氯胺酮在吗啡急性耐受大鼠的外周镇痛作用

我们产证明氯胺酮引起的外周镇痛作用与阿片受体的激活有关。本实验旨在建立吗啡外周镇痛耐受的大鼠模型，进一步观察氯胺酮的外周镇痛作用与阿片受体的关系。外周感受野局部皮下注射５μｌ吗啡（１０μｇ／μｌ）明显的抑制伤害性肌电反应。随吗啡注射次数的增加，伤害性反应的抑制逐渐减弱，一般于第五次注射，吗啡不再产生抑制，出现外周镇痛的急性耐受。但是，在耐受动物的同一部位注射０μｌ氯胺酮（５０μｇ／μｌ），仍产生很     

Assessment of individual vaccine status in a vaccinology experts' group

Rationale  Worldwide, experts in vaccinology have promoted the broad annual coverage of health care workers with the influenza vaccine. Furthermore, pertussis vaccination is now recommended for young adults and health care workers working with newborns.
Aim  To analyse the compliance with these guidelines among experts responsible for the development or dissemination of national immunization schedules.
Method  A cross-sectional survey was conducted in a vaccinology workshop group of French experts, using a self-administered questionnaire.
Results  Among 44 experts, the average rate of influenza vaccination was 69.5% (95% confidence interval, 61.6% to 77.3%) between the 2003/04 and 2005/06 flu seasons, whereas the rate of pertussis vaccination during this period was only 30%. The main reasons that the experts gave for not being vaccinated were a lack of time or simply not remembering to do so.
Conclusion  Experts had low coverage rates for influenza and pertussis vaccination. To improve these rates, a multifaceted intervention combining audit and feedback strategy with a vaccine day is planned.     

The contribution of twins to the study of cognitive ageing and dementia: The Older Australian Twins Study

Abstract

The Older Australian Twins Study (OATS) is a major longitudinal study of twins, aged ≥ 65 years, to investigate genetic and environmental factors and their interactions in healthy brain ageing and neurocognitive disorders. The study collects psychiatric, neuropsychological, cardiovascular, metabolic, biochemical, neuroimaging, genomic and proteomic data, with two-yearly assessments, and is currently in its third wave. The initial cohort comprises 623 individuals (161 monozygotic and 124 dizygotic twin pairs; 1 MZ triplets; 27 single twins and 23 non-twin siblings), of whom 426 have had wave 2 assessment. A number of salient findings have emerged thus far which assist in the understanding of genetic contributions to cognitive functions such as processing speed, executive ability and episodic memory, and which support the brain reserve hypothesis. The heritability of brain structures, both cortical and subcortical, brain spectroscopic metabolites and markers of small vessel disease, such as lacunar infarction and white matter hyperintensities, have been examined and can inform future genetic investigations. Work on amyloid imaging and functional magnetic resonance imaging is proceeding and epigenetic studies are progressing. This internationally important study has the potential to inform research into cognitive ageing in the future, and offers an excellent resource for collaborative work.     

DURATION-1: Exenatide Once Weekly Produces Sustained Glycemic Control and Weight Loss Over 52 Weeks

OBJECTIVE

In the Diabetes Therapy Utilization: Researching Changes in A1C, Weight and Other Factors Through Intervention with Exenatide Once Weekly (DURATION-1) study, the safety and efficacy of 30 weeks of treatment with the glucagon-like peptide-1 receptor agonist exenatide once weekly (exenatide QW; 2 mg) was compared with exenatide BID in 295 patients with type 2 diabetes. We now report the safety and efficacy of exenatide QW in 1) patients who continued treatment for an additional 22 weeks (52 weeks total) and 2) patients who switched from exenatide BID to exenatide QW after 30 weeks.

RESEARCH DESIGN AND METHODS

In this randomized, multicenter, comparator-controlled, open-label trial, 258 patients entered the 22-week open-ended assessment phase (n = 128 QW-only; n = 130 BID→QW). A1C, fasting plasma glucose (FPG), body weight, blood pressure, fasting lipids, safety, and tolerability were assessed.

RESULTS

Patients continuing exenatide QW maintained A1C improvements through 52 weeks (least squares mean −2.0% [95% CI −2.1 to −1.8%]). Patients switching from exenatide BID to exenatide QW achieved further A1C improvements; both groups exhibited the same A1C reduction and mean A1C (6.6%) at week 52. At week 52, 71 and 54% of all patients achieved A1C <7.0% and ≤6.5%, respectively. In both treatment arms, FPG was reduced by >40 mg/dl, and body weight was reduced by >4 kg after 52 weeks. Nausea occurred less frequently in this assessment period and was predominantly mild. No major hypoglycemia was observed.

CONCLUSION

Exenatide QW elicited sustained improvements in glycemic control and body weight through 52 weeks of treatment. Patients switching to exenatide QW experienced further improvements in A1C and FPG, with sustained weight loss.Type 2 diabetes is a complex and increasingly prevalent disease associated with interrelated comorbidities, including obesity, dyslipidemia, and hypertension. The importance of treating not only hyperglycemia, but also the associated comorbidities, is recognized as necessary to reduce the risk of complications, particularly cardiovascular disease (1). Lifestyle modification can improve glycemic control as well as body weight, blood pressure, and lipid profiles; however, behavioral modifications are inherently difficult, and most patients eventually require multiple medications (2–6). Although several classes of antihyperglycemic medications are currently indicated for the treatment of type 2 diabetes, most of them do not improve the comorbidities and several are associated with weight gain.Exenatide, a glucagon-like peptide-1 receptor (GLP-1R) agonist, improves glycemic control in patients with type 2 diabetes through multiple mechanisms of action: increased glucose-dependent insulin secretion, attenuated postprandial glucagon secretion, slowed gastric emptying, and increased satiety (7,8). The twice-daily formulation of exenatide (exenatide BID) improves both fasting and postprandial glucose control, resulting in A1C reductions of roughly 0.8–1.0% in placebo-controlled trials (9–12) and 1.0–1.4% in open-label trials (13–15). These improvements in glucose control were maintained in patients completing 3 years of treatment (−1.0%) (16). Exenatide therapy is also associated with weight loss and improvement in cardiovascular risk factors, including blood pressure and serum lipid profiles (16). Furthermore, the glucose-dependent mechanisms of action of exenatide minimize the risk of hypoglycemia. GLP-1R agonists have recently been added to the American Diabetes Association and European Association for the Study of Diabetes consensus algorithm for the treatment of type 2 diabetes as an option after the addition of metformin in patients in whom body weight and hypoglycemia risk are concerns (1).Exenatide BID is administered within the 60-min period before the morning and evening meals and primarily exerts its pharmacodynamic effects on glucose concentrations during the postprandial period. A long-acting once-weekly formulation of exenatide (exenatide QW) has been developed. Weekly administration of 2 mg exenatide QW results in therapeutic plasma exenatide concentrations within 2 weeks and steady-state plasma exenatide concentrations within the therapeutic target range 6–7 weeks after initiation of therapy (17,18).The Diabetes Therapy Utilization: Researching Changes in A1C, Weight and Other Factors Through Intervention with Exenatide Once Weekly (DURATION-1) trial was designed as a two-stage protocol. We previously reported the first stage, a randomized open-label comparison of exenatide QW to exenatide BID in patients with type 2 diabetes over 30 weeks (17). Both therapies improved glycemic control, and the improvement in A1C observed with exenatide QW treatment was significantly greater than that observed with exenatide BID (−1.9 vs. −1.5%, respectively). Similar improvements in body weight, blood pressure, and fasting lipids were demonstrated with both forms of exenatide therapy. We now describe 52-week results from the second phase of the DURATION-1 trial which examined the safety and efficacy of 1) switching from exenatide BID to exenatide QW after 30 weeks of treatment and 2) continuing exenatide QW treatment for an additional 22 weeks (52 weeks total).     

RETRACTED ARTICLE: Individual Placement and Support in Europe: The EQOLISE trial

We, the Editor and Publishers of International Review of Psychiatry, have retracted the following article:

Tom Burns, Sarah J. White & Jocelyn Catty For The Eqolise Group, Individual Placement and Support in Europe: The EQOLISE trial, International Review of Psychiatry, 20:6, 2008, 498–502, DOI: 10.1080/09540260802564516

The above article has been retracted as a result of the entire article already having been published in the Psychiatric Rehabilitation Journal as Burns, T., & Catty, J. (2008). IPS in Europe: The EQOLISE trial. Psychiatric Rehabilitation Journal, 31(4), 313–317. http://dx.doi.org/10.2975/31.4.2008.313.317. The authors have taken full responsibility for this error and have agreed to the retraction.

We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions.

The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.     

Carbon dioxide contributes to the beneficial effect of pressurization in a portable hyperbaric chamber at high altitude

Regional cerebral oxygenation (rSO2) and peripheral oxygen saturation (SpO2) have been studied in subjects inside a portable hyperbaric chamber at altitude during pressurization. The effects of the accumulation of carbon dioxide within the chamber on rSO2 and SpO2 have also been investigated. Three studies of cerebral regional oxygenation were undertaken, using near-IR spectroscopy, in subjects who had ascended to 3475 m in the Alps, 4680 m in the Andes or 5005 m in the Himalayas. At 3475 m and 5005 m the effects of the removal of inspired carbon dioxide by a soda lime scavenger were also studied. On pressurization of the chamber to 19.95 kPa, inspired carbon dioxide rose within the chamber from 0.03% (0.06 kPa) ambient to over 1% (1.3 kPa). At 5005 m, SpO2 rose from a baseline of 79.5% (S.D. 4.5%) to 95.9% (2.0%) (P<0.0001), and cerebral rSO2 rose from 64.6% (3.4%) to 69.4% (3.6%) (P<0.0001). The introduction of a soda lime CO2 scavenger into the breathing circuit resulted in a drop in SpO2 from 95.9% (2.03%) to 93.6% (2.07%) (P<0.001) and a fall in rSO2 from 69.4% (3.64%) to 68.5% (3.5%) (P<0.01). Chamber pressure was maintained throughout at 19.95 kPa. Similar changes were seen at the other altitudes. Cerebral rSO2 increased rapidly following pressurization at all three altitudes. Scavenging of inspired carbon dioxide was associated with a significant fall in cerebral rSO2 and SpO2, and we estimate that the contribution of carbon dioxide may account for up to one-third of the beneficial effect of the portable hyperbaric chamber.     

Neck Circumference Positively Related With Central Obesity, Overweight, and Metabolic Syndrome in Chinese Subjects With Type 2 Diabetes: Beijing Community Diabetes Study 4

OBJECTIVE

To investigate the association between neck circumference and central obesity, overweight, and metabolic syndrome in Chinese individuals with type 2 diabetes.

RESEARCH DESIGN AND METHODS

A total of 3,182 diabetic subjects (aged 20–80 years) were recruited from 15 community health centers in Beijing using a multistage random sampling approach.

RESULTS

Receiver operating characteristic analysis showed that the area under the curve for neck circumference and central obesity was 0.77 for men and 0.75 for women (P < 0.001). Furthermore, a neck circumference of ≥38 cm for men and ≥35 cm for women was the best cutoff point for determining overweight subjects. A neck circumference of ≥39 cm for men and ≥35 cm for women was the best cutoff point to determine subjects with metabolic syndrome.

CONCLUSIONS

In the present study, neck circumference is positively related with BMI, waist circumference, and metabolic syndrome in Chinese individuals with type 2 diabetes.Neck circumference (NC) as an index for upper-body subcutaneous adipose tissue distribution has been evaluated in relation to cardiovascular risk factors, insulin resistance, and biochemical components of metabolic syndrome (MS) (1–4). However, epidemiological population-based studies on the clinical significance of NC in connection with overweight and MS in diabetic people are lacking. The aim of this study was to determine whether NC alone can predict overweight and central obesity and to evaluate the association between NC and MS.     

Sepsis as a cause and consequence of acute kidney injury: Program to Improve Care in Acute Renal Disease

Purpose  

Sepsis commonly contributes to acute kidney injury (AKI); however, the frequency with which sepsis develops as a complication of AKI and the clinical consequences of this sepsis are unknown. This study examined the incidence of, and outcomes associated with, sepsis developing after AKI.     

Evaluating denoising strategies in resting‐state functional magnetic resonance in traumatic brain injury (EpiBioS4Rx)

Resting‐state functional MRI is increasingly used in the clinical setting and is now included in some diagnostic guidelines for severe brain injury patients. However, to ensure high‐quality data, one should mitigate fMRI‐related noise typical of this population. Therefore, we aimed to evaluate the ability of different preprocessing strategies to mitigate noise‐related signal (i.e., in‐scanner movement and physiological noise) in functional connectivity (FC) of traumatic brain injury (TBI) patients. We applied nine commonly used denoising strategies, combined into 17 pipelines, to 88 TBI patients from the Epilepsy Bioinformatics Study for Anti‐epileptogenic Therapy clinical trial. Pipelines were evaluated by three quality control (QC) metrics across three exclusion regimes based on the participant''s head movement profile. While no pipeline eliminated noise effects on FC, some pipelines exhibited relatively high effectiveness depending on the exclusion regime. Once high‐motion participants were excluded, the choice of denoising pipeline becomes secondary ‐ although this strategy leads to substantial data loss. Pipelines combining spike regression with physiological regressors were the best performers, whereas pipelines that used automated data‐driven methods performed comparatively worse. In this study, we report the first large‐scale evaluation of denoising pipelines aimed at reducing noise‐related FC in a clinical population known to be highly susceptible to in‐scanner motion and significant anatomical abnormalities. If resting‐state functional magnetic resonance is to be a successful clinical technique, it is crucial that procedures mitigating the effect of noise be systematically evaluated in the most challenging populations, such as TBI datasets.