[A Case Report of Kampo Medicine Improving the Symptoms of Antiresorptive Agent-related Osteonecrosis of the Jaw (ARONJ)].

A 56-year-old woman visited an oral surgery clinic in October X with sudden pain in the left mandible. She was diagnosed with left mandibular osteomyelitis based on head computed tomography examination findings. The pain did not reduce even with amoxicillin and loxoprofen sodium hydrate. The patient was then referred to our clinic for treatment. Hainosankyuto (7.5 g/d), loxoprofen sodium hydrate (180 mg/d), and mecobalamin (1500 µg/d) alleviated the pain. However, numbness and tingling pain in the left part of the chin increased. Pregabalin 50 mg/d was then prescribed and then increased from 50 to 100 mg/d. The patient was diagnosed with antiresorptive agent-related osteonecrosis of the jaw (ARONJ). As the pain was exacerbated by discontinuation of the hainosankyuto, it was used continuously. The patient experienced no pain, even after discontinuing the mecobalamin and pregabalin. Platycodon root in hainosankyuto promotes drainage. The patient did not show any significant swelling because she took hainosankyuto during the early stages of inflammation. In addition, the pain resolved even when only hainosankyuto was used, possibly due to the analgesic effect of platycodon root, glycyrrhiza root, and peony root. Hainosankyuto may be an effective adjunctive treatment for patients with ARONJ whose pain is difficult to control with general treatment.

A rat model for inducing temporomandibular anterior disc displacement experimentally.

The aim of this study was to establish an experimental rat model of temporomandibular joint (TMJ) anterior disc displacement (ADD). A pilot study was conducted to determine the most appropriate surgical protocol. In the main experiment, 40 rats were used. Twenty-four rats were subjected to ADD in the right TMJ, and subsequently thereafter six, nine, and nine rats were sacrificed at 1, 4, and 8 weeks, respectively, for gross evaluation. Twelve rats that underwent a sham operation were equally divided and sacrificed at each of the above time points. Four non-treated control rats were sacrificed at the beginning of the study. TMJ blocks were harvested for radiological and histological assessment. Gross examination showed that 14 rats in the ADD group (58.3%) had anterior displacement of the TMJ disc. In the ADD joints, posterior condylar cartilage thickness decreased during the follow-up period; however, there was no significant difference between the sham-treated and ADD joints, or among the follow-up time points (P > 0.05). The anterior condylar cartilage exhibited obvious qualitative alterations. Radiologic signs of osteoarthrosis appeared after ADD surgery, but this became attenuated with time. The model investigated in this study successfully induced ADD in rats, and should be useful for assessment of progressive changes in the TMJ following ADD.

Assessment of Assistance in Smoking Cessation Therapy by Pharmacies in Collaboration with Medical Institutions- Implementation of a Collaborative Drug Therapy Management Protocol Based on a Written Agreement between Physicians and Pharmacists.

This study built a protocol for drug therapy management (hereinafter "the protocol") that would enable continuous support from the decision making of smoking cessation therapy to the completion of therapy through the collaboration of physicians and community pharmacists, after which we evaluated whether the use of this protocol would be helpful to smoking cessation therapy. This study utilized the "On the Promotion of Team-Based Medical Care", a Notification by the Health Policy Bureau as one of the resources for judgment, and referred to collaborative drug therapy management (CDTM) in the United States. After the implementation of this protocol, the success rate of smoking cessation at the participating medical institutions rose to approximately 70%, approximately 28-point improvement compared to the rate before the implementation. In addition to the benefits of the standard smoking cessation program, this result may have been affected by the intervention of pharmacists, who assisted in continuing cessation by advising to reduce drug dosage as necessary approximately one week after the smoking cessation, when side effects and the urge to smoke tend to occur. Additionally, the awareness survey for the intervention group revealed that all respondents, including patients who failed to quit smoking, answered that they were satisfied to the question on general satisfaction. The question about the reason for successful cessation revealed that the support by pharmacists was as important as, or more important than, that by physicians and nurses. This infers that the pharmacists' active engagement in drug therapy for individual patients was favorably acknowledged.

Suppression of IGF binding protein-3 by palmitate promotes hepatic inflammatory responses.

IGF-binding protein-3 (IGFBP-3) is a liver-derived, anti-inflammatory molecule that is decreased in obesity, a key risk factor for nonalcoholic fatty liver disease (NAFLD). It was not known whether IGFBP-3 levels were altered in NAFLD, whether such alterations could be the result of lipotoxicity, and whether altered IGFBP-3 could affect pathways that are involved in hepatic and systemic inflammation. Serum IGFBP-3 was decreased in patients with NAFLD, whereas liver and circulating IL-8 levels were increased. Palmitate inhibited IGFBP-3 secretion by THP-1 macrophages and enhanced IL-8 expression. Exposure of palmitate-treated THP-1 macrophages to IGFBP-3-deficient conditioned medium led to a 20-fold increase in palmitate-induced IL-8 expression by hepatocytes. Conversely, overexpression of IGFBP-3 suppressed JNK and NF-κB activation and blocked palmitate-induced IL-8 expression in hepatocytes. Silencing IGFBP-3 in Huh7 cells enhanced JNK and NF-κB activity and increased palmitate-induced IL-8 secretion. These data indicate that IGFBP-3 serves as an anti-inflammatory brake in hepatocytes against JNK and NF-κB and limits their activation and downstream production of proinflammatory cytokines. Under lipotoxic conditions, palmitate inhibits hepatic macrophage secretion of IGFBP-3, thereby releasing the brake and enhancing palmitate-induced IL-8 synthesis and secretion.-Min, H.-K., Maruyama, H., Jang, B. K., Shimada, M., Mirshahi, F., Ren, S., Oh, Y., Puri, P., Sanyal, A. J. Suppression of IGF binding protein-3 by palmitate promotes hepatic inflammatory responses.

Trigeminal neuralgia: differences in magnetic resonance imaging characteristics of neurovascular compression between symptomatic and asymptomatic nerves.

OBJECTIVES: Neurovascular compression (NVC) of the trigeminal nerve is the primary cause of trigeminal neuralgia (TN) but is known to occur in both symptomatic and asymptomatic nerves. The purposes of this study were to evaluate the relationship between the magnetic resonance imaging (MRI) findings regarding the site of NVC and the manifestation of TN symptoms. METHODS: In 147 patients with unilateral TN, the presence or absence of NVC was evaluated on MRI in both symptomatic and asymptomatic nerves. In cases with NVC, the shortest distance from the trigeminal nerve root to the responsible vessel was measured. RESULTS: The mean distance from the trigeminal nerve root to the site of NVC in asymptomatic nerves (3.85 ± 2.69 mm) was significantly greater than that in symptomatic nerves (0.94 ± 1.27 mm). When the distance was 3 mm or less, the rate of the manifestation of TN symptoms was 83.1% (103/124). On the other hand, it was only 19.6% (9/46) in cases with a distance of greater than 3 mm. CONCLUSIONS: Whether or not NVC of the trigeminal nerve was symptomatic was closely related to the distance from the trigeminal nerve root to the responsible blood vessel.

Metachronous early gastric cancer over a period of 13 years after eradication of Helicobacter pylori.

Stomach cancer can occur during chronic inflammation from Helicobacter pylori (HP) infection, and its occurrence can be suppressed by eradication of HP. However, the effects of suppressing stomach cancer by HP eradication are limited, and the cancer is known to recur even after eradication of this infection. Here, we report the case of a 56-year-old male patient with gastric cancer who, although undergoing HP eradication after treatment of early gastric cancer with endoscopy, experienced five metachronous cancer recurrences over a period of 13 years. Whether observation of patients who undergo eradication of HP due to peptic ulcers or chronic gastritis and patients who undergo eradication after endoscopic treatment for early gastric cancer should be performed at the same interval is an issue that must be addressed in the future. The appropriate observation period for each patient must be established while considering the burdens to the patient and from the medical economic perspective.

Features of lateral cephalograms associated with difficult laryngoscopy in Japanese children undergoing oral and maxillofacial surgery.

BACKGROUND: Difficult laryngoscopy and tracheal intubation are occasionally encountered in children with congenital anomalies or micrognathia. However, no study has elucidated anatomical etiology in relation to craniofacial development. METHODS: Two hundred ten patients aged 8 months-18 years were analyzed. We analyzed the lateral cephalograms of: (i) eight patients in whom laryngoscopy was anticipated as difficult before anesthesia and who were unable to be intubated by direct laryngoscopy and needed fiberoptic bronchoscopy (group A); (ii) 11 patients in whom laryngoscopy was anticipated as difficult before anesthesia but who were able to be intubated by direct laryngoscopy (group B); and (iii) 191 patients in whom laryngoscopy was anticipated as easy before anesthesia and was actually found to be easy (group C). Eight cephalometric parameters were measured and age-parameter relationships were plotted. Logistic regression analysis was performed to characterize group A children for each of the cephalometric variables. RESULTS: Apparently insufficient growth of the mandible was observed in the group A children. Furthermore, the group A children of aged <4 years had undeveloped maxilla, longer mandibular plane-hyoid distances (≥1.3 cm), and deeper depth of the oropharynx; those of aged ≥4 years showed increased inclination of the mandible (sella-nasion plane to mandibular plane angle of ≥46.5°). CONCLUSIONS: Difficult laryngoscopy and tracheal intubation are expected in children aged <4 years with lower-positioned hyoid bone caused by caudal larynx as well as undeveloped maxilla and mandible, and in those aged ≥4 years with increased inclination of the mandible as well as undeveloped mandible.

Combination of midazolam and a cyclooxygenase-2 inhibitor inhibits lipopolysaccharide-induced interleukin-6 production in human peripheral blood mononuclear cells.

CONTEXT: Interleukin-6 (IL-6) plays an important role in immune and inflammatory responses. Midazolam has been reported to modulate IL-6 response. Cyclooxygenase (COX) inhibitors, which are used together with midazolam in some patients undergoing surgery, also modulate it. We hypothesized that their combination results in eliciting the synergistical effect on the IL-6 response. OBJECTIVE: The aim of the present study was to evaluate the effect of the combination of midazolam and a COX inhibitor on IL-6 production. MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from healthy volunteers and incubated with lipopolysaccharide (LPS), midazolam, and/or COX inhibitors, including indomethacin, SC-560, a COX-1 selective inhibitor, and NS-398, a COX-2 selective inhibitor. The supernatant concentrations of IL-6 and prostaglandins (PGs), including PGE2, PGF2α, PGD2, and 15-deoxy-Δ¹²,¹4-prostaglandin J2 (15dPGJ2) were measured. RESULTS: Midazolam had no effect on IL-6 production in the cells incubated for 12 h, and any COX inhibitors also had no effect. However, the combination of midazolam and NS-398 significantly inhibited it. Midazolam raised the concentration of 15dPGJ2 in the supernatant of the cells, but not the concentration of other PGs. DISSCUSSION AND CONCLUSION: The results in the present study demonstrated that the combination of midazolam and a COX-2 inhibitor inhibited LPS-induced IL-6 production in human PBMCs even if each drug separately did not have any effect on it. The finding suggests that their combination is effective against excessive IL-6 production such as severe inflammatory response and that the effect of midazolam on IL-6 production is possibly elicited via 15dPGJ2.

Modulation of paratrigeminal nociceptive neurons following temporomandibular joint inflammation in rats.

To evaluate the involvement of paratrigeminal nucleus (Pa5) nociceptive neurons in temporomandibular joint (TMJ) inflammation-induced pain and its autonomic correlates, we conducted behavioral, single unit recording and Fos immunohistochemical studies in anesthetized rats. Nocifensive behaviors to mechanical, heat or cold stimulation of the lateral face over the TMJ region were significantly enhanced in the TMJ-inflamed rats for 10-14 days after injection of complete Freund's adjuvant (CFA) into the TMJ and gradually decreased at the end of the 14-day observation period. Lowering of the nocifensive threshold in TMJ-inflamed rats lasted longer in vagus nerve-transected rats than vagus nerve-intact rats. A large number of Fos-like immunoreactive (LI) cells were observed in the Pa5, and half of them were retrogradely labeled with Fluorogold (FG) injected into the parabrachial nucleus. Background activity of Pa5 wide dynamic range and nociceptive specific neurons was significantly higher in the TMJ-inflamed rats when compared with controls. Responses to mechanical stimuli were significantly higher in NS neurons in the TMJ-inflamed rats. All thermal responsive Pa5 neurons were exclusively sensitive to cold and the response to cold was significantly higher in the TMJ-inflamed rats compared with control rats. Vagus nerve stimulation significantly decreased responses to mechanical and cold stimuli as well as the background activity in TMJ-treated rats but not in TMJ-untreated rats. The present findings suggest that populations of Pa5 neurons are nociceptive and involved in TMJ inflammation-induced pain as well as in autonomic processes related to TMJ pain.

Oral midazolam for sedation in minor oral operations in children: a retrospective study.

Our aim was to find out the optimal dose of oral midazolam to sedate children according to age. Thirty-five patients aged 10 or under who had minor oral operations under sedation with midazolam were enrolled. Correlations between age (X) and dose of midazolam (mg/kg; Y) were analysed by Pearson's correlation coefficient, and relations were fitted by simple regression. Doses of midazolam were significantly reduced as age increased (Y=0.969-0.04X; R=0.48) in the satisfactory group (n=25), whereas those in the overdose group (n=10) (patients who vomited, became agitated, or took some time to come round) were significantly higher, decreased with age, and showed a better correlation coefficient (Y=1.375-0.65X; R=0.78). These findings suggest that both the requirement and threshold of midazolam decreases with age.

Usefulness of a combined evaluation of the serum adiponectin level, HOMA-IR, and serum type IV collagen 7S level to predict the early stage of nonalcoholic steatohepatitis.

OBJECTIVE: Since nonalcoholic steatohepatitis (NASH) may progress to cirrhosis, it is important to differentiate NASH from simple steatosis, especially in its early stages. However, a liver biopsy cannot be performed in all patients with nonalcoholic fatty liver disease (NAFLD). We herein investigated whether serum biochemical markers are useful for predicting early-stage NASH. METHOD: Nineteen patients with simple steatosis and 66 patients with early-stage NASH (stage 1-2 in Brunt's criteria) were studied. The area under the receiver operating characteristic curve (AUC) was used to illustrate the diagnostic ability of serum biochemical parameters to distinguish between simple steatosis and early-stage NASH. RESULTS: The serum adiponectin level was found to be significantly lower with early-stage NASH group (3.6 mug/mL) than in the simple steatosis group (6.0 mug/mL) (P < 0.001). The AUC was high (0.765) in the early-stage NASH group, and it was also the highest among all other markers. The sensitivity of the serum adiponectin level in the diagnosis of early-stage NASH was 68%, which was higher than for any other factors, while its specificity was 79%. The corresponding sensitivity and specificity of HOMA-IR were 51% and 95%, respectively. For type IV collagen 7S, sensitivity was 41% and specificity 95%. The sensitivity of the combination of three markers was 94%, with a specificity of 74%. CONCLUSION: Approximately 90% of the patients with early-stage NASH can be predicted by a combined evaluation of the serum adiponectin level, HOMA-IR, and serum type IV collagen 7S level.

Dental management of a patient with takotsubo cardiomyopathy: a case report.

Takotsubo cardiomyopathy (TCM) is a relatively new concept in cardiovascular disease. The clinical symptoms of TCM are similar to those of a myocardial infarction, but both the mechanism and the management of TCM are different from those of myocardial infarction. The cause of TCM is unclear, but it is suggested to occur in conjunction with excessive circulating catecholamines due to stress. Thus, control of the stress reaction and restriction of catecholamine levels are considered important for prevent of TCM onset. We report the dental management of a patient with intellectual disability who had anamnesis of TCM and cardiopulmonary arrest under restraint during a previous dental appointment in another dental clinic. We used intravenous sedation with both midazolam and propofol, by which the excessive hormonal reaction that caused TCM onset and cardiopulmonary arrest was controlled, for dental treatment in our facility. All planned dental treatment was then performed without any problems.

Effects of isoflurane-induced and prostaglandin E(1)-induced hypotension on cytokine responses to oral and maxillofacial surgery.

STUDY OBJECTIVE: To evaluate the effect of induced hypotension with isoflurane or prostaglandin E(1) (PGE(1)) on cytokine responses to surgery. DESIGN: Prospective, randomized study. SETTING: University hospital. PATIENTS: 24 ASA physical status I and II patients undergoing elective oral and maxillofacial surgery. INTERVENTIONS: Patients were randomly allocated to three groups be anesthetized in the normotension (Control group), isoflurane-induced hypotension (Isoflurane-H group), and PGE(1)-induced hypotension (PGE(1)-H group). Mean arterial pressure during hypotension was maintained at approximately 80% of baseline values. MEASUREMENTS AND MAIN RESULTS: Blood samples were taken before induction of anesthesia and during and after hypotension. Plasma tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-10 (IL-10) levels were measured using enzyme-linked immunosorbent assay. There were no differences in TNF-alpha or IL-10 levels among the groups. However, the elevation of the plasma IL-6 level in the PGE(1)-H group was found during hypotension, compared with the control group (p < 0.05). CONCLUSIONS: PGE(1)-induced hypotension has an effect on IL-6 response to oral and maxillofacial surgery.

Management of oral surgery in patients with hereditary or acquired angioedemas: review and case report.

Angioedemas are a rare but significant event in simple oral surgery because they can cause an acute life-threatening laryngeal edema. We report a case of a tooth extraction in a patient with hereditary angioedema, for which the C1-inhibitor (C1-INH) concentration administered effectively controlled edema during and after extraction. We also review case reports of oral surgery management in patients with hereditary and acquired angioedemas. In 2 of 36 cases, laryngeal edema occurred after teeth extraction. One was considered to be a type 2 acquired angioedema, which tolerates replacement therapy with fresh frozen plasma. The other case was managed only with danazol, and it was suggested that this was on occasion insufficient. Safety of oral surgery on patients with angioedema depends on the type of angioedema and the availability of C1-INH concentration. An exact diagnosis of the type of angioedema is needed to know the effect of replacement therapy with C1-INH.

Nonalcoholic steatohepatitis: risk factors for liver fibrosis.

The purpose of this study was to clarify the clinicopathological features of nonalcoholic steatohepatitis (NASH) and identify risk factors for severe hepatic fibrosis. MATERIALS AND METHODS: Eighty-one patients with biopsy-proven NASH were studied. In all patients, the diagnosis of NASH was established on the basis of following criteria: (1) the presence of steatosis, lobular inflammation, and ballooning degeneration on liver biopsy, (2) intake of less than 20 g of ethanol per week, and (3) appropriate exclusion of other liver diseases. RESULTS: The median age was 54 years (range: 21-82 years) and 41 patients were women (51%). Obesity was present in 58 patients (72%), while 25 patients (31%) had diabetes mellitus and 33 patients (41%) had hyperlipidemia. Histologically, 58 patients (72%) had trivial to moderate fibrosis, 6 patients (7%) had bridging fibrosis, and 17 patients (21%) had established cirrhosis. Multiple logistic regression analysis assessed clinical, laboratory and histological factors showed that the risk factors for fibrosis were a low platelet count (P=0.0016), a high AST/ALT ratio (P=0.0229), and the presence of Mallory bodies (P=0.0209). To exclude factors that were a consequence of liver cirrhosis, variables included in the multiple logistic analysis were age, gender, diabetes, obesity, and hyperlipidemia. This showed that older age (P=0.0037) and the absence of hyperlipidemia (P=0.0150) were risk factors for fibrosis. CONCLUSIONS: We found that a low platelet count, a high AST/ALT ratio, and the presence of Mallory bodies were significant predictors of severe liver fibrosis.

Hepatocellular carcinoma in patients with non-alcoholic steatohepatitis.

We describe six patients with non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). From 1990 to 2001, we treated 82 patients with NASH and observed six patients (three men and three women, aged 56-72 years) in this group who were referred with HCC or developed the complication during follow-up. In five of these six patients, NASH was associated with obesity (cases 3, 4 and 5), hyperlipidemia (case 5), or diabetes mellitus (cases 1, 3 and 6). We confirmed the presence of HCC by ultrasonography-guided tumor biopsy or surgery except in case 3 where we diagnosed the tumor by ultrasonography, computed tomography and selective hepatic arteriography. The carcinomas measured 1.5-6.0 cm in diameter and three were well differentiated. When HCC was diagnosed, cirrhosis was present in all instances. Four of the six tumor patients also had esophageal varices but only one patient had a history of variceal bleeding and ascites. Treatment of HCC consisted of surgery (cases 1 and 5), transcatheter arterial embolization or infusion and/or percutaneous ethanol injection (cases 2, 3, 4, and 6). In patients with NASH cirrhosis, the development of treatable HCC is sufficiently common to warrant regular screening for this grave complication.