Naotaka Kishimoto

Supplementation of strontium to a chondrogenic medium promotes chondrogenic differentiation of human dedifferentiated fat cells.

Dedifferentiated fat cells (DFAT cells) isolated from adipose tissue have been demonstrated to differentiate into chondrogenic cells in vitro. Nevertheless, an efficient method to facilitate its chondrogenic differentiation is still unexplored, hampering the extensive application of these cells in cartilage regeneration therapies. Here we provide the evidence that supplementation of strontium ions (Sr) in a chondrogenic medium (CM) significantly promotes early chondrogenic differentiation of DFAT cells. Human DFAT cells and the mesenchymal stem cell line (RCB2153) were subjected to the CM supplemented with/without Sr. After 14 days, alcian blue staining intensity significantly increased in DFAT cells, but not in RCB2153, subjected to CM with Sr. mRNA expression analysis revealed that the CM with 1.5 mM Sr increased the expression of chondrogenic marker, collagen type 2 alpha 1, whereas there was no significant change in osteogenic markers, collagen type 1 alpha 1, runt-related transcription factor 2, and osteocalcin, and hypertrophic chondrogenic marker, collagen type 10 alpha 1. Inhibitors for extracellular signal-regulated kinase 1/2 (ERK1/2), Akt, and calcium-sensing receptor (CaSR) pathways significantly diminished the alcian blue staining intensity, providing the first evidence that these signal pathways are associated with chondrogenic differentiation of DFAT cells. CaSR and ERK1/2 pathways independently induced Sr-mediated early chondrogenic differentiation. These results suggest that Sr supplementation into the CM may provide a powerful platform for preparing chondrogenically differentiated DFAT cells for cartilage regeneration.

Comparison of Metal Stylet, Small Tracheal Tube and Combined Introducer-Aided Insertions of the Flexible Reinforced Laryngeal Mask Airway with the Conventional Method: a Manikin Study

Purpose: The present study compared the conventional method (without any adjunct) and three different adjunct-aided methods (a metal stylet, a small tracheal tube, and a combined introducer) with regard to the time required for insertion of the flexible reinforced laryngeal mask airway (FLMA). We also surveyed participants’ views on the ease of FLMA insertion with each method. Methods: Thirty dental students inserted the FLMA in a manikin by each method and the times required for insertion were measured. Subjects were asked to rate the ease of insertion with each method using a 100-mm visual analogue scale (VAS; from 0 mm = extremely easy to 100 mm = extremely difficult). Results: Insertion time was significantly shorter with the small tracheal tube compared with the conventional method. However, insertion times with the metal stylet-aided insertion and the combined introducer-aided insertion were not significantly different as compared to the conventional method. With regard to the ease of insertion as rated using the 100-mm VAS, the dental students rated tracheal tube-aided insertion and combined introducer-aided insertion as being significantly easier, and the metal stylet-aided insertion as significantly more difficult than the conventional method. Conclusions: The small tracheal tube-aided insertion and the combined introducer-aided insertion each appear to possess advantages over the conventional method. The small tracheal tube-aided insertion seems overall more favorable in terms of ease and time to insertion.

Changes in blood pressure during induction of anesthesia and oral and maxillofacial surgery by type and timing of discontinuation of antihypertensive drugs.

The purpose of this study was to evaluate the effects of an antihypertensive drug class and the timing of discontinuation of antihypertensive therapy on blood pressure during oral and maxillofacial surgery for 129 patients on antihypertensive therapy receiving general anesthesia. Blood pressures at loss of response to stimulation and 5-15 minutes after intubation were significantly lower than those before induction, although the type of antihypertensive therapy did not affect changes in blood pressure. No significant correlation was observed between systolic blood pressure (SBP) on the ward and change in SBP during surgery, though patients with higher blood pressure on the ward tended to exhibit larger differences between SBP on the ward and the lowest SBP during surgery. Frequency of use of vasopressors during surgery was significantly higher in patients who discontinued antihypertensive therapy on the day before surgery than in those who continued antihypertensive therapy on the day of surgery. These findings suggest that appropriate preoperative antihypertensive therapy is important for minimizing change in blood pressure during surgery and preventing perioperative complications. Patients undergoing antihypertensive therapy should be carefully monitored perioperatively by observation for interactions between antihypertensive and anesthetic agents and minimizing interruption schedules for antihypertensive therapy.

Utility of the Portex Introducer, Ivory Type, as a Tube Exchanger

PURPOSE This study compared the Portex introducer, ivory type (PII) (Portex Tracheal Tube Introducer; SIMS Portex, Hythe, Kent, England), and Cook Airway Exchange Catheter (CAEC) (Cook, Letchworth, Hertfordshire, England) with regard to success rate of and time required for tracheal intubation by use of each device by oral and maxillofacial surgeons on a manikin. MATERIALS AND METHODS The subjects comprised 17 oral and maxillofacial surgeons who intubated the trachea of the manikin with each device. The PII or CAEC was inserted into the trachea of the manikin and advanced 26 cm from the upper incisor, and the time required for intubation was measured. The subjects were then asked to rate the difficulty of intubation using a 10-cm visual analog scale. RESULTS The mean intubation time, averaged over 3 attempts, was significantly shorter for the PII (7.92 +/- 3.15 seconds) than for the CAEC (11.44 +/- 3.98 seconds) (P < .001). The rate of successful intubation with the PII (88.2%) was significantly greater than that with the CAEC (37.3%) (P < .001). With regard to the overall difficulty of intubation, as rated by the 10-cm visual analog scale, the PII (median, 45 mm [10th-90th percentile, 32-53 mm]) was considered less difficult than the CAEC (median, 66 mm [10th-90th percentile, 52-84 mm]) (P < .001). CONCLUSIONS Intubation is faster, more sure, and easier by use of the PII as a tube exchanger than with the CAEC. This may be particularly important for patients undergoing oral and maxillofacial surgery as a result of anatomic changes in the airway, because edema or hematoma in the upper airway often leads to failed intubation. We conclude that the PII is useful as a tube exchanger.

Gene expression profiles of early chondrogenic markers in dedifferentiated fat cells stimulated by bone morphogenetic protein 4 under monolayer and spheroid culture conditions in vitro

Abstract Purpose Human dedifferentiated fat (hDFAT) cells are thought to be a promising cell source for cartilage regeneration therapy. Nevertheless, the responses of hDFAT cells to bone morphogenetic proteins (BMPs) are still unclear. Here, we elucidated the effects of BMP-4 on the mRNA expression of early chondrogenic markers in hDFAT cells under monolayer or pellet cell culture conditions. Materials and methods Monolayer and pellet cell cultures of hDFAT cells were grown with control medium or chondrogenic medium (CM) with or without BMP-2, BMP-4, or BMP-7. Real-time polymerase chain reaction was used to analyze the mRNA expression levels of nine genes: chondrogenic markers, i.e., SOX9, SOX5, SOX6, aggrecan, type 2 collagen, type 10 collagen, and matrix metalloproteinase (MMP) 13; type 1 collagen; and MMP3. The BMP signaling inhibitor dorsomorphin was used to verify the mechanisms of BMP-4-induced chondrogenesis. Results Recombinant BMP-4 (100 ng/mL) increased the expression of SOX9, SOX6, and aggrecan mRNAs in monolayer cells compared with that in cells treated with BMP-2 or BMP-7 on day 3. Chondrogenically differentiated hDFAT cells induced by CM containing BMP-4 showed higher expression of eight genes (excluding SOX5) in monolayer cultures and nine genes (including SOX5) in pellet cultures compared with those in control medium on day 14. Dorsomorphin attenuated the effects of BMP-4. Conclusion These results showed that BMP-4 had the potential to modulate the early chondrogenesis of hDFAT cells under both monolayer and pellet cell culture conditions.

Second-degree atrioventricular block type II and third-degree atrioventricular block requiring cardiac pacing after tooth extraction

Because atrioventricular block can cause cardiovascular collapse, the rapid management of this condition is necessary. An 82‐year‐old man complained of discomfort after tooth extraction, and electrocardiography showed second‐ and third‐degree atrioventricular blocks. Dentists should monitor patients who report discomfort using electrocardiography because of the possibility of life‐threatening arrhythmia.

Optimal Concentration of Sevoflurane to Prevent Cardiovascular Depression after Induction of General Anesthesia with Remifentanil and Propofol

Background: We examined the optimal concentration of sevoflurane to prevent cardiovascular depression after induction of general anesthesia with remifentanil and propofol. Methods: Seventy-five adult patients were randomized to one of three groups (n = 25). Midazolam (0.025 mg/kg) and remifentanil (0.5 ?g/kg/min) were administered to all patients, followed by propofol (1.0 mg/kg) and rocuronium (0.6 mg/kg) after 2 min. The lungs were ventilated manually with sevoflurane and oxygen via a tightly fitted face mask. The trachea was intubated when end-tidal sevoflurane concentration reached 1%, 1.5%, and 2% in each group, respectively. Three min after the start of administration, remifentanil was decreased to 0.25 ?g/kg/min. The effect-site concentration of remifentanil was 6.0 ng/ml for 4 min after it was started. Hemodynamic variables were recorded from before induction of anesthesia to 15 min after tracheal intubation. Results: There were no serious adverse events such as severe bradycardia or asystole. Relative change of mean arterial pressure after induction of general anesthesia in the end-tidal sevoflurane 1% group was smaller than that of the end-tidal sevoflurane 1.5% and end-tidal sevoflurane 2% groups. Conclusion: An end-tidal sevoflurane concentration of 1% was sufficient when general anesthesia was induced with an effect-site concentration of remifentanil of 6.0 ng/mL and propofol of 1 mg/kg.

Comparison of Parker-tipped and Murphy-tipped tracheal tubes in Airway Scope-assisted intubation in a manikin

PurposeWe tested our hypothesis that a Parker-tipped tracheal tube could improve the reliability of tracheal tube passage as compared to a Murphy-tipped tracheal tube during Airway Scope-assisted intubation in a manikin.MethodsTwenty-seven resident doctors performed Airway Scope-assisted intubations using both tracheal tubes, and the number of times the tracheal tube tip touched the glottis or other laryngeal structures was counted on the Airway Scope monitor.ResultsThe incidence of the tracheal tube tip touching the glottis during Airway Scope-assisted intubation using the Parker-tipped tracheal tube (7.4%; 2 of 27 attempts) was significantly less than that obtained using the Murphy-tipped tracheal tube (33.3%; 9 of 27 attempts; P = 0.039).ConclusionWhen the advancement of a conventional tracheal tube during Airway Scope-assisted intubation is likely to result in collision with the glottis or other laryngeal structures, the selection of a Parker-tipped tracheal tube is a better option.

Recurrent Coronary Artery Spasm Induced by Vasopressors During Two Operations in the Same Patient Under General Anesthesia

Variant angina is caused by coronary artery spasm (CAS) with ST-segment elevation. We herein report a case of recurrent CAS during 2 operations in the same patient. An 80-year-old woman was scheduled to undergo tracheostomy, submandibular dissection, left partial maxillectomy, and coronoidectomy. We administered ephedrine and phenylephrine to manage hypotension during general anesthesia. Immediately after the administration of these drugs, the ST segment elevated. We decided to cease the operation and transport the patient to the department of cardiology. Computed tomography angiography revealed pneumomediastinum. The cardiologists considered that the electrocardiography findings had changed secondary to pneumomediastinum. About 6 weeks later, a second operation was scheduled. We administered ephedrine and phenylephrine to manage hypotension during general anesthesia. Immediately after the administration of these drugs, ST-segment elevation occurred. We discontinued use of these drugs, and the ST-segment elevation did not recur. We considered that the cause of the ST-segment elevation was vasopressor-induced CAS because the vasopressors were administered immediately before the occurrence of CAS. Vasopressors such as ephedrine or phenylephrine are frequently used to manage hypotension during general anesthesia. Therefore, anesthesiologists should consider the occurrence of CAS before using vasopressors and know how to manage CAS well.

Management of infusion reactions associated with cetuximab treatment: A case report

Cetuximab is a drug targeting the epidermal growth factor receptor, which is indicated for the treatment of unresectable advanced or recurrent head and neck or colorectal cancer. Cetuximab also enhances the cytotoxic effects of radiation in squamous cell carcinoma. The severity of infusion reactions (IR) is categorized from grade 1 to 5; grades 3 and 4 are associated with life-threatening reactions (anaphylaxis), whereas grade 5 indicates death. The incidence of grade 3–4 IR with premedication is reported to be 1.1%. We herein describe a case of a 77-year-old man who developed IR during intravenous administration of cetuximab. The patient developed grade 3–4 anaphylaxis with pruritus, rash and urticaria, followed by hypotension and bradycardia. The timely diagnosis and treatment with intravenous infusion of a vasopressor drug and Ringers acetate solution proved to be effective. The case presented herein demonstrated an unfeatured aspect of cetuximab-related IR as dermatological reactions over the entire body followed by circulatory collapse.