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ABSTRACT: The distribution and abundance of the calcium binding protein, calbindin D-28k (CB) immunoreactivity in the taste buds of the circumvallate papillae and larynx were compared between normoxic and chronically hypoxic rats (10% O2 for 8 weeks). In the normoxic rats, CB immunoreactivity was observed in some cells and fibers of the intragemmal region of the taste buds in the circumvallate papillae. In contrast, in the subgemmal region of the laryngeal taste buds, fibers but not cells were immunoreactive for CB. In chronically hypoxic rats, CB immunoreactive cells and fibers in the taste buds were decreased in the circumvallate papillae. In the laryngeal taste buds, the density of the subgemmal CB immunoreactive fibers in chronically hypoxic rats was greater than in normoxic rats. It is considered that function of the laryngeal taste buds is different from that of the lingual taste buds, so that laryngeal taste buds may be involved in chemosensation other than taste. The altered density of CB immunoreactive cells and fibers in the lingual and laryngeal taste buds is a predominant feature of hypoxic adaptation, and chronic hypoxic exposure might change the chemical sensitivity of the circumvallate papillae and larynx through the regulation of intracellular Ca2+.
Histology and histopathology 01/2007; 21(12):1271-6. · 2.48 Impact Factor
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ABSTRACT: Three types of hypoxia with different levels of carbon dioxide (hypocapnic, isocapnic, and hypercapnic hypoxia) have been called systemic hypoxia. The systemic hypoxic carotid bodies were enlarged several fold, but the degree of enlargement was different for each. The mean short and long axes of hypocapnic and isocapnic hypoxic carotid bodies were 1.6 (short axis) and 1.8-1.9 (long axis) times larger than normoxic control carotid bodies, respectively. Those of hypercapnic hypoxic carotid bodies were 1.2 (short axis) and 1.5 (long axis) times larger than controls, respectively. The rate of enlargement in hypercapnic hypoxic carotid bodies was lower than in hypocapnic and isocapnic hypoxic carotid bodies. The rate of vascular enlargement in hypercapnic hypoxic carotid bodies was also smaller than in hypocapnic and isocapnic hypoxic carotid bodies. Thus, the enlargement of hypoxic carotid bodies is mainly due to vascular dilation. Different levels of arterial CO2 tension change the peptidergic innervation during chronically hypoxic exposure. The characteristic vascular arrangement was under the control of altered peptidergic innervation. During the course of hypoxic adaptation, the enlargement of the carotid bodies with vascular expansion began soon after the start of hypoxic exposure. During the course of recovery, the shrinking of the carotid bodies with vascular contraction also started at a relatively early period after the termination of chronic hypoxia. These processes during the course of hypoxic adaptation and during the course of recovery were under the control of peptidergic innervation. These findings may provide a standard for further studies of hypoxic carotid bodies.
Histology and histopathology 08/2005; 20(3):987-97. · 2.48 Impact Factor
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ABSTRACT: Morphological changes in the rat carotid bodies 1, 2, 4, and 8 weeks after the termination of chronically hypocapnic hypoxia (10% O2 for 8 weeks) were examined by means of morphometry and immunohistochemistry. The rat carotid bodies after 8 weeks of hypoxic exposure were enlarged several fold with vascular expansion. The carotid bodies 1 and 2 weeks after the termination of 8 weeks of hypoxic exposure were diminished in size, although their diameter remained larger than the normoxic controls. The expanded vasculature in chronically hypoxic carotid bodies returned to the normoxic control state. In the carotid bodies 1 week after the termination of chronic hypoxia, the density of NPY fibers was remarkably increased and that of VIP fibers was dramatically decreased in comparison with the density in chronically hypoxic carotid bodies. In the carotid bodies 2 and 4 weeks after the termination of hypoxia, the density of SP and CGRP fibers was gradually increased. In the carotid bodies 8 weeks after the termination of hypoxia, the appearance of the carotid body returned to a nearly normoxic state, and the density of SP, CGRP, VIP, and NPY fibers also recovered to that of normoxic controls. These results suggest that the morphological changes in the recovering carotid bodies start at a relatively early period after the termination of chronic hypoxia, and a part of these processes may be under the control of peptidergic innervation.
Histology and histopathology 11/2004; 19(4):1133-40. · 2.48 Impact Factor
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H Katori,
M Tsukuda,
I Mochimatu,
J Ishitoya,
S Kawai,
Y Mikami, H Matsuda,
Y Tanigaki,
C Horiuchi,
Y Ikeda,
T Taguchi,
M Ono,
T Yoshida,
S Hirose,
Y Sakuma,
K Yamamoto
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ABSTRACT: The aim of this study was to evaluate the efficacy and toxicity of a concurrent chemoradiotherapy using docetaxel, cisplatin and 5-fluorouracil (5-FU) (TPF) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). In total, 19 patients with previously untreated stage III-IV SCCHN were entered onto this trial. Patients received two cycles of chemotherapy. Cycles were repeated every 4 weeks. The starting doses (dose level 1) were docetaxel 60 mg m(-2), cisplatin 70 mg m(-2), and 5-day continuous infusion of 5-FU 600 mg m(-2) day(-1). Radiation was targeted to begin on the first day of chemotherapy, day 1. The total radiation dose to the primary tumour site and neck lymph nodes was between 63.0 and 74.0 Gy. At least three patients were examined at each dose level before advancing to the next level. The maximum-tolerated dose (MTD) of this regimen was docetaxel 60 mg m(-2), cisplatin 60 mg m(-2) and 5-FU 600 mg m(-2) day(-1). The main toxicities were mucositis (grade 3 and 4, 79%), leukocytopenia (grade 3 and 4, 53%), neutropenia (grade 3 and 4, 42%), anaemia (grade 3, 16%), liver dysfunction (grade 3, 11%) and renal dysfunction (grade 2, 11%). The overall response rate was 100%, including 84% complete responses (CRs). This concurrent chemoradiotherapy with TPF was safe and well tolerated. The high CR rate justifies further evaluation of this chemoradiotherapy modality in advanced SCCHN patients.
British Journal of Cancer 02/2004; 90(2):348-52. · 5.04 Impact Factor
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ABSTRACT: The distribution and abundance of neuropeptide-containing nerve fibers were examined in the carotid bodies of rats exposed to hypocapnic hypoxia (10% O2 in N2) for 2, 4, and 8 weeks. The carotid bodies after 2, 4, and 8 weeks of hypoxic exposure were enlarged by 1.2-1.5 times in the short axis, and 1.3-1.7 times in the long axis in comparison with the normoxic control ones. The enlarged carotid bodies contained a number of expanded blood vessels. Mean density per unit area (10(4) microm2) of substance P (SP) and calcitonin gene-related peptide (CGRP) immunoreactive fibers was transiently high in the carotid bodies after 4 weeks of hypoxic exposure, and decreased significantly to nearly or under 50% after 8 weeks of hypoxic exposure. Density of vasoactive intestinal polypeptide (VIP) immunoreactive fibers increased significantly in all periods of hypoxic exposure observed, and was especially high in the carotid bodies after 4 weeks of hypoxic exposure. Density of neuropeptide Y immunoreactive fibers was unchanged in the carotid bodies during hypoxic exposure. These characteristic changes in the density of SP, CGRP, and VIP fibers in the carotid bodies after 4 weeks of hypoxic exposure suggest that the role of these neuropeptide-containing fibers may be different in the carotid bodies after each of three periods of hypoxic exposure, and that the peptidergic innervation after 8 weeks of hypoxic exposure may show an acclimatizing state.
Histology and histopathology 05/2003; 18(2):409-18. · 2.48 Impact Factor
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ABSTRACT: The abundance of neuropeptide Y (NPY)-, vasoactive intestinal polypeptide (VIP)-, substance P (SP)-, and calcitonin gene-related peptide (CGRP)-immunoreactive nerve fibers in the carotid body was examined in chronically hypercapnic hypoxic rats (10% O2 and 6-7% CO2 for 3 months), and the distribution and abundance of these four peptidergic fibers were compared with those of previously reported hypocapnic- and isocapnic hypoxic carotid bodies to evaluate the effect of arterial CO2 tension. The vasculature in the carotid body of chronically hypercapnic hypoxic rats was found to be enlarged in comparison with that of normoxic control rats, but the rate of vascular enlargement was smaller than that in the previously reported hypocapnic- and isocapnic hypoxic carotid bodies. In the chronically hypercapnic hypoxic carotid body, the density per unit area of parenchymal NPY fibers was significantly increased, and that of VIP fibers was unchanged, although the density of NPY and VIP fibers in the previously reportetd chronically hypocapnic and isocapnic hypoxic carotid bodies was opposite to that in hypercapnic hypoxia as observed in this study. The density of SP and CGRP fibers was decreased. These results along with previous reports suggest that different levels of arterial CO2 tension change the peptidergic innervation in the carotid body during chronically hypoxic exposure, and altered peptidergic innervation of the chronically hypercapnic hypoxic carotid body is one feature of hypoxic adaptation.
Histology and histopathology 02/2002; 17(1):21-9. · 2.48 Impact Factor
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ABSTRACT: We present a case of nasal septal schwannoma. The patient was a 62-year-old female complaining of bilateral nasal obstruction. Anterior rhinoscopy revealed a smooth-surfaced mass arising from the nasal septum in both nasal cavities. Computed tomography scan showed a mass with enhancement in the two nasal cavities and the ethmoid sinuses, and this mass extended to the skull base. Lateral rhinotomy was performed under general anesthesia. The tumor arose from the nasal septum, occupied both nasal cavities, and extended to the anterior ethmoid sinuses. It was encapsulated and could be totally removed en bloc. Pathological examination of the excised specimen showed that it was an Antoni type A schwannoma. The tumor cells were immunoreactive for S-100 protein. The patient is doing well with no evidence of recurrence.
Auris Nasus Larynx 05/2001; 28(2):173-5. · 0.76 Impact Factor
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ABSTRACT: The distribution and ultrastructural characteristics of calbindin D-28k immunoreactive nerve fibers were examined in the carotid body of the normoxic control rats by light and electron microscopy, and the abundance of calbindin D-28k fibers in the carotid body was compared in normoxic and chronically hypoxic rats (10% O2 and 3.0-4.0% CO2 for 3 months). Calbindin D-28k immunoreactivity was recognized in nerve fibers within the carotid body. Calbindin D-28k immunoreactive nerve fibers appeared as thin processes with many varicosities. They were distributed around clusters of glomus cells, and around blood vessels. Immunoelectron microscopy revealed that the calbindin D-28k immunoreactive nerve terminals are in close apposition with the glomus cells, and membrane specialization is visible in some terminals. Some dense-cored vesicles in the glomus cells were aggregated in this contact region. The chronically hypoxic carotid bodies were found to be enlarged several fold, and a relative abundance of calbindin D-28k fibers was lesser than in the normoxic carotid bodies. When expressed by the density of varicosities per unit area of the parenchyma, the density of calbindin D-28k fibers associated with the glomus cells in chronically hypoxic carotid bodies was decreased by 70%. These immunohistochemical findings indicate a morphological basis for involvement of calcium binding protein in the neural pathway that modulates carotid body chemoreception.
Histology and histopathology 11/2000; 15(4):1019-25. · 2.48 Impact Factor
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ABSTRACT: The distribution of substance P (SP)- and calcitonin gene-related peptide (CGRP)-immunoreactive nerve fibers in the taste buds of the epiglottis and aryepiglottic folds was compared between normoxic control and chronically isocapnic hypoxic rats (10% O2 and 3-4% CO2 for 3 months). In the normoxic laryngeal taste buds, SP- and CGRP-immunoreactive fibers were detected within the taste buds, where they appeared as thin processes with many varicosities. Most CGRP fibers showed coexistence with SP, but a few fibers showed the immunoreactivity of CGRP only. The density of intra- and subgemmal SP and CGRP fibers penetrating into the laryngeal taste buds was significantly higher in chronically hypoxic rats than in normoxic control rats. Water intake in the hypoxic rats was significantly lower than in the normoxic rats. These results indicate that the increased density of SP- and CGRP-containing nerve fibers within the laryngeal taste buds is a predominant feature of hypoxic adaptation. The altered peptidergic innervation and reduced water intake support the hypothesis that the laryngeal taste buds are involved in water reception, and that the water reception may be under the control of peptidergic innervation.
Histology and histopathology 08/2000; 15(3):683-8. · 2.48 Impact Factor
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ABSTRACT: The antitumor effect of the angiogenesis inhibitor TNP470, O-(chloro-acetyl-carbamoyl) fumagillol, a synthetic analogue of fumagillin, was studied in vitro and in vivo on, cell line KB which produced interleukin (IL)-8. In vitro, TNP470 reduced the production of IL-8 from KB cells, the same as anti-IL-8 antibody (Ab.) The combination of anti-IL-8 Ab (10 micrograms/ml) and TNP470 (10 ng/ml) significantly inhibited the proliferation of KB cells, compared to no treatment (p < 0.05). Proliferation of KB cells was also significantly more suppressed by simultaneous treatment of cisplatin and TNP470 (1 mg/ml), than cisplatin alone. The in vivo antitumor effect of TNP470 was studied using anti-IL-8 Ab, anti-vascular endothel growth factor (VEGF) Ab, and TNP470, in administered by different routes, i.e., intratumoral (i.t.), intraperitoneal (i.p.), and intravenous. TNP470 (10 mg/ml) showed an antitumor effect, and intratumoral administration of TNP470 was the most effective route. Combined administration of anti-IL-8 Ab (i.p.) and TNP470 (i.t.) reduced tumor volume more than anti-IL-8 Ab alone did. These results suggest that the combination of TNP470, cisplatin, and anti-IL-8 Ab could be a beneficial treatment for solid tumors of the head and neck.
Nippon Jibiinkoka Gakkai Kaiho 07/2000; 103(7):821-8.
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Advances in experimental medicine and biology 02/2000; 475:623-30. · 1.09 Impact Factor
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Advances in experimental medicine and biology 02/2000; 475:793-9. · 1.09 Impact Factor
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ABSTRACT: The distribution and abundance of substance P (SP) and calcitonin gene-related peptide (CGRP) immunoreactive nerve fibers in four different regions of the laryngeal mucosa were compared between normoxic and chronically hypoxic rats (10% O2 and 3.0-4.0% CO2 for 3 months). In the chronically hypoxic laryngeal mucosa, the number of SP and CGRP fibers within and just beneath the epithelium, and around the laryngeal gland was increased in comparison with those in the normoxic controls. Especially in the epiglottic and arytenoid regions, the number of intraepithelial SP fibers was increased remarkably. Most intraepithelial SP and CGRP fibers penetrated into the epithelium to extend to the luminal surface. There was no distinct difference in the distribution and abundance of these peptidergic fibers in the mucosa of the normoxic and chronically hypoxic vocal cord regions. These results suggest that the increased density of SP and CGRP fibers within the epithelium of the upper laryngeal mucosa is a predominant feature of hypoxic adaptation, and this may be involved in airway protection, swallowing, and other functions in the chronically hypoxic environment. In addition, the increased SP and CGRP fibers around the laryngeal gland suggest an enhanced mucous secretion, and this may participate in the airway defense mechanism in low O2 conditions.
Histology and histopathology 08/1999; 14(3):735-41. · 2.48 Impact Factor
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ABSTRACT: The abundance of substance P (SP)-, calcitonin gene-related peptide (CGRP)-, vasoactive intestinal polypeptide (VIP)-, and neuropeptide Y (NPY)-immunoreactive nerve fibers in the carotid body was compared between normoxic and chronically hypoxic rats (10% O2 and 3.0-4.0% CO2 for 3 months). The immunoreactive fibers appeared as thin processes with many varicosities, and were distributed mainly around the vasculatures. In the normoxic control carotid body, NPY fibers were more numerous than VIP, CGRP, and SP fibers. In the chronically hypoxic rats, the carotid body was enlarged several fold, and the mean absolute number of VIP and NPY fibers was 3.88 and 2.22 times higher than in the normoxic carotid body, respectively, although that of SP and CGRP fibers was not changed. When expressed as density per unit area of the parenchyma, the density of SP and CGRP fibers in the chronically hypoxic carotid body decreased significantly to under 50%, the density of VIP fibers increased significantly 1.80 times, and the density of NPY fibers were unchanged. Immunoreactivity for four neuropeptides was not found in the glomus cells of normoxic or chronically hypoxic carotid bodies. These results suggest that altered peptidergic innervation of the chronically hypoxic carotid body is one feature of hypoxic adaptation. Because these neuropeptides are vasoactive in nature, altered carotid body circulation may contribute to modulation of the chemosensory mechanisms by chronic hypoxia.
Brain Research 10/1998; 806(2):165-74. · 2.73 Impact Factor
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ABSTRACT: The distribution of nitric oxide synthase (NOS) immunoreactive nerve fibers in the carotid body was compared between normoxic and chronically hypoxic rats (10% O2 and 3.0-4.0% CO2 for 3 months). NOS immunoreactive fibers appeared as thin processes with many varicosities. They were distributed predominantly around small arteries and arterioles, and around clusters of glomus cells. When expressed by the density of varicosities per unit area in the parenchyma, the density of NOS fibers associated with the vasculature and with the glomus cells in the chronically hypoxic carotid bodies was significantly decreased. Because nitric oxide (NO) is an inhibitory neuronal messenger in the normoxic carotid body, the present findings suggest that the sensory mechanisms in the hypoxic carotid body may be involved in 'disinhibition' resulting from reduced NO synthesis.
Brain Research 07/1998; 795(1-2):292-6. · 2.73 Impact Factor
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ABSTRACT: The occurrence and distribution of neuropeptide-containing nerve fibres in the human circumvallate papillae were examined by the peroxidase-antiperoxidase immunolocalisation method using surgical specimens that had not been subjected to radiotherapy, and the abundance of neuropeptide-containing fibres was expressed as the percentage of total nerve fibres demonstrated by protein gene product (PGP) 9.5 immunoreactivity for a quantitative representation of these peptidergic fibres. Substance P (SP) and calcitonin gene-related peptide (CGRP) immunoreactive (IR) nerve fibres were densely distributed in the connective tissue core of the circumvallate papillae, and some SP and CGRP-IR fibres were associated with the taste buds. A moderate number of vasoactive intestinal polypeptide (VIP)-IR fibres and a few galanin (GAL)-IR fibres were also seen in the connective tissue core and subepithelial layer. There were, however, no VIP-IR or GAL-IR fibres associated with the taste buds. Neuropeptide Y (NPY)-IR fibres were few and were associated with the blood vessels. Within the epithelium of the circumvallate papillae, no peptidergic fibres were found, although a number of PGP 9.5-IR fibres were detected. The abundance of SP, CGRP, VIP, and GAL-IR fibres expressed as the percentage of total PGP 9.5 IR fibres was 25.35+/-3.45%, 22.18+/-3.26%, 10.23+/-1.18%, and 4.12+/-1.05%, respectively. The percentage of NPY-IR fibres was below 3%. In a deeper layer of the papillae, a few VIP, GAL, and NPY-IR ganglion cells were found, and VIP immunoreactivity was detected in a few cells of the taste buds. There was no somatostatin, leucine enkephalin, or methionine enkephalin immunoreactivity in the circumvallate papillae. These results suggest that the dense SP and CGRP-IR fibres within the connective tissue core of the human circumvallate papillae may be involved in the deep sensation of the tongue.
Journal of Anatomy 06/1998; 192 ( Pt 4):557-64. · 2.37 Impact Factor
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ABSTRACT: Distribution of vasoactive intestinal polypeptide (VIP)-immunoreactive nerve fibers and VIP-receptor (VIP-R)-immunoreactive sites in the human submandibular gland were examined by the peroxidase-antiperoxidase method using the specimens taken from patients that had not received radiotherapy. VIP-immunoreactive fibers were found around both serous and mucous acini, the duct system, and those around the mucous acini were more numerous than those around the serous acini. VIP-R immunoreactivity was restricted to the mucous acini and the intercalated duct segment. The serous acini, striated duct, and excretory ducts lacked VIP-R immunoreactivity. These findings suggest that the mucous acinar cells contain VIP-R, and that VIP-R-mediated VIP action is involved in regulating synthesis of viscous saliva and its release.
Histology and histopathology 05/1998; 13(2):373-8. · 2.48 Impact Factor
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ABSTRACT: The distribution of substance P-immunoreactive and calcitonin gene-related peptide-immunoreactive nerve fibers in the nasal mucosa was compared between normoxic and chronically hypoxic rats (10% O2 and 3.0-4.0% CO2 for 3 months). In the normoxic nasal mucosa, substance P- and calcitonin gene-related peptide-immunoreactive nerve fibers were found within and under the epithelium and around the glands and blood vessels in the lamina propria. These immunoreactive fibers have many varicosities. In the chronically hypoxic nasal mucosa, the relative density of intra- and subepithelial substance P-immunoreactive and calcitonin gene-related peptide-immunoreactive fibers and those in the lamina propria was higher than in normoxic mucosa. The length of substance P-positive fibers within the chronically hypoxic olfactory and respiratory epithelium was 1.66 and 2.45 times higher than within the normoxic epithelium, respectively. The length of calcitonin gene-related peptide-immunostained fibers within the chronically hypoxic olfactory and respiratory epithelium was 1.56 and 1.84 times higher, respectively. Because substance P and calcitonin gene-related peptide are the predominant signal peptides of primary sensory neurons, the increased number of these fibers may represent enhanced sensory mechanisms in the hypoxic nasal mucosa. In addition, considered together with the findings in chronically hypoxic tracheal mucosa, the increased density of intraepithelial fibers containing substance P and calcitonin gene-related peptide suggests that this is a predominant feature of hypoxic adaptation throughout the upper and lower respiratory tracts.
Brain Research Bulletin 05/1998; 45(6):563-9. · 2.82 Impact Factor
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ABSTRACT: The time of appearance and distribution of substance P (SP)-like immunoreactivity in the granular convoluted tubule cells of the developing male mouse submandibular glands were examined, and the subcellular localization of SP-like immunoreactivity was investiagted by electron microscopy. At 25 days of age, SP-like immunoreactivity was first detected in the supranuclear cytoplasm of the granular convoluted tubule cells, which occurred either singly or in small clusters. At 30 and 35 days of age, granular convoluted tubule cells with SP-like immunoreactivity were more numerous than in the earlier stages, as the volume ratio of the cells increased. Not all granular convoluted tubule cells demonstrated SP-like immunoreactivity. The number of cells with SP-like immunoreactivity decreased at 60 days of age, and these cells had completely disappeared at 90 days of age. Most, but not all, secretory granules in the granular convoluted tubule cells were strongly labeled with gold particles, indicating that the subcellular site of SP-like substance is in the secretory granules within the cells. The findings suggest that the physiological role of the SP-like substance secreted from the GCT cells is restricted to the early postnatal stages, and that it may be involved in the development of the oral mucosa or digestive tract as a trophic factor.
Cell and Tissue Research 04/1998; 292(1):177-80. · 3.11 Impact Factor
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ABSTRACT: The significance and usefulness of image transmission in laryngology were evaluated retrospectively on the basis of daily clinical practice.
The subjects consisted of 29 patients with laryngeal disease, whose laryngeal findings had been already recorded on videotape. Patient data were sent to a major hospital by Internet e-mail. Two laryngeal images, during breathing at rest and phonation, were transmitted as an attached file. Using a rigid or flexible endoscope coupled with a one-chip CCD camera, laryngeal images were recorded. Pictures of these laryngeal images were printed by a video printer, digitized by a compact print scanner, and saved as JPEG files.
The diagnosis made by the three specialists in laryngology (receivers), who referred to the transmitted images and text files of the patient's history, was identical to the diagnosis made by the general otolaryngologist (sender), who referred to the original pictures and patient data. All images were displayed with sufficient quality to evaluate morphologic abnormalities, and the disturbance of cordal movements was detectable by comparing images during breathing at rest with those obtained during phonation.
The image-transmitting system was a useful tool for consultation between otolaryngologists and for referrals from general practitioners to otolaryngologists.
Telemedicine Journal 02/1998; 4(4):329-33.
