Causality between local field potentials of the subthalamic nucleus and electromyograms of forearm muscles in Parkinson’s disease

Deep brain stimulation of the subthalamic nucleus is an effective treatment for Parkinson’s disease, although its precise mechanisms remain poorly understood. To gain further insight into the mechanisms underlying deep brain stimulation, we analysed the causal relationship between forearm muscle activity and local field potentials derived from the subthalamic nucleus. In 19 patients suffering from Parkinson’s disease of the akinetic‐rigid subtype, we calculated the squared partial directed coherence between muscles of the contralateral forearm and the subthalamic nucleus or zona incerta during both a rest and a hold condition of the arm. For both recording regions, data analysis revealed that, during the rest condition, electromyographic activity was significantly more often ‘Granger‐causal’ for the local field potentials than the opposite causation. In contrast, during the hold condition, no significant difference was found in the occurrence of causalities. Contrary to the existing basal ganglia model and the current concept of Parkinson’s disease pathophysiology, we found the subthalamic nucleus to receive more ‘afferences’ than it emitted ‘efferences’, suggesting that its role is more complex than a simple driving nucleus in the basal ganglia loop. Therefore, the effect of deep brain stimulation in the subthalamic nucleus could, at least in part, result from a blockade of pathological afferent input.     

Modified Trochanteric Slide for Complex Hip Arthroplasty : Clinical Outcomes and Complication Rates

The sliding trochanteric osteotomy preserves vastus lateralis continuity with the osteotomized greater trochanter (GT) and the abductors. The modified trochanteric sliding osteotomy (MTSO) also preserves the posterior capsule and external rotators to reduce the risk of dislocations. The purpose of this study was to evaluate our clinical and radiographic results of the MTSO exposure. Eighty-three MTSOs were reviewed. Follow-up range was 12 to 126 months. Seventy osteotomies (84.4%) healed with bony union, 9 (10.8%) had fibrous union, and 4 (4.8%) had nonunion. There was no correlation between the width of the osteotomy, intraoperative fragmentation of the GT, or the type of femoral component and the rate of union. Six (7.2%) patients developed a new abductor lurch. Patients with union of the GT had 2.8% of a lurch, and patients with either fibrous union or nonunion had a 30.7% of a lurch (P < .05). There were 4 (4.8%) postoperative dislocations. The benefits of MTSO have been well described, and this study provides evidence of an acceptably low complication rate.     

Chronic kidney disease aggravates arteriovenous fistula damage in rats

Neointimal hyperplasia (NIH) and impaired dilatation are important contributors to arteriovenous fistula (AVF) failure. It is unclear whether chronic kidney disease (CKD) itself causes adverse remodeling in arterialized veins. Here we determined if CKD specifically triggers adverse effects on vascular remodeling and assessed whether these changes affect the function of AVFs. For this purpose, we used rats on a normal diet or on an adenine-rich diet to induce CKD and created a fistula between the right femoral artery and vein. Fistula maturation was followed noninvasively by high-resolution ultrasound (US), and groups of rats were killed on 42 and 84 days after surgery for histological and immunohistochemical analyses of the AVFs and contralateral femoral vessels. In vivo US and ex vivo morphometric analyses confirmed a significant increase in NIH in the AVFs of both groups with CKD compared to those receiving a normal diet. Furthermore, we found using histological evaluation of the fistula veins in the rats with CKD that the media shrank and their calcification increased significantly. Afferent artery dilatation was significantly impaired in CKD and the downstream fistula vein had delayed dilation after surgery. These changes were accompanied by significantly increased peak systolic velocity at the site of the anastomosis, implying stenosis. Thus, CKD triggers adverse effects on vascular remodeling in AVFs, all of which contribute to anatomical and/or functional stenosis.     

Immediate recovery room radiographs after primary total knee arthroplasty—why do we keep doing them?

Recovery room radiographs (RRR) are routinely performed after total knee arthroplasty (TKA). This study investigates the utility of these radiographs. Twenty four arthroplasty surgeons were surveyed to rank the value of RRRs. Since RRRs were primarily valued for educational purposes, we examined the ability of 49 orthopaedic trainees to determine the coronal alignment of TKA performed in cadaveric specimens based on these radiographs in neutral, 10° internal and external rotations. Surgeons rated the quality of the RRRs to be significantly lower than the radiographs taken in the radiology suite (5.5 ± 2.5 versus 8.9 ± 0.9, p < 0.0001). Of an estimated 65,910 TKAs performed by these surgeons, only eight cases (0.01%) required same day revision based on the RRR. Neutral alignment was significantly more accurately (p < 0.0001) interpreted than valgus or varus (69.4% versus 42.9% and 16.3%, respectively). Surprisingly, internal rotation of the limb significantly improved interpretation of both varus (from 16.3% to 40.8%, p = 0.014) and valgus (from 42.9% to 63.3%, p = 0.048). Increased level of orthopaedic training did not significantly affect the accuracy of interpretation (p = 0.46). Interpretation of RRRs for coronal malalignment is inaccurate and has a limited educational value.     

Combined lung-sound and reflux-monitoring: a pilot study of a novel approach to detect nocturnal respiratory symptoms in gastro-oesophageal reflux disease

Aliment Pharmacol Ther 2011; 33: 592–600

Summary

Background Increased prevalence of respiratory symptoms has been commonly reported in patients with gastro‐oesophageal reflux disease (GERD). Aim To introduce a novel Lung‐Sound‐Monitoring device that allows simultaneous measurement of both nocturnal respiratory symptoms and episodes of acidic and biliary refluxes. Methods Nocturnal respiratory symptoms (coughing and wheezing) were continuously recorded in 20 healthy subjects and 30 reflux patients with respiratory symptoms in parallel to combined pH‐monitoring and Bilitec measurement. Results Analysis could be completed in 20 healthy subjects and in 25 patients with reflux. A clear temporal correlation to reflux phases was detected in 49% of coughing and 41% of wheezing events, respectively. Moreover, 89% of the coughing and 100% of the wheezing events succeeded reflux episodes. Finally, the technique was capable of assessing a statistically significant difference between patients and controls regarding the occurrence of these symptoms. Conclusions Our pilot study establishes the Lung‐Sound‐Monitoring system as a unique tool to measure objectively the temporal correlation between gastroesophageal reflux and the appearance of respiratory symptoms. It represents a useful technique to identify patients with respiratory symptoms due to reflux, and therefore allows one to determine and quantify the impact of therapeutic interventions such as antireflux therapy on respiratory symptoms.     

Nasal epithelial lesions in F344 rats following a 90-day inhalation exposure to naphthalene

Naphthalene (NA) was shown to be carcinogenic, causing respiratory epithelial adenoma in the nasal cavity of male F344 rats and olfactory epithelial neuroblastoma in female F344 rats at exposure concentrations of 10-60?ppm in a 2-year inhalation study conducted by the National Toxicology Program. To explore the exposure-response relationship and threshold for nasal epithelial effects in F344 rats, a 90-day (6?h/d, 5?d/wk) inhalation study was conducted at 0, 0.1, 1, 10 and 30?ppm NA vapor. Group size for nasal cavity histopathology was 10/sex with an additional 10/sex evaluated 4?wk post-exposure. NA exposure concentrations were measured by GC/MS, and aerosol testing verified that solid NA particles were not present. There were no NA exposure-related clinical observations and mild decreases in body weight (<10%) and food/water consumption were observed primarily in the 30?ppm rats. Rat heads were cross-sectioned at six levels for microscopic examination. There were no nasal cavity lesions related to NA exposure in rats of the 0.1?ppm group. Minimal hyperplasia was observed in the transitional/respiratory epithelium of rats exposed to 1?ppm. Mild hyperplasia and minimal squamous metaplasia were observed in the respiratory epithelium of rats exposed to 10 or 30?ppm. Lesions in the olfactory epithelium were observed only in rats of the 10 or 30?ppm groups and consisted of degeneration, necrosis, areas of re-epithelialization and basal cell hyperplasia. There was remarkable recovery of effects after 4 weeks, but residual olfactory epithelial degeneration and basal cell hyperplasia were still evident.     

The inflammasome: an integrated view

An inflammasome is a multiprotein complex that serves as a platform for caspase-1 activation and caspase-1-dependent proteolytic maturation and secretion of interleukin-1β (IL-1β). Though a number of inflammasomes have been described, the NLRP3 inflammasome is the most extensively studied but also the most elusive. It is unique in that it responds to numerous physically and chemically diverse stimuli. The potent proinflammatory and pyrogenic activities of IL-1β necessitate that inflammasome activity is tightly controlled. To this end, a priming step is first required to induce the expression of both NLRP3 and proIL-1β. This event renders the cell competent for NLRP3 inflammasome activation and IL-1β secretion, and it is highly regulated by negative feedback loops. Despite the wide array of NLRP3 activators, the actual triggering of NLRP3 is controlled by integration a comparatively small number of signals that are common to nearly all activators. Minimally, these include potassium efflux, elevated levels of reactive oxygen species (ROS), and, for certain activators, lysosomal destabilization. Further investigation of how these and potentially other as yet uncharacterized signals are integrated by the NLRP3 inflammasome and the relevance of these biochemical events in vivo should provide new insight into the mechanisms of host defense and autoinflammatory conditions.     

Spinophilin is required for normal morphology, Ca2+ homeostasis and contraction but dispensable for ��-adrenergic stimulation of adult cardiomyocytes

Spinophilin (SPN) is a ubiquitously expressed scaffolding protein that interacts through several binding modules with a variety of target proteins. Thus, SPN bundles F-actin, targets protein phosphatase 1 to the ryanodine receptor, and targets regulators of G-protein signaling to G-protein coupled receptors in cardiomyocytes. In this work we studied the role of SPN on cardiomyocyte morphology, function, and β-adrenergic responsiveness using a homozygous SPN knock-out mouse model (SPN-/-). We show that spinophilin deficiency significantly (1) reduced cardiomyocyte length, (2) increases both Ca(2+) amplitude and maximal rate of Ca(2+) rise during systole, and (3) decreased shortening amplitude and maximal rate of shortening, while (4) β-adrenergic stimulation remained intact. Our data suggest that spinophilin is an upstream regulator required for normal growth and excitation-contraction coupling, but is dispensable for β-adrenergic stimulation of adult cardiomyocytes.     

Beneficial effects of cannabinoids (CB) in a murine model of allergen-induced airway inflammation: role of CB1/CB2 receptors

The endocannabinoid system (ECS) consists of two cannabinoid (CB) receptors, namely CB₁ and CB₂ receptor, and their endogenous (endocannabinoids) and exogenous (cannabinoids, e.g. delta-9-tetrahydrocannabinol (THC)) ligands which bind to these receptors. Based on studies suggesting a role of THC and the ECS in inflammation, the objective of this study was to examine their involvement in type I hypersensitivity using a murine model of allergic airway inflammation. THC treatment of C57BL/6 wildtype mice dramatically reduced airway inflammation as determined by significantly reduced total cell counts in bronchoalveolar lavage (BAL). These effects were greatest when mice were treated during both, the sensitization and the challenge phase. Furthermore, systemic immune responses were significantly suppressed in mice which received THC during sensitization phase. To investigate a role of CB_1/2 receptors in this setting, we used pharmacological blockade of CB₁ and/or CB₂ receptors by the selective antagonists and moreover CB₁/CB₂ receptor double-knockout mice (CB₁^−/−/CB₂^−/−) and found neither significant changes in the cell patterns in BAL nor in immunoglobulin levels as compared to wildtype mice. Our results indicate that the activation of the ECS by applying the agonist THC is involved in the development of type I allergies. However, CB₁/CB₂ receptor-independent signalling seems likely in the observed results.