Hideyuki Fukushima

Recruitment of T lymphocytes and induction of tumor necrosis factor in thyroid cancer by a local immunotherapy

SummaryTo elucidate the mechanism of action for intratumoral injection of immunopotentiators, infiltrating mononuclear cells and tumor necrosis factor (TNF) were assayed by immunostaining tissue samples of differentiated thyroid cancer resected with or without presurgical local application of OK-432, a streptococcal preparation. Frozen sections of resected specimens were stained with monoclonal antibodies using either a conventional or a modified immunoperoxidase method. The tumors injected with OK-432 showed increased T lymphocyte infiltration and HLA-DR expression on cancer cells as compared to the non-injected controls. Among these T cells, the CD4+ subset was more numerous than the CD8+ population. In four out of the seven cases constituting the injected group, numerous TNF-positive cells were seen in clusters or lines as well as scattered, while none of the seven cases in the control group was associated with a considerable amount of these cells. In their morphology and distribution pattern, these TNF-positive cells appeared to be of macrophage lineage. Thus local injection of OK-432 in thyroid cancer was shown to recruit T lymphocytes of predominantly the CD4+ subset and to induce in situ production of TNF, a known potent tumoricidal cytokine. The present data warrant further studies in this direction besides wider clinical intratumoral application of the reagent.

Evaluation of statokinesigram using 3-D plotting and discriminant function.

The 3-D plot of the statokinesigram, together with X-Y histograms and discriminant function studies are proposed towards a better understanding of the righting reflexes which maintain the erect stable posture in humans. Ninety samples taken from 30 healthy persons were analysed using on-line digital processing system. 3-D plot is an expression of the distribution map of the cumulative frequency of the sway of the center of gravity and helps intuitive recognition of the patterns of the righting reflexes. Parameters representing the distribution map are developed showing as good discriminant ratios as in the analyses of the locus and the area of the statokinesigram.

Role of the cervical and lumbar proprioceptors during stepping. An electromyographic study of the muscular activities of the lower limbs.

To obtain evidence of the role of the cervical and lumbar proprioceptors during stepping, the following investigations were carried out. 1) 10 normal, healthy subjects and vertiginous patients, particularly those with lumbar pain, were examined. 2) Fukudas stepping test was first carried out, followed by two modified stepping tests, i.e., stepping after fixing the waist with a corset and after fixing the neck with a collar. 3) Electromyograms (EMGs) of the gastrocnemius muscles of the extensor of the lower limbs were analysed as regards the foot contact with the ground. The following results were obtained. In the original way of Fukudas stepping test, normal subjects tended to show EMG discharges from the gastrocnemius muscles before foot contact with the ground, whereas in the modified stepping tests, the generation of EMG discharges was delayed, especially in the test requiring fixing of the waist with a corset. The results of these stepping tests were reversed in the vertiginous patients, particularly in those with lumbar pain. We conclude that the lumbar proprioceptors participate especially in the smooth performance of stepping by promoting the anticipatory activity of the extensor of the lower limbs.

Meningocele of the Temporal Bone

We report a case of meningocele of the temporal bone. A 22-year-old female consulted our hospital complaining of high grade fever and vomitting. Meningitis was detected and treated with antibiotics. About one month after the initial hospitalization, meningitis recurred. CT examination demonstrated bone defect at the skull base of mastoid cavity. We diagnosed this patient as having cholesteatoma or meningocele.Surgery was performed by the trans-mastoid approach. After mastoidectomy, a round mass was found and the mass decreased after leakage of liquor. Meningocele of the temporal bone was confirmed. Reduction of meningocele was performed using bone fragment and temporal muscle. Postoperatively, there has not been any recurrence of meningitis to date.

Pain Relief Surgery for Lumbar Metastasis of Parotid Gland Cancer

We report an experience of pain relief surgery for lumbar metastasis of parotid gland cancer. A 52-year-old male visited our hospital with the complaint of lower back pain. His left parotid gland had been extirpated ten years previously because of adenoid cystic carcinoma. As a result of investigation, lumbar metastasis of adenoid cystic carcinoma was identified. Lower back pain decreased after radiotherapy, but the pain worsened again approximately six months after radiotherapy.We used morphine for pain relief, but the effect was insufficient. So an operation for pain relief was performed by an orthopedic surgeon. Posterior decompression and stabilization reduced the pressure of the vertebral lesion on the spinal cord. Lower back pain was well controlled after surgery until his death from respiratory failure due to the lung metastasis.

Electoroneuronography (ENoG); Preoperative Facial Nerve Assessment for Parotid Gland Tumors.

Parotid gland tumor are often associated with carcinomatous infiltration into facial nerves without overt manifestations of facial nerve palsy, which makes preoperative predictions of carcinomatous infiltration difficult. ENoG has been shown to be a useful approach to evaluate facial nerve degeneration. Here, we measured facial nerve function by performing ENoG preoperatively on patients with parotid gland tumors prior to investigate the usefulness of ENoG in preoperative examination of these tumors.Subjects: Twenty healthy individuals without any history of facial nerve palsy and 18 patients with parotid gland tumors (13 with benign tumors and 5 with malignant tumors) but no overt facial nerve palsy.Results: Mean ENoG values obtained for each groups were 103.5% (control), 82.2% (benign) and 48.1% (malignant). The mean ENoG values for the malignant group was significantly different compared to the other two groups (p<0.05). Differences in sizes or regions of tumors did not affect ENoG values significantly.Conclusion: ENoG was useful for the preoperative evaluation of facial nerve function. We suggest that a 50% reduction or more in ENoG values may predict the malignancy of tumor and a high risk for carcinomatous infiltration into facial nerves without any manifestations of facial nerve palsy.

Idiopathic Sudden Sensorineural Hearing Loss and Sensation of Aural Fullness

The relationship between the sensation of aural fullness and average hearing level, tinnitus and vertigo, the typical symptoms of idiopathic sudden sensorineural hearing loss was studied. Forty-six patients with idiopathic sudden sensorineural hearing loss of more than 50 dB from intial average hearing level were treated with interferon therapy. The sensation of aural fullness was classified into 4 grades: very strong, intermediate, subtle and nothing, on the basis of patient complaints. We found that the levels of hearing loss did not always correlate with the degree of sensation of aural fullness but there was an tendency toward improvement of the sensation of aural fullness in accordance with the recovery of hearing. In addition, there was no statistical relationship between the sensation of aural fullness and the presence of vertigo, but there was a statistical correlation with tinnitus. These results suggest a close relationship between the sensation of aural fullness and dysfunction of the cochlea.

Idiopathic Sudden Sensorineural Hearing Loss and Cell-mediated Immunity.

In order to characterize the immunological mechanisms responsible for idiopathic sudden sensorineural hearing loss (ISSHL), changes in the ratio of the Tcell-subsets in the peripheral blood were investigated before and after treatment in 77 ISSHL patients who visited our clinic within 1 week from the onset of their ISSHL. Forty-three patients who had an average hearing ability of≥60dB before treatment (group I) received interferon therapy. Thirty-four patients who had an average hearing ability of≤59dB before treatment (group II) received steroid tapering therapy.Upon the first examination of many cases of from group I, a decreased number of whole lymphocytes, a decreased ratio of Tcells (CD3) in the lymphocytes population, especially CD4+Tcells (Helper T/Inducer Tcell), and a decreased ratio of CD4/CD8 cells were observed. After treatment in almost all cases from group I, the ratio of the Tcell-subsets recovered from these low levels to their CD4 dominant state. These changes in the ratios of the Tcell-subset were not observed in almost all of the cases in group II. Therefore, in ISSHL, there is a difference in cellmediated immune function according to the degree of hearing loss.These results suggest that one of possible etiologies for ISSHL is an immunological disorder caused by viral infection, etc.

IFN for Treatment of Severe Idiopathic Sudden Sensorineural Hearing Loss. IFN Therapy without Steroids.

The severe type of idiopathic sudden sensor-ineural hearing loss (ISSHL) was treated with recombinant interferon alpha-2a (IFN-α) (3MU/day for 10 days) without steroids. Complete recovery was observed in nine out of eleven patients with severe ISSHL, and the hearing of the remaining two patients recovered ≥30dB.Ototoxicity, including sensorineural hearing loss has been reported to be induced by IFN. Our results with IFN in ISSHL suggest that, although IFN can be ototoxic at high doses, low dose IFN may be effective in the treatment of ISSHL caused by inner ear damage.Thus, IFN may actually be an effective substitute for steroids in ISSHL therapy.

Rhabdomyosarcoma of Sphenoid Sinus; A Case Report. Remote Afterloading System Radiotherapy through Sphenoid Sinus for Residual Tumor.

A 20-year-old female complained of left visual disturbance and eyeball pain, CT scan and MRI revealed a tumor of which the main lesion was in the sphenoid sinus, the histopathological diagnosis was embryonal type rhabdomyosarcoma.External beam irradiation with 50Gy and simultaneous chemotherapy with vincristine failed to eliminate the tumor in the sphenoid sinus. Remote afterloading system radiotherapy (RALS) was administered through the sphenoid sinus, which was opened surgically. The residual tumor had vanished by the end of RALS therapy.This method is an effective means of controlling residual tumor in paranasal sinuses.