Wei-Hung Chan

Prophylactic intravenous ondansetron reduces the incidence of intrathecal morphine-induced pruritus in patients undergoing cesarean delivery.

Pruritus is a common side effect of intrathecal morphine injection for postoperative pain control. Its incidence is especially high in patients undergoing cesarean delivery. We investigated the effectiveness of ondansetron in preventing intrathecal morphine-induced pruritus in such patients. We included 60 consecutive nonbreastfeeding women who were scheduled for elective cesarean delivery. After the administration of spinal anesthesia with bupivacaine and intrathecal morphine 0.15 mg injection, the patients were randomly divided into three groups. Group 1 received placebo (normal saline) IV injection, Group 2 diphenhydramine 30 mg IV injection, and Group 3 ondansetron 0.1 mg/kg IV injection. The incidence of pruritus was significantly lower in the ondansetron group (25%) when compared with that in the placebo group (85%) and in the diphenhydramine group (80%) (both P < 0.05). The postoperative pain score and time to flatus passage were not significantly different among the three groups. There were no headache or extrapyramidal signs associated with ondansetron use. In conclusion, ondansetron prophylaxis significantly reduced the incidence of intrathecal morphine-induced pruritus in patients undergoing cesarean delivery. Implications Ondansetron prophylaxis significantly decreases the incidence of pruritus, a common side effect of intrathecal morphine used to treat postcesarean delivery pain.

A randomised double-blind controlled study evaluating the hypothermic effect of 150 μg morphine during spinal anaesthesia for Caesarean section

We studied the hypothermic effect of adding 150 μg morphine during spinal anaesthesia in 60 parturients scheduled for elective caesarean section. All the parturients received intrathecal injection of a solution containing 150 μg morphine or normal saline in addition to 10–12 mg hyperbaric bupivacaine 0.5%. In both groups, a significant decrease in body temperature was noted. There was no difference in the area under the curve for temperature against time for the two groups; however, the maximum decrease in temperature from baseline was significantly larger after morphine than after saline injection (mean (SD) 1.11 (0.61) °C vs 0.76 (0.39) °C, respectively; p = 0.01) and the time to nadir temperature was significantly longer (59.5 (17.6) min vs 50.4 (15.9) min, respectively; p = 0.047). The lowest temperature observed in the morphine group was 34.3 °C. We conclude that intrathecal injection of 150 μg morphine intensified the intra‐operative hypothermic effect of bupivacaine spinal anaesthesia for caesarean section.

Induction of Rat Hepatic Cytochrome P-450 by Ketamine and its Toxicological Implications

Ketamine is a common intravenous anesthetic and a frequent drug of abuse, alone or in combination with cocaine. However, the pharmacokinetic effects of ketamine have not been fully investigated. This study determined the effects of ketamine on cytochrome P-450 (P-450)-dependent catalytic activities, protein levels, and hepatotoxicity using male Wistar rats treated with 10, 20, 40, or 80 mg/kg ketamine intraperitoneally twice daily for 4 d. Treatment with ketamine produced a dose-dependent increase of pentoxyresorufin O-dealkylation activity of liver microsomes. Treatment with 80 mg/kg ketamine resulted in 14-, 3-, and 2-fold rise in O-dealkylation of pentoxyresorufin, ethoxyresorufin, and methoxyresorufin of rat liver microsomes, respectively. The treatment produced 31% and 86% increases in 7-ethoxycoumarin O-deethylation and erythromycin N-demethylation, respectively. In addition, aniline hydroxylation activity was elevated by 62%. Protein blot analysis of liver microsomal proteins revealed that 80 mg/kg ketamine induced P-450 1A, 2B, 2E1, and 3A proteins by 2-, 13-, 2-, and 2-fold, respectively. In reversibility study, ketamine-induced pentoxyresorufin O-dealkylation, 7-ethoxycoumarin O-deethylation, erythromycin N-demethylation, and methoxyresorufin O-demethylation activities of liver microsomes prepared from rats 4 d after ketamine treatment were 75%, 48%, 29%, and 38% lower than the respective activities of liver microsomes prepared from rats 1 d after treatment. Protein blot analysis showed that ketamine-induced P-450 2B1/2 proteins also decreased in a time-dependent manner in 4 d. In hepatotoxicity study, treatment of rats with 1 ml/kg CCl4 produced a 7-fold increase in serum alanine aminotransferase activity level and a 17-fold rise in rats pretreated with 80 mg/kg ketamine for 4 d. Treatment of ICR mice with 120 mg/kg cocaine produced a 17% mortality, whereas the same dose of cocaine produced a 50% mortality in mice pretreated with ketamine. Treatment of mice with 100 mg/kg cocaine produced a 76-fold increase in serum alanine aminotransferase activity level and a 260-fold rise in mice pretreated with 80 mg/kg ketamine for 4 d. The present study shows that ketamine induces the expression of multiple forms of P-450 in rat liver microsomes and increases CCl4-induced liver toxicity and cocaine-mediated acute toxicity. Other potential pharmacological or toxicological events related to ketamine use need to be further explored.

Fatal Massive Hemorrhage Caused by Nasogastric Tube Misplacement in a Patient with Mediastinitis

Nasogastric tube insertion is a routine procedure in medical care. However, misplacement of the tube can cause a variety of complications, which can be life threatening in some instances. We report a case of fatal hemorrhagic shock immediately after nasogastric tube insertion in a patient undergoing debridement by video-assisted thoracoscopic surgery for mediastinitis. Emergency endoscopy showed that the bleeding came from the nasogastric tube which had perforated the esophagus and possibly tore an intrathoracic large vessel. The nasogastric tube insertion was considered to have directly produced the perforation because no esophageal perforation had been found on preoperative endoscopy. Factors contributing to the risk of esophageal perforation in this case included coexisting mediastinitis, surgical manipulation, endotracheal intubation, inability to cooperate during general anesthesia, and repetitive advancement of the nasogastric tube. Prompt clamping of the nasogastric tube or delayed insertion after failed attempts might have improved the outcome. This report illustrates the complication of massive bleeding that can occur immediately after misplaced insertion of a nasogastric tube. Extraordinary care should be taken to avoid misplacement of the nasogastric tube during insertion.

Factors from Human Embryonic Stem Cell-derived Fibroblast-like Cells Promote Topology-dependent Hepatic Differentiation in Primate Embryonic and Induced Pluripotent Stem Cells

The future clinical use of embryonic stem cell (ESC)-based hepatocyte replacement therapy depends on the development of an efficient procedure for differentiation of hepatocytes from ESCs. Here we report that a high density of human ESC-derived fibroblast-like cells (hESdFs) supported the efficient generation of hepatocyte-like cells with functional and mature hepatic phenotypes from primate ESCs and human induced pluripotent stem cells. Molecular and immunocytochemistry analyses revealed that hESdFs caused a rapid loss of pluripotency and induced a sequential endoderm-to-hepatocyte differentiation in the central area of ESC colonies. Knockdown experiments demonstrated that pluripotent stem cells were directed toward endodermal and hepatic lineages by FGF2 and activin A secreted from hESdFs. Furthermore, we found that the central region of ESC colonies was essential for the hepatic endoderm-specific differentiation, because its removal caused a complete disruption of endodermal differentiation. In conclusion, we describe a novel in vitro differentiation model and show that hESdF-secreted factors act in concert with regional features of ESC colonies to induce robust hepatic endoderm differentiation in primate pluripotent stem cells.

Motorcycle Exhaust Induces Reproductive Toxicity and Testicular Interleukin-6 in Male Rats

Motorcycle exhaust (ME) from two-stroke engines contains many toxicants and poses a potential health hazard. The major objectives of the present study were to investigate the male reproductive toxicity of ME and the underlying mechanisms of toxicity. Male Wistar rats were exposed to ME by inhalation 1 h each in the morning and afternoon, Monday through Friday. Exposures to 1:50 diluted ME for 4 weeks or to 1:10 diluted ME for 2 and 4 weeks showed concentration- and time-dependent decreases of testicular weight, spermatid number, and cauda epididymal sperm number. Subsequent studies were done using 4-week exposure to 1:10 diluted ME. ME caused histopathological changes including testicular spermatocytic necrosis and seminiferous tubule atrophy and cauda epididymal formation of clusters of pyknotic and necrotic sperm cells. ME-exposed male rats mated with untreated females showed decreases of male mating index and female fertility index and an increase of implantation site loss. ME decreased 7-ethoxycoumarin O-deethylase and superoxide dismutase activities but induced proinflammatory cytokine interleukin-6 (IL-6) messenger RNA (mRNA) in the testis. Male rats were exposed to ME with or without cotreatment with 50 mg/kg vitamin E orally for 4 weeks. ME decreased serum testosterone concentration. This effect was reversed by cotreatment with vitamin E. ME decreased testicular spermatid number and induced IL-6 mRNA and protein. These effects were also reversed by the vitamin E cotreatment. The present findings show that ME causes male reproductive effects and induces testicular IL-6 in rats by mechanisms involving induction of oxidative stress and inhibition of steroidogenesis.

Induction of CYP1A1, 2B, 2E1 and 3A in rat liver by organochlorine pesticide dicofol.

The present study has determined the ability of dicofol, an organochlorine pesticide, to induce cytochrome P450 using rats treated with 1, 10, and 25mg/kg dicofol intraperitoneally for 4 days. Treatments with 10 and 25mg/kg dicofol produced dose-related increases of cytochrome P450 and cytochrome b(5) contents and NADPH-cytochrome c reductase, 7-ethoxyresorufin O-deethylase, pentoxyresorufin O-dealkylase, aniline hydroxylase, and erythromycin N-demethylase activities in liver microsomes. The treatments also increased glutathione S-transferase and superoxide dismutase activities in liver cytosol. Dicofol at 1mg/kg produced a general trend towards increases of the aforementioned enzyme levels. The results of immunoblot analyses showed that 10 and 25mg/kg dicofol increased protein levels of CYP1A1, CYP2B, CYP2E1, and 3A in liver. RT-PCR data indicated that dicofol induced mRNA expression of liver CYP1A1, CYP2B, and CYP3A. Pretreatments of rats with 10 and 25mg/kg dicofol decreased phenobarbital-induced sleeping time by 34% and 39%, respectively. Dicofol pretreatment at 25mg/kg increased CCl4-induced serum alanine aminotransferase activity by 4.3-fold and aspartate aminotransferase activity by 4.1-fold. The present study demonstrates that dicofol has the ability to induce CYP1A1, CYP2B, CYP2E1, and CYP3A in the liver and increase phenobarbital metabolism and CCl4 toxicity in rats.

Target-controlled infusion of propofol versus intermittent bolus of a sedative cocktail regimen in deep sedation for gastrointestinal endoscopy: comparison of cardiovascular and respiratory parameters.

To investigate whether target‐controlled infusion (TCI) with propofol, a method that has theoretically better control of drug concentration, produces less cardiovascular and respiratory suppression than an intermittent bolus of a sedative cocktail regimen in deep sedation for gastrointestinal endoscopy.

Induction of Hepatic Glutathione S-Transferase and UDP-Glucuronosyltransferase Activities by Ketamine in Rats

BACKGROUND Ketamine has been shown to induce rat cytochrome P-450 in a way similar to phenobarbital. However, whether ketamine is able to induce glutathione S-transferase (GST) and UDP-glucuronosyltransferase (UGT), two major phase II drug-metabolizing enzymes, remains unclear. The present study aimed to investigate the effect of ketamine on GST and UGT activities in rats. METHODS In a dose-response study, male adult Wistar rats were treated with 10, 20, 40 or 80 mg/kg ketamine intraperitoneally twice daily for 4 days. Livers were removed 1 day after ketamine treatment and hepatic GST and UGT activities were determined. In a reversibility study, rats were treated with 80 mg/kg ketamine intraperitoneally twice daily for 4 days and killed 1, 2, 3 or 4 days after the last dose of ketamine. Livers were removed and hepatic GST and UGT activities were determined. RESULTS The results of the dose-response study showed that treatment of rats with 10, 20, 40, or 80 mg/kg ketamine produced 19%, 20%, 18%, and 25% increases respectively in the catalytic activity of hepatic cytosolic GST, and 41%, 41%, 35%, and 38% increases respectively in the catalytic activity of microsomal UGT. The results of the reversibility study showed that the GST activities of the rats killed 1, 2, 3, or 4 days after ketamine treatment were 62%, 88%, 46% and 65% higher than the activity of the control group. The UGT activities of the rats killed 1, 2, 3, or 4 days after ketamine treatment were 56%, 53%, 54% and 72% higher than the activity of the control group. CONCLUSION Ketamine is able to induce the activities of hepatic GST and UGT in rats. The induced GST and UGT activities persist for at least 4 days after cessation of ketamine. The results suggest the possibility of interactions of drugs related to phase II enzyme induction in chronic ketamine users.

The absence of arterial oxygen desaturation during massive oxygen embolism after hydrogen peroxide irrigation.

For decades, water-mill murmur, decrease in end-tidal CO(2) (Petco(2)), hypotension, and hypoxemia have been accepted as diagnostic criteria for gas embolism. In this case report, a 19-yr-old male patient developed a sudden reduction in Petco(2) and profound circulatory collapse 15 min after intramedullary irrigation with H(2)O(2). However, arterial oxygen desaturation never developed throughout the entire course of resuscitation from presumed massive oxygen embolism.