OK-432 Treatment of Ranula Intruding into the Cervical Region.

OBJECTIVES: Plunging ranula intruding into the cervical region is rare and a standard therapy has not yet been consolidated. This paper investigates the outcomes and side effects of OK-432 treatment in patients with a ranula extending into the cervical region. METHODS: The study design and setting consisted of a planned data collection at Tohoku Medical and Pharmaceutical University and Fukase Clinic. Eight patients with ranula extending into the cervical region received OK-432 treatment between January 2016 and February 2019. OK-432 treatment was performed for patients with ranula extending into the cervical region. RESULTS: In all patients, a total shrinkage and marked reduction in lesions were observed without local scars or deformations after OK-432 treatment. Complications were local swelling and mild fever (37.5-38.5 °C), which lasted a few days in half of the patients. CONCLUSIONS: OK-432 treatment is straightforward, secure, and efficacious and can be substituted for surgery in the treatment of ranula extending into the cervical region.

OK-432 treatment of pediatric patients with recurrent thyroglossal duct cyst after surgery.

<b>Introduction:</b> Recurrent thyroglossal duct cyst after surgery is not a rare condition and first-line treatment has not been established yet.<br/><br/> <b>Aim:</b> Evaluation of outcomes and complications of OK-432 treatment in patients with recurrent thyroglossal duct cyst after surgery. <br/><br/> <b>Material and methods:</b> This study is designed as a case series with planned data collection at Tohoku Medical and Pharmaceutical University and Fukase Clinic. Five patients with recurrent thyroglossal duct cyst after surgery received this therapy between January 2014 and February 2020 on an outpatient basis, without hospitalization. OK-432 solution was injected into the lesion using an 18- or 27-gauge needle, depending on the location and size of the lesion, as well as on possible complications.<br/> <br/> <b>Results:</b> Lesions showed marked reduction or total shrinkage in all patients, with no local scarring or deformity at the injection site. Side effects manifested as local pain at the site of injection and fever (37.5-38.5°C) observed in three patients, but the symptoms resolved within a few days.<br/> <br/> <b>Conclusions:</b> Since OK-432 therapy is simple, easy, safe and effective, it can be used as an alternative to surgery in the treatment of recurrent thyroglossal duct cyst after surgery.

[Examination about positive ratio of pollen antigens by scratch test].

BACKGROUND: Japanese cedars and grass are famous for causing pollen allergy with antigen. But recently, many other antigens causing pollen allergy are coming to the front. We investigated positive ratios of pollen antigens of the consultation patients. METHODS: 151 subjects (90 males and 61 females) were examined for allergic reactions by a scratch test. We used Yasueda's method to take pollen extracts. RESULTS: A positive ratio of Cocksfoot (Dactylis glomerata) (51%) was higher than that of cedar (Cryptomeria japonica) (45%). Each positive ratio of birch (Betula platyphylla var. japonica), walnut (Juglans mandshurica), sheep sorrel (Rumex acetosella), oak (Quercus serrata) and willow (Salix spp.) was 13%, 8%, 9%, 11%, 10%, respectively. These were lower than that of Cocksfoot or cedar, but higher than that of Fungi: Alternaria, Candida and Aspergillus. CONCLUSION: Grass (Gramineae) pollens and pollens of birch, walnut, sheep sorrel, oak and willow, which are in the air around the same time as grass pollens, are important in clinical medicine, because of their high positive ratio. And in this research, each positive ratio is overlapping, so it is necessary to search an antigen hemology.

Treatment of Auricular Hematomas by OK-432: How and Why It Works.

OBJECTIVES: The aim of this article was to investigate the effectiveness and underlying mechanisms of OK-432 therapy in patients with auricular hematomas. STUDY DESIGN AND SETTING: Case series with planned data collection. SUBJECTS AND METHODS: We tried this therapy in 47 patients with auricular hematoma between April 2008 and August 2018. We aspirated as much of the fluid content of each lesion as possible with a 21-gage needle. We injected OK-432 solution into the lesion with the same needle that we used for aspiration. We performed this treatment at an outpatient basis without hospitalization. RESULTS: Disappearance and marked reduction of the lesion were observed in all patients who had this therapy, and local scarring and deformity of the auricle did not occur in any patients. As adverse effects, local pain at the injection site and fever (37-38.5°C) were observed in some cases of the patients who had this therapy. The concentrations of various cytokines in each aspirate before and after OK-432 therapy were investigated. The production of tumor necrosis factor-α, interleukin-6, interleukin-8, interferon gamma, vascular endothelial growth factor, and periostin was significantly elevated in the aspirate fluid after OK-432 therapy. CONCLUSION: OK-432 therapy is simple, easy, safe, effective, and can be used as a substitute for surgery in the treatment of auricular hematoma.

NADPH-dependent reductases and polyol formation in human leukemia cell lines.

Because of the limited availability of human tissues, leukemia cell lines are often utilized as the models for human leukocytes. In this study, we investigated the NADPH-dependent reductases and polyol pathway in commonly utilized human leukemia cell lines. The relative amounts of aldose and aldehyde reductases were estimated by separating two enzymes with chromatofocusing. The flux of glucose through the polyol pathway was examined by 19F-NMR using 3-fluoro-3-deoxy-D-glucose (3FG) as substrate. Sugar alcohol analysis was conducted by gas chromatography. In myelocytic leukemia cells, the major reductase was aldehyde reductase, and levels of aldose reductase were extremely low. Although lymphocytic cells also contained both aldose and aldehyde reductases, the levels of aldose reductase appeared to be higher in lymphocytic cells than myeolcytic cells. In two lymphocytic cells MOLT-4 and SKW6.4, aldose reductase is clearly dominant. When incubated in medium containing D-galactose, all cell lines quickly accumulated galactitol. There was correlation between galactitol levels and aldose reductase levels. The aldose reductase inhibitor FK 366 significantly reduced the formation of galactitol. 19F-NMR of the cells cultured with 3FG as substrate demonstrated the formation of 3-fluoro-3-dexoy-sorbitol in all the cell lines examined in this study. The relative amounts of sorbitol and fructose varied significantly among the cells. The data confirm that the polyol pathway is present in both myelocytic and lymphocytic leukemia cell lines. However, there is a large variation among the cell lines in the levels of enzymes and flux of glucose through the polyol pathway.

Treatment of ranula wth intracystic injection of the streptococcal preparation OK-432.

Intracystic injection of OK-432 was developed as a therapy for operatively difficult lymphangioma (cystic hygroma) and is currently becoming a treatment of first choice for this disease. We tried this therapy in 32 patients with ranula (oral floor type in 21 cases and plunging type in 11 cases). Disappearance or marked reduction of the lesion was observed in 31 patients (97%) who had this therapy, and local scarring did not occur in any patient. As side effects, local pain at the injection site and fever (37 degrees C to 39 degrees C) were observed in almost half of the patients who had this therapy, but such problems resolved within a few days. We treated the initial 4 cases in the hospital for 4 to 5 days, but after the safety of this method had been confirmed, we treated the other 28 cases on an outpatient basis. Thus, we confirmed that intracystic injection therapy with OK-432 is relatively safe and can be used as a substitute for surgery in the treatment of ranulas.

Immunological responses in acute low-tone sensorineural hearing loss and Ménière's disease.

OBJECTIVE: The autoimmune response appears to play an important role in some types of acute sensorineural hearing loss. Endolymphatic hydrops associated with fluctuating hearing loss has also been suggested to be caused by an immunological mechanism. Acute low-tone hearing loss (ALHL) associated with Ménière's disease (MD) is characterized by fluctuating hearing loss, and its etiology is thought to involve endolymphatic hydrops. The aim of this study was to attempt to determine the etiology of ALHL in MD. MATERIAL AND METHODS: A flow cytometer was used to analyze intracellular cytokine levels in peripheral blood from 19 patients with ALHL and 26 patients with MD and the data compared to those obtained from age- and gender-matched healthy volunteers. RESULTS: The patients with ALHL showed significantly increased levels of Th1 subsets (interferon-gamma-producing helper T cells) as compared to those in normal controls. The levels of Th2 (IL-4-producing helper T cells) subsets did not differ from those in the control group and thus Th1 predominated in ALHL patients. The patients with MD showed significantly increased natural killer cell activity but no Th1 dominance. These patients had no obvious systemic or local disease except in the inner ear. CONCLUSION: An abnormality of the Th1/Th2 balance in ALHL and increased natural killer cell activity in MD are thought to relate to inner ear disorder. These results are consistent with the possibility that the etiology of ALHL and MD involves an immune response.

Th1 and Th2 CD4+ T cells and Tc1 and Tc2 CD8+ T cells of patients with Wegener's granulomatosis.

A Th1/Th2 cytokine imbalance with a predominance of Th1 cytokines has been suggested to be of pathogenic importance in Wegener's granulomatosis. To evaluate the role of Th1/Th2 cytokines in Wegener's granulomatosis, the subsets of Th1, Th2, Tc1 and Tc2 cells from patients with active Wegener's granulomatosis were examined by intracellular cytokine flow cytometry. The population of Tc1 cells (72.0 +/- 14.4 per cent) in Wegener's granulomatosis was significantly increased compared with Tc1 cells (37.3 +/- 14.6 per cent) in control (p<0.05). Th1, Th2 and Tc2 cells in Wegener's granulomatosis were not significantly increased compared with the control cells. These results indicate that the predominance of Tc1 cells might contribute to the mechanism of the pathogenesis of Wegener's granulomatosis.

OK-432 treatment of ranula extending to the parapharyngeal space.

CONCLUSIONS: Our results confirmed that OK-432 therapy is simple, easy, safe, and effective and can be used as a substitute for surgery in the treatment of ranula extending to the parapharyngeal space. OBJECTIVE: The aim of this study was to evaluate the outcome and complications of the OK-432 treatment of patients with ranula extending to the parapharyngeal space. METHODS: This was a case series with planned data collection at Yamagata University and Fukase clinic. We tried this therapy in six patients with ranula extending to the parapharyngeal space, between January 2001 and February 2012. We injected OK-432 solution into the lesion with an 18 or 27 gauge needle depending on the patient's condition (location and size of ranula and complications). This treatment was performed on an outpatient basis without hospitalization. RESULTS: Disappearance or marked reduction of the lesion were observed in all patients who had this therapy, and local scarring and deformity of the injection sites did not occur in any patients. As side effects, local pain at the injection site and fever (37-39°C) were observed in 40% of the patients who had this therapy, but such problems resolved within a few days.

Aortic aneurysm rupture as a rare complication of granulomatosis with polyangiitis: a case report.

INTRODUCTION: Granulomatosis with polyangiitis is characterized by systemic inflammation of medium and small blood vessels. Aortic involvement in granulomatosis with polyangiitis is extremely rare. As far as we know this is the first reported case of successful treatment in a patient with granulomatosis with polyangiitis complicated with aortic aneurysm rupture. CASE PRESENTATION: We describe a case of granulomatosis with polyangiitis in a 38-year-old Japanese man who developed an aortic aneurysm rupture 22 years after disease onset. The patient was operated on and a J-graft was inserted. He recovered uneventfully. CONCLUSION: Recommendations in regard to, and consideration of, aortic involvement should be kept in mind in the long-term careful follow up of granulomatosis with polyangiitis.

Treatment of salivary mucocele of the lower lip by OK-432.

OBJECTIVE: The aim of this paper was to evaluate the outcome and complications of the treatment of patients with salivary mucocele by intralesional injection therapy with OK-432. METHODS: We tried OK-432 therapy in 20 patients with salivary mucocele. We injected OK-432 solution into the lesion with a 27-gauge needle to prevent any leakage of the agent from the mucocele. RESULTS: Disappearance of the lesion was observed in 16 of 20 patients. Marked reduction was observed in 4 of 20 patients. No local scarring or deformity of the lower lip occurred in any patients. As side effects, local discomfort at the injection site was observed in two of the patients, but such problems resolved within a few days. We performed this treatment on an outpatient basis without hospitalization. CONCLUSION: Our results confirmed that OK-432 therapy is simple, easy, and relatively safe, and can be used as a substitute for surgery in the treatment of salivary mucocele.

In situ expression of CD23 in lymph nodes of patients with Kimura's disease.

OBJECTIVE: The aim of this study was to investigate the expression of CD23 (Fcɛ RII) in the lymph nodes (LNs) of patients with Kimura's disease (KD). METHODS: Expression of CD23 was examined immunohistochemically. The concentrations of soluble CD23 and titers of IgE in sera from patients with KD were studied by enzyme-linked immunosorbent assay (ELISA). RESULTS: In the germinal centers (GCs) of LNs from patients with KD, overexpression of CD23 on well-developed follicular dendritic cells (FDCs) was observed. GC lymphocytes in the LNs of KD patients were intensely positive for CD23, and positive cells were also observed in both the light and dark zones. In contrast, in the LNs of normal patients, CD23-positive cells were restricted to the light zone of the GCs. Although serum IgE titers were raised in all KD patients, serum concentrations of soluble CD23 were not elevated. CONCLUSION: These results suggest that CD23 and FDCs play important roles in the pathogenesis of KD.

Increase of Th2 and Tc1 cells in patients with Kimura's disease.

OBJECTIVE: A Th1/Th2 cytokine imbalance with a predominance of Th2 cytokines has been suggested to be of pathogenic importance in Kimura's disease. METHODS: To evaluate the role of Th1/Th2 cytokines in Kimura's disease, the subsets of Th1, Th2, Tc1 and Tc2 cells from patients with Kimura's disease were examined by intracellular cytokine flow cytometry. The expressions of IL-5, eotaxin and RANTES in the lesions were investigated by RT-PCR. RESULTS: The population of Th2 and Tc1 cells in Kimura's disease was significantly increased compared with these cells in control (p<0.05). Th1 and Tc2 cells in Kimura's disease were not significantly increased compared with control subjects. The titers of IgE and the number of Th2 cells were correlated. The expression of IL-5 and RANES was observed in the lesions of patients with Kimura's disease. CONCLUSION: These results indicate that the predominance of Th2 and Tc1 cells might contribute to the mechanism in pathogenesis of Kimura's disease.

Treatment of auricular hematoma by OK-432.

OBJECTIVES: Intralesional injection therapy with OK-432 was developed as a therapy for operatively difficult lymphangioma (cystic hygroma) and is currently becoming a first-choice treatment for this disease. The aim of this article was to evaluate the outcome and complications of the treatment of patients with auricular hematoma by OK-432 therapy. STUDY DESIGN: Case series with planned data collection. SETTING: Yamagata University School of Medicine. SUBJECTS AND METHODS: We tried this therapy in 21 patients with auricular hematoma between January 2001 and February 2009. We injected OK-432 solution into the lesion with a 27-gauge needle to prevent the leak of the agent out of the hematoma. We performed this treatment on an outpatient basis without hospitalization. RESULTS: Disappearance or marked reduction of the lesion were observed in all patients who had this therapy, and local scarring and deformity of the auricle did not occur in any patients. As for side effects, local pain at the injection site and fever (37 degrees C-38 degrees C) were observed in a few of the patients who had this therapy, but such problems resolved within a few days. CONCLUSION: These results may allow us to speculate that intralesional injection therapy with OK-432 is simple, easy, safe, and effective and can be used as a substitute for surgery in the treatment of auricular hematoma.

Treatments of various otolaryngological cystic diseases by OK-4321: its indications and limitations.

OBJECTIVES/HYPOTHESIS: The aim of this study was to evaluate the indications for, and outcomes and limitations of, OK-432 therapy in various otolaryngological cystic diseases. STUDY DESIGN: A retrospective clinical study at Yamagata University School of Medicine and the Fukase Clinic in Japan. METHODS: Between April 1996 and November 2009 we tried OK-432 therapy in 148 patients with otolaryngological cystic diseases. In cases of plunging ranulas, lymphangiomas, branchial cleft cysts, thyroglossal duct cysts, thyroid cysts, and cervical lymphocele, we aspirated as much of the fluid content of each cystic lesion as possible, and we then replaced the volume of aspirated fluid with about half the volume of OK-432 solution. RESULTS: Disappearance of the lesion was observed in 119 of 148 patients (80%). Marked reduction was observed in 20 of 148 patients (14%). Partial reduction was observed in four patients (3%), and no response was seen in five patients (3%). Plunging ranula, lymphangioma, thyroglossal duct cyst, thyroid cyst, auricular hematoma, and salivary mucocele showed better responses to OK-432 therapy than did branchial cleft cyst. Serious complications with OK-432 therapy were infrequent, and the therapy seemed to have no influence on future surgery. CONCLUSIONS: Our results confirmed that OK-432 therapy is simple, easy, safe, and effective and can be used as a substitute for surgery in the treatment of various otolaryngological cystic diseases.

Effects and mechanism of OK-432 therapy in various neck cystic lesions.

CONCLUSION: Our results confirmed that OK-432 therapy is simple, easy, safe, and effective and can be used as a substitute for surgery in the treatment of benign neck cysts. In OK-432 therapy, inflammatory cytokines may play important roles in shrinkage of the cystic spaces. OBJECTIVE: The aim of this study was to evaluate the outcome and mechanism of action of OK-432 therapy in benign neck cysts. METHODS: We tried OK-432 therapy in 83 patients with benign neck cysts between April 1997 and August 2009. We aspirated as much of the fluid content of each cystic lesion as possible, and then replaced the volume of aspirated fluid with about half the volume of OK-432 solution. We evaluated the mechanism of action of OK-432 in 43 of the patients. The intracystic fluid in the cysts was aspirated before and after OK-432 therapy, and cytokine production in each aspirate was analyzed by ELISA. RESULTS: Disappearance of the lesion was observed in 63 of 83 patients (76%). Marked reduction was observed in 13 of the 83 patients (16%). Partial reduction was observed in two patients (2%) and no response was seen in five (6%). Local discomfort at the injection site and low-grade fever were side effects observed in half of the patients, but such problems resolved within a few days. No local scarring or deformity of the injected sites occurred in any patient. We performed OK-432 therapy on an outpatient basis without hospitalization. Levels of various cytokines, including tumor necrosis factor, interleukin-8, interleukin-6, interferon gamma, and vascular endothelial growth factor, were significantly elevated in each aspirate after OK-42 therapy.

Serum concentrations of eosinophil cationic protein and eosinophils of patients with Kimura's disease.

BACKGROUND: To clarify the role of eosinophils in the pathogenesis of Kimura's disease and the values of measuring serum levels of eosinophil cationic protein (ECP) for monitoring disease activity might be very important, but there are few reports about this matter. METHODS: A total 14 serum and 7 tissue samples from patients with Kimura's disease were studied. The concentrations of ECP and cytokines (interleukin-4 (IL-4), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin 5 (IL-5)) in sera from patients with Kimura's disease were measured by enzyme-linked immunosorbent assay (ELISA). The density of eosinophils and the degree of activation of eosinophils in the tissue were also studied immunohistochemically. RESULTS: The concentration of ECP in sera from patients with Kimura's disease was significantly higher than that in the control group (p<0.05). At the time of the remission, a significant decrease of ECP was observed. In interfollicular areas, most infiltrated eosinophils were positive for EG2 antibody (64.0-94.0%) and the mean percentage of EG2-positive eosinophils was 75.7%. The concentrations of IL-4, GM-CSF, and IL-5 in sera from patients with Kimura's disease were within normal ranges or below the detectable level in all sera examined. CONCLUSIONS: Our findings suggest that eosinophils play an important role in the pathogenesis of Kimura's disease and ECP may be used as an additional parameter of disease activity.