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Koji Iida

Publications and source records attributed to Koji Iida.

At least 19 recordsLinked to original sources
PubMed2006

Effects of heat stress on Young's modulus of outer hair cells in mice.

Intense sound exposure causes permanent hearing loss due to hair cell and cochlear damage. Prior conditioning with sublethal stressors, such as nontraumatic sound, heat stress and restraint protects the ear from acoustic injury. However, the mechanisms underlying conditioning-related cochlear protection remain unknown. In this paper, Young's modulus and the amount of filamentous actin (F-actin) of outer hair cells (OHCs) with/without heat stress were investigated by atomic force microscopy and confocal laser scanning microscopy, respectively. Conditioning with heat stress resulted in a statistically significant increase in Young's modulus of OHCs at 3-6 h after application, and such modulus then began to decrease by 12 h and returned to pre-conditioning level at 48 h after heat stress. The amount of F-actin began to increase by 3 h after heat stress and peaked at 12 h. It then began to decrease by 24 h and returned to the pre-conditioning level by 48-96 h after heat stress. These time courses are consistent with a previous report in which heat stress was shown to suppress permanent threshold shift (PTS). In addition, distortion product otoacoustic emissions (DPOAEs) were confirmed to be enhanced by heat stress. These results suggest that conditioning with heat stress structurally modifies OHCs so that they become stiffer due to an increase in the amount of F-actin. As a consequence, OHCs possibly experience less strain when they are exposed to loud noise, resulting in protection of mammalian hearing from traumatic noise exposure.

Acoustic Stimulation↗
PubMed2006

Imaging by atomic force microscopy of the plasma membrane of prestin-transfected Chinese hamster ovary cells.

The high sensitivity of mammalian hearing is achieved by amplification of the motion of the cochlear partition. This cochlear amplification is thought to be generated by the elongation and contraction of outer hair cells (OHCs) in response to acoustical stimulation. This motility is made possible by a membrane protein embedded in the lateral membrane of OHCs. Although a fructose transporter, GLUT-5, was initially proposed to be this protein, a later study identified the gene of the motor protein distributed throughout the OHC plasma membrane. This protein has been named "prestin." However, although previous morphological studies by electron microscopy and atomic force microscopy (AFM) found the lateral wall of OHCs to be covered with 10-nm particles, believed to be motor proteins, it is unknown whether such particles consist only of prestin or are a complex of GLUT-5 and prestin molecules. To determine if the 10-nm particles are indeed constituted only of prestin, plasma membranes of prestin-transfected and untransfected Chinese hamster ovary (CHO) cells, which do not express GLUT-5, were observed by AFM. First, the cells attached to a substrate were sonicated so that only the plasma membrane remained on the substrate. The cytoplasmic face of the cell was observed by the tapping mode of the AFM in liquid. As a result, particle-like structures were recognized on the plasma membranes of both the prestin-transfected and untransfected CHO cells. Comparison of the difference in the frequency distribution of these structures between those two cells showed approximately 75% of the particle-like structures with a diameter of 8-12 nm in the prestin-transfected CHO cells to be possibly constituted only by prestin molecules. Our data suggest that the densely packed 10-nm particles observed on the OHC lateral wall are likely to be constituted only of prestin molecules.

Animals↗
PubMed2006

Local mechanical properties of mouse outer hair cells: atomic force microscopic study.

OBJECTIVES: Outer hair cells (OHCs) are capable of altering their cell length in response to changes in membrane potential. Due to this electromotility, OHCs probably subject the basilar membrane to force, resulting in cochlear amplification. To understand the mechanism of such amplification, knowledge of the mechanical properties of OHCs is required since the force produced by OHC electromotility is thought to depend on such properties. Various studies have been conducted to investigate the mechanical properties of guinea pig OHCs. With regard to mice, however, although various kinds of transgenic and knockout mice possess great potential as research models, the mechanical properties of mouse OHCs have not as yet been reported since the cells and/or tissues in the mouse hearing organ are relatively small and vulnerable to external stimuli, rendering sample preparation difficult. In this study, therefore, to establish indicators of the mechanical properties of OHCs in mice, such properties were measured by atomic force microscopy (AFM). METHODS: CBA/JNCrj strain male mice aged 10-12 weeks (25-30 g) were used. Cochleae were dissected out from the animal and both the basilar membrane and the organ of Corti were simultaneously unwrapped from the modiolus with forceps. Dissected coiled tissue was then incubated with an enzymatic digestion medium for 15 min. After digestion, OHCs were isolated by gently triturating the coiled tissue. Local mechanical properties of the OHCs were then measured by an indentation test using an AFM. RESULTS: Young's modulus and stiffness of the OHC in the apical turn of the mouse cochlea were 2.1+/-0.5 kPa and 4.4+/-1.2 mN/m, respectively. CONCLUSIONS: Young's modulus of the OHC in the apical turn of the cochlea in mice was roughly the same as that in the apical turn of the cochlea in guinea pigs; however, the stiffness of the former was about two times greater than that of the latter because the cell length of the former was shorter than that of the latter.

Animals↗
PubMed2006

Efficacy of dexamathasone on cerebral swelling and seizures during subdural grid EEG recording in children.

PURPOSE: To evaluate the impact of steroid treatment on cerebral swelling and seizures during subdural grid EEG (SGEEG) monitoring. METHODS: We reviewed data from 37 pediatric patients with intractable epilepsy who underwent SGEEG monitoring and divided the patients into those who received dexamethasone and those who did not. We then correlated administration of steroids to incidence of cerebral swelling on computed tomography (CT) scans and to frequency of seizures during SGEEG. RESULTS: Twenty-three patients received dexamethasone prophylactically every 6 hours (dosage range, 1-7.5 mg; mean, 3.2 mg) from the first day of SGEEG placement (group A); 14 patients received no dexamethasone (group B). Eight (21.6%) of 37 patients experienced cerebral swelling on CT: two (9%) were in group A, and six (42.9%) were in group B (p < 0.05). SGEEG monitoring time for recording habitual seizures that localized cortical areas for surgical excision was longer in group A (1-6 days; mean, 3.0) than it was in group B (1-3 days; mean, 2.2), (p < 0.05). Habitual seizures were recorded in 36 patients. One group A patient experienced obtundation due to cerebral swelling, and monitoring in this patient was discontinued. CONCLUSIONS: The prophylactic administration of steroids to pediatric patients during SGEEG monitoring is efficacious for reducing cerebral swelling. Although it decreases the frequency of habitual seizures and increases seizure-monitoring time, dexamethasone reduces the risk of complications from cerebral swelling during the SGEEG procedure.

Adolescent↗
PubMed2006

Natural course of incidentally found nonfunctioning pituitary adenoma, with special reference to pituitary apoplexy during follow-up examination.

OBJECT: The increase in the incidental detection of asymptomatic pituitary adenomas, known as "pituitary incidentalomas," led the authors to conduct a survey of the natural course of these lesions. METHODS: Forty-two patients with clinically nonfunctioning pituitary adenomas who had manifested no neurological or endocrinological disorders were monitored with magnetic resonance imaging studies. The follow-up period ranged from 10.8 to 168.2 months (mean +/- standard deviation, 61.9 +/- 38.2 months). The mean initial tumor size was 18.3 +/- 7 mm. In 21 patients, the tumor increased by at least 10% of its measured size on detection. This increase was first detected between 8.4 and 58.8 months (mean 31.8 +/- 17.6 months) after diagnosis. There was no correlation between the original tumor size, patient age, or the presence of intratumoral cysts and tumor growth. Symptoms were noted in 10 patients during follow up; in four, extensive tumor necrosis accompanied hemorrhage, leading to severe headache, acute ophthalmological symptoms, and panhypopituitarism, which was indicative of pituitary apoplexy. Transsphenoidal surgery was performed in 12 patients with enlarged tumors, including three with apoplexy. With the exception of one apoplectic patient, visual function was recovered in all who underwent surgery. All apoplectic patients continue to manifest hypopituitarism. CONCLUSIONS: In the course of 4 years, the size of the incidentalomas increased in 40% of 42 patients and became symptomatic in 20%. During the 5-year follow up, pituitary apoplexy developed in 9.5%. These findings may justify early intervention, especially in young individuals with incidentally found macroadenoma.

Adenoma↗
PubMed2006

Preoperative simulation of intracerebral epileptiform discharges: synthetic aperture magnetometry virtual sensor analysis of interictal magnetoencephalography data.

OBJECT: Magnetoencephalography (MEG) has been used for the preoperative localization of epileptic equivalent current dipoles (ECDs) in neocortical epilepsy. Spatial filtering can be applied to MEG data by means of synthetic aperture magnetometry (SAM), and SAM virtual sensor analysis can be used to estimate the strength and temporal course of the epileptic source in the region of interest. To evaluate the clinical usefulness of this approach, the authors compare the results of SAM virtual sensor analysis to the results of ECD analysis, subdural electroencephalography (EEG) findings, and surgical outcomes in pediatric patients with neocortical epilepsy. METHODS: Ten pediatric patients underwent MEG, invasive subdural EEG, and cortical resection for neocortical epilepsy. The authors compared the morphological characteristics, quantity, location, and distribution of the epileptiform discharges assessed using SAM and ECD analysis, and subdural EEG findings (interictal discharges and ictal onset zones). In nine patients, MEG revealed clustered ECDs. The region exhibiting the maximum percentage (> or = 70%) of spikes/sharp waves on SAM was colocalized to clustered ECDs in seven patients. In six patients, SAM demonstrated focal spikes; in two, diffuse spikes; and in two others, focal rhythmic sharp waves. These epileptiform discharges were similar to those recorded on subdural EEG. In nine patients, concordant regions containing the maximum percentage of spikes/sharp waves were revealed by SAM and subdural EEG data. The region of the maximum percentage of spikes/sharp waves as demonstrated by SAM was colocalized to the ictal onset zone identified by subdural EEG findings in seven patients and partially colocalized in two. CONCLUSIONS: The SAM virtual sensor analysis revealed morphological characteristics, location, and distribution of epileptiform discharges similar to those shown by subdural EEG recordings. By using SAM it is possible to predict intracerebral interictal epileptiform discharges in the region of interest from noninvasively collected preoperative MEG data. The maximum interictal discharge zone identified by SAM virtual sensors correlated to clustered ECDs and the ictal onset zone on subdural EEG findings. Complementary analyses of ECDs and SAM on three-dimensional MR images can improve delineation of epileptogenic zones and lesions in neocortical epilepsy.

Adolescent↗
PubMed2006

Zygomatic osteotomy for resection of medial temporal cavernous angioma in dominant hemisphere after subdural grid electroencephalographic study.

We report the treatment of a patient suffering from intractable epilepsy caused by a large cavernous angioma in the hippocampus of his dominant hemisphere. Surgical removal of a lesion and epileptic focus located in the surrounding brain tissue significantly improves seizure conditions. However, total removal of a large cavernous angioma in the medial temporal structure of dominant hemisphere is occasionally difficult because of the depth of the lesion and its contiguity with eloquent brain structures. Furthermore, when an intracranial electrocorticogram with grid electrodes is adopted, swelling of soft tissue caused by the initial operation for the installation of the grid electrodes narrows the operative view obtained by conventional frontotemporal craniotomy. We added a zygomatic osteotomy to the operative procedure for the present patient, and this enabled us to push soft tissue down and away from the operative field to provide a wider operative corridor through which total removal of the lesion and epileptic focus was accomplished. The patient has had a favorable postoperative course without suffering any seizure for 4 years.

Adult↗
PubMed2005

Construction of an expression system for the motor protein prestin in Chinese hamster ovary cells.

The electromotility of outer hair cells (OHCs) is believed to be a major factor in cochlear amplification that enables the high sensitivity of hearing in mammals. This motility is thought to be based on voltage-dependent conformational changes of a motor protein embedded in the lateral wall of the OHC. In 2000, this motor protein was identified and termed prestin. To obtain knowledge on the function of prestin, research at the molecular level is necessary. For this purpose, a method of obtaining a large amount of prestin is required. In this study, an attempt was therefore made to construct an expression system for prestin. Prestin cDNA was introduced into Escherichia coli (E. coli), insect cells and Chinese hamster ovary (CHO) cells, and the expression of prestin was examined by Western blotting. As CHO cells expressed prestin well, we generated prestin-expressing cell lines using CHO cells by limiting dilution cloning. The stable expression and the activity of prestin in generated cell lines were then confirmed. Finally, to obtain prestin from these cell lines efficiently, culture conditions of the cells were examined, and it was clarified that cells should be cultured in serum-free medium and harvested around 48 h after passage.

Animals↗
PubMed2005

Cortical resection with electrocorticography for intractable porencephaly-related partial epilepsy.

PURPOSE: We evaluated the results of cortical resection of epileptogenic tissue for treatment of intractable porencephaly-related epilepsy. METHODS: We examined clinical features, electrophysiological data, surgical findings, and seizure outcomes after cortical resection in eight patients with intractable epilepsy related to porencephalic cysts. RESULTS: All eight patients had hemiparesis. Five retained motor function in the hemiparetic extremities; six retained visual fields. All had partial seizures, six with secondary generalization. Seven patients had simple and three had complex partial seizures (CPSs); two also had drop attacks. Four patients had multiple seizure types. Long-term scalp video-EEG (LVEEG) localized interictal epileptic abnormalities that anatomically corresponded to the cyst location in three patients. LVEEG recorded ictal-onset zones in five; these anatomically corresponded to the cyst location in three of the five. EEG recorded generalized seizures in two patients, hemispheric in one, and multifocal in two. Intraoperative electrocorticography (ECoG) revealed interictal epileptic areas extending beyond the margins of the cyst in seven patients. We resected ECoG-localized interictal epileptic areas completely in five patients and partially in two. Cortical resection was based on seizure semiology and LVEEG in one patient whose ECoG showed no epileptiform discharges. After a minimum follow-up of 1 year, six patients had excellent seizure outcome (Engel class I), and two had a >90% seizure reduction (Engel class III) without complications. CONCLUSIONS: Cortical resection guided by ECoG allows preservation of motor function and visual field and provides an effective surgical procedure for treatment of intractable epilepsy secondary to porencephaly.

Adolescent↗
PubMed2005

Characterizing magnetoencephalographic spike sources in children with tuberous sclerosis complex.

PURPOSE: Tuberous sclerosis complex (TSC) often causes medically intractable seizures. Magnetoencephalography (MEG) localizes epileptiform discharges. To evaluate the use of MEG spike sources (MEGSSs) for localizing epileptic zones in TSC patients, we characterized MEGSSs and correlated them to EEG and magnetic resonance imaging (MRI) results. METHODS: We analyzed data from seven children who underwent prolonged video-EEG, MEG, and MRI. We classified MEGSSs as clusters (six or more spike sources, 1 cm between sources regardless of number of sources). RESULTS: A single, unilateral cluster with additional scatters occurred in two patients; these predominantly lateralized dipoles correlated to prominent tubers on MRI and ictal/interictal EEG zones. Bilateral clusters with scatters existed in two patients; cluster locations partly overlapped multiple prominent tubers. These patients also had bilateral or diffuse interictal discharges, bilateral or generalized seizures, and changing seizure types and EEG findings. Only bilateral scatters occurred in three patients; scatters partly overlapped EEG interictal/ictal-onset regions; one patient had coexisting generalized seizures. In one patient with equally bilateral scatters, scatters overlapped a prominent tuber and interictal/ictal-onset zones in the right frontal region. CONCLUSIONS: MEG contributes to information from EEG and MRI for localizing epileptogenic zones in children with TSC. A single cluster with scatters in a unilateral hemisphere predicts a primary epileptogenic zone or hemisphere; bilateral or multiple clusters indicate bilateral primary or potential epileptogenic zones; and bilateral scatters without clusters may indicate epileptogenic zones that are hidden within extensive areas of scattered MEGSSs.

Brain Mapping↗
PubMed2005

Neurophysiologic findings of neuronal migration disorders: intrinsic epileptogenicity of focal cortical dysplasia on electroencephalography, electrocorticography, and magnetoencephalography.

We define specific neurophysiologic characteristics for focal cortical dysplasia, a neuronal migration disorder. We reviewed data from published reports and our patients with focal cortical dysplasia. Our patients underwent preoperative scalp video-electroencephalography (EEG), magnetic resonance imaging (MRI), magnetoencephalography, and intraoperative or extraoperative electrocorticography monitoring. Scalp EEG showed trains of rhythmic epileptiform spike or sharp waves. Positive spikes correlated with early seizure onset, MRI lesion around the rolandic fissure, hemiparesis, and a less favorable outcome. Interictal electrocorticography showed continuous epileptogenic discharges: repetitive electrographic seizures and bursting discharges or continuous or quasicontinuous rhythmic spiking. Ictal electrocorticography showed paroxysmal fast and/or repetitive spiking. Magnetoencephalography showed clustered spike sources within and extending from the lesion. Cortical stimulation gave more frequent, lower-threshold afterdischarges and higher-threshold primary motor function. Focal cortical dysplasias are highly and intrinsically epileptogenic. For surgical seizure control, EEG, electrocorticography, and magnetoencephalography must delineate the intrinsic epileptogenic zone within and extending from the focal cortical dysplasia identified by MRI.

Brain Mapping↗
PubMed2005

Identifying the primary epileptogenic hemisphere from electroencephalographic (EEG) and magnetoencephalographic dipole lateralizations in children with intractable epilepsy.

We used electroencephalographic (EEG) and magnetoencephalographic dipole lateralizations to identify the primary epileptogenic hemisphere in 41 children with intractable localization-related epilepsy. We compared EEG and magnetoencephalographic dipole lateralizations, EEG ictal onsets, and magnetic resonance images (MRIs). Concordant lateralization of EEG and magnetoencephalographic dipoles (> 50% of each lateralizing to the same hemisphere) occurred in 34 patients, with EEG ictal onsets in the same hemisphere in 23 (68%) and concordant MRI lesions in 23 (68%). Focal resection in 16 of 20 patients resulted in a good surgical outcome. Of the seven children with nonconcordant magnetoencephalographic and EEG lateralizations, one (14%) had EEG ictal onset and one (14%) had MRI lesions that lateralized; none had surgery. The relationship between lateralized EEG and magnetoencephalographic dipoles forecasts surgical candidacy. Concordant lateralizations predict good seizure control after surgery by identifying the primary epileptogenic hemisphere. Discordant lateralizations signify an undetermined epileptogenic hemisphere and contraindicate surgery without further testing.

Child↗
PubMed2005

Hypothalamic hamartoma.

The incidence of hypothalamic hamartomas (HHs) has increased since the introduction of magnetic resonance (MR) imaging. The etiology of this anomaly and the pathogenesis of its peculiar symptoms remain unclear, but recent electrophysiological, neuroimaging, and clinical studies have yielded important data. Categorizing HHs by the degree of hypothalamic involvement has contributed to the accurate prediction of their prognosis and to improved treatment strategies. Rather than undergoing corticectomy, HH patients with medically intractable seizures are now treated with surgery that targets the HH per se, e.g. HH removal, disconnection from the hypothalamus, stereotactic irradiation, and radiofrequency lesioning. Although surgical intervention carries risks, total eradication or disconnection of the lesion leads to cessation or reduction of seizures and improves the cognitive and behavioral status of these patients. Precocious puberty in HH patients is safely controlled by long-acting gonadotropin-releasing hormone agonists. The accumulation of knowledge regarding the pathogenesis of symptoms and the development of safe, effective treatment modalities may lead to earlier intervention in young HH patients and prevent the decline in their cognitive abilities and quality of life. This review of hypothalamic hamartomas presents current classifications, pathophysiologies, and treatment modalities.

Hamartoma↗
PubMed2005

Characterizing magnetic spike sources by using magnetoencephalography-guided neuronavigation in epilepsy surgery in pediatric patients.

OBJECT: The authors sought to validate magnetoencephalography spike sources (MEGSSs) in neuronavigation during epilepsy surgery in pediatric patients. METHODS: The distributions of MEGSSs in 16 children were defined and classified as clusters (Class I), greater than or equal to 20 MEGSSs with 1 cm or less between MEGSSs; small clusters (Class II), 6 to 19 with 1 cm or less between; and scatters (Class III), less than 6 or greater than 1 cm between spike sources. Using neuronavigation, the MEGSSs were correlated to epileptic zones from intra- and extraoperative electrocorticography (ECoG), surgical procedures, disease entities, and seizure outcomes. Thirteen patients underwent MEGSSs: nine had clusters; two had small clusters, one with and one without clusters; and three had scatters alone. All 13 had scatters. Clusters localized within and extended from areas of cortical dysplasia and at margins of tumors or cystic lesions. All clusters were colocalized to ECoG-defined epileptic zones. Four of 10 patients with clusters and/or small clusters underwent complete excisions, and six underwent partial excision with or without multiple subpial transections. In the three patients with scatters alone, ECoG revealed epileptic zones buried within MEGSS areas; these regions of scatters were completely excised and treated with multiple subpial transections. Coexisting scatters were left untreated in nine of 10 patients. Postoperatively, nine of 13 patients were seizure free; the four patients with residual seizures had clusters in unresected eloquent cortex. Three patients in whom no MEGSSs were demonstrated underwent lesionectomies and were seizure free. CONCLUSIONS: Magnetoencephalography spike source clusters indicate an epileptic zone requiring complete excision. Coexisting scatters remote from clusters are nonepileptogenic and do not require excision. Scatters alone, however, should be examined by ECoG; an epileptic zone may exist within these distributions.

Adolescent↗
PubMed2005

Startle-induced seizures associated with infantile hemiplegia: implication of the supplementary motor area.

This case illustrates an uncommon form of symptomatic startle-induced epilepsy associated with infantile hemiplegia. Seizure semiology, neuroimaging and neurophysiological findings support involvement of the supplementary motor area in the generation of this seizure type. We present the case of an 11-year-old girl with an uncommon form of startle-induced seizures, illustrated on video-EEG, against the background of left infantile hemiplegia associated with extensive right hemispheric porencephaly but preserved cognitive functioning. The epileptic focus appears to be in the dorsolateral frontal lobe, with seizure semiology involving the supplementary motor cortex.

Child↗
PubMed2004

Three-dimensionally reconstructed magnetic source imaging and neuronavigation in pediatric epilepsy: technical note.

OBJECTIVE: To determine the role of reconstructing three-dimensional magnetic source imaging (MSI) data on cortical resections for children undergoing epilepsy surgery using neuronavigation. METHODS: Magnetoencephalographic recordings were analyzed in 16 children under 18 years of age with intractable epilepsy. The data were transferred to the neuronavigation workstation for intraoperative localization of MSI spike sources in selected patients. With the aid of neuronavigation, the MSI spike sources were resected. Intraoperative electrocorticography was then used to survey the surrounding field for residual epileptiform activity. RESULTS: MSI spike sources were obtained in 13 of 16 patients. MSI spike sources localized the cortical and subcortical discharges before intraoperative electrocorticography in nine patients and before extraoperative subdural grid electroencephalographic monitoring in four patients. The localization of MSI spikes sources was characterized by clustered spike sources in 10 patients. By use of neuronavigation, the clustered spike sources were correlated to the interictal zone indicated by intraoperative electrocorticography in six patients and to the ictal onset zone shown on extraoperative subdural grid electroencephalography in three patients. Cortical excision of the spike cluster focus was then performed in these six patients. The technique used here to resect MSI spike source clusters that correlate with the ictal onset zone by invasive subdural grid monitoring is illustrated in one patient who underwent cortical resection for epilepsy surgery. CONCLUSION: Three-dimensional reconstruction of MSI data linked to neuronavigation is a promising technique to facilitate resections around eloquent cortex in children with epilepsy.

Adolescent↗
PubMed2003

Mortality in 154 surgically treated patients with acromegaly--a 10-year follow-up survey.

To determine the effects of surgery and adjuvant therapy on the mortality rate of Japanese patients with acromegaly, 154 surgically treated patients were followed until death or December 2000. Mean follow-up period was 10.0 +/- 6.5 (SD) years. Postoperative GH levels, mean values of GH levels measured in the first postoperative month, were <2.5 ng/mL in 73 (47.4%), 2.5-5.0 ng/mL in 50 (32.5%), and >5.0 ng/mL in 31 patients (20.1%). Three of 123 patients with postoperative GH levels <5.0 ng/mL underwent a second transsphenoidal surgery (TSS), the other 120 received no further treatment. Additional treatments, including second TSS, medical treatment, and gamma-knife irradiation for residual tumor, were administered to 25 of 31 patients whose postoperative GH was >5.0 ng/mL. Among the total 154 patients surveyed, 11 (7.1%) died during the follow-up period. The standard mortality ratio (SMR) was 1.17, not different from age- and sex-matched controls. The SMR of the 72 patients with postoperative GH <2.5 ng/mL was better than that of the 51 patients whose postoperative GH was 2.5-5.0 ng/mL (1.09 vs. 1.64); however, the difference was not statistically significant. In conclusion, TSS and adequate adjuvant treatment decreased the excess mortality rate of acromegalics to nearly the same level as that of the general Japanese population.

Acromegaly↗