cartilaginous tracheal rings. After the establishment of digestive continuity with the jejunal graft, a side-to-side anastomosis is created by approximating the incised margin of the jejunal mucosa to that of the tracheal flap. The tracheal flap is tubed to construct the tracheojejunal shunt. In addition, the incised margin of the jejunal serosa is sutured to the lateral wall of the shunt to reinforce the approximation of the shunt to the jejunal graft. Thirteen of the 16 patients (81%) were initially capable of voice production. The length of time during which tracheojejunal speech has been used ranges from 18 to 122 months, with a mean of 55 months. During follow-up, 12 of the 13 patients (92%) have been able to swallow without aspiration.

Acoustic analyses clarify voiced-voiceless distinction in tracheoesophageal speech.

In order to clarify the ability of the voice to achieve voiced voiceless distinction in [ce1]tracheoesophageal (TE) speech, acoustic cues such as closure duration, onset and offset of vibration during closure period and voice onset time (VOT), in conjunction with intraoral pressure, were analyzed in 40 TE speakers. Both closure period and VOT during [p] production were longer in TE speakers with high intelligibility compared with laryngeal speakers; during [b] production these parameters were similar between the two groups. TE speakers with high intelligibility and laryngeal speakers showed significant differences between [p] and [b] production in terms of both closure duration and VOT. TE speakers with low intelligibility of [b] had higher values of VOT during [b] production compared with those with high intelligibility. TE speakers with low intelligibility of [p] had lower values of VOT during [p] production compared with those with high intelligibility. It is concluded that these characteristic acoustic cues reflect voicing ability in TE speech.

Congenital defects of the vomer.

Six cases of congenital defect of the vomer, a rare nasal anomaly, are reported. All 6 patients visited Kobe University Hospital with other complaints, and the anomaly was incidentally detected. In all cases, the nasal septum showed a defect at the posteroinferior portion that appeared to coincide with the location of the vomer. None of the patients had a past history of nasal trauma, nasal surgery, drug abuse, or infectious disease. This anomaly may be attributable to an embryological disorder based on an immature ossification center of the vomer.

Induction of S100A4 gene expression inhibits in vitro invasiveness of human squamous cell carcinoma, KOSC-3 cells.

S100A4 is considered functionally involved in metastasis and invasiveness of rodent and human mammary tumors. We screened the expression of S100A4 in human squamous cell carcinoma cell lines, and found 2 cell lines which were highly invasive, but did not express any noticeable extent of S100A4. To examine whether the expression of S100A4 regulated invasiveness of squamous cell carcinoma, we transfected S100A4 cDNA into KOCS-3 and HSC-4 squamous cell carcinoma cells. The transfectants from KOSC-3 cells expressing sense S100A4 decreased invasiveness by 80% compared with cells of the wild type or those with the vector only.

Evaluation of speech function after mesopharyngeal reconstruction with radial forearm flap.

This study examined postoperative speech function in ten patients who underwent mesopharyngeal resection and reconstruction using radial forearm flap. Patient age ranged from 49 to 71 years (mean 60 years) with 9 males and 1 female. Speech function was assessed by articulatory and velopharyngeal function. Articulatory function was judged by intelligibility of monosyllables and sentences. The percentage of 100 Japanese monosyllables perceived as correct in each case were scored. Intelligibility of sentences was evaluated using the Hirose standard. Velopharyngeal function was fiberoptically examined both in soft-blowing and at rest, and visual information about velopharyngeal closure was obtained. Correlation between the extent of resection and the speech function was then analysed. In order to maintain over 50% speech intelligibility and an excellent state in the Hirose standard, the extent of resection in the soft palate is particularly important. This result has to be explained in correlation with the resected range of the levator muscle, which is important for velopharyngeal closure. Surgically treated mesopharyngeal cancer patients face several functional problems. In order to counsel patients more meaningfully before surgical intervention, information about the postoperative speech function should be made available. The goal of reconstruction is to achieve acceptable speech in order to maintain the patients' quality of life. The results in this study reveal that resection which doesn't extend to the opposit side of the soft palate, can achieve the goal by utilization of the foream flap, because its pliable nature brings out the residual function of the levator.

Esophageal contractility synchronous with expiration.

On the basis of our previous finding that the cervical esophagus was closed during tracheoesophageal phonation, we postulated that the muscle of the cervical esophagus actually contracted during expiration and speculated on its possible regulation by the recurrent laryngeal nerve. Electromyography of the esophageal musculature and fluoroscopy of the esophagus were performed in laryngectomees to demonstrate whether the esophagus contracted during expiration or not. Electromyography, performed in 2 subjects, revealed a burst of discharges synchronous with expiration. Fluoroscopy during tracheoesophageal phonation was performed in 13 subjects to investigate the influence of resection of the esophageal branch of the recurrent nerve on esophageal motor activity. Among 13 subjects, 4 subjects who underwent paratracheal dissection (PTD) at the time of laryngectomy showed a lower superior limit of esophageal closure than did the 9 subjects without PTD, indicating that the cervical esophagus in PTD loses its contractility with the sacrifice of the esophageal branch of the recurrent nerve. We concluded that the cervical esophagus is closed by muscle contraction synchronous with expiration, preventing air entry into the stomach during deep expiration or phonation, and that the esophageal branch of the recurrent nerve is involved.

Dynamics of subneoglottic lumen in tracheoesophageal phonation.

The patient who employs tracheoesophageal (TE) phonation uses expiratory air passing through the TE fistula to vibrate the mucosa of the neoglottis located in the hypopharynx. To clarify the dynamics of the subneoglottic lumen during phonation, we performed fiberoptic endoscopy and fluoroscopy in 13 TE speakers. During phonation, fiberoptic endoscopy showed concentric closure of the esophagus with ballooning of the subneoglottic lumen, followed by opening of the esophagus during inspiration. Fluoroscopy revealed a dilated subneoglottic lumen and a closure of the esophagus at the bottom of the lumen during phonation. These findings provide evidence for a mechanism to protect against the influx of air deep into the esophagus during TE phonation. We conclude that during TE phonation, a closed airway is established from the lung to the neoglottis that enables the TE speaker to use expiratory air effectively for phonation.

[Proliferative potential of the ear drum in the process of gerbiline cholesteatoma formation].

Mongolian gerbil frequently develop spontaneous cholesteatoma. As we reported previously, in the process of gerbiline cholesteatoma formation, effusions inside the pars flaccida are always found in the ears during the early stage, and epidermal growth factor (EGF) is also localized in the pars flaccida, especially in the mucous layer. In this study, to clarify the process of gerbiline cholesteatoma formation, we studied 22 gerbiline temporal bones by using a monoclonal antibody against bromodeoxyuridine (BrdU). BrdU-labeled cells demonstrate a proliferative potential. We also used a carbon dye method to label the micro-vase in 14 gerbiline temporal bones. Cells showing BrdU uptake were more abundant, as demonstrated immunohistochemically, in the pars flaccida of ears with early cholesteatomas than in the pars flaccida of normal ears (p < 0.01). The pars flaccida of ears with early cholesteatomas showed hypertrophy of both epithelial layers, and hyperkeratosis of the epidermal layer. BrdU-labeled cells in the pars flaccida were more localized in the mucous layers than in the epidermal layers. In contrast, in ears with cholesteatomas, BrdU-labeled cells were less abudant than in ears with early cholesteatomas. In addition, BrdU-labeled cells in the pars tensa and external auditory epidermal layers were not increased in ears with any stage of cholesteatoma formation. We used a carbon dye method to detect the micro-vasa in the intermediate layer of the ear drum. Carbon-dye-labeled vasa were more numerous in the pars flaccida with early cholesteatomas than in the pars flaccida of normal ears or ears with cholesteatomas. It is highly suspected that angiogenesis was stimulated in the pars flaccida with early cholesteatomas, because stimulation of angiogenesis by EGF has been reported. The above findings suggest that the mucous layer of the pars flaccida has the greatest proliferative potential in the process of cholesteatoma formation. Angiogenesis in the pars flaccida appears to be a reaction to proliferative changes in the mucous and epidermal layers. These changes are probably stimulated by effusion inside the pars flaccida.

Antibodies directed against ZAP-70 cross-react with a 66 kDa tyrosine kinase in the rat brain.

ZAP-70 is another member of Syk family tyrosine kinases which plays an essential role in growth, differentiation, and function of T lymphocytes. In this study, we report the specific expression of a 66 kDa tyrosine kinase that is specifically cross-reacted with anti-ZAP-70 antibodies in the developing neurons. By immunoblot and immunoprecipitation assay using various anti-ZAP-70 antibodies, a 66 kDa tyrosine kinase was detected in lysates from rat brain. During the development of rat brain, expression levels of this 66 kDa tyrosine kinase were highest around 3 weeks after birth and decreased thereafter in the adult. In addition, immunoblot analysis demonstrated that this 66 kDa tyrosine kinase was expressed almost solely in the nervous system. These results suggest that this ZAP-70-related tyrosine kinase may play an important role in growth and differentiation in the developing neurons. Our observations will provide the clue to approach the regulatory system common to neurogenesis and immune response.

Mechanism of UV-induced apoptosis in human leukemia cells: roles of Ca2+/Mg(2+)-dependent endonuclease, caspase-3, and stress-activated protein kinases.

Ultraviolet light (UV) induced rapid apoptosis of U937 leukemia cells, concurrent with DNA fragmentation and cleavage of poly(ADP-ribose)polymerase (PARP) by activated caspase-3. The in vitro reconstitution of intact HeLa S3 nuclei and apoptotic U937 cytosolic extract (CE) revealed that (i) Ca2+/Mg(2+)-dependent, Zn(2+)-sensitive endonuclease activated in the apoptotic CE induced DNA ladder in HeLa nuclei at pH 6.8-7.4, (ii) activated caspase-3 cleaved PARP in HeLa nuclei, and (iii) when the apoptotic CE was treated with the caspase-3 inhibitor (1 microM Ac-DEVD-CHO) or the caspase-1 inhibitor (10 microM Ac-YVAD-CHO), the former, but not the latter, caused a 50% inhibition of DNA fragmentation and the complete inhibition of PARP cleavage in HeLa nuclei. Similarly, Ac-DEVD-CHO (100 microM) inhibited apoptosis and DNA ladder by 50% and PARP cleavage completely in UV-irradiated U937 cells, but Ac-YVAD-CHO (100 microM) did not. Thus, UV-induced apoptosis of U937 cells involves the Ca2+/Mg(2+)-dependent endonuclease pathway and the caspase-3-PARP cleavage-Ca2+/Mg(2+)-dependent endonuclease pathway. The former pathway produced directly 50% of apoptotic DNA ladder, and the latter involved activated caspase-3 and PARP cleavage, followed by formation of the remaining 50% DNA ladder by the activated endonuclease. In UV-irradiated B-cell lines, further, p53-dependent increase of Bax resulted in a greater caspase-3 activation compared to its absence. However, UV-induced activation of JNK1 and p38 was not affected by the caspase-1 and -3 inhibitors in U937 cells, so that caspases-1 and -3 do not function upstream of JNK1 and p38.

GABA-activated conductance in cultured rat inferior colliculus neurons.

With the use of a whole cell voltage-clamp technique and fura-2 fluorescence measurements, the actions of gamma-aminobutyric acid (GABA) on cultured neurons from rat inferior colliculus were investigated. GABA (10-1,000 microM) induced currents in neurons held under voltage clamp that were inhibited by bicuculline (20 microM). Muscimol (100 microM) also evoked the currents, whereas baclofen (100 microM) affected neither the holding currents nor K+ conductance due to depolarizing pulses. The current density-voltage relation of GABA-induced currents, with equal concentrations of Cl- in the internal and external solutions, reversed near 0 mV. Reduction of the internal Cl- concentration shifted the-reversal potential in the negative direction as predicted from the Cl- equilibrium potential. Baclofen did not affect Ca2+ conductance due to depolarizing pulses. The extracellular application of 150 mM.KCl or 1.0 mM glutamate increased the intracellular Ca2+ concentration ([Ca2+]i) of cultured inferior colliculus neurons only when neurons were bathed in a Ca(2+)-containing external solution. However, GABA (1.0 mM) failed to increase [Ca2+]i at all concentrations of external Ca2+ used, indicating that GABA neither depolarized the cultured inferior colliculus neurons sufficiently to activate the voltage-dependent Ca2+ conductances nor evoked Ca2+ release from intracellular stores. These results suggest that in cultured rat inferior colliculus neurons, GABAA receptor channels may be predominantly responsible for the membrane conductance evoked by GABA and subsequent hyperpolarization of the neurons.

Neovascularization of the intestinal graft transplanted in subcutaneous pocket in rats.

Clinically, the intestinal graft can survive without blood supply through its vascular pedicle for a certain period after transplantation, which is generally considered to be due to newly formed vessels from the surrounding tissue to the graft. Vascular synthesis from the surrounding tissue to the pedicled intestinal graft, transplanted subcutaneously was studied in rat model. Both the carbon dye infusion technique and hematoxylin-eosin stain were employed. After transplantation of the intestine, the number and diameter of carbon stained vessels were scored on days 2, 5, 7, 10, 14, 28, and 56, when the pedicle was ligated. All the histological specimens of the intestinal grafts were analyzed and then classified into three phases depending on the extent of surviving mucosa: 'necrosis', no live mucosa were observed; 'incomplete take', some islands of mucosa were alive; and 'complete take', all mucosa were alive. We characterized the relationship between the changes of the newly formed (carbon-dyed) vessels and the three histological phases. At 'necrosis', the newly formed vessels were rare and did not reach the intestinal graft. At 'incomplete take', random thin vascular networks were observed and some of them reached the graft. Some specimens were in the 'incomplete take' phase. At 'complete take', regular large vascular networks were observed. This transformation of the vascular networks seemed to reduce the the resistance of the vascular flow and to finally lead to the 'complete take' of the graft.

Significance of tubal resection in surgical treatment of middle ear carcinoma.

We successfully carried out total en bloc resection of squamous cell carcinoma of the middle ear in two patients. Both patients have been free of the disease for 32-39 months. In one of the cases, the eustachian tube was resected totally with the temporal bone. Postoperative histopathological examination proved tumor invasion into the cartilaginous part of the tube. We would like to emphasize the significance of total resection of the eustachian tube when neoplastic invasion into the tube is highly suspected. Axial computed tomography is of great value for preoperative evaluation of such invasion. Anterior mobilization of the carotid artery from the carotid canal facilitates resection of the petrous apex and should be done after management of the eustachian tube. The carotid canal is best exposed ventrally, since lateral exposure is at high risk for injuring the bony part of the eustachian tube and may possibly disseminate tumor cells.

[Histological study of the tracheal adventitia, perichondrium and annular ligament].

The trachea begins at the lower border of the cricoid cartilage and passes down to bifurcate into the left and right mainstem bronchi. The presence of tracheal invasion is crucial factor influencing the prognosis for patients with cancers of the thyroid gland, hypopharynx, esophagus, etc. In order to understand the manner of invasion of the above tumors, precise knowledge of the normal tracheal structure is indispensable. This study was undertaken to clarify the normal microscopic structure of the trachea. Five normal tracheal specimens obtained at surgery were examined histologically and immunohistochemically. The loose connective tissue around the trachea, known as adventitia, was divided into a loose outer and a dense inner layer by hematoxylin and eosin (HE) staining. This two-layer pattern was clearly seen near the annular ligament but was obscured away from it. The connective tissue of the inner layer ran obliquely to joint the connective tissue of the annular ligament and ended in the submucosal layer. This arrangement of connective fibers seems to play a role in allowing the trachea to stretch and bend. Tracheal cartilage is covered with a dense fibrous membrane known as the perichoundrium. Between the superficial fibrous membrane and mature cartilage cells lies zone of immature cartilage made up of oval or spindle cells, and the inclusion of this zone in the perichondrium has long been a subject of controversy. In our study, the zone was homogeneously stained red by the elastica van Gieson's stain and was clearly distinguished from other structures. Immunohistochemical staining revealed a wide distribution of type I and type III collagen on the fibrous membrane and the zone of immature cartilage cells, while mature cartilage cells did not show such collagen. Based on these findings, we conclude that the zone of immature cartilage cells belongs to the periochondrium, which thus contains two layers, an outer fibrous layer and an inner transitional layer of immature cartilage cells. Our conclusions are as follows: 1. Tracheal adventitia is divided into two layers, an outer loose and an inner dense fibrous layer. 2. Tracheal perichondrium also consists of two layers, an outer fibrous layer and an inner transitional layer. 3. The fibrous bundle originating from the adventitia joins the connective tissue of the annular ligament, probably in order to allow the trachea to stretch and bend.

Radiotherapy of T1 and T2 glottic cancer: analysis of anterior commissure involvement.

From January 1984 to December 1993, 184 patients with previously untreated T1 and T2 (UICC 1987) laryngeal glottic cancer underwent radiotherapy at Hyogo Medical Center for Adults. The prognostic variables analyzed included sex, age, smoking index, T stage, tumor size, tumor type, gross anterior commissure involvement (gross ACI), histological differentiation, administered dose, TDF, overall treatment time, chemotherapy, initial response, and the dose required to achieve CR. Both univariate and multivariate analyses were performed. The T stage, tumor size, and gross ACI were significant variables in univariate analysis, while the tumor type and gross ACI were significant on multivariate analysis. The 5-year recurrence-free survival of patients with gross ACI was significantly worse than that of those without ACI (57.6% vs. 89.9%). Among gross ACI patients, the recurrence-free survival of those treated with 70-72 Gy was superior to that of those receiving 60-62 Gy, suggesting that at least 70 Gy was necessary to control such diseases.