NK3 receptors mediate an increase in firing rate of midbrain dopamine neurons of the rat and the guinea pig

This in vitro study investigates and compares the effects of NK3 receptor ligands on the firing rate of rat and guinea pig midbrain dopamine neurons. The findings are discussed in the light of choosing suitable animal models for investigating pharmacological properties of NK3 receptor antagonists, which have been proposed to possess therapeutic activity in neuropsychiatric diseases like e.g. schizophrenia. In vitro midbrain slice preparations of both species were used to record (extracellularly) the firing rates of dopamine neurons located in the substantia nigra (SN) and ventral tegmental area (VTA). Furthermore, the effect of the D2 receptor agonist quinpirole on guinea pig SN and VTA dopamine neurons was investigated. The efficacy of quinpirole in inhibiting guinea pig dopamine neuron firing activity was much less as compared to that of rat dopamine neurons, suggesting a lower dopamine D2 autoreceptor density on the guinea pig neurons. The NK3 receptor agonist senktide induced in subpopulations of rat SN (55%) and VTA (79%) and guinea pig SN (50%) and VTA (21%) dopamine neurons an increase in firing rate. In responsive neurons this effect was concentration‐dependent with EC₅₀ values of 3–5 nM (for both species). The selective NK3 receptor antagonist osanetant (100 nM) was able to partly block the senktide‐induced increase in firing rates of dopamine neurons and shifted the concentration‐response relation curves for senktide to the right (pA₂ values were ～7.5). The fractional block of the senktide responses by osanetant appeared to be larger in guinea pig dopamine neurons, indicating that osanetant is a more potent blocker of NK3 receptor‐mediated responses with noncompetitive properties in the guinea pig. Synapse 2011. © 2011 Wiley‐Liss, Inc.     

Imaging of the Subthalamic Nucleus for Deep Brain Stimulation: A Systematic Review

It is still debated which neuroimaging technique should be preferred in targeting the subthalamic nucleus (STN) for implantation of stimulating electrodes. In the present study, we systematically analyzed the different imaging techniques and their outcome in reports describing original data on bilateral STN stimulation in advanced Parkinson's disease. Five different imaging techniques to target the STN for implantation of stimulating electrodes were reported: magnetic resonance imaging (MRI), MRI in combination with ventriculography, MRI in combination with computed tomography (CT), CT, and CT in combination with ventriculography. We found that patients who underwent STN deep brain stimulation with MRI (regardless the use of an additional imaging technique) had a significantly better Unified Parkinson's Disease Rating Scale motor score (mean improvement 58%) as compared to patients who underwent STN deep brain stimulation with CT imaging (regardless the use of an additional imaging technique; mean improvement 47%).     

Calcifying tendinitis of the shoulder: Advances in imaging and management

Calcifying tendonitis of the shoulder is a common, acute or chronic, painful disorder characterized by calcifications in the rotator cuff tendons. A natural cycle exists during which the tendon repairs itself. In chronic calcific tendonitis, however, this cycle is blocked at one of the healing stages. Because chronic presentation with exacerbations is usual, initial treatment should be conservative, including rest, physical therapy, nonsteroidal anti-inflammatory drugs, and, in later stages, subacromial infiltration with corticosteroids. Surgery is recommended when conservative treatment fails. This article discusses advances in imaging and medical, physical, and surgical management, as well as current evidence for the treatment of calcifying tendonitis of the shoulder.     

The Hospital Trauma Index Impact of Equal Injury Severity Grades in Different Organ Systems

Background and Purpose:   

The Injury Severity Score (ISS) is a widely used trauma scoring system which, based on the Hospital Trauma Index (HTI), categorizes injury into six different organ systems. A possible limitation is the equal weight given to each body region, although this equal qualification is not appropriate when predicting mortality. This study was undertaken to determine the impact on mortality of equal injury severity in different body regions.     

The "Oxford Heup Score": the translation and validation of a questionnaire into Dutch to evaluate the results of total hip arthroplasty

BACKGROUND: The evaluation of a total hip prosthesis would be most complete if the opinion of the patient, surgeon and the radiographs are combined. Disease specific patient outcome questionnaires are scarce, especially in Dutch. METHODS: The disease-specific 12-item questionnaire on the perception of patients with total hip replacement was translated into Dutch. We also investigated the extra value of two specific hip items, "the need for walking aids" and "sexual problems because of the hip", four general items on overall satisfaction and one question about patient classification. The 14 hip-specific items were each scored from 1 (least difficulties) to 5 (most difficulties). The Dutch translation, the "Oxford Heup Score" (OHS) was tested on psychometric quality in a multicenter prospective study. RESULTS: The psychometric results of the OHS proved to be adequate. In the first postoperative year the score was very sensitive to changes, whereas in the second year it did not change significantly. The two added hip-specific questions were both filled out positively by more than 50% of the patients and thus fit perfectly into a hip-specific patient outcome questionnaire such as the OHS. INTERPRETATION: The OHS proves to be an appropriate instrument for assessment of the outcome of total hip replacement from the patient's perspective. Together with the judgement of the surgeon, it provides useful insights into the question of whether this operation has been a success or not.     

Unsatisfactory results with the cementless Omnifit acetabular component due to polyethylene and severe osteolysis

A high incidence of acetabular osteolysis (43%), associated with osteolytic lesions in the proximal femur (22.6%) and leading to a high revision rate, was experienced with the Omnifit total hip prosthesis. We reviewed the clinical and radiological results with 429 Omnifit total hips in 356 patients after a mean follow-up of 60 months. Time to revision and wear of the polyethylene liner with different acetabular shell types were specifically analysed. Pelvic osteolysis first became manifest in the acetabular bone opposite to the holes in the metal shell. Osteolysis occurred predominantly adjacent to the central hole in the metal shell of threaded cups; widespread and larger defects were found in press fit cups with peripheral screw holes. Kaplan Meier survival analysis demonstrated a higher probability for retaining the threaded cup at 6 years (96%; 95%-confidence interval: 93-99%) compared to the survival of the press fit cup (66%; 95%-CI: 56-77%). The results suggest a negative relationship between backside wear, the larger number of holes in the cup, the extent of osteolysis and survival rate of the press fit cups. Based on these findings and supported by similar reports about osteolysis related to the same cup design, it was hypothesised that backside wear due to the insufficient locking mechanism of the Omnifit acetabular cup was the major cause of the unsatisfactory results in our patients. For this reason we discontinued using this type of uncemented socket.     

The skin in primary immunodeficiency disorders

Primary immunodeficiency disorders comprise serious and rare diseases, predominantly in children. The skin may be involved in a primary immunodeficiency and the cutaneous alterations such as infections, eczematous dermatitis, erythroderma, autoimmune dermatoses and vasculitis may be the basis for the ultimate diagnosis. Dermatologists may realize something is wrong with the immunity of their patient and prompt diagnosis of the defect can lead to lifesaving treatment. Since atypical presentations of well known dermatoses are common in immunodeficiency disorders, histopathology and bacterial, fungal or viral tests of the skin lesions are often indispensable. The knowledge of skin findings in primary immunodeficiency diseases may help dermatologists to play a role in the early detection of these diseases. Key findings constitute specific skin symptoms combined with unusual or severe infections.     

Characterization of the effects of reuptake and hydrolysis inhibition on interstitial endocannabinoid levels in the brain: an in vivo microdialysis study

The present experiments employed in vivo microdialysis to characterize the effects of commonly used endocannabinoid clearance inhibitors on basal and depolarization-induced alterations in interstitial endocannabinoid levels in the nucleus accumbens of rat brain. Compounds targeting the putative endocannabinoid transporter and hydrolytic enzymes (FAAH and MAGL) were compared. The transporter inhibitor AM404 modestly enhanced depolarization-induced increases in 2-arachidonoyl glycerol (2-AG) levels but did not alter levels of N-arachidonoyl-ethanolamide (anandamide, AEA). The transport inhibitor UCM707 did not alter dialysate levels of either endocannabinoid. The FAAH inhibitors URB597 and PF-3845 robustly increased AEA levels during depolarization without altering 2-AG levels. The MAGL inhibitor URB602 significantly enhanced depolarization-induced increases in 2-AG, but did not alter AEA levels. In contrast, the MAGL inhibitor JZL184 did not alter 2-AG or AEA levels under any condition tested. Finally, the dual FAAH/MAGL inhibitor JZL195 significantly enhanced depolarization-induced increases in both AEA and 2-AG levels. In contrast to the present observations in rats, prior work in mice has demonstrated a robust JZL184-induced enhancement of depolarization-induced increases in dialysate 2-AG. Thus, to further investigate species differences, additional tests with JZL184, PF-3845, and JZL195 were performed in mice. Consistent with prior reports, JZL184 significantly enhanced depolarization-induced increases in 2-AG without altering AEA levels. PF-3845 and JZL195 produced profiles in mouse dialysates comparable to those observed in rats. These findings confirm that interstitial endocannabinoid levels in the brain can be selectively manipulated by endocannabinoid clearance inhibitors. While PF-3845 and JZL195 produce similar effects in both rats and mice, substantial species differences in JZL184 efficacy are evident, which is consistent with previous studies.