Disruption of morphine‐conditioned place preference by a δ2‐opioid receptor antagonist: study of μ‐opioid and δ‐opioid receptor expression at the synapse

The addictive properties of morphine limit its clinical use. Learned associations that develop between the abused opiate and the environment in which it is consumed are engendered through Pavlovian conditioning processes. Disruption of the learned associations between the opiate and environmental cues may be a therapeutic approach to prevent morphine dependence. Although a role for the δ‐opioid receptor in the regulation of the rewarding properties of morphine has already been shown, in this study we further characterized the role of the δ‐opioid receptor in morphine‐induced conditioned responses by examining the effect of a selective δ2‐opioid receptor antagonist (naltriben), using a conditioned place preference paradigm in rats. Additionally, we used a subcellular fractionation technique to analyze the synaptic localization of μ‐opioid and δ‐opioid receptors in the hippocampus, in order to examine the molecular mechanisms that may underlie this morphine‐induced conditioned behavior. Our data show that the administration of 1 mg/kg naltriben (but not 0.1 mg/kg) prior to morphine was able to block morphine‐induced conditioned place preference. Interestingly, this naltriben‐induced disruption of morphine conditioned place preference was associated with a significant increase in the expression of the δ‐opioid receptor dimer at the postsynaptic density. In addition, we also observed that morphine conditioned place preference was associated with an increase in the expression of the μ‐opoid receptor in the total homogenate. Overall, these results suggest that modulation of the δ‐opioid receptor expression and its synaptic localization may constitute a viable therapeutic approach to disrupt morphine‐induced conditioned responses.     

The neural response to changing semantic and perceptual complexity during language processing

Speech comprehension involves processing at different levels of analysis, such as acoustic, phonetic, and lexical. We investigated neural responses to manipulating the difficulty of processing at two of these levels. Twelve subjects underwent positron emission tomographic scanning while making decisions based upon the semantic relatedness between heard nouns. We manipulated perceptual difficulty by presenting either clear or acoustically degraded speech, and semantic difficulty by varying the degree of semantic relatedness between words. Increasing perceptual difficulty was associated with greater activation of the left superior temporal gyrus, an auditory‐perceptual region involved in speech processing. Increasing semantic difficulty was associated with reduced activity in both superior temporal gyri and increased activity within the left angular gyrus, a heteromodal region involved in accessing word meaning. Comparing across all the conditions, we also observed increased activation within the left inferior prefrontal cortex as the complexity of language processing increased. These results demonstrate a flexible system for language processing, where activity within distinct parts of the network is modulated as processing demands change. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.     

The learning curve for endorectal ultrasonography in rectal cancer staging

Background  

Endorectal ultrasound (ERUS) is an emerging technique for preoperative rectal cancer staging. It is an operator-dependent examination with accuracy closely related to endosonographer experience. In this study, we prospectively analyzed our results of ERUS staging for rectal cancer, aiming to determine its accuracy and to define the learning curve of the procedure.     

The National Authority for Health and new cooperation

The concept of new forms of cooperation between healthcare professionals was introduced by the "Hospital, patients, health and territories" law and clarified by the relevant implementing provisions. The French National Authority for Health has recently established guidelines for healthcare professionals in order to help them in drawing up cooperation protocols.     

Variations in the Application of Various Perfusion Technologies in Great Britain and Ireland—A National Survey

In an attempt to reduce the negative sequelae of cardiopulmonary bypass (CPB), a variety of new technologies have been created. This study investigates variations in the application of these technologies throughout Great Britain and Ireland (GB & I). All perfusion departments within GB & I were surveyed about equipment and technologies used in CPB. Eighty‐five percent of units use a standard arterial line filter in all cases. Forty percent of units occasionally use leukocyte‐depleting filters in various sites within the circuit. Sixteen percent always use some element of heparin‐bonded circuit, but 62% never use them. Twenty‐five percent use solely rotary pumps, 18% use solely centrifugal pumps, and 56% use both. Finally, 20% are now using minimal extracorporeal circulation in certain clinical scenarios. These decisions are most frequently affected by clinician preference and cost. This survey has highlighted significant variation in the utilization of various technologies used in CPB. While some variation between centers is to be expected, as innovative technologies are adopted at varying rates, surveys such as this are useful for alerting clinicians to gaps between evidence‐based knowledge and clinical practice.     

Oral estroprogestin: an alternative low cost therapy for women with postoperative persistent acromegaly?

Oral estrogens reduce GH-induced IGF-1 production and preliminary studies have shown that adjuvant estroprogestin (EP) therapy with octreotide LAR may control disease activity in some female patients who are partially responsive to octreotide LAR. Our aim was to verify if EP alone or in combination with octreotide LAR can achieve remission of acromegaly in selected cases of patients uncontrolled by surgery. Eleven women with persistent active acromegaly following surgery participated in this unblinded open label pilot study. Their mean age was 49.8 ± 4.3 years. Two patients were drug naïve, two patients had stopped octreotide LAR because of intolerance and seven were treated with octreotide LAR. The patients received either EP (EP pill, 20 μg ethinylestradiol, 100 μg levonorgestrel) alone (4 patients) or added to octreotide LAR (7 patients). Fasting GH, IGF-1, glucose, HDL- and LDL-cholesterol, and triglycerides were measured at baseline and at last visit. MRI was controlled at baseline and at last visit. Duration of estrogen treatment was 3.1 ± 0.5 years. Serum IGF-1 levels were normalized in 8/11 patients (73%). Serum GH concentrations did not change significantly during treatment (11.6 ± 5.6 μg/L prior to EP vs 5.5 ± 1.2 μg/L following EP). In patients treated with EP alone, remission was achieved in 2/4 patients (IGF-1 percentages of the upper limit of normal age-matched range (%ULN): 211 ± 40% before EP compared to 95 ± 15% after EP, P = 0.028). In the seven patients treated by EP added to octreotide LAR, remission was achieved in 6 patients (IGF-1%ULN: 158 ± 9% before EP compared to 86 ± 4% after EP, P = 0.0003). Glucose and cholesterol levels were unchanged by EP treatment (data not shown). MRI did not show any evidence of tumour progression with EP in patients who had a tumour remnant. In conclusion, oral estrogen treatment appears to normalize serum IGF-1 concentrations in over 70% of women with acromegaly uncured by surgery irrespective of their sensitivity to octreotide LAR. We suggest that estrogens may be a temporary cost-effective and safe treatment for women with postoperative persistent acromegaly.     

Prevention of gestational diabetes mellitus: a review of studies on weight management

Entering pregnancy with overweight, obesity or gaining excessive gestational weight could increase the risk of gestational diabetes mellitus (GDM), which is associated with negative consequences for both the mother and the offspring. The objective of this article was to review scientific evidence regarding the association between obesity and GDM, and how weight management through nutritional prevention strategies could prove successful in reducing the risk for GDM. Studies published between January 1975 and January 2009 on the relationship between GDM, pre‐pregnancy body mass index (BMI), gestational weight gain and nutritional prevention strategies were included in this review. Results from these reports suggest that maternal obesity assessed by pre‐pregnancy BMI is associated with an increased risk of GDM. They also show an association between gestational weight gain and increased risk for GDM. Higher dietary fat and lower carbohydrate intakes during pregnancy appear to be associated with a higher risk for GDM, independent of pre‐pregnancy BMI. Some studies showed that restricting energy and carbohydrates could minimize gestational weight gain. However, a firm conclusion on the most effective nutritional intervention for the control of gestational weight gain and glycaemic responses could not be reached based on available studies. In light of the studies reviewed, we conclude that weight management through nutritional prevention strategies could be successful in reducing the risk of GDM. Further studies are required to identify the most effective diet composition to prevent GDM and excessive gestational weight gain. Copyright © 2009 John Wiley & Sons, Ltd.     

The Association of Provider Communication with Trust among Adults with Sickle Cell Disease

Background  

Adults with sickle cell disease often report poor interpersonal healthcare experiences, including poor communication with providers. However, the effect of these experiences on patient trust is unknown.