Potential for Drug Repositioning of Midazolam as an Inhibitor of Inflammatory Bone Resorption.

Drug repositioning is a method for exploring new effects of existing drugs, the safety and pharmacokinetics of which have been confirmed in humans. Here, we demonstrate the potential drug repositioning of midazolam (MDZ), which is used for intravenous sedation, as an inhibitor of inflammatory bone resorption. We cultured a mouse macrophage-like cell line with or without MDZ and evaluated its effects on the induction of differentiation of these cells into osteoclasts. For in vivo investigations, we administered lipopolysaccharide (LPS) together with MDZ (LPS+MDZ) to the parietal region of mice and evaluated the results based on the percentage of bone resorption and calvaria volume. Furthermore, we examined the effects of MDZ on the production of reactive oxygen species (ROS) in cells and on its signaling pathway. MDZ inhibited osteoclast differentiation and bone resorption activity. In animal studies, the LPS+MDZ group showed a decreasing trend associated with the rate of bone resorption. In addition, the bone matrix volume in the LPS+MDZ group was slightly higher than in the LPS only group. MDZ inhibited osteoclast differentiation by decreasing ROS production and thereby negatively regulating the p38 mitogen-activated protein kinase pathway. Thus, we propose that MDZ could potentially be used for treating inflammatory bone resorption, for example, in periodontal disease.

Successful Transcatheter Aortic Valve Replacement Approached Via a Simultaneously Implanted Y-graft Vascular Prosthesis.

Transcatheter aortic valve replacement (TAVR) is mainly performed using the transfemoral (TF) approach. If the TF approach is difficult, the transapical (TA) or transaortic (TAo) approach is used; however, the complication rate is higher in such cases. In this case, abdominal aortic aneurysm (AAA) replacement and TAVR via artificial vessels were performed simultaneously because of anatomical difficulties in stent graft implantation and TF-TAVR for severe aortic stenosis (AS) associated with AAA. Performing TAVR simultaneously with AAA replacement avoids TA- or TAo-TAVR and allows for postoperative management in the absence of AS. Additionally, there is no need to create a new access for TAVR using artificial vessels. Since the long-term results of AAA are better with open surgery than with endovascular aneurysm repair and the age of indication for TAVR is expected to decrease due to valve-in-valve and other factors, simultaneous surgical AAA replacement and TAVR using a Y-graft vascular prosthesis is an effective treatment option when TF-TAVR is difficult to perform.

A Case of Anterior Arytenoid Cartilage Dislocation During Nasal Tracheal Intubation Using an Indirect Video Laryngoscope.

Arytenoid cartilage dislocation can occur as a complication of tracheal intubation and laryngeal trauma, but its occurrence with indirect video laryngoscopy has not been reported. This paper reports anterior arytenoid dislocation occurring after nasotracheal intubation performed under indirect laryngoscopy using a video laryngoscope (McGRATH MAC; Medtronic). The dislocation is presumed to have resulted from the laryngoscope blade being initially inserted too deeply and applying pressure to the posterior aspect of the left cricoarytenoid joint. This patient's anterior arytenoid dislocation was treated conservatively using speech therapy with resolution occurring approximately 40 days postoperatively. On the 74th day after surgery, fibroscopic examination confirmed recovery and healing of the dislocation. However, other types of arytenoid dislocations and laryngeal injuries may require alternative treatment. Early consultation with an otolaryngologist is recommended if arytenoid dislocation is suspected.

Anesthetic Management in Mitochondrial Encephalomyopathy: A Case Report.

We report on a morbidly obese 16-year-old boy (weight, 116 kg; height, 176 cm; body mass index, 35.5 kg/m2) with mitochondrial encephalomyopathy and a history of cerebral infarction, epilepsy, and severe mental retardation. The patient was scheduled for elective surgery under general anesthesia for multiple dental caries and entropion of the left eye. Preoperative examination results, including an electrocardiogram, were normal. No obvious cardiac function abnormalities were observed on echocardiography. Midazolam (10 mg) was administered orally as premedication 30 minutes before transfer to the operating room; however, the patient was uncooperative, and his body movements were difficult to control upon entering the operating room. This complicated our attempts to establish a peripheral intravenous line and necessitated volatile inhalational induction, followed by maintenance using total intravenous anesthesia. General anesthesia was used to minimize metabolic system stress. We did not use an infusion solution containing sodium lactate. The operation and subsequent clinical course until discharge were uneventful. Because aerobic metabolism is already compromised in patients with mitochondrial encephalomyopathy, anesthetic management should be designed to avoid placing additional stress on the metabolic system.

Hypoesthesia associated with mandibular movement after sagittal split ramus osteotomy.

PURPOSE: This retrospective study investigated the relationship between the degree of neurosensory disturbance (NSD) and mandibular movement distance after sagittal split ramus osteotomy (SSRO) and assessed sensory recovery. METHODS: Lower lip hypoesthesia was evaluated at 1 week, 1 month, and 2 months after SSRO in 38 patients categorized according to the distance of mandibular movement: S group (0-7 mm; n = 17, 4 males and 13 females) and L group (7-14 mm; n = 21, 7 males, 14 females). Symptoms were evaluated by visual analog scale (VAS), tactile-threshold (SW) test, static 2-point discrimination (s-2PD) test, and current perception threshold (CPT) test. RESULTS: The two groups did not differ significantly in gender and age. The Aß fiber results of the CPT test differed significantly between the groups at 1 week and 1 month postsurgery (P < 0.05). There were no significant differences between the groups throughout the period in terms of VAS, SW, s-2PD, Aδ fiber, and C fiber of CPT. CONCLUSIONS: Post-SSRO, the incidence of NSD in terms of tactile sensation may be greater in the L group early postoperatively. This may assist surgeons in explaining postoperative hypoesthesia to patients preoperatively.

An analysis of green discoloration of urine caused by propofol infusion.

BACKGROUND: Propofol is a short-acting, intravenous sedative-hypnotic agent that is widely used for the induction and maintenance of general anesthesia and sedation. An uncommon adverse effect of propofol is green discoloration of the urine, which has been reported not only under general anesthesia but also with sedation. Although it is assumed that the phenolic derivatives of propofol can cause green discoloration of the urine, the actual origin remains unknown. The aim of this report was to identify the origin of the green discoloration of the urine using liquid chromatography-mass spectrometry (LC-MS). CLINICAL FEATURES: The patient, a 51-year-old man, was scheduled for his oral surgery under general anesthesia using propofol. Postoperatively, the color of his urine was observed to be green. We compared and analyzed both the green urine and the normal urine using LC-MS. CONCLUSION: We experienced a case of a patient with green discoloration of the urine after general anesthesia using propofol. Although LC-MS analysis showed 2 unique peaks in the green urine at 490 and 590 nm, obvious causes were not revealed.

Case of Vasovagal Syncope With Asystole Associated With Propofol Sedation.

Few cases of bradycardic complications occurring under intravenous sedation have been reported. Here, we report a case of vasovagal syncope with asystole (7.2 seconds) associated with propofol sedation.

Effects of intraoperative administration of carbohydrates during long-duration oral and maxillofacial surgery on the metabolism of carbohydrates, proteins, and lipids.

PURPOSE: Insulin resistance in patients undergoing invasive surgery impairs glucose and lipid metabolism and increases muscle protein catabolism, which may result in delayed recovery and prolonged hospital stay. We examined whether intraoperative administration of carbohydrates during long-duration oral and maxillofacial surgery under general anesthesia affects carbohydrate, proteins, and lipid metabolism and the length of hospital stay. METHODS: We studied 16 patients with normal liver, kidney, and endocrine functions, and ASA physical status I or II, but without diabetes. Patients were randomly assigned to receive 0.1 g/kg/h of (n = 8) or lactated Ringer's solution (n = 8). Blood was collected before (T0) and 4 h after (T1) the start of surgery. We analyzed the plasma levels of glucose, ketone bodies, 3-methylhistidine (3-MH), and the length of hospital stay. RESULTS: At T0, no statistically significant differences were observed in the levels of glucose, ketone bodies, and 3-MH between the groups. At T1, no statistically significant difference in glucose levels was found between the groups. However, ketone bodies were significantly lower, and the changes in 3-MH levels were significantly less pronounced in the glucose-treated group compared with controls. No significant differences were observed between the groups in terms of length of hospital stay. CONCLUSIONS: The administration of low doses of glucose during surgery was safe, did not cause hyperglycemia or hypoglycemia, and inhibited lipid metabolism and protein catabolism. Additional experiments with larger cohorts will be necessary to investigate whether intraoperative management with glucose facilitates postoperative recovery of patients with oral cancer.

Trousseau syndrome with nonbacterial thrombotic endocarditis in a patient with uterine cancer.

This paper aims to describe the usefulness of transthoracic echocardiography in the follow-up of recurrent nonbacterial thrombotic endocarditis (NBTE) associated with neoplastic conditions. A 60-year-old woman with advanced uterine cancer developed recurrent areas of aseptic vegetation on the mitral valve along with cerebral, renal and splenic embolisms. Echocardiographic assessments revealed vegetation and thrombotic events on three occasions. In this case, transthoracic echocardiography was effective in following the decreased frequency of attachment of the NBTE vegetation to the mitral valve and reductions in the size of the area of vegetation following treatment with unfractionated heparin infusion, hysterectomy and chemotherapy.

Propofol drip infusion anesthesia for MRI scanning: two case reports.

The magnetic resonance imaging (MRI) room is a special environment. The required intense magnetic fields create unique problems with the use of standard anesthesia machines, syringe pumps, and physiologic monitors. We have recently experienced 2 oral maxillofacial surgery cases requiring MRI: a 15-year-old boy with developmental disability and a healthy 5-year-old boy. The patients required complete immobilization during the scanning for obtaining high-quality images for the best diagnosis. Anesthesia was started in the MRI scanning room. An endotracheal intubation was performed after induction with intravenous administration of muscle relaxant. Total intravenous anesthesia via propofol drip infusion (4-7 mg/kg/h) was used during the scanning. Standard physiologic monitors were used during scan pauses, but special monitors were used during scanning. In MRI scanning for oral maxillofacial surgery, general anesthesia, with the added advantage of having a secured airway, is recommended as a safe alternative to sedation especially in cases of patients with disability and precooperative chidren.

Effects of implant surgery on blood pressure and heart rate during sedation with propofol and midazolam.

PURPOSE: Intravenous (IV) sedation is commonly used in dentistry. However, no report has yet been published regarding age, hypertension, and antihypertensive drugs during implant surgery and their relationship with changes in blood pressure (BP) and heart rate in implant surgery under IV sedation with propofol and midazolam. MATERIALS AND METHODS: Medical records of 252 patients who underwent implant surgery were retrospectively analyzed. Patients were classified into four groups according to their age (in years) and hypertension status: A=≤64, no hypertension; B=≥65, no hypertension; C=≤64, hypertension; or D=≥65, hypertension. Hypertensive patients were further characterized by their antihypertensive medications: E=calcium channel blockers (CCBs), F=angiotensin II receptor blockers (ARBs), G=CCBs+ARBs, or H=no medication. IV sedation was administered in two stages. After midazolam injection to prevent angialgia, propofol was infused at the rate of 4 mg/kg/h, followed by a dose reduction. Systolic and diastolic BP and heart rate were recorded before, during, and after surgery. RESULTS: Systolic BP increased significantly after patients were draped in groups A, C, and D, with group D showing the most pronounced increase. Sedatives decreased BP in all groups. Diastolic BP in group F decreased significantly compared to group H after induction and before infiltration of local anesthetic. After infiltration, systolic BP decreased more significantly in group G than in group H. Intraoperative hypotension was observed in 25% of patients. The incidence of intraoperative hypertension in group D was markedly higher than in group A (23% vs 4%). CONCLUSION: IV sedation using midazolam and propofol reduces hypertensive risks during implant surgery. Nevertheless, care must be taken, especially in older hypertensive patients and in hypertensive patients on ARBs or ARBs+CCBs.

[Utilization of radionuclide therapy facility and assembly-temporary type therapeutic facility for medical treatment of radioactivity contaminated patients in nuclear emergency].

Medical management of patients internally contaminated in nuclear emergency needs, in addition to general medical treatment, to evaluate doses due to intakes of radioactive materials, to conduct effective treatment with stable isotopes and chelating agents and to keep public away from radioactive materials in and excreted from patients. The idea of medical treatment for internal contamination is demonstrated in the general principles on medical management of victims in nuclear emergency issued by the Cabinet Office in Japan. However, if impressive number patients with internal contamination are generated, the current medical management scheme in nuclear emergency is not able to admit them. The utilization of radionuclide therapy facilities where patients with thyroid diseases are treated with radioisotope and assembly-temporary housing type treatment facilities dedicated for internal contaminated patients may be expected to complement the medical management scheme in nuclear emergency. The effect or more medical management system for patients internally contaminated may become one of the safety nets in the contemporary society that inclines to use nuclear energy on account of accessibility.