Striatal dopamine D<Subscript>2</Subscript> receptors in medication-naive patients with major depressive disorder as assessed with [<Superscript>11</Superscript>C]raclopride PET

Rationale Among other monoamine neurotransmitters, dopamine is implicated in the pathophysiology of major depression. Experimental studies suggest the involvement of the mesolimbic dopamine system in the mechanism of action of antidepressant drugs. Previous in vivo imaging studies have studied striatal dopamine D₂ receptor availability in depression but the results are equivocal thus far. Objective To study the striatal and thalamic dopamine D₂ receptor availability in drug-naive patients with major depression was the aim of this study. Materials and methods Caudate, putamen, and thalamic dopamine D₂ receptor availability was estimated using positron emission tomography and [¹¹C]raclopride in 25 treatment-seeking drug-free patients (of whom 24 were drug-naive) with major depression (primary care patients) as well as in 19 demographically similar healthy control subjects. Receptor availability was expressed as the binding potential (BP_ND), and analyses were carried out based on both regional and voxel-level BP_ND estimates. Results No statistically significant differences in [¹¹C]raclopride BP_ND were observed between the groups either in the caudate nucleus (+1.7%, CI −4.8% to +8.3%), putamen (−1.0%, CI −7.2% to 5.1%), thalamus (−2.4%, CI −8.7% to 4.0%), or ventral striatum (−3.8%, CI −9.3% to +1.6%). In the patients, depressive symptoms were not associated with [¹¹C]raclopride BP_ND in any region. Conclusions The findings in this sample of treatment-seeking, drug-naive and predominantly first-episode patients with major depression do not support the involvement of striatal dopamine D₂ receptors in the pathophysiology of the illness, but do not exclude the potential importance of dopaminergic mechanisms in antidepressant drug action.     

Adenosine receptor-dopamine receptor interactions in the basal ganglia and their relevance for brain function

The dopamine D1 and D2 receptors are major receptors in the regulation of striatal function and striatal adenosine A1 and A2A receptors are major modulators of their signaling. The evidence suggests the existence of antagonistic A1-D1 heteromeric receptor complexes in the basal ganglia and prefrontal cortex and especially in the direct striatonigral-striatoentopeduncular GABA pathways. The neurochemical and behavioral findings showing antagonistic A1-D1 receptor interactions can be explained by the existence of such A1-D1 heteromeric receptor complexes and of antagonistic interactions at the level of the second messengers. In contrast, A2A-D2 receptor heteromers may exist in the dorsal and ventral striato-pallidal GABA pathways, where activation of A2A receptors reduces D2 receptor recognition, coupling and signaling. As a result of the A2A receptor-induced reduction of D2 receptor signaling, the activity of these GABA neurons is increased resulting in reduced motor and reward functions mediated via the indirect pathway, causing a reduced glutamate drive to the prefrontal and motor areas of the cerebral cortex. Thus, A2A receptor antagonists and A2A receptor agonists, respectively, may offer novel treatments of Parkinson's disease (reduced D2 receptor signaling) and of schizophrenia and drug addiction (increased D2 receptor signaling).     

I can't recognize your face but I can recognize its movement

Idiosyncratic facial movements can provide a route to facial identity (review in Roark, Barrett, Spence, Abdi, & O'Toole, 2003). However, it is unclear whether recognizing a face in this way involves the same cognitive or neural mechanisms that are involved in recognizing a static face. Three studies on a developmental prosopagnosic (C.S.) showed that although he is impaired at recognizing static faces, he can discriminate between dynamic identities (Experiments 1a and 1b) and can learn to name individuals on the basis of their idiosyncratic facial movements (Experiment 2), at levels that are comparable to those of matched and undergraduate control groups. These results suggest a possible cognitive dissociation between mechanisms involved in dynamic compared to static face recognition. However, future work is needed to fully understand this dissociation.     

Feasibility of a computerized alcohol screening and personalized written advice in the ED: opportunities and obstacles

This study evaluates the feasibility of a computerized alcohol screening and intervention in patients seeking care at an emergency department. The aim of the study was to explore prevailing attitudes among nursing staff to alcohol prevention in general and the computerized screening concept before the introduction of the computerized screening procedure. Interviews were performed with six nursing staff members and a written questionnaire applied to all staff participating in training before the implementation of the concept. Observation was done in order to evaluate how the screening was performed and implemented in order to gain more knowledge about possible obstacles to alcohol screening at an emergency department. The project concept of computerized screening and low staff involvement was found to be a feasible way to overcome organizational barriers such as time limitation but there were still important attitudinal barriers among staff; thus a great disparity in practices between different staff members was observed. The results suggest that it is possible, given the time limitation, to include a computerized screening and intervention in the routines of an emergency department, when the staff regard prevention as part of their responsibilities. The findings provide evidence about the acceptability by nursing staff and feasibility of a computerized screening and personalized print out as feed back to the patients.     

Reference intervals for procalcitonin and C-reactive protein after major abdominal surgery

Procalcitonin (PCT). a new marker proposed as a diagnostic tool for bacterial infections, triggers a systemic-inflammatory reaction in the body (sepsis, septic shock) and has potential use in a wide range of patient settings. To interpret the results from PCT measurements, we depend on reference intervals established from relevant populations. PCT and C-reactive protein (CRP) concentrations were analysed in 47 patients with a normal postoperative course after major abdominal surgery. The mean concentration of PCT declines from the first day and reaches half its initial values on the second day after the operation. whereas the mean concentration of CRP increases in the first 48 h and reaches half its maximum value on the fifth day after the operation. We present a continuous reference interval for plasma PCT and CRP concentrations in the first week following major abdominal surgery. For PCT we also present a graphic display of expected mean and expected upper reference limits predicted from the value measured on the first postoperative day.     

Increased spinal N-methyl-D-aspartate receptor function after 20 h of carrageenan-induced inflammation

Spinal N-methyl-D-aspartate (NMDA) receptors are thought to be important in states of central hyperexcitability induced by e.g. inflammation or painful neuropathies. The carrageenan model of inflammatory pain has been and still is widely used as is the NMDA receptor antagonist 2-amino-5-phosphonopentanoic acid (AP5) to investigate NMDA receptor function. Here we present two novel findings using electrophysiological technique: the NMDA receptor function in the spinal cord is increased following 20 h of carrageenan-induced inflammation and further that only the D-isomer of AP5 is active in the spinal cord. Exogenous NMDA (0.5 and 5 nmol) applied onto the dorsal spinal cord produced a significantly greater facilitation and D-AP5 (1.25 micromol) a significantly greater inhibition of the C-fibre evoked response of the wide dynamic range (WDR) neurones studied in carrageenan (20 h after injection) compared to control rats. The present and two recent studies suggest central changes are different and possibly greater in the later (20 h) compared to the earlier (2-6 h) phase of carrageenan-induced inflammation. In conclusion, 20 h of carrageenan-induced inflammation increases the function of spinal NMDA receptor involved in nociceptive transmission and in addition the D-isomer of AP5 should be used when NMDA receptor antagonism is wanted in the spinal cord.     

Early changes in left ventricular volume and function are predictors for long-term remodeling in patients with acute transmural myocardial infarction and preserved systolic function.

BACKGROUND: We sought to describe the degree of long-term left ventricular (LV) remodeling after acute transmural myocardial infarction with preserved LV systolic function, and to evaluate whether Doppler echocardiographic parameters in the early phase could predict this process. METHODS: A total of 60 patients without heart failure and with LV ejection fraction > or = 0.40 (mean 0.48 +/- 0.054), were followed up with Doppler echocardiographic examinations at baseline, 3 months, and 1 and 2 years. RESULTS: There was a significant increase in LV end-diastolic volume index of 7% (P =.006) and LV end-systolic volume index of 8% (P =.03), and no change in ejection fraction. This remodeling was confined to 7 patients (12%) with a significant increase in LV end-diastolic volume index above 20 mL/m(2). There was also a significant increase in the deceleration time of both the early mitral filling wave (Delta early mitral filling wave = 58 milliseconds, P <.0005) and the diastolic forward component of pulmonary venous flow (Delta diastolic forward component of pulmonary venous flow = 61 milliseconds, P <.0005), and a shift in filling pattern with increasing prevalence of abnormal relaxation. Changes in end-diastolic volume index were predicted by baseline early mitral filling wave less than 100 milliseconds, but the most powerful predictors of 2-year remodeling were volume changes at 3 months. CONCLUSION: Twelve percent of patients with Q-wave infarction and ejection fraction > or = 0.40 experienced significant LV dilatation at 2 years, and this late remodeling was partly related to baseline filling characteristics.     

Alfentanil increases cortical dopamine D2/D3 receptor binding in healthy subjects

Animal studies have shown that opioids modulate the function of dopaminergic neurons. The effect of alfentanil on cortical and thalamic binding of the D2/D3 receptor ligand [(11)C]FLB 457 was evaluated in eight healthy subjects with positron emission tomography. The simplified reference tissue model was used to calculate tracer binding potential (BP) during a baseline condition and target-controlled infusion of alfentanil, and the results were analyzed using a comparison group not receiving opioid. Behavioral and analgesic effects of alfentanil were also evaluated. In the region-of-interest analysis, alfentanil increased the BP of [(11)C]FLB 457 in the medial frontal cortex (P=0.0027), dorsolateral prefrontal cortex (P=0.027) superior temporal cortex (P=0.028), and medial thalamus (P=0.003) These results were confirmed in a voxel-based analysis, which further revealed an opioid-induced increase in [(11)C]FLB 457 BP in the anterior cingulate cortex (P<0.001). Alfentanil induced euphoria (P=0.003) and analgesia (P=0.006) Cheerfulness (r=0.918, P=0.001) and euphoria (r=0.982, P<0.001) were associated with increased BP of [(11)C]FLB 457 in the left posterior cingulate cortex, but the analgesic effect of alfentanil did not correlate with changes in [(11)C]FLB 457 BP. The results of this study demonstrate opioid-dopamine interactions in frontal and temporal cortical regions and the thalamus in healthy subjects. Increased D2/D3 tracer binding during opioid infusion may reflect decreased synaptic dopamine levels. The association of the uplifting effect of alfentanil with increased D2/D3 binding in the posterior cingulate cortex suggests that cortical dopamine may be involved in the behavioral effects of opioids.     

Impact of job adjustment,pain location and exercise on sick leave due to lumbopelvic pain in pregnancy: a longitudinal study

Objective: To identify factors associated with sick leave due to lumbopelvic pain (LPP) in pregnancy.

Design: Prospective cohort study using participants from a randomized controlled trial (RCT) designed to study the effect of exercise during pregnancy on pregnancy related diseases.

Setting: St. Olavs Hospital, Trondheim University Hospital and Stavanger University Hospital, April 2007 to December 2009.

Subjects: Healthy pregnant women.

Main outcome measures: Self-reported sick leave due to LPP in late pregnancy (gestation week 32–36).

Results: In total, 532/716 (74%) women reported LPP at 32–36 weeks of pregnancy, and 197/716 (28%) reported sick leave due to LPP. Not receiving job adjustments when needed (Odds ratio, OR with 95% confidence interval, CI, was 3.0 (1.7–5.4)) and having any pain in the pelvic girdle versus no pain (OR 2.7 (1.3–5.6), OR 2.7 (1.4–5.2) and OR 2.2 (1.04–4.8)) for anterior, posterior and combined anterior and posterior pain in the pelvis respectively, were associated with sick leave due to LPP in late pregnancy. Also higher disability, sick listed due to LPP at inclusion and lower education, were significant explanatory variables. There was a trend of reduced risk for sick leave due to LPP when allocated to the exercise group in the original RCT (OR 0.7 (0.4–1.0)).

Conclusion: Facilitating job adjustments when required might keep more pregnant women in employment. Furthermore, pain locations in pelvic area, disability, lower education and being sick listed due to LPP in mid pregnancy are important risk factors for sick leave in late pregnancy.

• Key points

• Current awareness:

• More than half of pregnant women are on sick leave during pregnancy and the most frequently reported cause is lumbopelvic pain.

• This paper adds:

  • Inability to make job adjustments, pain locations in pelvic area, disability and lower education level were the most important risk factors for sick leave in late pregnancy. Facilitating early job adjustment might be a precaution to keep more pregnant women in work. Allocation to an exercise group tended to reduce the risk of sick leave in late pregnancy.Registration number: Clinical trial gov (NCT 00476567).

     

Multivariate analysis of cytokine profiles in pregnancy complications

Problem

The immunoregulation to tolerate the semiallogeneic fetus during pregnancy includes a harmonious dynamic balance between anti‐ and pro‐inflammatory cytokines. Several earlier studies reported significantly different levels and/or ratios of several cytokines in complicated pregnancy as compared to normal pregnancy. However, as cytokines operate in networks with potentially complex interactions, it is also interesting to compare groups with multi‐cytokine data sets, with multivariate analysis. Such analysis will further examine how great the differences are, and which cytokines are more different than others.

Methods

Various multivariate statistical tools, such as Cramer test, classification and regression trees, partial least squares regression figures, 2‐dimensional Kolmogorov‐Smirmov test, principal component analysis and gap statistic, were used to compare cytokine data of normal vs anomalous groups of different pregnancy complications.

Results

Multivariate analysis assisted in examining if the groups were different, how strongly they differed, in what ways they differed and further reported evidence for subgroups in 1 group (pregnancy‐induced hypertension), possibly indicating multiple causes for the complication.

Conclusion

This work contributes to a better understanding of cytokines interaction and may have important implications on targeting cytokine balance modulation or design of future medications or interventions that best direct management or prevention from an immunological approach.