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Resolvin D1, a specialized pro-resolving lipid mediator produced from docosahexaenoic acid by 15- and 5-lipoxygenase, exerts anti-inflammatory effects driving to the resolution of inflammation. The present study aimed to elucidate its role in small intestinal damage induced by nonsteroidal anti-inflammatory drug (NSAID). Indomethacin was administered orally to C57BL/6J male mice, which were sacrificed 24 h later to collect small intestine specimens. Before administration of indomethacin, mice were subjected to intraperitoneal treatment with resolvin D1 or oral administration of baicalein, a 15-lipoxygenase inhibitor. Small intestinal damage induced by indomethacin was attenuated by pretreatment with resolvin D1. Furthermore, resolvin D1 reduced the gene expression levels of interleukin-1β, tumor necrosis factor-α, and CXCL1/keratinocyte chemoattractant. Conversely, the inhibition of 15-lipoxygenase activity by baicalein increased the expression of genes coding for these inflammatory cytokines and chemokine, leading to exacerbated small intestinal damage, and reduced the concentration of resolvin D1 in the small intestinal tissue. Exogenous treatment with resolvin D1 negated the deleterious effect of baicalein. 15-lipoxygenase was mainly expressed in the epithelium and inflammatory cells of the small intestine, and its gene and protein expression was not affected by the administration of indomethacin. Inhibition of the resolvin D1 receptor, lipoxin A4 receptor /formyl peptide receptor 2, by its specific inhibitors Boc-1 and WRW4 aggravated indomethacin-induced small intestinal damage. Collectively, these results indicate that resolvin D1 produced by 15-lipoxygenase contributes to mucoprotection against NSAID-induced small intestinal damage through its anti-inflammatory effect.

Patients with asymptomatic esophageal eosinophilia (aEE) do not exhibit clinical symptoms because of esophageal dysfunction, although they have endoscopic and histological findings similar to those of eosinophilic esophagitis (EoE). The cause of the symptoms and the differences between aEE and EoE are unclear. The aim of this study is to determine whether aEE and EoE are same disease entities by comparing immune-related tissue biomarkers using immunohistological staining. Esophageal biopsy specimens from 61 patients, including 18 with aEE and 43 with EoE, were analyzed. Immunofluorescence staining was performed to quantify the immune-related tissue biomarkers such as major basic protein, eosinophil-derived neurotoxin, eotaxin-3, and immunoglobulin G4. Data are presented as median (interquartile range). There were no significant differences in clinical, endoscopic, or histological features, between patients with aEE and EoE, with the exception of body mass index. There were no significant differences in all immune-related tissue biomarkers between both groups. In conclusions, EoE and aEE displayed similar immunohistological profiles. Hence, they may be similar disease entities with some common pathogenic mechanisms. Our findings suggest that patients with aEE also have histopathological esophageal inflammation.

Periodontal disease is accompanied by inflammation of the gingiva and destruction of periodontal tissues, leading to alveolar bone loss in severe clinical cases. The chemical mediator prostaglandin E2 (PGE2) and cytokines such as interleukin- (IL-)6 and IL-8 have been known to play important roles in inflammatory responses and tissue degradation. In the present study, we investigated the effects of a kampo medicine, kakkonto (TJ-1), on the production of prostaglandin E2 (PGE2), IL-6, and IL-8 by human gingival fibroblasts (HGFs) treated with lipopolysaccharide (LPS) from Porphyromonas gingivalis. Kakkonto concentration dependently suppressed LPS-induced PGE2 production but did not alter basal PGE2 levels. In contrast, kakkonto significantly increased LPS-induced IL-6 and IL-8 production. Kakkonto decreased cyclooxygenase- (COX-)1 activity to approximately 70% at 1 mg/mL but did not affect COX-2 activity. Kakkonto did not affect cytoplasmic phospholipase A2 (cPLA2), annexin1, or LPS-induced COX-2 expression. Kakkonto suppressed LPS-induced extracellular signal-regulated kinase (ERK) phosphorylation, which is known to lead to ERK activation and cPLA2 phosphorylation. These results suggest that kakkonto decreased PGE2 production by inhibition of ERK phosphorylation which leads to inhibition of cPLA2 phosphorylation and its activation. Therefore, kakkonto may be useful to improve gingival inflammation in periodontal disease.

We present two cases of salivary duct carcinoma in this paper. Both cases were middle-aged men. They were treated with total parotidectomy and postoperative radiotherapy. Both cases have been followed up for 18 and 15 months respectively with no evidence of local recurrence or distant metastasis.Sixty-six cases of salivary duct carcinoma, including ours, have been reported in the Japanese literature. We reviewed the clinical characteristics of this unusual tumor. Most cases were male (90%) and occured in the parotid gland (84%). The average age was 61 years, ranging from 36 to 91. In 44% of patients, parotid tumors are accompanied by facial nerve paralysis. Total parotidectomy or extended parotidectomy followed by radiotherapy was the most common treatment for patients with salivary duct carcinoma in the parotid gland. The prognosis was poor and the 5-year survival rate was 28%.

Intrathyroidal parathyroid carcinoma is very rare. To our knowledge, only 2 cases of intrathyroidal parathyroid carcinoma had been reported in Japan. Recently, we encountered a case of hyperfunctioning Intrathyroidal parathyroid carcinoma.A 16-year-old female had complained of thirst, polyposia and polyuria for 6 months. An elastic hard nodule 2 cm in diameter was palpated on the right thyroid lobe. The serum calcium level was 16.2 mg/dl and serum intact-PTH level was 1100 pg/ml (normal value in serum: 10-60 pg/ml). Based on ultrasonography and 201T1 subtraction 99mTc scanning, primary hyperparathyroidism due to a hyperfunctioning parathyroid gland in the right thyroid lobe was suspected. A right lobectomy and local dissection was performed. The tumor was histologically diagnosed as an Intrathyroidal parathyroid carcinoma. The patient was asymptomatic and normocalcemic 29 months after surgery.

Objective To evaluate the parameters associated with significant gastrointestinal (GI) involvement in Henoch-Schönlein Purpura (HSP), and construct a scoring system for the identification of patients at high risk of gross blood in stools. Study design Data for HSP patients hospitalized at each of seven institutes were retrospectively analyzed. Patients were divided into four groups according to the consequent severity of GI involvement. Identification of laboratory parameters at the time of admission were then used to differentiate the groups, and a scoring system to predict gross intestinal bleeding was constructed. Prognostic efficiency, correlation with the subsequent duration of abdominal pain, and association with manifestations excluding abdominal pain were also analyzed. Results An analysis of variance (ANOVA) test showed significant intergroup differences in white blood cell (WBC) count, neutrophil count, serum albumin, potassium, plasma D-dimer and coagulation factor XIII activity. A scoring system consisting of these parameters showed a good prognostic value for gross intestinal bleeding in a receiver operating characteristic (ROC) analysis, and a cut-off value of 4 points showed a sensitivity of 90.0% and specificity of 80.6%. The score was also correlated with the duration of abdominal pain after admission. A significantly higher score (s) was observed in patients presenting with nephritis, although the predictive value was poor. Conclusion A scoring system consisting of generally available parameters was of use in predicting severe GI involvement in HSP patients. Although further study is needed, initial therapy in accordance with disease activity may be taken into consideration using this scoring system.

The incidence of functioning thyroid nodules is considered to be low in Japan. However, we perform 123I scintiscan in most cases of thyroid tumors and when thyroid nodules are hot on scintiscan, we advise patients that thyroid nodules should be excised. In this study, we retrospectively reviewed the incidence, diagnostic and operative methods and pathologic characteristics of functioning thyroid nodules from 1991 to 1997 at Tenri Hospital.Among 1177 cases of thyroid diseases in which scintiscans were performed, ninety-one cases (7.7%) had hot nodules and the incidence of functional thyroid nodules is higher than has been reported in Japan.The incidence of euthyroid nodules was higher than expected among those clearly diagnosed as autonomously functioning thyroid nodules by triiodothyronin (T3) suppression test. This result and one false positive case of preoperative fine needle aspiration cytology showed the importance of 123I scintigrams as an initial diagnostic method of thyroid nodules.Thyroid lobectomies or total thyroidectomies were performed in 48 cases. Papillary carcinomas coexisted in eleven cases (22.8%), and four functioning nodules themselves were papillary carcinomas. In consideration of this data and the difficulty of controlling hyperthyroidism due to functioning thyroid nodules, operations should be used as a primary treatment method, even though in our study, postoperative hypothyroidism occurred in ten cases (22.2%) in which thyroid lobectomy was performed.

Paraganglioma is not a particularly rare type of tumor, but intravagal paraganglioma is very rare. We recently treated a case of intravagal paraganglioma arising in the parapharyngeal space. A 70 year-old male was examined following complaints of infra-auricular swelling. A preoperative carotid angiogram revealed that the tumor had high vascularity and that the carotid bifurcation was not widened. We were able to remove the tumor transcervically with a partial submandibulectomy. Postoperatively, the patient complained only of hoarseness.

Purpose: After neck dissection, where the accessory nerve is often excised patients usually complain of impaired shoulder movements. The accessory nerve forms a plexus with branches of the cervical nerves C2, C3, and C4. In the present study, the accessory nerve was examined during neck dissections to clarify the incidence of motor fibers in joining branches, and the function of the motor fibers was evaluated postoperatively in relation to shoulder movements. Materials and Methods: Presence of cervical contributions to the accessory nerve were examined in 20 neck sides in 15 patients. Postoperative function of the shoulder movements was evaluated by manual muscle testing (MMT) and electromyography (EMG). Results: Motor fibers in cervical contributions were noted on four sides (20%) by stimulation of joining branches. When the accessory nerve was excised, scapular elevation was rarely impaired even if there were no motor fibers in the cervical contributions. Excision of the accessory nerve caused poor scapular adduction and impaired scapular depression and adduction in most cases even if motor fibers in the cervical contributions existed. Conclusion: Postoperative impairment of scapular movements was not attributed to the presence or absence of motor fibers in joining branches. Results obtained with electromyography did not represent the practical function of the muscle.

Patients with tinnitus were treated with Ternelin® (tizanidine hydrochloride) alone or in combination with Hydergine® (dihydroergotoxine mesylate). The following results were obtained.1) When overall improvement was assessed at the end of the dosing period, 36% of the 136 patients who received Ternelin and Hydergine® (the combined therapy group) showed moderate or marked improvement, while 61.8% of the patients in this group showed slight, moderate or marked improvement. The combined therapy was rated as moderately or highly useful in 35.3% and slightly to highly useful in 61% of all cases.2) Of the 24 patients who received Ternelin alone (the solo therapy group), 25% showed moderate or marked improvement, and 66.7% showed slight, moderate or marked improvement. Solo therapy was rated as moderately or highly useful in 25% and slightly to highly useful in 66.7%.3) of the 153 patients who received combined therapy (including 17 patients who were only included in the safety assessment), 9 developed adverse reactions (3 cases of drowsiness, and one each of orthostatic syncope, hypotonia, dizziness, gastric pain, constipation and oral thirst). None of the patients given Ternelin® alone showed any adverse reactions.4) The percentage of cases showing marked or moderate improvement was higher in the combined therapy group than in the solo therapy group, although this difference was not significant. In the ombined therapy group, the reduction in tinnitus peaked 2 to 4 weeks afterr the start of treatment. In the solo therapy group, the number of patients responding to the drug increased gradually with time, and more time was needed to obtain maximal effects than that in the combined therapy group.

Spindle cell carcinoma is a rare controversial lesion which has been reported in many organs including the larynx. It consists of an admixture of carcinomatous and sarcomatous elements.We recently treated a 78 year-old male with spindle cell carcinoma of the larynx who complained of hoarseness.The tumor was a large polypoid mass originating in the right false cord which had invaded the right vocal cord. We performed total laryngectomy and bilateral modified neck dissection. H-E and keratin staining of the tumor revealed spindle cell carcinoma.

A 56-year-old woman visited our hospital because of nasal pain. Physical examination revealed a gray mass in the right nasal cavity. Precontrast CT scan showed a lesion with iso-density relative to the muscles, which had intermediate signal intensity on Ti-weighted MR image and high, partially low, signal intensity on T2-weighted image. The mass was totally removed by an endonasal approach, and histological examination showed interlacing bundles of tumor cells, confirmed as smooth muscle cells by immunohistochemistry and electron microscopy.

We recently treated a 59-year-old male case with Forestier's disease who complained of hoarseness. X-ray examination revealed severe ossification of the anterior bodies of C3, C4 and C5. Fiberscopy also revealed a left vocal cord palsy. We concluded that the cause of the patient's hoarseness was not recurrent laryngeal nerve paralysis, but arytenoid fixation due to inflammation.

Myonal® was used to treat 36 patients with tinnitus.1. The rate of effectiveness was 47.2%.2. Myonale was effective in aged patients, patients with presbycusis, and patients with stiff shoulders.3. Tinnitus was reduced in most patients with improvement of stiff shoulders and the sense of fullness in the ears.4. There were no side effects.

A 33-year-old woman and a 26-year-old man, who developed horizontal, vertical and oblique nystagmus that changed its direction only under Frenzelglasses, were evaluated by neurological and neuro-otological examinations.The results were as follows:(1) The alternating nystagmus was detected only through the Frenzelglasses. It could not be detected under conditions of light, dark with eyes open or with eyes closed. It was elicited by photostimulation of the electric light of the Frenzelglasses.(2) The nystagmus changed its direction irregularly. In the first patient the main nystagmus was upward vertical and oblique, and in the second it was horizontal.(3) They suffered from sudden onset of rotatory vertigo for several days or two weeks without tinnitus or impaired hearing.(4) The righting reflex, Fukuda's stepping test, eye tracking test and optokinetic nystagmus were all in normal range. Caloric nystagmus revealed normal and leftdirectional predominance, respectively.A similar case report has not been yet reported in the literature and etiology of this nystagmus is unknown, but we concluded the following.(1) The brain-stem may be responsible for this nystagmus, particularly the midbrain was suspected to be the region of disorder in the first patient and the pons was in the second.(2) This may be a reversible disorder because it was a short-term illness and organic change or wide-spread lesion could be ruled out.(3) The most important point of this peculiar nystagmus was that it was elicited by photostimulation under the condition in which the eye fixation was impossible.

Sixteen patients with progressive bilateral perceptive deafness due to unknown causes were examined using various hearing tests and equilibrium tests with the following results.1. Among the 11 patients examined 11 showed inner ear deafness and 3 showed inner ear deafness combined with retrocochlear one.2. With reference to the appearance and progress of deafness, the deafness of this type was divided into the following two:One was frequently observed in younger patients under twenty and was characterized by the tendency that bilateral deafness which appeared simultaneously and deteriorated equally, showed gradual, high-tone hearing loss. Thus, the hearing loss in these patients tended to be similar in pattern. i) between the first and the last examinations and ii) between the right and the left ears. Furthermore, the deafness of this type was rarely accompanied by vertiginous attacks.The other was frequently found in older patients, of above twenty and was characterized by the tendency that deafness of both ears did not appear simultaneously and did not deteriorate equally. Furthermore, the deafness of this type was sometimes accompanied by vertiginous attacks in anamnesis.3. Among the 16 patients examined, 4 showed fluctuating hearingloss. Furthermore, one of the 3 patients who underwent the glycerol test showed a positive sign. From the above mentioned findings the following conclusions were drawn:(1) There may be differences between the 2 groups of patients, younger and older with regard to the etiological factors of the progressive bilateral perceptive deafness due to unknown causes, although both groups showed inner ear deafness. The deafness in the former group may be induced by congenital factors and may be regarded as a kind of premature presbyacusis. In contrast, the deafness in the later may be induced, at least partly, by acquired factors.(2) Some patients showed findings suggestive of the existence of labyrinthine hydrops. These are valuable in considering the mechanism and treatment of the deafness of this type.

Using the test for the convergence reflex and the test for the righting reflex and convergence reflex (Ushio and Hinoki, 1971), effects of a prismatic lens over the paralytic eye were examined in 33 patients with head and neck injuries, in connection with the disturbance of the convergence reflex and the convergence-induced disturbances of the righting reflex. In the test for the righting reflex and a convergence reflex, the subject is asked to maintain Romberg's position daring which the convergence reflex is induced. The results obtained were as follows:(1) Disturbance of the convergence reflex was alleviated in 24 of the 33 patients (73%), unchanged in 9 (27%), aggravated in 6 (18%), when a prismatic lense was placed over the paralytic eye with the apex of the lens toward the nose.(2) Convergence-induced disturbance of the righting reflex was alleviated in 18 of the 33 patients (55%), unchanged in 9 (27%), aggravated in 6 (8%) when a prismatic lens was placed over the paralytic eye.(3) There was a positive correlation between the results from the test for the convergence reflex and those from the test for the righting reflex and convergence reflex when a prismatic lens was placed over the paralytic eye.(4) Fourteen patients who fell backward on Romberg's position and had cerebellar symptoms were examined using the test for the righting reflex and convergence reflex and the tests for cerebellar ataxia of the upper limbs. Both kinds of tests were carried out while placing a prismatic lens over the paralytic eye.Through these examinations, it was found that the above-mentioned falling backward was significantly ameliorated, i. e., at the rate of 85.7% when the former test was carried out. In contrast, improvement in cerebellar ataxia of the upper limbs was less obvious, i. e., at the rate of 28.5% when the latter test was performed.From a series of examinations, the following conclusions were drawn:(1) Disturbances of the convergence reflex can be a factor in inducing and/or aggravating bodily disequilibrium due to post-concussion states.(2) Disturbance of the convergence reflex can induce and/or increase bodily disequilibrium in collaboration with the cerebellar vermis. In contrast, such disturbance does not significantly correlate with the cerebellar hemispheres, with regard to the development and/or increase of bodily disequilibrium.

A 21-year-old man, who suffered from Wilson's disease and showed spontaneous up-beat nystagmus, was examined using neurological, neurotological and biochemical examinations.The results obtained were as follows:(1) Neurological examination revealed the presence of the Kayser-Fleischer ring, dysarthria, dysphagia and cerebellar ataxia of the upper and lower limbs. CT examination showed moderate cerebral cerebellar atrophy, in addition.(2) Biochemical examination detected decrease in the ceruloplasmin and copper of the blood serum.(3) Neurotological examination revealed abnormalities of the oculomotor system, as indicated by spontaneous up-beat nystagmus, inhibitory response to both horizontal and vertical optokinetic stimulation and saccadic vertical eye movements on eye tracking. Furthermore, the spontaneous nystagmus described above was characterized by the following findings:1) It was intensified in frequency and amplitude when upward gaze was carried out. In contrast, it was lessened when downward gaze was made.2) It was lessened when the test for spontaneous nystagmus was carried out with Frenzel's spectacles.With reference to the previously reported investigations and the above-mentioned results, the following conclusions were drawn:(1) In a certain group of patients with Wilson's disease, the lesion is located not only at the basal ganglia, but also possibly extended to the cerebellum and the brain stem, particularly the midbrain tegmentum.(2) Dysfunction of the oculomotor system relating to vertical eye movements is possibly reinforced by the simultaneous presence of cerebellar dysfunction, which ensues the appearance of spontaneous up-beat nystagmus.

受傷後早期に検査可能であった頭部外傷性末梢性顔神麻痺27症例について, 鼓索神経機能検査 (顎下腺唾液流量検査, 電気味覚検査) 及び Neuronography を行ない, 以下の結果を得た. i) 鼓索神経機能検査を用いると早期に外傷性顔神麻痺の予後診断を行なうことが可能である. ii) 早期に判定を行なえば, 電気味覚検査も良い予後診断法の1つとなる. 健・患側の域値差16dB以上を示すものは予後は悪い. iii) 上記3種の検査成績を各々単独で判定するよりは, それらを組み合わせて判定する方が外傷性顔神麻痺の予後診断の効率を有意に高める. iv) 上記の鼓索神経機能検査は, Neuronography などの電気診断法で判定に迷うような症例において良い補助診断法となり得る.