論文

Conclusions. Cervical sympathetic chain schwannoma (CSCS) sometimes mimics carotid body tumor (CBT). Differential diagnosis between these tumors is sometimes difficult using MRI alone. MRA, color Doppler ultrasonography, and fine needle aspiration (FNA) after imaging may be helpful to rule out CBT. Surgical resection of CSCS is relatively effortless, and Horner's syndrome is an expected but acceptable postoperative complication. Intratumoral hemorrhage and vasodilation may be the main reasons for significant enhancement on MRI. Objectives. CSCSs are rare and known to mimic carotid body tumors. We report 9 cases of CSCS with an emphasis on imaging, surgical management, and pathological findings. Moreover, we describe the differential diagnosis of CSCS and CBT, and speculate the reasons behind significant enhancement on MRI. Patients and methods. Nine cases of CSCS treated at a tertiary referral center between 1996 and 2008 were reviewed. Results. MRI revealed 3 of 9 cases (33%) splayed the carotid bifurcation and displayed marked contrast enhancement with gadolinium. All patients underwent surgical excision of the mass with minimal blood loss. Postoperative Horner's syndrome was encountered in all patients, which required no treatment. Marked gadolinium enhancement tended to be associated with histological findings such as intratumoral hemorrhage and vasodilation.

It is known that oxidative stress plays some role in inner ear diseases, such as sensorineural hearing loss due to aging. Free radicals are produced as a result of oxidative stress, such as reactive oxygen species (ROS) and nitric oxide. Radical scavengers and antioxidants play a role in the protection against oxidative stress. Although some basic data have indicated a relationship between oxidative stress and endolymphatic hydrops, no clinical data have been published from patients. Diacron reactive oxygen metabolites (d-ROM) were measured by the Free Radical Analytical system 4 (FRAS 4) from the blood of 39 patients. The subjects consisted of 16 controls, 13 patients with Ménière's disease, and 10 patients with benign paroxysmal positional vertigo. The d-ROM value of the controls was 307.3 ± 42.5 U Carr, compared with 350.1 ± 50.5 U Carr in BPPV and 352.2 ± 71.5 U Carr in Meniere's disease subjects. Although no statistically significant differences were seen among the groups, patients with BPPV and Ménière's disease had slightly higher values than the controls, suggesting that free radicals were being produced in patients with both Ménière's disease and benign paroxysmal positional vertigo. It may be useful to control dizziness or vertigo by reducing free radicals as a product of oxidative stress, and controlling oxidative stress may be a valuable approach in the treatment of patients with dizziness due to Méniè re's disease or benign paroxysmal positional vertigo.

Three auditory ossicles including the malleus, incus, and stapes conduct sound in the middle ear from the tympanic membrane to the inner ear. Auditory ossicles are massively resorbed by osteoclasts in Opg-/- mice, which lack osteoprotegerin (OPG), a soluble decoy receptor for the osteoclastogenic cytokine RANKL. Opg-/- mice exhibit progressive hearing loss and are a model for juvenile Paget's disease. However, effects of antiresorptive treatment on auditory ossicles and on hearing function in Opg-/- mice are unknown. We intraperitoneally injected Opg-/- mice with bisphosphonate risedronate 5 d/wk for 9 wk. Morphology of auditory ossicles was examined microscopically, radiographically, and histologically. Hearing function was monitored by measuring the auditory brain stem response (ABR). Control Opg-/- mice exhibited thinning of all three ossicles and tibia. In contrast, risedronate treatment significantly inhibited bone loss in auditory ossicles as well as in long bones of Opg-/- mice. Bony fusion of the junction between the stapes and the otic capsule was reduced after treatment. Moreover, ABR measurement showed that hearing in Opg-/- mice was significantly improved by risedronate treatment. These data suggest that hearing loss in pathologies characterized, by excessive resorption of the auditory ossicles may be prevented by bisphosphonates.

Allergic rhinitis is a condition which shows a high prevalence throughout the world. Once a person is sensitized to a specific allergen, spontaneous resolution of the allergy occurs only very rarely and this results in a steady accumulation of patient population. Worldwide attention to this affliction is being paid from both the medical and the economic perspectives. In Japan, the most typical seasonal allergic rhinitis is caused by cedar pollen during the spring months of late February to early May. Rough estimates of a 15 to 20% prevalence rate have been reported and hence Japanese cedar pollinosis is deemed as a national disease. The efficacy and cost-effectiveness of the treatment are of great concern to the social medical system of Japan. Previously there have been several reports regarding the cost-effectiveness of new medications and desensitization immunotherapy. The authors have previously reported their experience of treating allergic rhinitis with the Nd:YAG laser and its efficacy. However there are no reports, as of yet, on the cost-effectiveness of this procedure. The authors compared the costs of three typical treatment protocols for cedar pollenosis: Nd:YAG laser treatment, anti-histamine prescription and desensitization immunotherapy. The results revealed that the direct costs associated with the Nd:YAG laser treatment were less compared to the two other treatment protocols. The authors also believe that the indirect economical losses associated with allergic rhinitis such as loss of work force for hospital visits was also lessened with the Nd:YAG laser treatment.

Case presentation: We present a case of a patient who suffered from phobic postural vertigo. A 37-year-old female complained of dizziness. She had started experiencing dizziness almost 3 years She was intractable to many sort of conventional therapy. In the end, her symptom disappeared after introduction of autogenic training.Conclusion: Autogenic training can be a viable and acceptable treatment option for phobic postural vertigo patients who fail to respond to other therapies. This case emphasizes the importance of autogenic training as a method to control symptom of phobic postural vertigo.Background: Patients suffering from dizziness due to vertigo are commonly encountered in the department of otolaryngology. If various clinical examinations do not reveal any objective findings, then the patients are referred to the department of internal medicine or psychiatry. In many cases, the diagnosis is psychological dizziness. Phobic postural vertigo, which was first reported by Brandt T et al in 1994, is supposed to be a type of psychological dizziness. The diagnosis is based on 6 characteristics proposed by Brandt et al. Patients are usually treated with conventional medical therapy, but some cases may be refractory to such a therapy. Psychotherapy is recommended in some cases; however, psychotherapy including autogenic training, which can be used for general relaxation, is not widely accepted. This paper describes the successful administration of autogenic training in a patient suffering from phobic postural vertigo.

Introduction: Meniere's disease is generally observed in persons aged between 30 and 50 years old. However, with the aging of the population, one may expect an increase in the number of elderly patients with the disease. The current study was aimed at clarifying the prevalence and clinical characteristics of Meniere's disease in the elderly, especially in patients aged >65 years old at the onset of the disease. Methods: Statistical analysis was performed on the recorded data of patients with Meniere's disease who visited Hino Municipal Hospital from 2004 to 2007. Results: Our sample comprised 47 patients with Meniere's disease, with an average age of 54.9 ± 14.2 years. Patients who developed Meniere's disease at the age of ≥65 years were classified as de novo patients; the remaining patients were classified as non-de novo patients. There were 13 (27.7%) de novo patients (3 males and 9 females; average age: 73.4 ± 4.9 years). The observations showed that the worst hearing level exhibited by the de novo patients was significantly different from that exhibited by the non-de novo patients. As treatment for Meniere's disease, 6 (46.2%) of the de novo patients underwent tympanic tube insertion, while 4 of the 6 patients underwent middle ear pressure treatment with a Meniett device. Conclusion: De-novo patients were more frequently admitted, but there was no difference in the duration of hospitalization between the de novo and non-de novo patients. It can be quite stressful for elderly patients with Meniere's disease to call an ambulance to transport them to the hospital during a vertigo attack. Tympanic tube insertion was undertaken as treatment in many of the patients, but none of the patients received intratympanic gentamicin. It is important that physicians who care for elderly patients with Meniere's disease take special care of those experiencing vertigo. Early diagnosis of Meniere's disease should be made in the elderly.

Objective: We report a case of delayed endolymphatic hydrops due to complicating mumps virus infection that was treated with the Meniett device. Method: Case reports and a review of the world literature on delayed development of endolymphatic hydrops after mumps virus infection are presented. Results: The case of a woman who presented with unilateral, reversible sensorineural hearing loss following mumps infection and was successfully treated with the Meniett device is presented. This woman developed profound sensorineural hearing loss and intractable vertigo spells a few months after contracting mumps. In this case, the incubation period interval between the development of mumps infection and the diagnosis of DEH was only one year. DEH (Delayed endolymphatic hydrops) is a clinical entity characterized by profound sensorineural hearing loss in one ear during its early phase; after a prolonged period of time, DEH enters the late phase, which is characterized by different otologic symptoms. Although the most common causes of DEH are inflammation, trauma and other unidentified events during childhood, viral infections, including mumps, represent one of the known causes of DEH. Mumps infection sometimes represents a confirmed etiology of DEH Sometimes DEH can definitively be diagnosed as being caused by mumps infection. Conclusion: This is the first case report to demonstrate the efficacy of the Meniett device in the treatment of DEH due to complicating mumps infection.

We report on the long-term follow-up of 15 patients with steroid-dependent sensorineural hearing loss (SDSNHL), which was steroid dose dependent. We classified the patients into 2 groups: group A consisted of 6 patients with systemic SDSNHL, and group B consisted of 9 patients with inner-ear-specific SDSNHL without systemic disease. Group B patients were further classified as patients with slowly or rapidly progressive hearing loss. The yearly rate of hearing deterioration was greater in group B than in group A. Thus, the long-term hearing prognosis of patients in group B was worse than those in group A. Although SDSNHL may have immune-related origins, we hypothesize that hearing deterioration may be caused by proinflammatory cytokines because many of our cases exhibited abnormal immunological laboratory values and because many of these cases responded favorably to steroid treatment.

Outer hair cell (OHC) loss in the auditory sensory epithelium is a primary cause of noise-induced sensory-neural hearing loss (SNHL). To clarify the participation of glial cells in SNHL, we used an Alexander disease (AxD) mouse model. These transgenic mice harbor the AxD causal mutant of the human glial fibrillary acidic protein (GFAP) under the control of the mouse GFAP promoter. It is thought that GFAP aggregates compromise the function of astrocytes. In the auditory pathway, the formation of GFAP aggregates was observed only in GFAP-positive cells of the cochlear nerve. The presence of GFAP aggregates did not change auditory function at the threshold level. To assess the change in vulnerability to auditory excitotoxicity, both transgenic and control mice were treated with intense noise exposure. Auditory threshold shifts were assessed by auditory brainstem responses (ABR) at 1 and 4 weeks after noise exposure, and OHC damage was analyzed by quantitative histology at 4 weeks after exposure. Transgenic mice showed more severe ABR deficits and OHC damage, suggesting that cochlear nerve glial cells with GFAP aggregates play a role in noise susceptibility. Thus, we should focus more on the roles of cochlear nerve glial cells in SNHL.

Background: Sentinel nodes (SNs) are the lymph nodes that directly receive lymphatic flow from a primary cancer lesion. The SN concept implies that lymphatic metastasis initially occurs at SNs. SN navigation surgery can be introduced for cancers in which the SN concept is established. In SN navigation surgery, lymph node dissection beyond SNs can be omitted if SNs are metastasis free. Although the SN concept has been investigated frequently for oral and oropharyngeal cancer, it has so far been investigated less for laryngeal and hypopharyngeal cancer. In this study, we investigated whether the SN concept is applicable for laryngeal and hypopharyngeal cancer. Methods: Twenty patients with T2-T4 and clinically N0 laryngeal and hypopharyngeal cancer were recruited. 99mTc-phytate was injected into several sites surrounding the tumor on the day before surgery. Lymphoscintigrams were acquired from at least two different viewpoints. SNs were surveyed intraoperatively, and neck dissections including at least levels II, III, and IV were performed. Results: SNs had occult metastases in five cases. In the remaining 15 cases, neither SNs nor other lymph nodes contained metastases, consistent with the SN concept. There was one false-negative case showing delayed nodal metastasis 2 years after initial surgery. The overall accuracy of the SN concept was 95%. Conclusion: Our study shows that SN biopsy is a reliable strategy to determine correct lymph node status in N0 laryngeal and hypopharyngeal cancer. SN detection was valuable in evaluating the need for neck dissection, whether ipsilaterally or bilaterally.

Objective: It is well known that mucoepidermoid carcinoma (MEC) displays a variety of biological behaviors. While the high-grade type is a highly aggressive tumor, its low-grade counterpart usually demonstrates a more benign nature and several systems have, therefore, been proposed to grade this neoplasm. Methods: This report analyzes 43 patients suffering from head and neck MEC, who were treated in our department during the period from 1989 to 2005. The relationship between clinical and pathologic characteristics and survival rate was investigated. Results: The 5-year overall and disease-free survival rate was 62.3 and 57.2%. Multivariate analysis demonstrated that the parameters that significantly affected survival were the patient's age (P = 0.040) and treatment method (P = 0.011). Conclusions: The patient's age and treatment method is the prognostic parameter in this study. Although complete surgical resection is the standard treatment for MEC, we should aggressively consider adjunctive radiotherapy in those cases that have a high risk of recurrence and poor prognosis.

Introduction: The importance of the relationship between vertigo and headache, especially migraine, has been recognized. Vertigo has been found to be three times more common in patients with migraine than in controls, and migraine is found at a prevalence of 30%-50% in patients presenting with vertigo. Several authors have proposed different diagnostic criteria for defining migrainous vertigo and vestibular migraine. In this study, we attempted to clarify the current situation of migraine-related dizziness at our institute. Subjects and Methods: A retrospective review of 9 patients with migraine-related vertigo who visited our institute was conducted. We used the diagnostic criteria proposed by Neuhauser (2001). Results: Of the 9 patients, 1 was male and 8 were female; 6 patients had visited a neurosurgeon once, 3 patients had been diagnosed once as having Meniere's disease, although they had normal hearing. Calcium channel blockers, antidepressants, SSRIs (Selective Serotonin Reuptake Inhibitors) and anxiolytics had been prescribed as prophylactic agents. Of the 9 patients, 5 improved with the prophylactic treatment, 2 improved slightly, and 2 showed no change. The patients who showed improvement in the migraine with the prophylactic treatment also showed improvement of their vertigo at the same time. As acute-phase treatment NSAIDs (Non-Steroidal Anti-Inflammatory Drugs) and triptans were prescribed. Three patients had a past history of BPPV (benign paroxysmal positional vertigo). Conclusion: The importance of diagnosis of migrane-associated vertigo was confirmed, since both prophylactic and acute-phase treatment were effective against both migraine and vertigo in these patients. To obtain further evidence for the treatment of migraine-associated vertigo, a more organized study should be conducted. The relationship between BPPV and migraine-associated vertigo should also be investigated in a future study.

BACKGROUND: The present study was performed to quantitatively analyze the three-dimensional morphology of the nasal septa of patients with alveolar and alveolopalatal clefts. METHODS: Twenty-five unilateral complete cleft lip patients with alveolar clefts only (alveolar cleft group) and 35 unilateral complete cleft lip patients with alveolar and palatal clefts (alveolar and palatal cleft group) were included in the study. Although no patient in either group had undergone alveoloplasty, all patients had undergone palatoplasty. The degree of nasal septum deviation was studied for each patient at three different depths along the anteroposterior axis using three-dimensional computed tomographic data; the data were compared between the two groups to elucidate whether the difference in cleft type affects the morphologic patterns of the nasal septum. RESULTS: The nasal septa of the alveolar and palatal cleft group patients presented more uneven morphologic patterns than those of the alveolar cleft group patients. In the alveolar cleft group, the nasal septa did not present significantly different degrees of deviation at their anterior and posterior parts. In the alveolar and palatal cleft group, however, the posterior parts of the nasal septa presented greater deviation than the anterior parts. In the alveolar and palatal cleft group, furthermore, a significant correlation was observed between the severity of the cleft and the degree of the nasal septum deviation. CONCLUSIONS: The nasal septa present different three-dimensional morphologic patterns between the patients with alveolar clefts only and those with alveolopalatal clefts. This difference should be considered when performing surgical treatments for these patients.

Oxidative stress, including reactive oxygen species and other free radicals, is thought to play an important role in neuronal cell death, including noise-induced hearing loss. 1-{3-[2-(1-Benzothiophen-5-yl)ethoxy]propyl}azetidin-3-ol maleate (T-817MA), a novel neurotrophic agent, protects against oxidative stress-induced neurotoxicity. This study examines the effects of T-817MA in noise-induced ototoxicity in the cochlea. Guinea pigs received treatment with T-817MA-enhanced water (0.2, 0.7 mg/ml) or untreated water (control) beginning 10 days prior to noise exposure and continuing through this study. All subjects were exposed to 4-kHz octave-band noise at 120-dB SPL for 5 h. Auditory thresholds were assessed by sound-evoked auditory brainstem response at 4, 8, and 16 kHz, prior to and 10 days following noise exposure. Hair cell damage was analyzed by quantitative histology. T-817MA significantly reduced threshold deficits and hair cell death. These results suggest T-817MA reduces noise-induced hearing loss and cochlear damage, suggesting functional and morphological protection.

There are a number of genetic diseases that affect the cochlea early in life, which require normal gene transfer in the early developmental stage to prevent deafness. The delivery of adenovirus (AdV) and adeno-associated virus (AAV) was investigated to elucidate the efficiency and cellular specificity of transgene expression in the neonatal mouse cochlea. The extent of AdV transfection is comparable to that obtained with adult mice. AAV-directed gene transfer after injection into the scala media through a cochleostomy showed transgene expression in the supporting cells, inner hair cells (IHCs), and lateral wall with resulting hearing loss. On the other hand, gene expression was observed in Deiters cells, IHCs, and lateral wall without hearing loss after the application of AAV into the scala tympani through the round window. These findings indicate that injection of AAV into the scala tympani of the neonatal mouse cochlea therefore has the potential to efficiently and noninvasively introduce transgenes to the cochlear supporting cells, and this modality is thus considered to be a promising strategy to prevent hereditary prelingual deafness.

Proteins of the Bcl-2 family have been implicated in control of apoptotic pathways modulating neuronal cell death, including noise-induced hearing loss. In this study, we assessed the expressions of anti- and proapoptotic Bcl-2 genes, represented by Bcl-xL and Bak following noise exposures, which yielded temporary threshold shift (TTS) or permanent threshold shift (PTS). Auditory brainstem responses (ABRs) were assessed at 4, 8, and 16 kHz before exposure and on days 1, 3, 7, and 10 following exposure to 100 dB SPL, 4 kHz OBN, 1 hr (TTS) or 120 dB SPL, 4 kHz OBN, 5 hr (PTS). On day 10, subjects were euthanized. ABR thresholds increased following both exposures, fully recovered following the TTS exposure, and showed a 22.6 dB (4 kHz), 42.5 dB (8 kHz), and 44.9 dB (16 kHz) mean shift on day 10 following the PTS exposure. PTS was accompanied by outer hair cell loss progressing epically and basally from the 4-kHz region. Additional animals were euthanized for immunohistochemical assessment. BcL-xL was robustly expressed in outer hair cells following TTS exposure, whereas Bak was expressed following PTS exposure. These results indicate an important role of the Bcl-2 family proteins in regulating sensory cell survival or death following intense noise. Bcl-xL plays an essential role in prevention of sensory cell death following TTS levels of noise, and PTS exposure provokes the expression of Bak and, with that, cell death.

We recently showed that acute energy failure in the rat cochlea induced by local administration of the mitochondrial toxin 3-nitropropionic acid (3-NP) causes hearing loss mainly due to degeneration of cochlear lateral-wall fibrocytes. In the present study, we analyzed the effect of the pan-caspase inhibitor z-Val-Ala-Asp(Ome)-fluoromethylketone (Z-VAD-FMK) on 3-NP-induced hearing loss in a model showing temporary threshold shifts at low frequencies and permanent threshold shifts at high frequencies. The model rats received an intraperitoneal injection of either Z-VAD-FMK or vehicle for 3 days starting 1 day prior to 3-NP treatment. One day after the administration of 3-NP, the auditory brain-stem response (ABR) threshold at 20 kHz was elevated to 70 dB in the Z-VAD-FMK group and to 85 dB in controls. The Z-VAD-FMK group completely recovered to the preoperative level within 14 days, whereas in the controls, the ABR threshold remained elevated at 50 dB even 28 days after the administration of 3-NP. Treatment with Z-VAD-FMK also improved recovery of hearing at 8 kHz but did not change recovery at 40 kHz. Histological examination demonstrated that treatment with Z-VAD-FMK inhibited progressive degeneration of the lateral-wall fibrocytes in the cochlear basal turn, as well as apoptosis of these fibrocytes. These results clearly indicate that caspase-dependent apoptosis of fibrocytes in the cochlear lateral wall plays an important role in hearing loss in the present animal model. Moreover, the results of the present study suggest that systemic administration of a caspase inhibitor may be an effective therapy for sensorineural hearing loss caused by acute energy failure such as that observed in cochlear ischemia.

Background: Psychological stress plays an important role in the onset and course of Meniere's disease. Surgical therapy and intratympanic gentamicin treatment are options for cases that are intractable to conventional medical therapy. Psychotherapy, however, including autogenic training (AT), which can be used for general relaxation, is not widely accepted. This paper describes the successful administration of AT in a subject suffering from intractable Meniere's disease. Case presentation: A 51-year-old male patient has suffered from fluctuating right sensorineural hearing loss with vertigo since 1994. In May 2002, he was first admitted to our hospital due to a severe vertigo attack accompanied by right sensorineural hearing loss. Spontaneous nystagmus toward the right side was observed. Since April 2004, he has experienced vertigo spells with right-sided tinnitus a few times per month that are intractable to conventional medical therapy. After four months, tympanic tube insertion was preformed in the right tympanic membrane. Intratympanic injection of dexamethasone was ineffective. He refused Meniett therapy and intratympanic gentamicin injection. In addition to his vertigo spells, he suffered from insomnia, tinnitus, and anxiety. Tranquilizers such as benzodiazepines and antidepressants such as serotonin selective re-uptake inhibitors (SSRIs) failed to stop the vertigo and only slightly improved his insomnia. In December 2006, the patient began psychological counseling with a psychotherapist. After brief psychological counseling along with cognitive behavior therapy (CBT), he began AT. He diligently and regularly continued his AT training in his home according to a written timetable. His insomnia, tinnitus, and vertigo spells disappeared within a few weeks after only four psychotherapy sessions. In order to master the six standard formulas of AT, he underwent two more sessions. Thereafter, he underwent follow-up for 9 months with no additional treatment. He is now free from drugs, including tranquilizers, and has continued AT. No additional treatment was performed. When we examined him six and nine months later for follow-up, he was free of vertigo and insomnia. Conclusion: AT together with CBT can be a viable and palatable treatment option for Meniere's disease patients who are not responsive to other therapies.

Most parapharyngeal space tumors are benign, and malignancies are rare. We report the results of a retrospective review of patients with primary parapharyngeal space malignant tumors treated at our institution from 1994 to 2007. During this period, 42 patients seen at our institution were found to have parapharyngeal space tumors. Six tumors (14.3%) were malignant and 36 (85.7%) were benign. Six of 21 (28.6%) prestyloid tumors were malignant, and malignant tumors were all found in the prestyloid region in MRI. There were three carcinoma ex pleomorphic adenomas and one each of salivary duct carcinoma and liposarcoma and chordoma. Four of the six tumors were diagnosed as benign preoperatively. Prestyloid parapharyngeal space tumors should be indicated for surgery even if they are asymptomatic, because preoperative diagnosis is difficult. It was difficult to deal with tumors that were revealed to be malignant postoperatively. Postoperative adjuvant therapy should be considered case by case by referring to the histology and surgical margin, because malignant parapharyngeal space tumors are heterogeneous. If tumors recur, it is important to follow up strictly to salvage them.

It is not easy to treat patients with intractable Meniere's disease. Intratympanic injection of gentamicin or steroid is one option. The other is a surgical procedure like endolymphatic shunt surgery. Middle ear pressure treatment using the Meniett device, which has not been approved by the Japanese government is widely accepted in foreign countries. We had a chance to use this Meniett device under approval of the ethic's committee of Hino Municipal Hospital since September 2004. (Methods) Four patients with intractable Meniere's disease who suffered intensive vertigo attack for more than 5 months with conservative medical treatment were employed in the study. Ages ranged from 67 to 72, with 3 females and 1 male. After a ventilation tube was inserted under local anesthesia, treatment with the Meniett was performed 3 times a day at home. (Results) Two patients improved and 2 slightly improved concerning vertigo attacks. One showed no change, 1 experienced a worsening, and 2 showed slight improvement concerning the hearing level. (Conclusion) The Meniett device is less invasive and may be suitable for elderly patients who prefer conservative treatment. The mechanism involved in the reduction of vertigo attacks is not clear so far, but we speculate that middle ear pressure may suppress serum vasopressin (antidiuretic hormone) secretion and thereby reduce endolymphatic hydrops. It is necessary to accumulate treatment data with the Meniett in Japan to obtain official approval by the government.