Yoshitaka Okamoto

The role of chemical mediators and mucosal hyperreactivity in nasal hypersecretion in nasal allergy.

This study was designed to elucidate, first, the degree of participation of direct effects of histamine on the nasal glands and the nasal vasculature in clinical manifestation of hyperrhinorrhea in nasal allergy and, second, the existence of hyperreactivity of the nasal glands to acetylcholine in nasal allergy. The study demonstrates that histamine released by degranulation of basophilic cells in the nasal mucosa causes nasal hypersecretion mostly by way of the reflexive pathway. Approximately 4% of the amount of nasal secretion induced by an antigen challenge in subjects with house-dust nasal allergy was due to a leakage of plasma. There were almost no direct effects of histamine on the nasal glands. Nasal secretion induced by nasal challenge with acetylcholine after vidian neurectomy comes from the nasal glands by its direct effects on the nasal glands, the amount of which indicates degree of reactivity of the nasal glands to acetylcholine independent of hypersensitivity of the mucosal sensory system. The nasal glands of vidian neurectomized subjects having nasal allergy reacted more excessively to extrinsic acetylcholine than nasal glands of subjects of the control group. This verifies the existence of hyperreactivity in the nasal glands to acetylcholine in nasal allergy. The nasal glands of nasal allergy patients may respond more excessively to a given amount of acetylcholine released from parasympathetic terminals.

Carotid artery resection for head and neck cancer

BACKGROUND Carotid artery resection has been shown to yield a chance of cure in patients with advanced head and neck carcinoma involving the carotid artery. However, the criteria for the identification of those who are vulnerable to neurologic injury after resection have not been established. Interposition grafting may minimize the risk of neurologic morbidity, although it is technically difficult when there is involvement of the internal carotid artery close to the skull base. METHODS We studied 24 patients with head and neck tumor involvement of the carotid artery. We performed carotid artery resection in 16 of them, including 10 in whom the carotid artery was reconstructed with interposition grafts covered with muscle flaps. When it was thought that the reconstruction would be difficult, positron emission tomography was performed during balloon test occlusion of the internal carotid artery to assess the adequacy of hemispheric collateral blood flow before carotid resection. In one patient with interposition graft, carotid rupture occurred as a result of wound infection, but none of the other patients experienced perioperative death, persistent hemiplegia, or delayed stroke. RESULTS Twelve patients have survived longer than 8 months, and seven (43.8%) were alive without disease at 12 months after resection, whereas all four patients who could not be treated operatively died within 8 months as a result of local primary tumors. CONCLUSIONS Carotid artery resection is the only therapy offering any potential for cure or palliation. Positron emission tomography is a rapid quantitative means of determining the cerebral blood flow, particularly when resection is planned without reconstruction.

INDUCTION OF INTERCELLULAR ADHESION MOLECULE-1 IN HUMAN NASAL EPITHELIAL CELLS DURING RESPIRATORY SYNCYTIAL VIRUS INFECTION

The effects of infection with respiratory syncytial virus (RSV) on expression of intercellular adhesion molecule (ICAM)‐1 was determined in vitro in nasal epithelial cell cultures. Functional consequences of changes in ICAM‐1 expression were assessed by measuring adhesion of a human leukaemic T‐cell line to RSV‐infected epithelial cells. Also, adhesion of phytohaemagglutinin‐activated tonsillar lymphocytes (TL) to RSV‐infected epithelial cells caused a significant increase in interleukin (IL)‐4 or IL‐5 production. Release of these cytokines was adhesion dependent as non‐adherent TL produced significantly less IL‐4 or IL‐5. However, no significant difference was observed for IL‐2 or interferon‐γ (IFN‐γ) production. These observations suggest that RSV‐infected epithelial cells may induce T‐helper type‐2 (Th2)‐like cytokines by mucosal lymphocytes during mucosal infection in vivo

Microcapsule Chemoembolization for Head and Neck Cancer

SummaryCisplatin (CDDP) was microencapsulated with ethylcellulose, and microcapsules (CDDP-mc) were infused into the maxillary arteries of patients with various head and neck carcinomas. We then found that the CDDP level in the circulating blood was significantly lower than that in patients administrated intravenous non-excapsulated CDDP. However, significantly high concentrations of CDDP were found in the tissues of patients treated with CDDP-mc. Our results suggest that selective arterial infusions of CDDP-mc can exert an intensive topical antitumor effect through microinfarction of malignant tissues. The prolonged release of drug from the microcapsules has also been associated with minimal systemic side effects.

Detection of genomic sequences of respiratory syncytial virus in otitis media with effusion in children.

The reverse transcriptase—polymerase chain reaction and the nested polymerase chain reaction were used for detection of respiratory syncytial virus (RSV) sequences in middle ear effusions collected from children with otitis media. Sequences of RSV were detected in 21 of 34 samples tested. These samples were collected during and/or after natural outbreaks of RSV infection in the community. In those patients from whose nasopharynges RSV was isolated, the viral sequences were highly detectable (75%) in the effusions. These observations suggest RSV as an important factor in the pathogenesis of otitis media with effusion.

Interleukin-5 Gene Expression in Nasal Mucosa and Changes in Amount of Interleukin-5 in Nasal Lavage Fluid After Antigen Challenge

Eosinophils and their products are known to cause hyperreactivity and swelling of the nasal mucosa in subjects with nasal allergy. Interleukin-5 (IL-5) not only induces differentiation and proliferation of immature eosinophils but also causes mature cells to accumulate and activate. This study shows that IL-5 is actually produced in the human nasal mucosa by antigen challenge, and it further investigates the changes in the amount of IL-5 in nasal lavage fluids after antigen challenge. Expression of mRNA for IL-5 in nasal mucosa was investigated using the reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot analysis. Among the 4 subjects with nasal allergy examined in this study, expression of mRNA for IL-5 was observed in 2 prior to antigen challenge; within 6 h after antigen challenge it was seen in 3 subjects. We also found that the amount of IL-5 in the nasal lavage fluids obtained consecutively after antigen challenge increased predominantly in the late phase, and that the number of eosinophils in the IL-5 positive group was significantly higher than that in the IL-5 negative group. These results strongly suggest that IL-5 contributes to the recruitment of eosinophils in the nasal mucosa of the subjects with nasal allergy.

Gait analysis in patients with vertigo.

SummaryGait analysis utilizing foot switches and electromyography of antigravity muscles was performed on 31 patients with vertigo. Twenty-one cases had peripheral vestibular lesions (such as vestibular neuronitis, Menieres disease, traumatic labyrinthitis, small acoustic neuroma), and 10 cases had central lesions (such as spinocerebellar degeneration, pontine glioma, cerebellar tumor and giant acoustic neuroma). Parameters employed for analysis included time from heel strike to forefoot strike (HA-I), time from heel off to forefoot off (HA-II) as well as durations of stance, swing and (initial) double supports (DS). Fourteen healthy adults served as controls. The overall incidence of abnormality was highest in HA-1, followed by stance and swing. The occurrence of abnormalities in stance, swing and DS was higher in the central lesion when compared with the group having peripheral lesions. The significance and usefulness of gait analysis for dizzy patients are discussed.

Effects of Female Hormones on the Muscarinic and α1-Adrenergic Receptors of the Nasal Mucosa

During pregnancy aggravation of nasal allergic symptoms is occasionally observed in subjects with nasal allergy. To evaluate the effect of female hormones on the muscarinic receptor and the alpha 1-adrenergic receptor of the nasal mucosa, receptor binding assay was performed using the nasal mucosa of pregnant guinea pigs and of male guinea pigs; the latter were treated either with estrogen or with progesterone. Pregnancy induced a significant decrease of the density of the alpha 1-adrenergic receptor of the nasal mucosa (p less than 0.05). Estrogen induced a significant increase of the density of the muscarinic receptor (p less than 0.05), while progesterone induced a significant decrease of the density of the alpha 1-adrenergic receptor of the nasal mucosa of guinea pigs. When similar changes of the receptor can be induced by female hormones in the nasal mucosa of the human subjects, this may facilitate secondary development of hyperreactive nasal symptoms in subjects who have been sensitized before without apparent nasal symptoms.

Analysis of Gait in Patients with Peripheral Vestibular Disorders

Analysis of gait in patients with acute unilateral peripheral vestibular disorders was performed using foot switches and electromyography, with the aid of a telemetry system. Among the eight parameters set for the analysis, the occurrence rate of abnormality in the coefficient of variation (CV) was the highest (78%) for the time from heel strike to forefoot strike, followed by that of the location of maximum monophasic contraction of the gastrocnemius during stance, swing and stance. No significant laterality concerning the abnormally increased CV value in those parameters was found except for swing of the foot contralateral to the lesion side. The CV value of each parameter was significantly increased by removing visual cues, suggesting the importance of visual input for steady locomotion. No significant change in CV values of double support was obtained during the acute stage of vestibular neuronitis, indicating that weight transfer from one leg to the other could be smooth even though some difficulty was expected. Abnormal parameters at an acute stage returned to normal limits at recovery stage. The physiological background of the obtained results is discussed.

Changes of Adrenergic and Muscarinic Cholinergic Receptors in Nasal Mucosa in Nasal Allergy

Receptor-binding assays were performed to evaluate the changes of beta- and alpha 1-adrenergic and muscarinic receptors in the nasal mucosa of subjects with nasal allergy and in guinea pigs sensitized with ovalbumin using radioligands 3H-DHA, 3H-prazosin and 3H-QNB, respectively. In subjects with nasal allergy, a decrease in density of beta- and alpha 1-adrenergic receptors and an increase in density of muscarinic cholinergic receptors were observed. An increase in density of muscarinic cholinergic receptors could be reproduced in the nasal mucosa of guinea pigs which were sensitized with ovalbumin and had typical hyperreactive nasal symptoms. These results indicate that the increase in the density of muscarinic receptors observed in the nasal mucosa of subjects with nasal allergy has been induced secondarily by an allergic reaction in the nasal mucosa with hyperreactive nasal symptoms, which in turn acts as an aggravating factor in the vicious circle promoting hyperreactivity of the nasal mucosa.