Alteration in the response properties of primary somatosensory cortex related to differential aversive Pavlovian conditioning

The effects of differential aversive Pavlovian conditioning on the functional organization of primary somatosensory cortex (SI) were examined in 17 healthy participants. Neuroelectric source imaging from 60 electrodes was employed while nine subjects received an innocuous electric stimulus (conditioned stimulus, CS) to one finger (left or right) that was followed by painful electric shock to the lower back (unconditioned stimulus, US) and an innocuous stimulus to the other finger that was never followed by pain. Eight subjects received a presentation of the innocuous and painful stimuli with equal probability to both fingers (control group). The data included the electromyogram (EMG) from the left m. corrugator, and judgments of intensity, aversiveness, and CS-US contingency. Only the experimental group displayed EMG conditioning, differential contingency judgments, as well as a change of dipole orientation for the CS and an enhanced dipole moment for the US in the electroencephalogram. Intensity and unpleasantness ratings were altered in a more unspecific manner and did not differ between groups and stimulus conditions. The data suggest that SI contributes to memory processes in associative learning. Pavlovian conditioning of tactile responses might be important in the altered processing of painful stimuli in chronic pain patients where enhanced conditioning has been demonstrated.     

EAU Guidelines on Urethral Trauma

Context

These guidelines were prepared on behalf of the European Association of Urology (EAU) to assist urologists in the management of traumatic urethral injuries.

Objective

To determine the optimal evaluation and management of urethral injuries by review of the world's literature on the subject.

Evidence acquisition

A working group of experts on Urological Trauma was convened to review and summarize the literature concerning the diagnosis and treatment of genitourinary trauma, including urethral trauma. The Urological Trauma guidelines have been based on a review of the literature identified using on-line searches of MEDLINE and other source documents published before 2009. A critical assessment of the findings was made, not involving a formal appraisal of the data. There were few high-powered, randomized, controlled trials in this area and considerable available data was provided by retrospective studies. The Working Group recognizes this limitation.

Evidence synthesis

The full text of these guidelines is available through the EAU Central Office and the EAU website (www.uroweb.org). This article comprises the abridged version of a section of the Urological Trauma guidelines.

Conclusions

Updated and critically reviewed Guidelines on Urethral Trauma are presented. The aim of these guidelines is to provide support to the practicing urologist since urethral injuries carry substantial morbidity. The diversity of urethral injuries, associated injuries, the timing and availability of treatment options as well as their relative rarity contribute to the controversies in the management of urethral trauma.     

Force Majeure: Therapeutic measures in response to restricted supply of imiglucerase (Cerezyme) for patients with Gaucher disease

Gaucher disease is the first lysosomal disorder for which clinically effective enzyme replacement therapy has been introduced. Lifelong treatment with imiglucerase, the recombinant glucocerebrosidase manufactured by the Genzyme Corporation (MA, USA), is administered intravenously — usually at biweekly intervals. An acute shortage of imiglucerase (to 20% of prior global supply) has occurred as a result of viral contamination of the production facility; production was halted, and a full supply of imiglucerase is not anticipated until January 2010. An urgent meeting of physicians, researchers, and patients was convened through the agency of the European Working Group for Gaucher Disease; this was instigated by patients internationally represented by the European Gaucher Alliance. Here we present a position statement based on the findings of the group, with key recommendations about identification and monitoring of at-risk patients threatened by the abrupt withdrawal of treatment, the equitable distribution of residual imiglucerase — and access to alternative treatments including those that have completed phase III clinical trials but have not yet been licensed.     

Insulinotropic activity of chromonyl-2,4-thiazolidinediones

Numerous compounds have been prepared in order to improve the pharmacological profile of insulinotropic activities. In the present paper, series of chromonyl-2,4-thiazolidinediones (Ia–e, IIa–e, and IIIa–e) were tested for their insulinotropic activities in INS-1 cells. Compounds IIb–d and IIId were very active even at a low concentration of 0.001 mg/ml. Compounds IIIa–c were active only at higher concentration (0.01 mg/ml). Increase of insulin release was observed in the presence of 5.6 mmol/l glucose.     

Distribution and characterization of estrogen receptor G protein-coupled receptor 30 in the rat central nervous system

The G protein-coupled receptor 30 (GPR 30) has been identified as the non-genomic estrogen receptor, and G-1, the specific ligand for GPR30. With the use of a polyclonal antiserum directed against the human C-terminus of GPR30, immunohistochemical studies revealed GPR30-immunoreactivity (irGPR30) in the brain of adult male and non-pregnant female rats. A high density of irGPR30 was noted in the Islands of Calleja and striatum. In the hypothalamus, irGPR30 was detected in the paraventricular nucleus and supraoptic nucleus. The anterior and posterior pituitary contained numerous irGPR30 cells and terminal-like endings. Cells in the hippocampal formation as well as the substantia nigra were irGPR30. In the brainstem, irGPR30 cells were noted in the area postrema, nucleus of the solitary tract, and dorsal motor nucleus of the vagus; a cluster of cells were prominently labeled in the nucleus ambiguus. Tissue sections processed with pre-immune serum showed no irGPR30, affirming the specificity of the antiserum. G-1 (100 nM) caused a large increase of intracellular calcium concentrations [Ca(2+) ](i) in dissociated and cultured rat hypothalamic neurons, as assessed by microfluorometric Fura-2 imaging. The calcium response to a second application of G-1 showed a marked homologous desensitization. Our result shows a high expression of irGPR30 in the hypothalamic-pituitary axis, hippocampal formation, and brainstem autonomic nuclei; and the activation of GPR30 by G-1 is associated with a mobilization of calcium in dissociated and cultured rat hypothalamic neurons.     

Decision making in ambiguous and risky situations after unilateral temporal lobe epilepsy surgery

Decision making is essential in everyday life. Though the importance of the mesial temporal structures in emotional processing and feedback learning is well established, decision making in patients after mesial temporal lobe surgery has rarely been studied. We studied 23 patients with mesial temporal lobe epilepsy after unilateral temporal lobe surgery and 26 healthy controls using two different gambling tasks, the Iowa Gambling Task (IGT) and the Probability-Associated Gambling (PAG) task. In the IGT, rules for gains and losses are implicit; in the PAG task, winning probabilities are well defined. Compared with healthy controls, patients performed poorly on the IGT (decisions under ambiguity). No group difference was found in the PAG task (decisions under risk). Results of the present investigation indicate that after mesial temporal lobe surgery, patients have difficulties in making decisions under ambiguity, whereas they decide advantageously when information about the decision situation is explicitly given.     

Preclinical anti‐myeloma activity of the novel HDAC‐inhibitor JNJ‐26481585

Pharmacological inhibitors of histone deacetylases (HDACs) are currently being developed and tested as anti‐cancer agents and may be useful to enhance the therapeutic efficiency of established anti‐myeloma treatments. This study preclinically evaluated the effects of the ‘second generation’ pan‐HDAC inhibitor JNJ‐26481585 on human multiple myeloma (MM) cells from established cell lines and primary MM samples (n = 42). Molecular responses in both groups of MM cells included histone acetylation, a shift in Bcl2‐family members towards proapoptotic bias, attenuation of growth and survival pathway activity and Hsp72 induction. Mcl‐1 depletion and Hsp72 induction were the most reliable features observed in JNJ‐26481585‐treated primary MM samples. The drug alone effectively induced myeloma cell death at low nanomolar concentrations. In vitro combination of JNJ‐26481585 with anti‐myeloma therapeutic agents generally resulted In effects close to additivity. In view of the favourable activity of this novel HDAC‐inhibitor towards primary myeloma cells further evaluation in a clinical setting is warranted.     

Venoplasty of innominate bridge during implantation of single-chamber ICD in a patient with a persistent left-sided superior vena cava

The persistent left-sided superior vena cava (PLSVC) is a common congenital abnormality, occurring in approximately 1% of patients. The presence of a PLSVC can complicate the implantation of a pacemaker or an automatic implantable cardioverter-defibrillator (AICD). In this case, we report a procedure, venoplasty of an innominate branch, to facilitate implantation of a right ventricular lead in a single-chamber AICD. This approach could potentially reduce procedure and fluoroscopy time in other similar cases.