Innervation of the brain,intracerebral Schwann cells and intracerebral and intraventricular schwannomas

The cerebral vasculature and the choroid plexus are innervated by peripheral nerves. The anatomy of the vascular supply to the brain and its related perivascular nerves is reviewed. Intracerebral and intraventricular schwannomas most likely come from neoplastic transformation of Schwann cells investing the perivascular nerves and nerves within the choroid plexus.     

A new mutation in GJC2 associated with subclinical leukodystrophy

Recessive mutations in GJC2, the gene-encoding connexin 47 (Cx47), cause Pelizaeus–Merzbacher-like disease type 1, a severe dysmyelinating disorder. One recessive mutation (p.Ile33Met) has been associated with a much milder phenotype––hereditary spastic paraplegia type 44. Here, we present evidence that a novel Arg98Leu mutation causes an even milder phenotype––a subclinical leukodystrophy. The Arg98Leu mutant forms gap junction plaques in HeLa cells comparable to wild-type Cx47, but electrical coupling was 20-fold lower in cell pairs expressing Arg98Leu than for cell pairs expressing wild-type Cx47. On the other hand, coupling between Cx47Arg98Leu and Cx43WT expressing cells did not show such reductions. Single channel conductance and normalized steady-state junctional conductance–junctional voltage (G _j–V _j) relations differed only slightly from those for wild-type Cx47. Our data suggest that the minimal phenotype in this patient results from a reduced efficiency of opening of Cx47 channels between oligodendrocyte and oligodendrocyte with preserved coupling between oligodendrocyte and astrocyte, and support a partial loss of function model for the mild Cx47 associated disease phenotypes.     

PTSD Symptoms and Pain in Canadian Military Veterans: The Mediating Roles of Anxiety,Depression, and Alcohol Use

Symptoms of posttraumatic stress disorder (PTSD) and pain are often comorbid among veterans. The purpose of this study was to investigate to what extent symptoms of anxiety, depression, and alcohol use mediated the relationship between PTSD symptoms and pain among 113 treated male Canadian veterans. Measures of PTSD, pain, anxiety symptoms, depression symptoms, and alcohol use were collected as part of the initial assessment. The bootstrapped resampling analyses were consistent with the hypothesis of mediation for anxiety and depression, but not alcohol use. The confidence intervals did not include zero and the indirect effect of PTSD on pain through anxiety was .04, CI [.03, .07]. The indirect effect of PTSD on pain through depression was .04, CI [.02, .07]. These findings suggest that PTSD and pain symptoms among veterans may be related through the underlying symptoms of anxiety and depression, thus emphasizing the importance of targeting anxiety and depression symptoms when treating comorbid PTSD and pain patients.     

Effects of angiotensin-converting enzyme inhibitor,captopril, on bone of mice with streptozotocin-induced type 1 diabetes

There are contradictory results about the effect of angiotensin-converting enzyme inhibitors (ACEIs) on bone. This study was performed to address the skeletal renin?angiotensin system (RAS) activity and the effects of the ACEI, captopril, on the bone of streptozotocin-induced type 1 diabetic mice. Histochemical assessment on bone paraffin sections was conducted by Safranin O staining and tartrate-resistant acid phosphatase staining. Micro-computed tomography was performed to analyze bone biological parameters. Gene and protein expression were determined by real-time polymerase chain reaction and immunoblotting, respectively. Type 1 diabetic mice displayed osteopenia phenotype and captopril treatment showed no osteoprotective effects in diabetic mice as shown by the reduction of bone mineral density, trabecular thickness and bone volume/total volume. The mRNA expression of ACE and renin receptor, and the protein expression of renin and angiotensin II were markedly up-regulated in the bone of vehicle-treated diabetic mice compared to those of non-diabetic mice, and these molecular changes of skeletal RAS components were effectively inhibited by treatment with captopril. However, treatment with captopril significantly elevated serum tartrate-resistant acid phosphatase 5b levels, reduced the ratio of osteoprotegerin/receptor activator of nuclear factor-κB ligand expression, increased carbonic anhydrase II mRNA expression and the number of matured osteoclasts and decreased transforming growth factor-β and osteocalcin mRNA expression in the tibia compared to those of diabetic mice. The present study demonstrated that the use of the ACEI, captopril, has no beneficial effect on the skeletal biological properties of diabetic mice. However, this could be attributed, at least partially, to its suppression of osteogenesis and stimulation of osteoclastogenesis, even though it could effectively inhibit high activity of local RAS in the bone of diabetic mice.     

A minimally invasive strategy for Mirizzi syndrome: the combined endoscopic and robotic approach

Background

Mirizzi syndrome (MS) is a rare complication of gallstone disease. Despite the fact that successful laparoscopic treatments have been reported, open surgery remains the gold standard approach for this disease due to technical difficulties involved.

Methods

A minimally invasive strategy combining endoscopic retrograde cholangiopancreatography (ERCP) and robotic surgery for the management of MS was implemented in early 2012. This consisted of a preoperative ERCP for definitive diagnosis and endoscopic stent insertion. Robotic surgical approach was used during operation to facilitate gall bladder removal and suture of defect over common duct. ERCP was repeated postoperatively for stent removal. Patient demographics and treatment outcomes were collected prospectively. A historical cohort of patients with MS who underwent conventional surgery between 1999 and 2011 was identified for comparison of treatment outcomes.

Results

Five patients with MS were managed with this strategy. Robotic subtotal cholecystectomy was successfully performed in all the patients without conversion or morbidity. When compared with a historical cohort of 17 patients who underwent surgery for MS, this group of patients had significantly less conversion and shorter hospital stay though the operation time was longer. It also showed less blood loss and less postoperative complications but these were not statistically significant.

Conclusion

Mirizzi syndrome can be effectively managed with a minimally invasive approach by adopting a robot-assisted surgery together with a planned pre- and postoperative ERCP.     

Feasibility of full-thickness gastric resection using master and slave transluminal endoscopic robot and closure by overstitch: a preclinical study

Background

Gastric submucosal tumors are often treated by laparoscopic wedge resection. This study aimed to examine the feasibility of gastric full-thickness resection through a totally endoscopic approach using the master and slave transluminal endoscopic robot (MASTER), and closure of the luminal defect with an endoscopic suturing device.

Methods

The operation was performed in two live porcine models under general anesthesia. First, the anterior wall of the stomach was slung to the abdominal wall using a percutaneous suturing device. An imaginary 5-cm lesion was marked using a needle knife. After the initial mucosal incision was made using an IT knife, the MASTER was introduced through a long overtube. A circumferential mucosal incision was completed with the MASTER to expose the muscularis propria which was grasped and incised to the serosal layer by electrocautery applied through the hook of the MASTER. The full-thickness resection of the gastric wall was completed with retraction using the grasper and dissection using the hook. While the defect was being created, the luminal space was maintained with traction of the percutaneous sutures. The defect was closed with suture plication using an Apollo Overstitch device.

Results

Two full-thickness gastric resections were performed in two nonsurvival porcine models (body weight = 30 and 35 kg, respectively) using the MASTER. The total procedure time was 56 min for the first model and 70 min for the second model. The luminal view was maintained during the whole procedure, and there was no damage to surrounding organs throughout the whole procedure. The gastric defects were closed successfully using Overstitch, with satisfactory gastric distension and no gas leakage afterward.

Conclusion

The current experiment demonstrated the feasibility and safety of a totally endoscopic approach for the treatment of gastric submucosal tumors: full-thickness resection with the MASTER and successful closure of the defect using Overstitch.     

Making sense of the spectrum of glomerular disease associated with complement dysregulation

Over recent years, complement has emerged as a major player in the development of a number of glomerular diseases, including atypical haemolytic uraemic syndrome, membranoproliferative glomerulonephritis and the recently described C3 glomerulonephritis. Some patients and pedigrees show overlapping features of these conditions. Intriguingly, a few complement gene mutations are common to different disease phenotypes. In this review, we explore the evidence for complement dysregulation in these diseases and the clinical interface between them, and present a hypothesis to explain the variable phenotype associated with dysregulation of the alternative complement pathway.     

Comparative gastrointestinal safety of bisphosphonates in primary osteoporosis: a network meta-analysis

Summary

We completed a network meta-analysis of published papers to compare bisphosphonate gastrointestinal safety. We found that zoledronic acid had the highest chance of causing gastrointestinal adverse events. Etidronate had the highest chance of discontinuation due to an adverse event. No difference was found for serious adverse events.

Introduction

Bisphosphonates are first-line treatment for osteoporosis. Gastrointestinal (GI) adverse events (AE) are the primary reason for non-adherence. Little is known about the comparative GI safety of bisphosphonates.

Purpose

Leverage published clinical trial data to examine the comparative GI safety of bisphosphonates.

Methods

We completed a systematic review of all English-language clinical trials that assessed bisphosphonate safety and/or efficacy in primary osteoporosis through to 2012. Randomized, blinded, and controlled studies were eligible. The primary outcome was any GI-related AE. Subanalyses were completed for upper GI symptoms, serious GI, nausea, esophageal-related events, and discontinuation due to AE. A Bayesian-based network meta-analysis was completed to allow for indirect comparisons. Results were reported as the probability that a specific drug had the highest number of events.

Results

We identified 50 studies: 32 alendronate, 12 risedronate, 5 etidronate, and 7 zoledronic acid. Zoledronic acid had the highest probability of having the highest number of any GI AE (91 %) and nausea (70 %). Etidronate (70 %) and zoledronic acid (28 %) had the highest probability of having the greatest attrition due to AE. Etidronate had the highest probability (56 %) of having the greatest number of upper GI symptoms among oral bisphosphonates.

Conclusion

Zoledronic acid had the highest probability of causing the greatest number of GI AE, possibly related to nausea. These results question the assumption that annual zoledronic acid will translate into better adherence. Little difference was found between alendronate and risedronate for serious AE. More research into real-world implications of the comparative safety of bisphosphonates is needed.     

The effects of anxiety sensitivity,pain hypervigilance,and pain catastrophizing on quality of life outcomes of patients with chronic pain: a preliminary,cross-sectional analysis

Purpose

In the fear-avoidance model (FAM) of chronic pain, pain-related fear is one of the most prominent predictors of negative adjustment outcomes. While existing data point to the effects of anxiety sensitivity, pain hypervigilance, and pain catastrophizing on pain-related fear, the nature of their multivariate relationships remains unclear. This study explored the possible mediating role of pain hypervigilance in the relationship of anxiety sensitivity and pain catastrophizing with pain-related fear, and their effects on quality of life (QoL) outcomes within the FAM framework.

Methods

A sample of 401 Chinese patients with chronic musculoskeletal pain completed the standardized measures assessing the FAM components and QoL. Structural equation modeling (SEM) was used to evaluate six hypothesized models.

Results

Results of SEM showed adequate data-model fit [comparative fit indexes (CFIs) ranging from 0.92 to 0.94] on models which specified pain hypervigilance as mediator of anxiety sensitivity and pain catastrophizing with pain-related fear on two QoL outcomes (QoL-Physical and QoL-Mental). Results consistent with net suppression effects of pain catastrophizing on anxiety sensitivity were found in SEM when both anxiety sensitivity and pain catastrophizing were included in the same full model to predict QoL-Physical (CFI = 0.95; Sobel z = 8.06, p < 0.001) and QoL-Mental (CFI = 0.93; Sobel z = 8.31, p < 0.001).

Conclusions

These cross-sectional analyses gave results consistent with pain hypervigilance, mediating the relationship of pain catastrophic cognition and anxiety sensitivity with pain-related fear. The net suppression effects of pain catastrophizing point to anxiety sensitivity, enhancing the effect of pain catastrophic cognition on pain hypervigilance. These findings elucidate how the interdependence of dispositional factors might influence pain adjustment and functioning.     

Optimization of GPR40 Agonists for Type 2 Diabetes

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