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We report a 54-year-old man, who presented with an acute onset of diplopia and ptosis on the left side. On admission, neurological examination showed left oculomotor and abducens nerve palsy. Brain MRI showed thickening of the left parieto-temporal dura mater with gadolinium enhancement. Whole-body CT revealed a mass lesion in the right submandibular gland, diffuse goiter, and bilateral hilar lymph node enlargement. Initially, IgG4-related disease was considered because of an elevated serum IgG4 level (240 mg/dl); however, biopsy of the submandibular gland showed non-caseating epithelioid cell granulomas that suggested sarcoidosis, which could be associated with the intracranial lesions causing his neurological manifestation. In cases of hypertrophic pachymeningitis, especially with increased serum IgG4 including our case, a careful assessment with pathological examination is critical for identifying various underlying conditions.

In the sublingual/submandibular gland complex (L/M complex hereafter), the submandibular gland process adjoins the sublingual gland. Therefore, it is speculated that the L/M complex in the fused state is due to excessive development of the submandibular gland process. However, we encountered a case of the L/M complex formed due to supernumerary glandular lobes (lobes A, B, and C) developing in the posterior 1/3 portion of the submandibular duct. Lobes A, B, and C showed the following macroscopic morphologies, constitutions, ducts, and histological morphologies. Lobe A was disc-shaped, and this lobe together with the major sublingual gland was wrapped with the minor sublingual gland. Lobe B was attached to lobe C, forming a cingulate lobe. Lobe B had an irregular shape and was attached to the superior area of lobe A, while lobe C was rod-shaped and attached to the posterior area of lobe B. The posterior area of lobe C was attached to the submandibular gland at the base of the submandibular duct. The excretory ducts of lobes A, B, and C joined, forming one duct, which joined the posterior 1/3 portion of the submandibular duct. The histological morphologies of lobes A, B, and C showed a predominance of serous cells over mucous cells, which was the same as the morphology of the submandibular gland. In this case, the L/M complex may have formed by the following mechanism. Supernumerary lobes A, B, and C of the submandibular gland formed in the posterior 1/3 portion of the submandibular duct, and lobe A together with the major sublingual gland was wrapped with the minor sublingual gland. Lobes B and C formed a cingulate lobe, and its posterior portion (posterior portion of lobe C) attached to the submandibular gland, resulting in a fused state.

A 14-year-old boy presented with a spontaneous anterior cervical fistula, which exuded a saliva-like fluid during eating. Cervical examination revealed a hole 7 mm posterior to the hyoid bone, 5mm left of the median. Magnetic resonance imaging showed a low-intensity spindly mass with high-intensity margins. The mass was connected to the left submandibular gland. Contrast radiography of the fistula using Gastrografin demonstrated an ascending fistula that extended to the submandibular area. Intraoperatively, the fistula was shown to have ascended superficial to the level of the anterior cervical muscles, and it formed a cyst anterior to the hyoid bone. It then continued to the left submandibular gland. The fistula and submandibular gland were removed together. Wharton's duct was not found, and the orifice of the duct was unclear. Pathological examination of the fistula showed the lining epithelium at the side of the submandibular gland to be composed of columnar epithelial cells with stratified squamous cells at the epidermal side. Several acinar systems were found along the orifice of the fistula. There have been no previous reports of the Wharton duct running from the submandibular gland to the anterior cervical skin.

A 40-year-old woman was scheduled for abdominal hysterectomy. Moderate difficulty in tracheal intubation was expected on preoperative evaluation. A size 3 laryngeal mask airway (LMA) was inserted after the induction of general anesthesia. The LMA insertion was accomplished smoothly at the first attempt and there was no air leakage during manual ventilation. Soon after the insertion, acute swellings were noted in the bilateral submandibular triangle regions. Enlargement and deformity of the submandibular glands were diagnosed by ultrasonography. The enlargements increased with elevated pressure of the LMA cuff, but disappeared completely in five minutes after removal of the LMA. Such enlargement did not occur with subsequent tracheal intubation. The patient had an uneventful postoperative course without any residual sequelae. We should pay attention to possible submandibular gland swelling by LMA insertion.

A repeated dose toxicity study of montirelin hydrate (NS-3), a new drug for the treatment of disturbance of consciousness, was conducted in Sprague-Dawley rats. Male and female rats were given the drug intravenously for 5 weeks at doses of 0 (control), 0.05, 0.5, 5 and 50 mg/kg. After discontinuation of the treatment, a 4-week recovery test was also conducted in the 0, 0.5 and 50 mg/kg groups. No deaths related to the treatment were observed. Tremor was seen in the 50 mg/kg group. Polyuria was observed in the 5 and 50 mg/kg groups. There were decreases in body weight gain in the 0.5 mg/kg group and over of males, and in food consumption in all male dose groups and increase in water consumption in the 5 and 50 mg/kg groups. In blood chemical examination, decrease in triglyceride was observed in the 5 and 50 mg/kg groups of males. Urinalysis showed increase in urine volume in the 0.5 mg/kg group and over. Ophthalmoscopic and hematologic examinations failed to show any abnormalities attributable to the treatment. Pathological examination disclosed serous cell hypertrophy of the submandibular gland in all dose groups and increase in its organ weight in the 0.5 mg/kg group and over. The changes mentioned above were satisfactorily reversible except for the serous cell hypertrophy of the submandibular gland in the 50 mg/kg group. The decrease in food consumption and serous cell hypertrophy of the submandibular gland in the 0.05 mg/kg group were considered to be of no toxicological significance. These results show that the NOAEL of montirelin hydrate is 0.05 mg/kg for 5-week repeated dose toxicity in rats.

A repeated dose toxicity study of montirelin hydrate (NS-3), a new drug for the treatment of disturbance of consciousness, was conducted in Sprague-Dawley rats. Male and female rats were given the drug intravenously for 26 weeks at doses of 0 (control), 0.0004, 0.02, 1 and 50 mg/kg. After discontinuation of the treatment, a 9-week recovery test was also conducted in the 0, 1 and 50 mg/kg groups. No deaths related to the treatment were observed. Tremor and polyuria were seen in the 50 mg/kg group. There were decrease in body weight gain, and increase in water consumption in the 1 and 50 mg/kg groups. In those dose groups of males, decrease in food consumption was observed. Ophthalmoscopic examination failed to show any abnormalities attributable to the treatment. Blood chemical examination disclosed decrease in total cholesterol in the 50 mg/kg group. There were also decreases in phospholipid in the 50 mg/kg group of females, and in triglyceride in the 1 and 50 mg/kg groups of males. Urinalysis and hematologic examination failed to show any abnormalities attributable to the treatment. In pathological examination, serous cell hypertrophy and increase in organ weight of the submandibular gland were observed in the 1 and 50 mg/kg groups, and increase in organ weight of thyroid was revealed in the 0.02 mg/kg group and over. The changes mentioned above were satisfactorily reversible except for the decrease in food consumption in the 50 mg/kg group of males. Increased thyroid weight in the 0.02 mg/kg group was considered to be of no toxicological significance. These results show that the NOAEL of montirelin hydrate is 0.02 mg/kg for 26-week repeated dose toxicity in rats.

Changes in the salivary glands, liver and pancreas in rats with experimentally induced liver injuries were examined. The injuries (experimental group) were induced by subcutaneous injections of carbon tetrachloride (0.01ml/kg body weight) in a 50% olive-oil solution. The injections were administered twice weekly for 10,20 and 40 weeks. Control animals received the same doses of olive oil during the same periods. 1. In the experimental group, serum glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) increased remarkably, whereas serum albumin decreased. 2. Swelling of the liver and multiple nodular formations occurred in the experimental group. Liver fibrosis with the formation of pseudolobules indicated a form of liver cirrhosis. 3. No significant histological changes were observed in the pancreases of animals in the 10- and 20-week experimental groups. Vacuolation in the acinar cells was observable in 3 of 8 cases in the 40-week experimental group. 4. In connection with histological findings of parotid glands, vacuolation of the acinar cells occurred in 7 of 12 cases in the 10-week experimental group, in 7 of 8 cases in the 20-week experimental group, and in all 8 cases in the 40-week experimental group. Vacuole numbers and sizes increased as the experimental period was prolonged. 5. Immunohistochemical investigation showed strong positive reactions to the anti-amylase antibody around vacuoles in acinar cells of parotid glands. In unvacuolated acinar cells, on the other hand, only slight positive reaction was observed. 6. Electronmicroscopic observation of the acini revealed greatly enlarged lumina and dilated intercellular canaliculi connected to the lumina. Small vacuoles were observed on the basement of the acini. 7. No such significant changes as fibrosis, vacuolation, and atrophy of acinar cells were observed in the submandibular and sublingual glands of the experimental animals. 8. Serum amylase activity increased more in the experimental than in the control rats. Electrophoretic patterns suggested that in the control group 95 percent of serum amylase was parotid type, and also in the experimental group 95 percent of serum amylase was parotid type. 9. Amylase activity in the parotid glands also increased more in the experimental than in the control animals.

This study was primarily designed to determine the tissue responses and the initial calcification profiles after the implantation of porous hydroxyapatite ceramics (HAP), and secondly, to find out the effects of chronic isoproterenol (IPR) administration on them. For the experiment 1, several granules of HAP were implanted in the submandibular glands of rats and for another experiment 2, chronic IPR administration was carried out to rats implanted HAP. The surrounding tissues of HAP implanted and the insides of its pores were observed and analyzed with a light microscope, an electron microscope and an analytical electron microscope one and three days, and five, eight and ten weeks after treatment. The results were as follows: 1. The outer layer of HAP was encapsulated by granulation tissues due mainly to the infiltration of inflammatory cells one and three days after treatment. Subsequently, the encapsulation was further enhanced by fibrous cells and collagen fibers, whereas no obstructive reactions were seen in the surrounding tissues of HAP implanted. 2. From the first day after treatment, tissue fluid-like matrix substances permeated inside HAP and at the same time, blood cells, phagocytic and mesenchymal cells were detected within the whole HAP. 3. Especially, in the layer within 100-200 microns inside the pores of HAP, a number of fibroblasts, collagen fibers and osteoblast-like cells were observed. 4. Within the pores with cells infiltrated into HAP, a layer, suggestive of the precipitation of calcium-phosphate salts, was formed from one week after treatment. By five weeks, particularly within the layer, amorphous substances with the high density were observed in general and, by eight and ten weeks, the substances were further increased in thickness. 5. By eight and ten weeks, amorphous substances with the high density were observed in a line with collagen fibers and around the cells within HAP. 6. The amorphous substances with the high density were calcified substances consisting of mainly Ca and P, as observed by an elemental analysis. 7. By administration of IPR, most of the acinar cells and the cells in the pores became degenerative after about five weeks and less calcified substances were observed along the collagen fibers. However, as seen in the experiment 1, calcified substances were also found in the precipitated layer within matrix-like substances of the pores.(ABSTRACT TRUNCATED AT 400 WORDS)

A submandibular gland enlargement produces complications in the diagnosis of a nodal metastasis during the follow-up period in patients who have been given interstitial irradiation therapy for their oral cancers. Thus, a retrospective study has been made of the records of such affected patients, to accumulate knowledge regarding the frequency, the time of appearance, and the symptoms leading to the gland enlargement. Among 155 cases of squamous cell carcinoma of the tongue, 73 cases were selected for this study by the following criteria: (1) the patients were free of metastatic adenopathy, (2) they had been interstitially irradiated, and, (3) they were followed-up without surgical treatment for more than 6 months after the radiotherapy. Gland enlargement was found to have developed in 70% of the studied patients, that is, in 49 of the 73 cases within 9 months after radiotherapy.