Analgesic effect of a lidocaine-ropivacaine mixture for extraction of impacted mandibular third molars: a randomized controlled trial.

OBJECTIVES: The painless postoperative period can be significantly prolonged by using long-acting local anesthetics such as ropivacaine, though these local anesthetics are known for their slower onset of action. To compensate for this, a mixture of short-onset (e.g., lidocaine) and long-acting local anesthetics is used. However, the efficacy of such an anesthetic cocktail has not been elucidated in the field of oral and maxillofacial surgery. MATERIALS AND METHODS: To address the research purpose, this prospective randomized controlled trial included 56 patients scheduled for impacted mandibular third molar extraction. All patients received the inferior alveolar nerve block (IANB) using either 2% lidocaine with epinephrine or a 1:1 mixture of 2% lidocaine with epinephrine and 0.75% ropivacaine. RESULTS: Patients anesthetized using the lidocaine-ropivacaine mixture showed significantly prolonged postoperative analgesia and pain control than those anesthetized using lidocaine only. CONCLUSIONS: IANB using a lidocaine-ropivacaine mixture can provide prolonged postoperative anesthesia and pain control with extraction of mandibular third molars. CLINICAL RELEVANCE: This method can be a noteworthy addition to existing methods of local anesthesia for the extraction of mandibular third molars. Trial registration number University Hospital Medical Information Network (No. UMIN000044315).

Implications of prostaglandin D2 and leukotrienes in exhaled breath condensates of asthma.

BACKGROUND: Various inflammatory eicosanoid levels in biomaterials from airways of asthma and their associations with clinical parameters remain uncertain. We hypothesized that prostaglandin and leukotriene levels differ between in exhaled breath condensates (EBCs) and in sputum in mild, moderate, and severe levels of asthma and that EBC and sputum eicosanoid levels are associated with indexes of pulmonary function and inflammation. OBJECTIVE: To determine the differences between EBC and sputum eicosanoid levels in healthy participants and patients with asthma with different asthma severity levels. METHODS: Collected EBC and sputum, as well as pulmonary function, were examined in adult patients with asthma and healthy participants. Exhaled breath condensate prostaglandin D2-methoxime (PGD2-MOX), cysteinyl leukotrienes (CysLTs), leukotriene B4 (LTB4), and thromboxane B2 levels, and some sputum eicosanoid and tryptase levels were measured. Differences in eicosanoid levels among participants and their associations with pulmonary function and tryptase and granulocyte levels in sputum were then evaluated. RESULTS: Analysis of 94 EBCs and 43 sputa revealed that EBC and sputum PGD2-MOX and CysLT levels were significantly higher in patients with asthma than in healthy participants. Exhaled breath condensate PGD2-MOX, CysLT, and LTB4 levels were significantly higher in patients with severe asthma. Exhaled breath condensate PGD2-MOX level was also significantly correlated with sputum tryptase levels and lower pulmonary function in patients with asthma. Sputum PGD2-MOX and CysLT levels were significantly correlated with the proportion of eosinophils among all cells in sputum in patients with asthma. CONCLUSION: The results suggest that EBC PGD2 levels are associated with impairment of pulmonary function in adults with asthma who have undergone guideline treatment. Exhaled breath condensate or sputum PGD2 and CysLTs may represent severity or airway inflammation in asthma.

A Case of Conjunctival Ulcer and Uveitis Caused by Acrophialophora Sp. in an Immunocompromised Patient: a Case Report and Riterature Review.

We report the first case of invasive ophthalmologic infection by Acrophialophora sp. that was successfully treated using voriconazole (VRCZ). Acrophialophora spp., which has been reported to be an opportunistic pathogen, is a rare thermotolerant soil fungus, but its pathogenicity remains unclear. A 77-year-old man had neutropenia and prostate carcinoma and was receiving hemodialysis. His right eye had been infected for 2 days. His conjunctiva was congested, and it partially formed an abscess. Liposomal amphotericin B (L-AMB) was administered following systemic itraconazole. However, the treatment was changed from L-AMB to systemic VRCZ and VRCZ eye drops because his eye symptoms worsened. Subsequently, his symptoms stabilized and his vision was maintained. Acrophialophora sp. was identified by analyzing regions of internal transcribed spacer and domain 1 and 2 of the ribosomal RNA gene. He completed the 7-week systemic VRCZ course. The mean minimum inhibitory concentration of VRCZ for Acrophialophora spp. has been reported to be the lowest among various antifungal agents, and our results indicated the efficacy of VRCZ treatment for Acrophialophora sp. infection. Our results suggest that invasive Acrophialophora sp. infection may require long-term therapy. Further analysis of the clinical spectrum of Acrophialophora spp. infection and adequate treatment methods are required in the future.

[ANALYSIS OF BACKGROUNDS AND LEVEL OF UNDERSTANDING OF TREATMENT OF POOR ADHERENCE AND DROPOUT CASES ON SUBLINGUAL IMMUNOTHERAPY FOR JAPANESE CEDAR POLLINOSIS IN THE FIRST FOLLOW-UP YEAR].

BACKGROUND: We considered the factors of poor adherence to and dropout from sublingual immunotherapy (SLIT) by verifying patient backgrounds 1 year after start of treatment. METHODS: We recruited 38 patients who began SLIT between November 2014 and September 2015. We analyzed their attributes and level of understanding of the treatment, and conducted a self-reported survey on factors behind dropout cases and poor adherence cases. RESULTS: Four patients dropped out 1 year after start of treatment. Three left for reasons related to anxiety about side effects. There were five cases of poor adherence. There was no significant difference between good adherence, poor adherence, and dropout regarding level of understanding of the treatment (p=0.59). In the comparison between good and poor adherence groups, except four dropout patients, the adherence tended to be poor in patients with short duration of disease, smoking patients, and young patients. Continuous rate of SLIT achieved about 90%, suggesting relatively high level of adherence. CONCLUSION: It appears possible that anxiety related to side effects could be a factor affecting dropout from SLIT. There was no significant difference regarding level of understanding of the treatment. The adherence tended to be poor in patients with short duration of disease, smoking patients, and young patients.

Elevated uric acid and adenosine triphosphate concentrations in bronchoalveolar lavage fluid of eosinophilic pneumonia.

BACKGROUND: Recent evidence has suggested that the innate immune response may play a role in the development of eosinophilic airway inflammation. We previously reported that uric acid (UA) and adenosine triphosphate (ATP), two important damage-associated molecular pattern molecules (DAMPs), activate eosinophil functions, suggesting that these molecules may be involved in the development of eosinophilic airway inflammation. The objective of this study was to measure the concentrations of DAMPs including UA and ATP in the bronchoalveolar lavage fluid (BALF) of patients with eosinophilic pneumonia (EP). METHODS: BAL was performed in patients with EP including acute and chronic eosinophilic pneumonia, and in patients with hypersensitivity pneumonia, and sarcoidosis. UA, ATP, and cytokine concentrations in the BALF were then measured. RESULTS: The UA concentration was increased in the BALF of EP patients. UA concentrations correlated with eosinophil numbers, and with eosinophil-derived neurotoxin and interleukin (IL)-5 concentrations. Furthermore, the ATP concentration was increased in the BALF of EP patients and ATP concentrations correlated with UA concentrations. Moreover, IL-33 was increased in EP patients and IL-33 concentrations correlated with UA and ATP concentrations. CONCLUSIONS: The UA and ATP concentration was increased in the BALF of EP patients. UA concentrations correlated with eosinophil numbers, and with ATP and IL-33 concentrations. Our findings suggest that DAMPs such as UA and ATP play a role in the pathogenesis of EP.

Report of a case of acinic cell carcinoma of the upper lip and review of Japanese cases of acinic cell carcinoma of the minor salivary glands.

Acinic cell carcinoma (ACC) is a malignant tumor of the salivary glands. The majority of ACCs occur in the parotid gland, and ACCs of the minor salivary glands (MSGs) are relatively infrequent. We describe here a patient with ACC of the upper lip. The patient was a 31-year-old male who presented with a nodular mass on the left upper lip. The preoperative diagnosis was benign tumor or cyst, and the lesion was surgically excised. The histological diagnosis was ACC. The postoperative course was uneventful. No recurrence or metastasis was detected at 13 months postoperatively. In addition, we retrospectively reviewed 21 reported Japanese patients with ACC of the MSGs. In 7 of the 21 patients, the preoperative diagnosis was benign tumor, and the tumors were resected without preoperative biopsy. Kaplan-Meier analysis showed that disease-free survival was worse in patients who underwent resection with a preoperative diagnosis of benign tumor than in patients who underwent resection with a preoperative diagnosis of malignant tumor. The rate of recurrence was higher for ACCs assumed to be benign lesions on a purely clinical basis, or without an accurate preoperative biopsy. ACCs of the MSGs are easy to be misdiagnosed for benign lesions such as mucous cysts or hemangiomas. Correct preoperative diagnosis and initial therapy may therefore be the most important prognostic factors. Key words:Acinic cell carcinoma, Kaplan-Meier analysis, minor salivary glands, prognosis, upper lip.

Eosinophil infiltration in the upper gastrointestinal tract of patients with bronchial asthma.

BACKGROUND: Eosinophilic esophagitis (EoE) is related to allergic diseases such as bronchial asthma (BA), atopic dermatitis, and allergic rhinitis. The aim of this study was to examine the eosinophil infiltration in the upper gastrointestinal (GI) tract in patients with BA using esophagogastroduodenoscopy. METHODS: Patients with BA who had upper GI tract symptoms were enrolled. Patients who received systemically administered steroids were excluded. Eosinophil infiltrations in the esophagus, stomach, and duodenum were examined with regard to the endoscopic findings and pathological findings of biopsy specimens (UMIN000010132). RESULTS: Ninety patients were enrolled from October in 2012 to September in 2014. Thirty-six were male, 54 were female, and the mean age was 57.5 years. Eighty-one (90%) used inhaled corticosteroids. Fourteen patients (15.6%) had reflux esophagitis, 8 of whom had grade A and 6 had grade B. No patient with EoE was observed. One female patient who had marked eosinophil infiltration in the esophagus, stomach, and duodenum was diagnosed as having eosinophilic gastroenteritis, but endoscopy showed only mucosal edema in the antrum. Another female patient who had marked eosinophil infiltration in the esophagus, stomach, and duodenum was diagnosed as having eosinophilic granulomatosis with polyangiitis, and endoscopy showed erosions in the antrum and the duodenum. Three patients had eosinophil infiltration in the stomach, but none of them had severe symptoms. CONCLUSIONS: Patients with asthma who had upper gastrointestinal symptoms rarely had eosinophilic gastrointestinal disorders. Biopsy specimens are of high importance in the diagnosis of eosinophilic gastrointestinal disorders even if there is no remarkable endoscopic finding.

Angioleiomyoma of the tongue: a case report and review of the literature.

Angioleiomyoma (AL) is a benign tumor derived from smooth muscle. The overwhelming majority of ALs occur in the uterus, gastrointestinal tract, or skin; AL of the oral cavity is infrequent, and AL of the tongue is particularly rare. The present report describes a case of AL of the tongue that resulted in a good outcome. We also review the literature with a special emphasis on the etiology of ALs. It is generally agreed that minor trauma, venous stasis, and hormonal changes are etiological factors for AL. The roles of estrogen and progesterone have been particularly emphasized, and the expression of progesterone receptors (PRs) and estrogen receptors (ERs) has been recently evaluated in some cases of AL. To our knowledge, the presence of PRs and ERs has only been evaluated in seven cases of AL arising in different regions of the body including the oral cavity. This is the first report to demonstrate negative expression of both receptors in an AL of the oral cavity. Further study and additional cases are needed to elucidate the influence of PRs and ERs in AL of the oral cavity.

ATP drives eosinophil effector responses through P2 purinergic receptors.

BACKGROUND: Eosinophils recognize various stimuli, such as cytokines, chemokines, immunoglobulins, complement, and external pathogens, resulting in their accumulation in mucosal tissues and the progression of inflammation. Eosinophils are also involved in innate Th2-type immune responses mediated through endogenous danger signals, including IL-33, uric acid (UA), or ATP, in non-sensitized mice exposed to environmental allergens. However, the mechanism involved in eosinophil responses to these danger signals remains insufficiently understood. METHODS: We examined migration, adhesion, superoxide production and degranulation of human eosinophils. Isolated eosinophils were incubated with monosodium urate (MSU) crystals and ATPγS, a non-hydrolysable ATP analogue. To determine the involvement of P2 or P2Y2 receptors in eosinophil responses to UA and ATP, eosinophils were preincubated with a pan-P2 receptor inhibitor, oxidized ATP (oATP), or anti-P2Y2 antibody before incubation with MSU crystals or ATPγS. RESULTS: MSU crystals induced adhesion of eosinophils to recombinant human (rh)-ICAM-1 and induced production of superoxide. oATP abolished eosinophil responses to MSU crystals, suggesting involvement of endogenous ATP and its receptors. Furthermore, exogenous ATP, as ATPγS, induced migration of eosinophils through a model basement membrane, adhesion to rh-ICAM-1, superoxide generation, and degranulation of eosinophil-derived neurotoxin (EDN). oATP and anti-P2Y2 significantly reduced these eosinophil responses. CONCLUSIONS: ATP serves as an essential mediator of functional responses in human eosinophils. Eosinophil responses to ATP may be implicated in airway inflammation in patients with asthma.

Effect of beta2-adrenergic agonists on eosinophil adhesion, superoxide anion generation, and degranulation.

BACKGROUND: Eosinophils play important roles in the development of asthma exacerbation. Viral infection is a major cause of asthma exacerbation, and the expression of IFN-γ-inducible protein of 10 kDa (IP-10) and cysteinyl leukotrienes (cysLTs) is up-regulated in virus-induced asthma. As ß2-adrenergic agonists, such as formoterol or salbutamol, are used to treat asthma exacerbation, we examined whether formoterol or salbutamol could modify eosinophil functions such as adhesiveness, particularly those activated by cysLTs or IP-10. METHODS: Eosinophils were isolated from the blood of healthy subjects and were pre-incubated with either formoterol or salbutamol, and subsequently stimulated with IL-5, LTD4, or IP-10. Adhesion of eosinophils to intercellular cell adhesion molecule (ICAM)-1 was measured using eosinophil peroxidase assays. The generation of eosinophil superoxide anion (O2(-)) was examined based on the superoxide dismutase-inhibitable reduction of cytochrome C. Eosinophil-derived neurotoxin (EDN) release was evaluated by ELISA as a marker of degranulation. RESULTS: Neither formoterol nor salbutamol suppressed the spontaneous adhesion of eosinophils to ICAM-1. However, when eosinophils were activated by IL-5, LTD4, or IP-10, formoterol, but not salbutamol, suppressed the adhesion to ICAM-1. Formoterol also suppressed IL-5, LTD4, or IP-10 induced eosinophil O2(-) generation or EDN release. CONCLUSIONS: These findings suggest that formoterol, but not salbutamol, suppresses eosinophil functions enhanced by IL-5, LTD4, or IP-10. As these factors are involved in the development of asthma exacerbation, our results strongly support the hypothesis that administration of formoterol is a novel strategy for treating asthma exacerbation.

Solid type primary intraosseous squamous cell carcinoma in the maxilla: report of a new case.

BACKGROUND: Primary intraosseous squamous cell carcinoma is a rare jaw bone tumor defined as squamous cell carcinoma arising within the jaw, having no initial connection with the oral mucosa and developing from residual odontogenic epithelium or from an odontogenic cyst or tumor. Solid type of this tumor arising in the maxilla is an even rarer presentation, because the majorities derive from cystic lesions and are found in the posterior mandible. CASE PRESENTATION: A 36-year-old Japanese man was referred to our clinic with a complaint of pain around the anterior maxillary region on the right side. Intraoral examination identified a firm, non-fluctuant mass with no ulceration in the vestibular region of teeth #11-13. Incisional biopsy was performed, leading to histological diagnosis of moderately differentiated squamous cell carcinoma. Contrast-enhanced computed tomography revealed a destructive tumor with no cystic lesion, >50 mm in diameter. There was no evidence of metastatic disease on chest radiography, upper gastric endoscopy or positron emission tomography. Based on these findings, solid type primary intraosseous squamous cell carcinoma was diagnosed. The patient underwent tumor ablative surgery. The surgical defect was reconstructed using a partially double-folded free radial forearm flap and prefabricated denture-based surgical obturator. The postoperative course was quite good. Neither recurrence nor metastasis had been found as of 3 years and 1 month postoperatively. CONCLUSION: To the best of our knowledge, the present case represents only the 10th case of solid type primary intraosseous squamous cell carcinoma arising in the maxilla to be reported.

Significant improvement in temporary dental rehabilitation by notable miniplate application in the hard palate for a patient with a large anterior maxillary defect: a case report/technique article.

UNLABELLED: The present report describes the application of a miniplate in the hard palate of a 36-year-old patient with a large anterior maxillary defect. The combination of orthodontic elastics with a titanium miniplate improved the stability of the prefabricated prosthesis. This structure retained the ointment gauze covering the wounds and maintained the facial contour. In addition, contracture deformity was prevented by insertion of the prefabricated prosthesis intraoperatively or immediately postoperatively. Furthermore, a soft diet could be ingested immediately postoperatively. The miniplate also supported the anterior part and the definitive prosthesis. This prosthesis restored adequate masticatory, deglutitive, and speech functions and maintained the facial contour with minimum overloading of the remaining teeth. KEYWORDS: Dental rehabilitation; Maxillary defect; Titanium miniplate.

Evaluation of serum levels of carcinoembryonic antigen in allergic bronchopulmonary aspergillosis.

BACKGROUND: The serum level of carcinoembryonic antigen (CEA) is a marker of malignant disease but can also be increased in benign diseases. Patients with allergic bronchopulmonary aspergillosis (ABPA) have bronchial asthma showing a wide variety of radiological findings. We measured serum CEA levels in patients with ABPA and evaluated the relationships of serum CEA levels with peripheral blood eosinophil counts, total blood levels of immunoglobin (Ig) E, and findings of computed tomography (CT) in ABPA. METHODS: The subjects were 13 patients (6 men and 7 women aged 34 to 76 years) who had been treated for ABPA at our hospital. Serum levels of CEA, peripheral blood eosinophil counts, total blood IgE levels, and CT findings were examined before and after treatment with prednisolone. RESULTS: Before the start of the treatment 7 of 13 patients had serum CEA levels higher than the upper limit of normal. The serum CEA level was not correlated with eosinophil counts or total IgE values. Serum CEA levels were examined after treatment in 9 patients and were found to have significantly decreased as pulmonary consolidation improved. Furthermore, serum CEA levels before treatment in patients with pulmonary consolidation were significantly higher than those in patients without consolidation. CONCLUSION: Serum CEA levels are elevated in some patients with ABPA; these elevations might be associated with consolidation in the lung. Elevated serum CEA levels decrease as the consolidation decreases after treatment. The elevation of serum CEA might be attributed to the presence of local inflammation in the lung.

Human eosinophils recognize endogenous danger signal crystalline uric acid and produce proinflammatory cytokines mediated by autocrine ATP.

Eosinophils are multifunctional leukocytes involved in various inflammatory processes, as well as tissue remodeling and immunoregulation. During inflammation and infection, injured cells and damaged tissues release uric acid and monosodium urate (MSU) crystals as important endogenous danger signals. Uric acid is also implicated in the immunogenic effects of an authentic Th2 adjuvant, aluminum hydroxide. Eosinophils often localize at sites of Th2-type chronic inflammation; therefore, we hypothesized that eosinophils may react to endogenous danger signals. We found that human eosinophils migrate toward soluble uric acid and MSU crystals in a gradient-dependent manner. Eosinophils incubated with MSU crystals, but not those incubated with uric acid solution, produced elevated levels of IL-6 and IL-8/CXCL8. Other cytokines and chemokines, including IL-1beta, IL-10, IL-17, IFN-gamma, CCL2, CCL3, CCL4, TNF-alpha, G-CSF, GM-CSF, fibroblast growth factor, vascular endothelial growth factor, and TGF-beta, were also produced by eosinophils incubated with MSU crystals. Eosinophils exposed to MSU crystals rapidly (i.e., within 1 min of exposure) released ATP into the extracellular milieu. Importantly, this autocrine ATP was necessary for eosinophils to produce cytokines in response to MSU crystals, and P2 nucleotide receptors, in particular P2Y(2), are likely involved in this positive feedback loop. Finally, at higher concentrations, MSU crystals promoted P2R-dependent release of a granule protein (eosinophil-derived neurotoxin) and cell death. Thus, human eosinophils may respond to particulate damage-associated endogenous danger signals. These responses by eosinophils to tissue damage may explain the self-perpetuating nature of chronic inflammation in certain human diseases, such as asthma.

Eosinophil superoxide anion generation induced by adhesion molecules and leukotriene D4.

RATIONALE: Eosinophils preferentially accumulate at sites of inflammation in the asthmatic airway. Participation of circulating eosinophils in the airway inflammation in asthma involves their interaction with adhesion molecules expressed on the endothelial cell surface and exposure to inflammatory mediators, such as cysteinyl leukotrienes (cysLTs). OBJECTIVE: To investigate whether interaction of eosinophils with adhesion molecules modifies the functions of these cells induced by cysLTs. METHODS: Eosinophils were isolated from the blood of healthy donors, incubated in the EIA plates coated with adhesion proteins, and then exposed to LTD4. The generation of superoxide anion (O2-), adhesion to the plates, and release of eosinophil-derived neutrotoxin (EDN) were evaluated. RESULTS: Neither VCAM-1 nor LTD4 (100 nM) independently induced eosinophil O2- generation, however, combined exposure to the two molecules synergistically induced eosinophil O2- generation. ICAM-1 by itself induced eosinophil O2- generation, which was enhanced by LTD4. On the contrary, P-selectin did not induce O2- generation, either in the presence or absence of LTD4. LTD4 significantly enhanced eosinophil adhesion to rh-VCAM-1 and rh-ICAM-1, but not to rh-P-selectin. Finally, we observed that combined exposure of eosinophils to LTD4 and VCAM-1 induced the release of EDN. CONCLUSION: Combined exposure to VCAM-1 or ICAM-1 and cysLT effectively induces the effector functions of eosinophils. Eosinophil adhesion to and migration across endothelial cells via these specific adhesion proteins and subsequent exposure to cysLTs may be mechanisms underlying activation of the effector functions of eosinophils in the asthmatic airway.

Differential effects of salbutamol and montelukast on eosinophil adhesion and superoxide anion generation.

BACKGROUND: Beta2-agonists, a representative class of bronchodilators used for asthma, have been shown to modulate some functions of eosinophils, including cell adhesion. Similarly, a leukotriene receptor antagonist (LTRA) may be beneficial in controlling inflammation in asthma, as cysteinyl leukotrienes (cysLTs) can cause accumulation or activation of eosinophils. Recent evidence suggests that the addition of an LTRA, but not a long-acting beta2-agonist, to inhaled corticosteroid additionally reduces the number of eosinophils in sputum and blood from patients with asthma. The present study examined whether a beta2-agonist and an LTRA differentially modify eosinophil adhesion and activation induced by cysLTs and other activators. METHODS: Eosinophils were isolated from blood of healthy donors and then incubated in the presence or absence of salbutamol (albuterol) or montelukast. Eosinophils were then exposed to leukotriene D4 (LTD4) or another activator, and the generation of superoxide anion (O2-) was evaluated by cytochrome C reduction assay. Eosinophil adhesion was examined by an eosinophil peroxidase assay. RESULTS: Montelukast, but not salbutamol (both at 1 microM), inhibited LTD4-induced (100 nM) eosinophil adhesion to recombinant human intercellular adhesion molecule 1. Both drugs similarly and partially inhibited the 100 pM interleukin-5-induced adhesive response of eosinophils to recombinant human intercellular adhesion molecule 1. Montelukast, but not salbutamol, blocked LTD4-induced eosinophil O2- generation of eosinophils. Finally, neither salbutamol nor montelukast modified phorbol myristate acetate (1 ng/ml)-induced O2- generation from eosinophils. CONCLUSION: These results confirm that LTD4 directly induces activation of eosinophils via the cysLT1 receptor. Furthermore, the results suggest that a beta2-agonist has no effect on eosinophil adhesion and activation induced by cysLTs. These results explain the differential effects of an LTRA and a beta2-agonist in the treatment of eosinophilic inflammation in asthma.