Suppression of colitis-related mouse colon carcinogenesis by a COX-2 inhibitor and PPAR ligands

Background  

It is generally assumed that inflammatory bowel disease (IBD)-related carcinogenesis occurs as a result of chronic inflammation. We previously developed a novel colitis-related mouse colon carcinogenesis model initiated with azoxymethane (AOM) and followed by dextran sodium sulfate (DSS). In the present study we investigated whether a cyclooxygenase (COX)-2 inhibitor nimesulide and ligands for peroxisome proliferator-activated receptors (PPARs), troglitazone (a PPARγ ligand) and bezafibrate (a PPARα ligand) inhibit colitis-related colon carcinogenesis using our model to evaluate the efficacy of these drugs in prevention of IBD-related colon carcinogenesis.     

Bilateral spontaneous cerebrospinal fluid otorrhea

We present a rare case of bilateral cerebrospinal fluid (CSF) otorrhea via multiple bony defects in the left tegmen and a single defect with the herniated brain tissue on the right side. Initially, the patient complained of left hearing loss and fullness and was diagnosed with serous otitis media. After myringotomy, the pulsating watery discharge suggested CSF otorrhea. Five months after surgical repair of the left side, right-side CSF leakage occurred. The right side was repaired surgically, and the patient recovered without incident. From our findings and a review of the literature, we postulate that bilateral CSF otorrhea resulted mainly from the thinness of the tegmen because of well-pneumatized mastoid air cells and the weakness of the dura after chronic inflammatory changes. In case of spontaneous CSF otorrhea, the roof of tegmen should be assessed bilaterally with care using radiologic examinations so as not to overlook a subclinical condition on the contralateral side.     

Optimal application time of lidocaine adhesive tape examined using current perception threshold measurement

BACKGROUND: We often use lidocaine adhesive tape (Penles, Wyeth Lederle Japan, Ltd., Tokyo, Japan) as a topical anesthetic prior to puncturing a vein with a needle. Since the tape is usually in place for a long time, we often experience problems with creasing and flaring when inserting the needle. We attempted to determine the optimal time for application of the tape as well as for vein puncture after its removal by measuring pain sensation in human subjects. METHODS: Lidocaine tape was applied to the dorsum of volunteer hands for 2, 4, 6, and 12 hours, and we evaluated changes after removal by determining current perception threshold (CPT), pain score, touch sensation score, diameter of the vein, pruritus, and flare. RESULTS: CPT levels were found to increase within 1 hour after removal of the lidocaine tape with all 3 electrical stimulus rates used (2000 Hz, 250 Hz, 5 Hz). Further, pain and touch sensation scores were low within 2 hours of removal regardless of application time. Notably, with 4 and 6 hours of application, scores were stable 4 and 6 hours after removal. However, vein diameter and pruritis results did not change regardless of application time, while crease and flare were only observed within 30 minutes after removal. CONCLUSIONS: We concluded that lidocaine tape provided maximum pain relief when applied 4 to 6 hours prior to vein puncture and up to 1 hour after removal.     

Effects of Malted Rice Amazake on Constipation Symptoms and Gut Microbiota in Children and Adults with Severe Motor and Intellectual Disabilities: A Pilot Study

Constipation is a frequent complication in patients with severe motor and intellectual disabilities (SMID). The aim of this study was to investigate changes in constipation symptoms and gut microbiota associated with the intake of malted rice amazake, a fermented food in Japan, in patients with SMID. Ten patients consumed the test food for six weeks, and their physical condition, dietary and medication status, and constipation assessment scale (CAS) were investigated. Comprehensive fecal microbiome analysis using the 16S rRNA sequence method was performed. The results showed a significant decrease in CAS, and a significant increase in Lactobacillales and decrease in Escherichia-Shigella after consuming malted rice amazake. To investigate the difference in the effects of malted rice amazake consumption, based on the characteristics of the original gut microbiota, the patients were grouped according to the similarity of their gut microbiota before the intervention; Firmicutes-rich Group 1 (n = 5), Actinobacteria-rich Group 2 (n = 4), and Proteobacteria-rich Group 3 (n = 1). The CAS decreased in Groups 1 and 2. The relative abundance of Bifidobacterium showed an increasing tendency both overall and in Group 1, but it was originally higher in Group 2. Our results suggest that malted rice amazake consumption reduces constipation symptoms and simultaneously changes the gut microbiota, but the changes may vary depending on the original composition of the gut microbiota.     

9trans,11trans Conjugated Linoleic Acid Inhibits the Development of Azoxymethane-Induced Colonic Aberrant Crypt Foci in Rats

We investigated the effects of 9trans,11trans (9t,11t)-conjugated linoleic acid (CLA) isomer on azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in rats. Male F344 rats were given 2 weekly subcutaneous injections of AOM (20 mg/kg bw) to induce colonic ACF. They also were fed a diet containing either 0.01%, 0.1%, or 1% 9t,11t-CLA for 4 wk starting 1 wk before the first dosing of AOM. The group that received a diet supplemented with 9t,11t-CLA had a significantly lower number of ACF/colon in comparison to the AOM alone group in a dose-dependent manner up to 0.1%. Furthermore, treatment with 9t,11t-CLA induced apoptosis and suppressed cell proliferation activity in the non-lesional crypts. The downregulation of cyclooxygenase-2 and cyclin D1 and the activation of peroxisome proliferators activated receptor γ were observed in the colonic mucosa of rats fed a diet supplemented with 9t,11t-CLA. Our findings thus provide some novel insight into the chemopreventive effect of 9t,11t-CLA against preinitiation as well as postinitiation stages of colorectal carcinogenesis.     

Citrus auraptene suppresses azoxymethane-induced colonic preneoplastic lesions in C57BL/KsJ-db/db mice

The current study was designed to investigate whether dietary citrus auraptene (AUR) suppresses the development of azoxymethane (AOM)-induced colorectal preneoplastic lesions in C57BL/KsJ-db/db (db/db) mice with obese and diabetic phenotypes. Female db/db and wild (+/+) mice were divided into the AOM + AUR, AOM alone, AUR alone, and the untreated groups in each phenotype. AOM was given 3 weekly intraperitoneal injections (10 mg/kg bw). AUR (250 ppm) was given in diet during the study (for 10 wk). Dietary AUR significantly reduced the number of aberrant crypt foci (ACF) and Beta -catenin-accumulated crypt (BCAC) in both phenotypes. The treatment also lowered cell proliferation activity and increased apoptotic cells in both lesions. Our findings indicate that dietary AUR is able to suppress the early phase of colon carcinogenesis in both phenotypes, suggesting possible application of AUR as a chemopreventive agent in both the high-risk and general populations for colorectal cancer.     

The performance of a novel ball‐tipped Flush knife for endoscopic submucosal dissection: a case–control study

Aliment Pharmacol Ther 2010; 32: 908–915

Summary

Background Endoscopic submucosal dissection (ESD) using short needle knives is safe and effective, but bleeding is a problem due to low haemostatic capability. Aim To assess the performance of a novel ball‐tipped needle knife (Flush knife‐BT) for ESD with particular emphasis on haemostasis. Methods A case–control study to compare the performance for ESD of 30 pairs of consecutive early gastrointestinal lesions (oesophagus: 12, stomach: 32, colorectum: 16) with standard Flush knife (F) vs. Flush knife‐BT (BT). Primary outcome was efficacy of intraprocedure haemostasis. Secondary outcomes included procedure time, procedure speed (dividing procedure time into the area of resected specimen), en bloc resection rate and recurrence rate. Results Median intraoperative bleeding points and bleeding points requiring haemostatic forceps were smaller in the BT group than in the F group (4 vs. 8, P < 0.0001, 0 vs. 3, P < 0.0001). There was no difference between groups for procedure time; however, procedure speed was shorter in the BT group (P = 0.0078). En bloc and en bloc R0 resection rates were 100%, with no perforation or post‐operative bleeding. No recurrence was observed in either group at follow‐up 1 year postprocedure. Conclusions Ball‐tipped Flush knife (Flush knife‐BT) appears to improve haemostatic efficacy and dissection speed compared with standard Flush knife.     

Effects of one-lung ventilation on cardiac autonomic nervous activity as evaluated by power spectral analysis of heart rate variability

The purpose of this prospective study was to evaluate the effects ofone-lung ventilation on the activity of the cardiac autonomic nervous system.Ten adult patients who underwent thoracotomy were endotracheally intubatedwith a double-lumen tube under general anesthesia using isoflurane. Afterinduction of anesthesia, a continuous, 256-sec electrocardiogram (ECG) wasobtained during bilateral lung ventilation (control) followed by recordingsduring one-lung ventilation of each side. Using the R–R intervaltachograms obtained for the 256-sec ECGs, low frequency (LF: 0.04–0.15Hz) and high frequency (HF: 0.15–0.40 Hz) bands of the spectral densityof the heart rate variability and the HF/LF ratio were analyzed using the fastFourier transform algorithm. Log(HF), which indicates parasympatheticactivity, increased during one-lung ventilation on each side, but did notdiffer between ventilated sides. Log(LF), which represents sympathetic andparasympathetic activity, increased similarly to log(HF) on both sides.Log(HF/LF), the balance of the sympathetic and parasympathetic activity, didnot change during one-lung ventilation. We suggest that one-lung ventilationalone does not substantially affect the cardiac autonomic nervous system.     

Survey of nerve injury associated with epidural/spinal anesthesia in Japan which occurred in the year 2004

BACKGROUND: The incidence of nerve injury associated with epidural/spinal anesthesia has not been sufficiently investigated in Japan. PURPOSE: The incidence of nerve injury caused by inappropriate epidural/spinal puncture or catheter placement was examined using data obtained by a survey conducted by the Japanese Society of Anesthesiologists for the year 2004. METHODS: In a survey for the year 2004, 1,218,371 anesthetic procedures were registered, among which 548,819 patients were estimated to be anesthetized under epidural/spinal procedures with or without general anesthesia. Twenty nine patients were reported to have incurred nerve injury due to inappropriate epidural/spinal puncture or catheter placement. RESULTS: Seven cases of spinal cord and 22 cases of peripheral nerve injury were reported, with estimated incidences of 1/78,000 and 1/25,000 procedures, respectively. Spinal cord injury developed before the start of surgery in 4 cases, intraoperatively in 1 case, and after the end of surgery in 2 cases. Permanent nerve damage developed in 4 patients with spinal cord injury and 7 patients with peripheral nerve injury. Eighty three percent of these events were reported to be preventable. CONCLUSIONS: The incidence of nerve injury caused by regional anesthesia in Japan seems to be comparable to those reported in the developed countries. To reduce the incidence of this complication, cautious evaluation of the risk/benefit balance in performing regional anesthesia, improving education and supervision of the procedures, and establishing better communication between anesthesiologists and surgeons concerning the timing of catheter removal and the postoperative coagulation state seem to be important.     

Cerebrovascular accidents developing in the operating theater: a JSA survey for the year 2004

BACKGROUND: The incidence of cerebrovascular accidents (CVA) developing in the operating theater has not been investigated on a large scale. In 2004, the Japanese Society of Anesthesiologists (JSA) started to survey neurological as well as life-threatening events in the operating theater. The incidence of CVA developing in the operating theater was examined using data obtained by the 2004 survey. METHODS: JSA has conducted annual surveys of life-threatening and neurological events in the operating theater by sending and collecting confidential questionnaires to all JSA certified training hospitals. The recovery rate was 91% (874/960 hospitals) in 2004. Seven hundred fourteen hospitals sent valid responses, and 1,218,371 anesthesias were registered. Among these cases, 123 patients were reported to have developed CVA in the operating theater. Incidences according to age class, ASA PS and surgical sites, causes, and their outcome were investigated. The patients with ASA PS 1 or 2 were classified as having good physical status, and those with ASA PS 3-5 were classified as having poor physical status. The causes of events were classified as follows: totally attributable to anesthetic management (AM), mainly to intraoperative pathological events (IP), to preoperative co-morbidity (PC), and to surgical management (SM). RESULTS: Overall incidence of CVA was 1.01/10,000 anesthesias. The incidence in patients aged 66 years or above was 2.00/10,000 anesthesias, which was 3.83-(95% confidential interval 2.57-5.71) fold higher than that in patients aged between 19 and 65 years. The incidences in elective and emergency patients with poor physical status were 3.27 and 7.91/10,000 anesthesias, respectively, which was 7.04- (4.56-10.87) and 17.06-(10.90-26.69) fold higher than that in elective patients with good physical status, respectively. The incidences in patients undergoing thoracotomy combined with laparotomy, craniotomy, or cardiovascular surgery were 2.76, 5.96 and 11.65/10,000 anesthesias, respectively, which were 7.22- (1.64-31.76), 15.59- (8.14-29.86), and 30.52- (16.80-55.44) fold higher than that in patients undergoing laparotomy alone. Among cardiovascular surgery, thoracic aortic surgery showed the highest number of incidents (57.98/10,000 anesthesias), followed by on-pump coronary artery bypass (11.07/10,000 anesthesias). Only one patient undergoing off-pump coronary artery bypass developed CVA, resulting in an 8.14- (1.00-66.18) fold lower incidence of CVA compared to that of on-pump coronary artery bypass. AM, IP, PC and SM were responsible for 4.1%, 24.4%, 27.6% and 35.0% of CVA. The incidence of CVA caused by AM or IP was calculated to be 0.29/ 10,000 anesthesias. If patients undergoing cardiovascular surgery or craniotomy were excluded, the incidence of CVA caused by AM or IP was calculated to be 0.13/ 10,000 anesthesias (15/ 1,134,398 anesthesias). The overall outcome of CVA was as follows: uneventful recovery 9.8%, death within 30 post-operative days 26.0%, vegetative state 6.5%, and sequelae involving deficits in the central nervous system 52.0%. The outcome of CVA caused by AM or IP was as follows: uneventful recovery 20.0%, death within 30 post-operative days 22.9%, vegetative state 8.6%, or sequelae involving deficits in central nervous system 45.7%. Twenty-seven point six percent of reported CVA were considered to have been preventable. CONCLUSIONS: The overall incidence of CVA developing in the operating theater in Japan was reported to be 123 among 1.2 million anesthesias. The incidence was high in elderly patients, in patients with poor physical status, and in patients undergoing cardiovascular surgery. Because the prognosis of CVA developing in the operating theater was poor, clinical strategies for prevention, early detection, prompt diagnosis, and appropriate treatment of CVA should be established.