Comparison of Dexmedetomidine–Ketamine with Isoflurane for Anesthesia of Chinchillas (Chinchilla lanigera)

The objective of this study was to compare isoflurane with a combination of dexmedetomidine and ketamine, administered intramuscularly, for anesthesia in chinchillas (Chinchilla lanigera). In a prospective, complete crossover study, adult chinchillas (n = 8; age, 2 to 5 y) were anesthetized with a combination of dexmedetomidine (0.015 mg/kg IM) and ketamine (4 mg/kg IM). Atipamezole (0.15 mg/kg) was injected subcutaneously 45 min after dexmedetomidine–ketamine administration. For comparison, anesthesia also was induced and maintained with isoflurane in 100% oxygen, delivered by facemask. Anesthetic and physiologic parameters were recorded during each anesthesia, including various reflexes, heart rate, respiratory rate, body temperature, and SpO₂. Food intake, fecal output, and body weight were recorded daily for 6 d after each anesthetic trial. Induction time, heart rate, respiratory rate, and body temperature did not differ significantly between the 2 anesthetic protocols. Recovery times were shorter and SpO₂ was higher in animals that received isoflurane delivered in 100% oxygen. Food intake and fecal output were reduced in the dexmedetomidine–ketamine group for as long as 3 d after anesthesia, whereas isoflurane had no signifcant effect on food intake or fecal output. Both anesthetic protocols provided effective anesthesia in chinchillas. However, when anesthetized with dexmedetomidine–ketamine, chinchillas received room air and became hypoxemic. Future studies are needed to evaluate the effect of oxygen supplementation on anesthetic recovery and on the recovery of food intake and fecal output in chinchillas.Abbreviation: DK, dexmedetomidine–ketamineChinchillas are used extensively in research to study otitis media, hearing loss, and ototoxicity.^1,11,19,25 In addition, chinchillas are becoming increasingly popular as companion animals and, therefore, are more frequently presented for veterinary care. Common diseases of chinchillas include dental disease, gastrointestinal disorders, and ocular disorders.^13,14 Chemical immobilization is often required to perform diagnostic (for example, radiography, CT), therapeutic, or experimental procedures.^3,5,7,21 Research regarding the efficacy and safety of anesthetic protocols in chinchillas is limited and currently recommended protocols rely largely on extrapolation from other species or anecdotal reports.^13,21,27Isoflurane is used routinely in chinchillas for the induction and maintenance of anesthesia. A study investigating the echocardiographic effects of isoflurane in chinchillas found significant effects on several echocardiographic parameters, but no complications or other side effects were reported.¹² Isoflurane typically is delivered by facemask to chinchillas, given that endotracheal intubation is technically challenging and therefore not performed routinely.^10,21 However, using a facemask increases the risk of exposure of the veterinary staff to waste gases, which is a significant occupational health concern.^20,23 Therefore, alternative anesthetic protocols that reduce waste-gas exposure are desired, such as exclusively using injectable anesthetic drugs for induction and maintenance of anesthesia. Intravascular access is challenging to obtain in conscious chinchillas, and thus parenteral, nonvascular protocols provide the most accommodating route for anesthesia induction and maintenance.¹⁴ Only one study in chinchillas has investigated the effects of various injectable anesthetics: a combination of medetomidine (0.06 mg/kg) and ketamine (5 mg/kg) was compared with other parenteral protocols.¹⁴ Although anesthesia was successful with this protocol, the authors reported respiratory and cardiac depression in the animals. Furthermore, although atipamezole is commonly administered in clinical and research settings to promote rapid recovery and prevent complications, such as hypothermia, it was not used in the cited study.¹⁴To our knowledge, no studies have been published that assess the effects of anesthetic protocols on recovery of food intake and fecal output in chinchillas. The objective of this study was to compare the anesthesia induced in chinchillas by using either dexmedetomidine and ketamine or isoflurane and to evaluate the effects of both anesthetic protocols on subsequent food intake, fecal output, and body weight.     

Preferential loss of maternal 9p alleles in childhood acute lymphoblastic leukemia.

Germ-line events, such as paternal mutation or genomic imprinting, contribute to the early onset of childhood cancers such as retinoblastoma, Wilms tumors, and neuroblastoma. Given the high frequency of deletion involving chromosome 9p in childhood acute lymphoblastic leukemia (ALL), this study investigated whether 9p deletion might reflect preexisting germ-line gene inactivation. To do this the parental origin of deletion was determined in 10 cases of ALL with 9p21 loss of heterozygosity. Of these cases, 9 showed loss of the maternally derived allele, suggesting that a germ-line event involving a 9p gene may play a role in the onset of childhood ALL.     

Canadian Association of Gastroenterology policy on the application for,and implementation of,clinical practice guidelines

An important mandate of the Canadian Association of Gastroenterology (CAG), as documented in the Association’s governance policies, is to optimize the care of patients with digestive disorders. Clinical practice guidelines are one means of achieving this goal. The benefits of timely, high-quality and evidenced-based recommendations include:

• Enhancing the professional development of clinical members through education and dissemination of synthesized clinical research;
• Improving patient care provided by members by providing focus on quality and evidence;
• Creating legislative environments that favour effective clinical practice;
• Enhancing the clinical care provided to patients with digestive disease by nongastroenterologists; and
• Identifying areas that require further information or research to improve clinical care.

The present document provides the foundation required to ensure that clinical practice guidelines produced by the CAG are necessary, appropriate, credible and applicable. These recommendations should be adhered to as closely as possible to obtain CAG endorsement.     

Bleeding events and associated factors in a cohort of adult patients taking warfarin in Sarawak,Malaysia

Evidence is emerging that rates of adverse events in patients taking warfarin may vary with ethnicity. This study investigated the rates of bleeds and thromboembolic events, the international normalised ratio (INR) status and the relationship between INR and bleeding events in Malaysia. Patients attending INR clinic at the Heart Centre, Sarawak General Hospital were enrolled on an ad hoc basis from May 2010 and followed up for 1 year. At each routine visit, INR was recorded and screening for bleeding or thromboembolism occurred. Variables relating to INR control were used as predictors of bleeds in logistic regression models. 125 patients contributed to 140 person-years of follow-up. The rates of major bleed, thromboembolic event and minor bleed per 100 person-years of follow-up were 1.4, 0.75 and 34.3. The median time at target range calculated using the Rosendaal method was 61.6 % (IQR 44.6–74.1 %). Of the out-of-range readings, 30.0 % were below range and 15.4 % were above. INR variability, (standard deviation of individuals’ mean INR), was the best predictor of bleeding events, with an odds ratio of 3.21 (95 % CI 1.10–9.38). Low rates of both major bleeds and thromboembolic events were recorded, in addition to a substantial number of INR readings under the recommended target range. This may suggest that the recommended INR ranges may not represent the optimal warfarin intensity for this population and that a lower intensity of therapy, as observed in this cohort, could be beneficial in preventing adverse events.     

Weight loss from lifestyle interventions and severity of sleep apnoea: a systematic review and meta-analysis

Background

Excess body weight is a risk factor for obstructive sleep apnoea (OSA). The aim of the systematic review was to establish whether weight loss via lifestyle interventions such as diet and exercise are useful in the treatment of OSA.

Methods

A literature search was conducted between 1980 and February 2012. Systematic reviews and randomised controlled trials (RCTs) with participants who had OSA, were overweight or obese, and who had undergone lifestyle interventions with the aim of improving sleep apnoea were included. Meta analyses were conducted for a subset of RCTs with appropriate data.

Results

Two systematic reviews and eight RCTs were included. Meta-analyses were conducted for four RCTs comparing intensive lifestyle interventions to a control. The overall weighted mean differences for weight change, change in apnoea -hypopnoea index (AHI) and change in oxygen desaturation index of ≥4% were as follows: −13.76 kg (95% confidence interval (CI) −19.21, −-8.32), −16.09 (95% CI −25.64, −6.54) and −14.18 (95% CI −24.23, −4.13), respectively. Although high heterogeneity within the meta analyses, all studies favoured the interventions. Long-term follow-up data from three RCTs suggest that improvements in weight and AHI are maintained for up to 60 months.

Conclusions

Intensive lifestyle interventions are effective in the treatment of OSA, resulting in significant weight loss and a reduction in sleep apnoea severity. Weight loss via intensive lifestyle interventions could be encouraged as a treatment for mild to moderate OSA.     

Salivary levels of mutans streptococci and Lactobacilli among Palestinian school children in East Jerusalem

Objectives

The aim of the present study was to investigate the distribution of oral cariogenic bacteria among 12-year-old Palestinian children attending schools in East Jerusalem.

Materials and methods

Salivary levels of mutans streptococci (MS) and Lactobacilli (LB) were examined by semi-quantitative commercial kits and then correlated to social–demographic parameters.

Results

Overall, 52.1 % of the examined children presented the highest possible ranking score categories for MS bacteria, with only 5.4 % in the lowest category. Only 12.6 % of the school children presented the highest LB score, while 25 % had the lowest ranking score. Salivary MS levels in children attending private schools were lower than those of children in government schools and United Nations Relief and Works Agency (UNRWA) schools. Conversely, levels of LB were lowest in children attending UNRWA schools compared to government and private schools. Girls had significantly higher amounts of MS and LB than boys (p?=?0.001). Lower MS levels were significantly related to the following socioeconomic variables: higher father’s education level (p?=?0.037), higher mother’s education level (p?=?0.063), mother’s employment status (p?=?0.012), and lower home density (p?=?0.001). For LB, the only significant socioeconomic variable was higher father’s employment level, which was related to lower LB level (p?=?0.025).

Conclusions

Levels of MS and LB were found to be strongly related with socioeconomic status among Palestinian children in East Jerusalem. The relatively high prevalence of cariogenic bacteria suggests that oral care prevention and treatment demands special attention from the health care institutions and authorities.     

老年抑郁症认知功能与血清同型半胱氨酸及血脂水平的相关性

目的 研究老年抑郁症患者血清同型半胱氨酸(Hcy)、血脂水平与认知功能之间的关系。方法 选取60例老年抑郁患者为研究组,以60例健康志愿者为对照组,测定两组血清Hcy、总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL C)、低密度脂蛋白胆固醇(LDL C)水平。用汉密尔顿抑郁量表（HAMD）评定病情严重程度,蒙特利尔认知评估量表(MoCA)评估患者的认知功能。结果 与对照组比较,研究组MoCA评分明显低于对照组（P＜0.05）,血清Hcy明显高于对照组（P＜0.05）,血清HDL C水平明显低于对照组（P＜0.05）。相关分析显示,研究组认知功能损害程度与病情严重程度呈正相关（r=0.327,P＜0.01）,认知功能评估中注意与集中、记忆、执行功能评分与血清Hcy水平呈负相关（r=-0.402,P=0.01）,其中执行功能评分与HDL C水平成正相关（r=0.562,P=0.008）。结论 老年抑郁症患者的认知功能损害与血清高水平Hcy和低水平HDL C水平有关,血清高水平Hcy和低水平HDL C可能是老年抑郁症患者的危险因素。     

Effect of cenobamate on the single‐dose pharmacokinetics of multiple cytochrome P450 probes using a cocktail approach in healthy subjects

This study was designed to evaluate the effects of cenobamate, an antiseizure medication for focal seizures, on the pharmacokinetics of cytochrome P450 probes (bupropion, CYP2B6; midazolam, CYP3A4/5; warfarin, CYP2C9; and omeprazole, CYP2C19) in healthy subjects. Probes were administered alone on days 1 (bupropion) and 7 (midazolam/warfarin/omeprazole), and with cenobamate 100 mg/day on day 69 (midazolam) and cenobamate 200 mg/day on days 99 (bupropion) and 105 (midazolam/warfarin/omeprazole). No significant interaction was concluded if 90% confidence intervals (CIs) for geometric mean ratios (GMRs) for area under the curve (AUC) and maximum concentration of CYP substrates and/or their metabolites were within the no‐effect interval (0.80–1.25). When co‐administered with cenobamate 100 mg/day, AUC from time of administration up to the time of the last quantifiable concentration (AUC_0–last) GMR (90% CIs) for midazolam was 0.734 (0.647–0.832). When co‐administered with cenobamate 200 mg/day, AUC_0–last GMRs (90% CI) for midazolam, bupropion, S‐warfarin, and omeprazole were 0.277 (0.238–0.323), 0.615 (0.522–0.724), 1.14 (1.10–1.18), and 2.07 (1.44–2.98), respectively. Co‐administration of cenobamate with midazolam and bupropion probes led to values that were outside and below the no effect boundary, indicating that cenobamate induces the CYP3A4/5 and CYP2B6 enzymes. Co‐administration of cenobamate led to omeprazole values which were outside and above the no‐effect boundary, but with high variability, suggesting that cenobamate may moderately inhibit CYP2C19 activity. No effect on CYP2C9 was observed with the cenobamate and warfarin combination. Co‐administration of cenobamate with these probes drugs was well‐tolerated. In this study, 200 mg/day cenobamate moderately induced CYP3A4/5 (dose‐dependently; 100 mg/day was a weak inducer), was a weak inducer of CYP2B6, moderately inhibited CYP2C19, and had a negligible effect on CYP2C9.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Drug‐drug interactions are a challenging aspect of managing epilepsy because many antiseizure medications (ASMs) induce or inhibit CYP450 enzymes, which are commonly involved in drug metabolism of many ASMs. Previous studies suggest that cenobamate, a US Food and Drug Administration (FDA)‐approved ASM for the treatment of adults with focal seizures, may affect the activity of certain CYP450 enzymes.

• WHAT QUESTION DID THIS STUDY ADDRESS?

This study was designed to determine the effects of cenobamate on the pharmacokinetics of drugs known to affect the activity of these CYP450 enzymes, known as probe drugs. These probe drugs include bupropion, (CYP2B6), midazolam (CYP3A4/5), warfarin (CYP2C9), and omeprazole (CYP2C19).

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

The results of this study indicate that cenobamate induces CYP2B6 activity, exhibits a dose‐dependent induction of CYP3A4/5 activity, inhibits CYP2C19 activity, and has a negligible effect on CYP2C9 activity.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

These findings suggest that dose adjustments may be required when agents metabolized through these CYP450 pathways are used in conjunction with cenobamate.